Alopecia areata universalis elicited during treatment with adalimumab

Adalimumab is a fully humanized recombinant anti-tumour-necrosis-factor (TNF-alpha) monoclonal antibody which has been approved for rheumatoid arthritis, active ankylosing spondylitis, psoriatic arthritis and Crohn's disease. We report a case of alopecia areata (AA) universalis occurring 6 months after administration of adalimumab monotherapy in a patient with a long-standing history of psoriatic arthritis and psoriasis. The diagnosis was confirmed by a scalp biopsy which showed a peribulbar infiltrate of both CD4+ and CD8+ T cells, CD1a+ dendritic cells as well as CD68+ and CD163+ macrophages. In addition, immunofluorescence staining for TNF-alpha was found in the mononuclear cell infiltrate. This case suggests a complex role of TNF-alpha in the induction of AA.

Increased expression of IL-12p70 and IL-23 by multiple dendritic cell and macrophage subsets in plaque psoriasis

BACKGROUND: Psoriasis is a chronic immune-mediated skin disease, in which interleukins 12 and 23 have been postulated to play a critical role. However, the cellular source of these cytokines in psoriatic lesions are still poorly defined and their relative contribution in inducing skin inflammation has been discussed controversially. OBJECTIVES: To investigate immunoreactivity of the bioactive forms of IL-12 and IL-23 in plaque psoriasis and to characterize the dendritic cell (DC) and macrophage subsets responsible for the production of these cytokines. METHODS: Immunohistochemistry was performed on normal skin (n=11) as well as non-lesional (n=11) and lesional (n=11) skin of patients with plaque psoriasis using monoclonal antibodies targeting the bioactive forms of IL-12 (IL-12p70) and IL-23 (IL-23p19/p40) on serial cryostat sections using the alkaline phosphatase-antialkaline phosphatase. Co-localization of IL-12 and IL-23 with different dendritic cells and macrophage cell markers (CD1a, CD11c, CD14, CD32, CD68, CD163, CD208/DC-LAMP) was performed using double immunofluorescence staining. RESULTS: Immunoreactivity for IL-12 and IL-23 was significantly enhanced in lesional psoriatic skin as compared to non-lesional and normal skin. No difference was observed between IL-12 and IL-23 immunoreactivity in any skin types. Both IL-12 and IL-23 immunoreactivity was readily detected mainly in CD11c+, CD14+, CD32+, CD68+ and some CD163+, DC-LAMP+ cells. IL-12 and occasionally IL-23 were also found in some CD1a+ dendritic cells. In addition, an enhanced expression mainly of IL-23 was observed in keratinocytes. CONCLUSIONS: Bioactive forms of IL-12 and IL-23 are highly expressed in various DC and macrophage subsets and their marked in situ production suggest that both cytokines have crucial pathogenic role in psoriasis.

Human beta-defensin-2 and psoriasin are overexpressed in lesions of acne inversa

BACKGROUND: Acne inversa is a chronic inflammatory disorder of apocrine gland-bearing skin. The role of the innate immune system in the pathogenesis of the disease is controversial. OBJECTIVES: We investigated the expression of antimicrobial peptide/proteins in acne inversa. METHODS: Tissue samples were obtained from patients with acne inversa and compared with normal-appearing skin. The expression of psoriasin and human beta-defensin (hBD)-2 on messenger RNA and protein level was analyzed. RESULTS: Both messenger RNA and protein levels of psoriasin and hBD-2 were significantly increased in acne inversa. Macrophages expressing hBD-2 were found in the dermis. LIMITATIONS: Small sample size is a limitation. CONCLUSIONS: Antimicrobial peptide/proteins are overexpressed in acne inversa lesions as compared with normal-appearing skin. The site of the major expression depends on the particular antimicrobial peptide/protein. Psoriasin is overexpressed in epidermal keratinocytes whereas hBD-2 is produced mainly by dermal macrophages, leaving a relative deficiency of hBD-2 in the epidermis of acne inversa lesions.

A comparative study of the expression of cytotoxic proteins in allergic contact dermatitis and psoriasis: spongiotic skin lesions in allergic contact dermatitis are highly infiltrated by T cells expressing perforin and granzyme B

Recent reports indicate that cytotoxic T cells are critically involved in contact hypersensitivity reactions in animals. In this study we sought to investigate the in vivo expression of cytotoxic granule proteins in the elicitation phase of allergic contact dermatitis in humans. Skin biopsy specimens were obtained from patients with allergic contact dermatitis (n = 8) and psoriasis (n = 6) and from controls with normal skin (n = 6). Expression of perforin and granzyme B was investigated by in situ hybridization and immunohistochemistry. In contrast to normal skin and psoriasis, a significant enhancement of perforin and granzyme B gene expression and immunoreactivity was observed in the mononuclear cell infiltrate of allergic contact dermatitis. Immunoreactivity for perforin and granzyme B was mainly found in the cytoplasm of lymphocytic cells, which were located in the dense perivascular infiltrate as well as at sites of marked spongiosis in the epidermis. Double immunostaining revealed that both CD4+ and CD8+ T cells are capable of expressing perforin and granzyme B. In conclusion, our data suggest that T-cell-mediated mechanisms involving cytotoxic granule proteins may elicit epidermal cell injury in vivo and thereby strongly contribute to the development of allergic contact dermatitis in humans.

Poverty in Israel

The paper deals with poverty within Israel. Against the background of the history of pre-state Israel and the developments after the establishment of the State of Israel in 1948 the historical roots of Israeli poverty are analyzed. Thus the ‘socialist’-Zionist project, ethnic exclusion, religious and intra-Jewish ethnic lines of conflict as well as the Bedouins, Druzes and Israeli Arabs as ‘specific’ Israeli citizen are discussed. Despite the economic growth in Israel since 2003 ‘the majority of Israeli wage earners (over 60percent) earned less than $1,450 a month last year’ (Goldstein 2007, p. 1). In 2004 1.3 million Israelis lived below the poverty line, a number which in 2005 increased to more than 1.5 million Israelis. In spite of growing economic prosperity the proportion of families belonging to the working-poor, i.e. families with at least one family member in paid employment, increased from 11.4 percent in 2004 to 12.2 percent in 2005. The percentage of poor families in the working population increased from 40.6 percent to 43.1 percent. Nearly 60 percent of the ‘working-poor’ were working fulltime (Sinai 2006a, Shaoul 2006). 42 percent of Israeli Arab families are living below the poverty line. The average wages are less than half the wages of Ashkenazi Jews. Every second Israeli Arab child lives in poverty. When in 1996 to 2001 the unemployment rate of the Jewish Israelis increased by about 53 percent, the unemployment rate of the Arab Israelis increased by 126 percent (cf. Shaoul 2006). 80 percent of Israelis regard themselves as poor. 23 percent of the pensioners are living below the poverty line. Poverty among children increased in 1988 to 2005 by about 50 percent. Approximately one fifth of all under-age children (714.000) in Israel are suffering from hunger (cf. Shaoul 2006). 75 percent of the poor families cannot afford medicine and 70 percent are dependant on food donations (cf. Sinai 2005b). Nearly one third of the Holocaust survivors are living in poverty. Some of the Holocaust survivors get $ 600,- per month from the German government, whilst other Holocaust survivors receive only $ 350,- per month from the Israeli Ministry of Finance and the Holocaust survivors that immigrated to Israel after 1953 (who amount to 70 percent of the Holocaust survivors in Israel) only receive the general national pension. Nearly 20 percent of the Holocaust survivors are at the present time 86 years and older, 70 percent are older than 76 years. (cf. Medina 2007, p. 1) They are not entitled to a supplementary payment or to compensation. But the problematic economic situation of the Holocaust survivors is neither new information nor an unknown fact. As a result of the precarious situation several are in need of the help of welfare organizations, because they cannot afford to some degree their necessary medicine.

[Second victim : Critical incident stress management in clinical medicine]

BACKGROUND Critical incidents in clinical medicine can have far-reaching consequences on patient health. In cases of severe medical errors they can seriously harm the patient or even lead to death. The involvement in such an event can result in a stress reaction, a so-called acute posttraumatic stress disorder in the healthcare provider, the so-called second victim of an adverse event. Psychological distress may not only have a long lasting impact on quality of life of the physician or caregiver involved but it may also affect the ability to provide safe patient care in the aftermath of adverse events. METHODS A literature review was performed to obtain information on care giver responses to medical errors and to determine possible supportive strategies to mitigate negative consequences of an adverse event on the second victim. An internet search and a search in Medline/Pubmed for scientific studies were conducted using the key words "second victim, "medical error", "critical incident stress management" (CISM) and "critical incident stress reporting system" (CIRS). Sources from academic medical societies and public institutions which offer crisis management programs where analyzed. The data were sorted by main categories and relevance for hospitals. Analysis was carried out using descriptive measures. RESULTS In disaster medicine and aviation navigation services the implementation of a CISM program is an efficient intervention to help staff to recover after a traumatic event and to return to normal functioning and behavior. Several other concepts for a clinical crisis management plan were identified. CONCLUSIONS The integration of CISM and CISM-related programs in a clinical setting may provide efficient support in an acute crisis and may help the caregiver to deal effectively with future error events and employee safety.

Iowa State Daily (April 6, 2012)

ContentsNew dimension in 3-DMissing the monarchPavilion aids all of Iowa State Big 12 changes gives softball fewer opponentsDoes Obama 'Hunger' for control?Eco Elvis sings sustainability for graduate English class

Agrarian learning processes in Switzerland 1918–1939

This paper examines the social impacts of weather extremes and the processes of social and communicative learning a society undertakes to find alternative ways to deal with the consequences of a crisis. In the beginning of the 20th Century hunger seemed to be expelled from Europe. Switzerland – like many other European countries – was involved in a global interdependent trade system, which provided necessary goods. But at the end of World War I very cold and wet summers in 1916/17 (causing crop failure) and the difficulties in war-trade led to malnutrition and enormous price risings of general living-standards in Switzerland, which shocked the people and caused revolutionary uprisings in 1918. The experience of malnutrition during the last two years of war made clear that the traditional ways of food supply in Switzerland lacked crisis stability. Therefore various agents in the field of food production, distribution and consumption searched for alternative ways of food supply. In that sense politicians, industrialists, consumer-groups, left-wing communitarians and farmers developed several strategies for new ways in food production. Traditionally there were political conflicts in Switzerland between farmers and consumers regarding price policies, which led mainly to the conflict in 1918. Consumers accused famers of holding back food to control extortionate prices while the farmers pointed to the bad harvest causing the price rising. The collaboration of these groups in search for new forms of food-stability made social integration possible again. In addition to other crisis-factors, weather extremes can have disastrous impacts and destroy a society’s self-confidence to its core. But even such crisis can lead to processes of substantial learning that allows a regeneration of confidence and show positive influence on political stabilization. The paper focuses on the process of learning and the alternative methods of food production that were suggested by various agents working in the field during the Interwar period. To achieve that goal documents of the various associations are analyzed and newspapers have been taken into consideration. Through the method of discourse-analysis of food-production during the Interwar period, possible solutions that crossed the minds of the agents should be brought to light.

Loss of DAXX and ATRX are associated with chromosome instability and reduced survival of patients with pancreatic neuroendocrine tumors

BACKGROUND & AIMS Sporadic pancreatic neuroendocrine tumors (pNETs) are rare and genetically heterogeneous. Chromosome instability (CIN) has been detected in pNETs from patients with poor outcomes, but no specific genetic factors have been associated with CIN. Mutations in death domain-associated protein gene (DAXX) or ATR-X gene (ATRX) (which both encode proteins involved in chromatin remodeling) have been detected in 40% of pNETs, in association with activation of alternative lengthening of telomeres. We investigated whether loss of DAXX or ATRX, and consequent alternative lengthening of telomeres, are related to CIN in pNETs. We also assessed whether loss of DAXX or ATRX is associated with specific phenotypes of pNETs. METHODS We collected well-differentiated primary pNET samples from 142 patients at the University Hospital Zurich and from 101 patients at the University Hospital Bern (both located in Switzerland). Clinical follow-up data were obtained for 149 patients from general practitioners and tumor registries. The tumors were reclassified into 3 groups according to the 2010 World Health Organization classification. Samples were analyzed by immunohistochemistry and telomeric fluorescence in situ hybridization. We correlated loss of DAXX, or ATRX, expression, and activation of alternative lengthening of telomeres with data from comparative genomic hybridization array studies, as well as with clinical and pathological features of the tumors and relapse and survival data. RESULTS Loss of DAXX or ATRX protein and alternative lengthening of telomeres were associated with CIN in pNETs. Furthermore, loss of DAXX or ATRX correlated with tumor stage and metastasis, reduced time of relapse-free survival, and decreased time of tumor-associated survival. CONCLUSIONS Loss of DAXX or ATRX is associated with CIN in pNETs and shorter survival times of patients. These results support the hypothesis that DAXX- and ATRX-negative tumors are a more aggressive subtype of pNET, and could lead to identification of strategies to target CIN in pancreatic tumors.