Effect of melasma on quality of life in a sample of women living in southern Brazil

Background Melasma can cause a significant effect on individual emotional well‐being. Melasma Quality of Life Scale (MELASQoL) is a specific questionnaire elaborated to assess the burden of melasma on patient's quality of life. Objective To evaluate the clinical aspects, severity and the influence of melasma on daily living of a sample of Brazilian women. Methods Cross‐sectional study that enrolled 85 women with melasma older than 15 years of age. Trained investigators asked 55 questions to collect epidemiological and clinical data. The disease severity was clinically assessed using Melasma Area and Severity Index (MASI). Patients answered the Portuguese version of 10‐item MELASQoL scale without coaching. Results The mean ± SD age was 41.1 ± 6.8 years, and the mean ± SD of MELASQoL score was 37.5 ± 15.2 (median, 35). Patients with previous psychiatric diagnosis had significantly higher MELASQoL scores (mean, 42.8; SD, 13.6) than patients without this antecedent (mean, 35.4; SD, 15.4; P < 0.05). Patients with less than 8 years of school attendance also had significantly higher MELASQoL score (mean, 44; SD, 16.9) than more graduated ones (mean, 34.4; SD, 13.5; P < 0.05). The mean ± SD MASI was 10.6 ± 6.6 (median, 10.2). There was no correlation between MASI and MELASQoL. Conclusions This study confirms that MELASQoL‐BP is easy to administer, adds important information about the impact of melasma on South American women's life and, finally, contributes to building evidence on the validity, reliability and cultural adaptation of the Portuguese language MELASQoL version.     

Antigen-specific regression of established tumors induced by active immunization with irradiated IL-12- but not B7-1-transfected tumor cells

Transfection of modestly immunogenic tumors to express B7 family co- stimulator molecules results in their rejection by syngeneic mice, suggesting a possible clinical application in cancer patients. Immunization of naive mice with irradiated B7-1-transfected P1.HTR cells is sufficient to induce specific cytolytic T lymphocytes (CTL) and to protect against tumor challenge. However, patients to be treated will have an existing tumor burden; thus, preclinical models should examine therapeutic efficacy in an established tumor setting. Contrary to expectations, immunization of mice with irradiated B7-1-transfected P1.HTR cells had no impact on the growth of pre-established control- transfected tumors. Mice bearing control-transfected P1.HTR tumors successfully rejected living B7-1 transfectants on the contralateral flank, demonstrating the ability of tumor-bearing mice to respond to B7 co-stimulation. Inasmuch as IL-12 is another important factor for CTL maturation, P1.HTR transfectants expressing B7-1 and/or IL-12 were then constructed. Remarkably, regression of pre-established tumors was achieved following immunization with irradiated IL-12 transfectants, even without co-expression of B7-1. Rejection required a shared antigen with the tumor used for immunization, could not be reproduced with rIL- 12 alone, depended on host T lymphocytes and correlated with a high IFN- gamma-producing T cell phenotype. In addition, IL-12-facilitated tumor rejection required co-operation with a CTLA-4 ligand provided by the host, and correlated with up-regulation of B7-1 and B7-2 on host antigen-presenting cells. Thus, active immunization in the established tumor setting is benefitted greatly by the provision of IL-12, which may recruit participation of sufficient B7 co-stimulation from the host that it need not be provided exogenously.      

Effects of early postnatal dexamethasone therapy on calcium homeostasis and bone growth in preterm infants with respiratory distress syndrome

The effects of dexamethasone therapy on calcium homeostasis and bone growth were evaluated in 49 infants (24 placebo and 25 dexamethasone) who participated in a double-blind trial of early dexamethasone therapy for the prevention of chronic lung disease. Dexamethasone (0.25 mg kg^-1 b.i.d. on d 1–7; 0.12 mg kg^-1 b.i.d. on d 8-14; 0.05mg kg^-1 b.i.d. on d 15-21; 0.02mg kg^-1 b.i.d. on d 22-28) or saline placebo was given i.v. Serum calcium (Ca), phosphorus (P) and parathyroid hormone (PTH), and the corresponding urinary excretion of calcium (FE_Ca) and phosphorus (FE_P) were measured on d 2, 3, 7, 10, 14, 21 and 28 after starting the study. Radiographic evaluations of bone growth were also evaluated. Infants in the dexamethasone group had significantly higher PTH on d 2 ( p < 0:01), 7 and 14 ( p < 0:05) than infants in the placebo group. The dexamethasone-treated infants also had significantly higher FE_P on d 2,7 and 14 ( p < 0:05) and lower FE_Ca on d 7 and 14 ( p < 0:05) than control infants. There was no significant difference between the groups in bone growth during the study. It was concluded that early dexamethasone therapy causes a transient elevation in PTH without apparent change in bone growth. The long-term effect remains to be evaluated further.     

Relationship between antibody to hepatitis B core antigen and retroviral infections in blood from volunteer donors

Background: The value of the test for antibody to hepatitis B core antigen (anti-HBc) as a surrogate screening assay in the time before sensitive, virus-specific screening tests were available has been well established. There is significant debate, however about the residual value of anti-HBc screening after the implementation of human immunodeficiency virus (HIV)-, human T-lymphotrophic virus (HTLV)-, and hepatitis C virus (HCV)-specific assays and, in particular, about its utility as a lifestyle marker to identify persons at risk for retrovirus infections. Study Design and Methods: Screening tests for antibodies to HIV, HTLV, and HBc, as well as confirmatory or supplemental test results for anti-HIV and anti-HTLV, were obtained from approximately 2.8 million donations collected from 1991 through 1993 by five blood centers within the United States. The sensitivity, positive predictive value, and relative prevalence of anti-HBc for each retrovirus were calculated and compared among demographic subgroups. Results: The overall relationship between anti-HBc and anti-HIV was similar to that between anti-HBc and anti-HTLV. When calculated from the measured endpoint of the prevalence of anti-HIV-positive and anti- HTLV-positive donations, the sensitivities were 31.1 and 26.2 percent, the positive predictive values were 0.18 and 0.21 percent, and the relative prevalences were 30.1 and 23.8, respectively. Among 27 anti- HIV-seroconverting donors and 9 anti-HTLV-seroconverting donors, the sensitivities were 7.4 percent (95% CI: 0.9–24.3%) and 0 percent (95% CI: 0.0–28.3%), respectively. It was estimated that for each HIV- infected window-period donation detected by anti-HBc, from 19,000 to 81,000 HIV-noninfected donations are discarded. Similarly, more than 33,000 HTLV-noninfected donations are likely to be discarded for each HTLV-infected donation detected by anti-HBc. Conclusion: Although anti- HBc-reactive donations are more likely to be seropositive for a retrovirus than are anti-HBc-nonreactive donations, the low positive predictive value limits the test's effectiveness. If the anti-HBc test is retained in the blood donor setting, efforts should be focused on reducing the number of false-positive results.     

Engagement of the adhesion receptor CD22 triggers a potent stimulatory signal for B cells and blocking CD22/CD22L interactions impairs T-cell proliferation

The B-lymphocyte-restricted adhesion protein CD22 mediates sialic acid- dependent cell-cell interactions. Engagement of CD22 on B lymphocytes with a CD22 monoclonal antibody (MoAb) HB22.7 that blocks the binding of CD22 to its ligand(s) directly stimulated B-cell proliferation. In addition, the HB22.7 MoAb costimulated B-cell proliferation with either anti-IgM, interleukin-2 (IL-2), IL-4, or CD40 and triggered predominantly B-cell IgG secretion with IL-2. Even more striking levels of B-cell proliferation occurred with HB22.7 MoAb under culture conditions that enhanced B-B-cell interactions. In contrast, a nonblocking CD22 MoAb (CD22.5) poorly costimulated in similar experiments. The functional differences between the two antibodies likely result from differing abilities to trigger downstream signaling events as significant differences in CD22 tyrosine phosphorylation and the recruitment of the tyrosine kinase p53/56lyn and the tyrosine phosphatase SH-PTP1C were found. Besides their role in B-cell stimulation, CD22/CD22L interactions may also assist in regulating T- cell proliferation because inhibition of CD22-CD22L engagement with the HB22.7 MoAb impaired T-cell proliferation in a costimulatory assay. Thus, CD22/CD22L interactions result in stimulatory signals for both B and T lymphocytes.     

The B7-2 (B70) costimulatory molecule expressed by monocytes and activated B lymphocytes is the CD86 differentiation antigen

T-cell activation is initiated after T-cell receptor binding to antigen, but also requires interactions between costimulatory molecules expressed on antigen-presenting cells. An important costimulatory molecule expressed by monocytes and activated B lymphocytes has been recently identified and termed B7-2 or B70. Independently, a new Cluster of Differentiation was defined in the Fifth International Leukocyte Differentiation Antigen Workshop as CD86, a molecule predominantly expressed by monocytes and activated B lymphocytes. In this study, the two monoclonal antibodies that defined CD86, FUN-1 and BU-63, were shown to bind to cDNA transfected cells expressing B7- 2/B70. The FUN-1 monoclonal antibody also completely blocked the costimulatory activity of B7-2/B70 in functional assays. Therefore, the serologically defined CD86 differentiation antigen is the B7-2/B70 molecule.     

Inhibition of leukocyte L-selectin function with a monoclonal antibody attenuates reperfusion injury to the rabbit ear

The leukocyte adhesion molecule L-selectin mediates neutrophil adhesive interactions with endothelial cells and is in part responsible for neutrophil rolling. We examined the role of L-selectin in ischemia- reperfusion injury of rabbit ears using a monoclonal antibody (MoAb) directed to a functional epitope of L-selectin. Arterial blood flow to the rabbit ear was occluded for six hours with ambient temperature at 23 degrees C to 24 degrees C. Rabbits were treated at reperfusion with saline (n = 8), the L-selectin function-blocking LAM1-3 MoAb (2 mg/kg), or the nonfunction-blocking LAM1-14 MoAb (2 mg/kg). Tissue injury was determined by measuring edema and necrosis. Edema in the LAM1-3 MoAb- treated group (peak = 25 +/- 4 mL) was significantly less (P < .05) than in saline-treated (peak = 40 +/- 8 mL) and LAM1-14 MoAb-treated (peak = 41 +/- 6 mL) groups. Tissue necrosis at 7 days was not observed in the LAM1-3 MoAb-treated group, whereas significant necrosis (P < .05) was seen in the saline- (8% +/- 3% necrosis) and LAM1-14 MoAb- treated (7% +/- 3% necrosis) group. We conclude that blocking L- selectin ameliorates necrosis and edema after ischemia and reperfusion in the rabbit ear, presumably by blocking neutrophil rolling.     

Synovial lining, endothelial and inflammatory mononuclear cell proliferation in synovial membranes in psoriatic and reactive arthritis: a comparative quantitative morphometric study

The extent of synovial cell proliferation in situ and its relationship to the destructive potential of rheumatoid arthritis (RA) is a matter of continuing debate. Notably, the situation has not been elucidated in other inflammatory arthritides [i.e. reactive (ReA) and psoriatic (PsA)], which, although they share some histopathological similarities with RA, develop different patterns of joint involvement. In order to estimate the proliferation of synovial cells in situ in PsA and ReA, and to compare this with RA and with 'non-inflammatory' joint lesions, we have utilized immunostaining of the Ki-67 antigen complemented with Ki-67/CD68 or Ki-67/leucocyte common antigen (LCA, clones 2B11 and PD7/26) double stainings to assess the extent of mononuclear inflammatory cell proliferation. Synovial samples analysed were from 33 patients: RA (n = 8), PsA (n = 13), ReA (n = 6) and six 'non- inflammatory controls' (degenerative or traumatic joint lesions). Thickening of the synovial lining (in particular in RA) and perivascular accumulations of mononuclear inflammatory cells, predominantly lymphocytes, were characteristic features in all synovitides. In contrast to the thickened avascular synovial lining in RA, in 5/13 cases with PsA, blood vessels were observed in the lining. The percentage of lining cells expressing Ki-67 antigen was higher in RA (median = 4.7, interquartile range [Q3-Q1] = 3.9, mean [95% CI] = 3.5 [1.7-5.2], P = 0.0063), PsA (median = 1.2, [Q3-Q1] = 1.9, mean [95% CI] = 1.6 [0.7-2.5], P = 0.007) and ReA (median = 1.4, [Q3-Q1] = 2.3, mean [95% CI] = 1.6 [0.1-3.1], P = 0.0235) than in controls (median = 0.1, [Q3-Q1] = 0.45, mean [95% CI] = 0.2 [0.07-0.5]). In this respect, the differences between different forms of the inflammatory arthritides were not statistically significant (P > 0.05). In RA, PsA and ReA, the percentage of labelled cells in the inflammatory mononuclear cell-rich areas was higher than in controls. The percentage of proliferating endothelial cells was also significantly higher in RA, PsA and ReA than in controls. However, in RA, endothelial expression of Ki-67 antigen was often seen in small blood vessels, whereas in PsA, Ki-67 antigen was preferably expressed in the medium to large blood vessels. Synovial lining cells of the monocyte/macrophage lineage (type A synoviocytes), but not stromal monocytes, demonstrated modest proliferation in situ. These results indicate that although proliferation of synovial lining fibroblasts is a prominent feature in RA, the extents to which this, or in situ proliferation of lymphocytes, contribute to the histopathology of PsA, ReA and RA are comparable. Vascular involvement is suggested by the proliferation of endothelial cells in RA, PsA and ReA in an overlapping manner, but, based on topological differences, such a response may represent diverse pathological features, such as angiogenesis, vascular enlargement and reparative responses to injury.