The management of moderate to severe atopic dermatitis in adults with topical fluticasone propionate. The Netherlands Adult Atopic DermatitisStudy Group.

This study was designed to investigate a long-term therapeutic strategy for the management of recurring atopic dermatitis (AD) in adults using fluticasone propionate (FP) ointment (CutivateTM) whereby FP could help to prevent a relapse of AD once symptoms were under control. Adult patients with chronic, moderate to severe AD entered this multicentre study. All patients were initially treated with FP 0.005% (g/g) ointment in two different regimens. Patients whose AD had been completely healed by these treatments then entered a long-term treatment phase applying FP or placebo ointment once daily, two times per week for 16 weeks to 'known' healed lesions. By the end of the initial treatment period, mean SCORAD values had significantly (P < 0.0005) improved from baseline. Patients who entered the maintenance phase and were treated with intermittent FP for up to 16 weeks, demonstrated its superior efficacy (P = 0.018) over placebo, maintaining the improvements achieved after the initial treatment phase, reducing risk of relapse and delaying time to relapse (P = 0.013). No significant changes were detected in either treatment group in serum cortisol levels or in skin thickness measurements. Intermittent FP applied two times per week maintained a significant level of control, and delayed relapse of AD by comparison with placebo.

Quantification of relative area of pS2 immunohistochemical staining and epithelial percentage in breast carcinomas: the effect of the latter on the interpretation of a cytosolic pS2 assay.

In immunochemical assays of specific cell constituents in cytosols from tumors, the relationship between epithelial and stromal fractions is not taken into account. This may influence the outcome of the measurements and result in incorrect categorization as negative or positive. In a setting addressing pS2 (only detectable in epithelial cells) in breast carcinomas, we investigated three possibilities that may overcome this problem using histologic sections of breast carcinomas of 50 patients: (a) visual estimation of area percentage of immunohistochemical staining of the cell constituent of interest performed by three independent individuals, (b) quantification of area percentage of the immunohistochemical results by true color image analysis, and (c) quantification of the epithelial and stromal compartments of the tumors in Heidenhain's-azan-stained tissue sections, using the true color image analysis system, to assess the epithelial percentage in the tumors. This percentage was used as a correction factor for data on pS2 obtained by cytosolic determinations. Visual estimation appeared to be subject to interobserver variation and, subsequently, becomes less applicable in the absence of strict scoring rules. Based on tests for correlation, image analysis system quantification seemed reproducible in both quantification procedures. However, due to the high magnification necessary to visualize the immunohistochemical staining product, the effect of field selection caused systematic differences between repeat measurements (Friedman test). As a result of the contrasting colors of the azan staining, the calculation of the epithelia percentage could be performed at a low magnification. Consequently, here the effect of field selection was not present. Correction of cytosolic values for epithelial percentage resulted in 8% of the cases changing category.(ABSTRACT TRUNCATED AT 250 WORDS)

An extra gonadal non-gestational choriocarcinoma in a woman treated for an endometrial carcinoma.

A patient was presented with a non-gestational non-gonadal choriocarcinoma and hyperthyroidism. Five years earlier, at the age of 36, she underwent an abdominal hysterectomy with bilateral adnexectomy for endometrial carcinoma. Despite intensive treatment with multiple chemotherapy the patient died. We concluded that this non-gestational, non-gonadal choriocarcinoma was a recurrence of her previous endometrial carcinoma or a new extra (non) gonadal germcell tumor with choriocarcinoma.

Quantification of area percentage of immunohistochemical staining by true color image analysis with application of fixed thresholds.

Most image analysis systems (IAS) use black-and-white cameras. However, true color IASs are considered to be useful for quantification of immunohistologically stained structures. Using a true color IAS, we evaluated two methods of segmentation for quantification of area percentage of staining: one using fixed, preset thresholds and one using thresholds interactively set per image. Furthermore, the effect of shading correction was evaluated, and measurements in both color and black-and-white mode were compared. The results of segmentation with fixed thresholds did not differ significantly from those of control percentages, established by interactive morphometry using a grid, which served as reference. Interactive segmentation was significantly different from the reference (t test, P = .0001). The effect of shading correction was negligible. Measurements with and without this procedure correlated highly (r = .99, P < .001). Comparison of the results obtained in color and black-and-white mode showed a significant difference in the latter from the reference (t test, P = .005). We conclude that it is possible to quantify, in a reliable way, area percentage of positive staining using a true color IAS with application of a segmentation method with fixed thresholds.

Pneumocystis carinii pneumonia associated with low dose methotrexate treatment for rheumatoid arthritis.

Since 1983 there have been several reports on Pneumocystis carinii pneumonia (PCP), complicating low dose methotrexate (MTX) therapy for rheumatoid arthritis (RA). Two additional cases of this opportunistic infection are reported and a review of the literature on the complication is presented. It is concluded that PCP is a serious complication of low dose MTX therapy for RA and should always be ruled out when a patient presents with pulmonary symptoms. Several factors may play a role in the occurrence of this opportunistic infection, but the exact mechanism has not yet been elucidated.

Squamous cell carcinoma arising in a residual cyst. A case report.

A case of squamous cell carcinoma (SCC) arising in a mandibular residual cyst in a 62-year-old man is presented. The treatment included enucleation followed by primary closure. Histologic examination revealed a poorly differentiated SCC in the cyst lining without invasion through the connective tissue wall. Eight and a half years later, the patient was still free from recurrence.

Image analysis in immunohistochemistry. Factors with a possible influence on the performance of VIDAS version 2.0, a commercially available true color image analysis system.

This paper describes the evaluation of several factors with a possible influence on the performance of a commercially available image analysis system capable of true color image analysis. The software used by this system is VIDAS Version 2.0. The following factors were evaluated: illumination, power supply, warming up, shading correction, averaging of image intake, hue luminance and saturation images and relation of illumination to quantification of area percentage (area %) of positively staining structures. The first six factors were evaluated by using a macro, with which it is possible to obtain information on variations over the image and over time. The last factor was evaluated by repeated measurement of area % of positive staining in a routinely processed tissue section. In our setting, stability of illumination and warmup time of the camera appeared to be the most important factors with influence on the performance of the image analysis system.

Epidermodysplasia verruciformis. Skin carcinoma containing human papillomavirus type 5 DNA sequences and primary hepatocellular carcinoma associated with chronic hepatitis B virus infection in a patient.

In a case of epidermodysplasia verruciformis with impaired cell-mediated immunity and multiple skin cancers human papillomavirus type 5 (HPV5) DNA sequences were demonstrated in a cutaneous squamous cell carcinoma. HPV5 and HPV8 were detected in the benign disseminated skin lesions together with three newly characterized HPVs: HPV17, HPV19 and HPV24. A chronic infection with hepatitis B virus resulting in macronodular cirrhosis associated with a primary hepatocellular carcinoma was also acquired by this patient. This case provides an example of the circumstantial evidence which suggests that certain types of HPV are potentially oncogenic and stresses the importance of immune surveillance in the protection against virus-associated tumors.

Cellular and humoral immune reactions in chronic active liver disease. II. Lymphocyte subsets and viral antigens in liver biopsies of patients with acute and chronic hepatitis B.

The characteristics and distribution of the inflammatory infiltrate in liver biopsies of 25 patients with hepatitis B viral (HBV) infection were studied in relation to the distribution and expression of HBV antigens. Mononuclear subsets were characterized with monoclonal (OKT, OKM, Leu) antibodies to surface antigens. For the demonstration of viral antigens directly conjugated antibodies to surface (HBsAg), core (HBcAg) and 'e' (HBeAg) antigen were used. For the study of mutual relations all methods were performed on serial cut tissue sections. In chronic active hepatitis B (CAH-B, n = 12) OKT8+ lymphocytes of T cell origin were the only cell type present in areas with liver cell degeneration and T cell cytotoxicity appears to be the only immune mechanism. In chronic persistent hepatitis B (CPH-B, n = 7) the only conspicuous feature was the presence of many Leu 3+ lymphocytes of the helper/inducer population in the portal tracts. In acute hepatitis B (AHB, n = 6) OKT8+ cells of non-T origin (OKT1-,3-) and Leu 7+ cells of presumed natural killer (NK) potential predominated in the areas with liver cell necrosis, and non-T cell cytotoxicity appears to be the predominant immune mechanism. In none of these disease entities a positive spatial relation could be established between the cytotoxic cells and the demonstrable expression of HBV antigens in hepatocytes. It is concluded that differences in immunological reaction pattern may explain the different course in the three forms of HBV infection studied.

Etretinate (Tigason) hepatitis in 2 patients.

A histologically confirmed, clinically inapparent and reversible hepatitis occurred in 2 patients (1 psoriasis, 1 basal cell nevus syndrome) within the first months after introduction of etretinate therapy. Causes of hepatitis other than etretinate were not found. Reintroduction of etretinate resulted in reactivation and/or persistence of the hepatitis in both patients. These data strongly suggest that the hepatitis in both patients was caused by etretinate. Later the basal cell nevus syndrome patient was given 13-cis-retinoic acid, which caused no liver test disturbances during a follow-up period of 6 months.

Histopathology of serial graft biopsies from liver transplant recipients.

Serial graft biopsies (n = 78) from 12 liver transplant recipients (followed clinically up to 47 months) were studied with the use of histology, histochemistry, immunostaining, and electron microscopy. Planned-protocol needle biopsy specimens were taken from the graft before removal from the donor, 1 hour after transplantation, on the eighth day, and at yearly intervals. Nonprotocol biopsies were taken when deterioration of the clinical condition made a decision on changes in the regimen necessary. The protocol biopsies provided a baseline for graft condition and diagnostic histopathologic features. In these biopsies signs of hyperacute rejection, chronic rejection, or the recipient's previous liver disease were not observed. Mild acute rejection was regularly present on the eighth day, possibly due to a lag phase in the effect of immunosuppression. The syndromes in the nonprotocol biopsies included "pure" parenchymal cholestasis, reversible acute rejection resembling chronic active hepatitis, viral infection, and acute bacterial cholangitis. Each of these syndromes correlated with a separate histopathologic entity. Therefore, these entities proved to be of diagnostic value. It is concluded that a graft biopsy may substantially add to the pathogenetic interpretation, differential diagnosis, and management of major graft syndromes in orthotopic liver transplant recipients.

Cellular and humoral immune reactions in chronic active liver disease. I. Lymphocyte subsets in liver biopsies of patients with untreated idiopathic autoimmune hepatitis, chronic active hepatitis B and primary biliary cirrhosis.

In liver biopsies of 37 patients with chronic active liver disease (CALD) the inflammatory infiltrate was studied with monoclonal antibodies to the surface antigens on helper/inducer (OKT4+), suppressor/cytotoxic (OKT8+), killer/natural killer (OKM1,2+) cells and common T cell antigens (OKT1+, OKT3+). Furthermore OKT11 antibody was applied, which defines the E rosette receptor. Special emphasis was given to areas with piece-meal necrosis (PMN). In areas with PMN in idiopathic autoimmune CALD (IA-CALD, n = 15) OKT8+ and OKM+ lymphocytes and IgG plasma cells were present, whereas in hepatitis B-CALD (HB-CALD, n = 12) almost exclusively OKT8+ cells were found. In PBC (n = 10) OKT4+ cells in central parts of portal tracts and OKT8+ cells in areas with PMN predominated. These findings indicate that in IA-CALD antibody-dependent cell-mediated cytotoxicity (ADCC), as well as T cell cytotoxicity may be responsible for liver cell damage, while in HB-CALD T cell cytotoxicity seems to be the only mechanism. In PBC liver cell damage also predominantly is the result of T cell cytotoxicity. In addition, helper T lymphocytes seem to play a role since these are found in central areas of the portal tracts.