Eruptive pseudoangiomatosis in adults with immune system disorders: A report of two cases.

Eruptive pseudoangiomatosis is a cutaneous disease of unknown origin, characterized by the sudden appearance of small, asymptomatic angioma-like erythematous papules surrounded by a pale halo that resolves spontaneously. It occurs due to transitory dermal blood vessel dilation and has been associated with viral infections and hematologic disorders. To this day, it remains a disease that affects mostly the lower spectrum of life. Most of the cases have been reported in children and few reports have described its association with immune system disorders. The diagnosis is based upon clinical presentation. Histopathological analysis has no pathognomonic findings and can include dilated dermal blood vessels, perivascular lymphocytic infiltration and plump endothelial cells. We report a 21-years-old female diagnosed with HIV in AIDS stage and a 19- years-old male diagnosed with non- Hodgkin's lymphoma.

Inhibition of type I insulin-like growth factor receptor signaling attenuates the development of breast cancer brain metastasis.

Brain metastasis is a common cause of mortality in cancer patients, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF-IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that IGF-IR is constitutively autophosphorylated in brain-seeking breast cancer sublines. Knockdown of IGF-IR results in a decrease of phospho-AKT and phospho-p70s6k, as well as decreased migration and invasion of MDA-MB-231Br brain-seeking cells. In addition, transient ablation of IGFBP3, which is overexpressed in brain-seeking cells, blocks IGF-IR activation. Using an in vivo experimental brain metastasis model, we show that IGF-IR knockdown brain-seeking cells have reduced potential to establish brain metastases. Finally, we demonstrate that the malignancy of brain-seeking cells is attenuated by pharmacological inhibition with picropodophyllin, an IGF-IR-specific tyrosine kinase inhibitor. Together, our data suggest that the IGF-IR is an important mediator of brain metastasis and its ablation delays the onset of brain metastases in our model system.

Do men with eating disorders differ from women in clinics, psychopathology and personality?

OBJECTIVE: To determine if male and female eating disorders differ in clinics, psychopathology and personality traits when compared with a healthy group. METHODS: Sixty male and 60 female eating disorder individuals (16% anorexia nervosa, 42% bulimia nervosa and 42% eating disorder not otherwise specified), matched for age and diagnostic, were compared with 120 healthy-eating participants (60 male and 60 female participants). All were diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Assessment measures included Eating Disorder Inventory--2, Symptom Checklist--Revised and Temperament and Character Inventory--Revised, as well as other clinical and psychopathological indices. RESULTS: Male eating disorder participants reported significant lower laxative abuse (p = 0.020) and significant higher vomiting episodes (p = 0.019) than female eating disorder participants. Differences on drive for thinness, body dissatisfaction and some Symptom Checklist--Revised scales were found across genders in eating disorder participants. Male eating disorder participants scored significantly lower than female participants with eating disorders on harm avoidance, reward dependence and cooperativeness. CONCLUSIONS: Although eating disorder clinical features were similar across genders, male eating disorder participants had less body image concern and general psychopathology than female eating disorder participants.

Prediction of clinical outcomes in primary biliary cirrhosis by serum enhanced liver fibrosis assay.

UNLABELLED: Primary biliary cirrhosis (PBC) is sometimes diagnosed based on a positive antimitochondrial antibody in the appropriate clinical setting without a liver biopsy. Although a liver biopsy can assess the extent of liver fibrosis and provide prognostic information, serum fibrosis markers avoid biopsy complications and sampling error and provide results as a continuous variable, which may be more precise than categorical histological stages. The current study was undertaken to evaluate serum fibrosis markers as predictors of clinical progression in a large cohort of PBC patients. Serial liver biopsy specimens and serum samples were collected every 2 years in 161 PBC subjects for a median of 7.3 years. Clinical progression was defined as development of one or more of the following events: varices, variceal bleed, ascites, encephalopathy, liver transplantation, or liver-related death. Serum hyaluronic acid, tissue inhibitor of metalloproteinase 1, and procollagen III aminopeptide were measured and entered into the previously validated enhanced liver fibrosis (ELF) algorithm. The ability of ELF, histological fibrosis, bilirubin, Model for End-Stage Liver Disease (MELD), and Mayo Risk Score to differentiate between individuals who would experience a clinical event from those who would not was evaluated at different time points. Event-free survival was significantly lower in those with high baseline ELF. Each 1-point increase in ELF was associated with a threefold increase in future complications. The prognostic performance of all tests was similar when performed close to the time of the first event. However, at earlier times in the disease process (4 and 6 years before the first event), the prognostic performance of ELF was significantly better than MELD or Mayo R score. CONCLUSION: The ELF algorithm is a highly accurate noninvasive measure of PBC disease severity that provides useful long-term prognostic information.

Sertraline as a first-line treatment for cholestatic pruritus.

UNLABELLED: Pruritus is frequently the most debilitating symptom of cholestatic liver diseases. Moreover, existing therapies are often ineffective. Recent small, retrospective case series reports suggest that serotonin reuptake inhibitors can improve pruritus. This study was undertaken to establish the dose of sertraline and to evaluate its efficacy for cholestatic pruritus. Twenty one subjects with chronic pruritus due to liver disease (including primary biliary cirrhosis, primary sclerosing cholangitis, chronic hepatitis C, and postnecrotic cirrhosis) initially underwent an open-label, dose escalation to determine the dose with optimal efficacy and tolerability. After a washout period, 12 of the subjects entered a randomized, double-blind, placebo-controlled trial. Participants quantified their pruritus using a 0-10 visual analog scale, and pruritus was assessed for distribution, timing, degree of disability, and physical evidence of scratching. The optimum sertraline dose (75-100 mg/day) was well tolerated. In the controlled portion of the study, itch scores improved in patients taking sertraline, but worsened in patients taking placebo (P=0.009). Changes in itch distribution, duration, direction, and physical evidence of scratching paralleled changes in the visual analog pruritus score. CONCLUSION: Sertraline seems to be an effective, well-tolerated treatment for pruritus due to chronic liver disease. These results suggest that serotonergic pathways are important in the perception of itch.

Correlation of human decidual and cord blood mononuclear cell cytokine production.

Human decidua has been shown to produce a number of cytokines. We hypothesized that decidual cytokine production influences cord blood mononuclear cell (CBMC) cytokine production and that cytokine profiles of decidua from allergic women differ from those of decidua from nonallergic women. Using enzyme-linked immunosorbent assay, we measured unstimulated and concanavalin A/phorbol myristate acetate-stimulated production of interleukin-4 (IL-4), IL-5, IL-10, IL-13 and interferon- gamma (IFN-gamma) by decidual explants from 59 healthy women delivered by unlabored cesarean section and from corresponding CBMCs in 39 of the 59. Except for IL-10, there was little or no unstimulated cytokine production. There was a strong correlation between stimulated decidual and stimulated CBMC IFN-gamma production (p = 0.01). In allergic women the ratio of IL-13 to IL-4 production was increased in stimulated explants (p = 0.03). Stimulated CBMCs from infants of allergic mothers were more likely to produce detectable levels of IL-5 than those from infants of nonallergic mothers (p = 0.04) and had a tendency toward higher IL-13 levels as well (p = 0.07). These results suggest that maternal and fetal IFN-gamma production is closely linked and that maternal allergy appears to influence cytokine production in the neonate for IL-5 and possibly IL-13.

The calpain system in human placenta.

The calpain system is involved in a number of human pathologies ranging from the muscular dystrophies to Alzheimer's disease. It is important, therefore, to be able to obtain and to characterize both mu-calpain and m-calpain from human tissue. Although human mu-calpain can be conveniently obtained from either erythrocytes or platelets, no readily available source of human m-calpain has been described. Human placenta extracts contain both mu-calpain and m-calpain in nearly equal proportions and in significant quantities (3-4 mg mu-calpain and 4-5 mg m-calpain/1000 g placenta tissue). Placenta also contains calpastatin that elutes off ion-exchange columns over a wide range of KCl concentrations completely masking the mu-calpain activity eluting off these columns and even partly overlapping m-calpain elution. Placenta mu-calpain requires 50-70 microM Ca2+ and placenta m-calpain requires 450-460 microM Ca2+ for half-maximal proteolytic activity. Western analysis of washed placenta tissue shows that placenta contains both mu- and m-calpain, although some of the mu-calpain in whole placenta extracts likely originates from the erythrocytes that are abundant in the highly vascularized placenta. Placenta calpastatin could not be purified with conventional methods. The most prominent form of calpastatin in Western analyses of placenta obtained as soon as possible after birth was approximately 48-51 kDa; partly purified preparations of placenta calpastatin also contained 48-51 and 70 kDa polypeptides. Human placenta extracts likely contain two different calpastatin isoforms, a 48-51 kDa "placenta calpastatin" and a 70 kDa erythrocyte calpastatin.