Trauma and suicidality in war affected communities.

PURPOSE: The aim was to assess whether experiences of war trauma remain directly associated with suicidality in war affected communities when other risk factors are considered. MATERIALS AND METHODS: In the main sample 3313 participants from former Yugoslavia who experienced war trauma were recruited using a random sampling in five Balkan countries. In the second sample 854 refugees from former Yugoslavia recruited through registers and networking in three Western European countries. Sociodemographic and data on trauma exposure, psychiatric diagnoses and level of suicidality were assessed. RESULTS: In the main sample 113 participants (3.4%) had high suicidality, which was associated with number of potentially traumatic war experiences (odds ratio 1.1) and war related imprisonment (odds ratio 3) once all measured risk factors were considered. These associations were confirmed in the refugee sample with a higher suicidality rate (10.2%). DISCUSSION AND CONCLUSIONS: Number of potentially traumatic war experiences, in particular imprisonment, may be considered as a relevant risk factor for suicidality in people affected by war.

Course of post-traumatic stress disorder following war in the Balkans: 1-year follow-up study.

BACKGROUND: Prevalence rates of post-traumatic stress disorder (PTSD) following the experience of war have been shown to be high. However, little is known about the course of the disorder in people who remained in the area of conflict and in refugees. Method We studied a representative sample of 522 adults with war-related PTSD in five Balkan countries and 215 compatriot refugees in three Western European countries. They were assessed on average 8 years after the war and reinterviewed 1 year later. We established change in PTSD symptoms, measured on the Impact of Events Scale - Revised (IES-R), and factors associated with more or less favourable outcomes. RESULTS: During the 1-year period, symptoms decreased substantially in both Balkan residents and in refugees. The differences were significant for IES-R total scores and for the three subscales of intrusions, avoidance and hyperarousal. In multivariable regressions adjusting for the level of baseline symptoms, co-morbidity with depression predicted less favourable symptom change in Balkan residents. More pre-war traumatic events and the use of mental health services within the follow-up period were associated with less improvement in refugees. CONCLUSIONS: Several years after the war, people with PTSD reported significant symptom improvement that might indicate a fluctuating course over time. Co-morbid depression may have to be targeted in the treatment of people who remained in the post-conflict regions whereas the use of mental health services seems to be linked to the persistence of symptoms among refugees.

Health services and the treatment of immigrants: data on service use, interpreting services and immigrant staff members in services across Europe.

BACKGROUND: The number of immigrants using health services has increased across Europe. For assessing and improving the quality of care provided for immigrants, information is required on how many immigrants use services, what interpreting services are provided and whether staff members are from immigrant groups. METHODS: Structured interviews were conducted with 15 health services (9 primary care, 3 emergency departments, 3 mental health) located in areas with high immigrant populations in each of 16 European countries (n=240). Responses were collected on the availability of data on service use by immigrant patients, the provision of interpreting services and immigrant staff members. RESULTS: Data on service use by immigrants were recorded by only 15% of services. More than 40% of services did not provide any form of interpreting service and 54% of the services reported having no immigrant staff. Mental health services were more likely to use direct interpreting services, and both mental health and emergency services were more likely to have immigrant staff members. DISCUSSION: For assessing and improving the quality of care provided for immigrants, there is a need to improve the availability of data on service use by immigrants in health services throughout Europe and to provide more consistent access to interpreting services.

[Angioedema caused by angiotensin-converting enzyme inhibitors]. / Angioedem izazvan lekovima inhibitorima enzima ACE.

Angioedema is a rare, but important effect of arterial hypertension treatment with drugs which inhibit angiotensin-converting enzyme. Usually, it develops in the first week of therapy, but some atypical cases of the development of angioedema after several months to few years after the onset of the therapy have been reported. Undesired reactions caused by these drugs are probably not allergic, but they are caused by pharmacological effect of these drugs in persons with risk of allergic reaction. In this paper we present some patients with angioedema.

[The role of eosinophilic leukocytes in allergic inflammation]. / Uloga eozinofilnih leukocita u alergijskoj inflamaciji.

Eosinophilic leukocytes are tissue cells of granulocytic structure and secretory nature. They are produced in the bone marrow and transported to the targeted tissue via the blood where they are present in concentrations hundred times higher than in peripheral circulation. Eosinophilic leukocytes are the essential effector of allergic inflammation, which is a pathophysiological basis of allergic diseases. These diseases are characterized by disturbed distribution of eosinophilic leukocytes, i.e., peripheral eosinophilia and/or infiltration of the affected organs. Migration of these cells from the peripheral circulation into the targeted tissues, i.e., affected with the allergic inflammation, is influenced by helper T2 cells-dependent cytokines, and other mediators of inflammation. Subsequent to their activation, eosinophilic leukocytes release numerous made and newly produced mediators of inflammation and also present antigens which define their effector function in allergic inflammation. In this way, eosinophilic leukocytes participate in numerous pathological and pathophysiological disorders characteristic of allergic diseases which clearly confirm the active role of these cells in their production.

[The role of endothelial cells in allergic inflammation reactions]. / Mesto i uloga celija endotela u reakcijama alergijske inflamacije.

Inflammatory response in tissue results from a complex network of interactions between inflammatory cells (mast cells, eosinophils, basophils, macrophages) and resident cells belonging to the lung structure (like endothelial cells, fibroblasts, epithelial cells). Among structural cells, endothelial cells play a critical role. The important role of endothelium is also reflected in the fact that it occupies an area exceeding 1000 m2. Thus, endothelium is the largest and the most active paracrine organ in the body, producing potent vasoactive, procoagulant, anticoagulant, and proinflammatory substances. Endothelial cells have four key functions that alter in the process of inflammation: 1 a) Regulation and control of leukocyte traffic through the expression of adhesion molecules (selectins E and P, molecules of immunoglobulin superfamily ICAM-1, ICAM-2, VCAM); 1 b) They are also able to amplify leukocyte activation through the production of proinflammatory cytokines like IL-1, IL-6 and chemokines like IL-8 and RANTES molecules; 2) Regulation of vascular tone by production of PGI-2, EDRF/NO and elements of local renin-angiotensin system; 3) Regulation of local coagulation by controlling the production of t-PA and PAI-1; 4) Regulation of the vascular permeability. In the states of acute inflammation, the endothelial cell takes on a proinflammatory phenotype and as such becomes chemoattractant, facilitating leukocyte adhesion, activation and migration, becomes prothrombotic and demonstrates enhanced vascular permeability.

[Epithelial cells in bronchial asthma]. / Epitelne celije u bronhijalnoj astimi.

The paper deals with the current data on the morphologic and functional damages to the epithelium in asthma. Structure of the normal airway epithelium is briefly described. Damage to the epithelium disrupts the barrier to the external environment, and may result in changes in mucous secretion, and mucociliary clearance; induce bronchoconstriction; promote chemotaxis of inflammatory cells. Epithelial cells can present antigens to T-lymphocytes. Epithelium is both target and effector in asthma. Hypothesis that eosinophils contribute to the damage of the epithelium gained increasing recognition.

[T lymphocytes in allergic inflammation]. / Limfociti T u alergijskoj inflamaciji.

T lymphocytes are the crucial cells in immunopathogenesis of allergic diseases since they regulate the occurrence of allergic sensitisation, synthesis of immunoglobulin E and allergic inflammation. The importance of lymphocyte T is reflected on the fact that after activation by a specific antigen they are able to produce different cytokines responsible for activation and aggregation of specific inflammatory cells in target tissues, promoting the occurrence and maintenance of allergic inflammation. Discovery of functional dichotomy of activated lymphocytes T CD4+ capable of suppressing synthesis of immunoglobulin E (Th1) or stimulate immunoglobulin E and allergic inflammation (Th2) is an important element in elucidation of pathogenesis of allergic inflammation and inadequate synthesis of immunoglobulin E. The immunoglobulin synthesis is regulated by a complex combination of factors and signals where lymphocytes CD4+ play the central regulatory role.

[Leukotrienes in allergic inflammatory reactions]. / Leukotrijeni u reakcijama alergijske inflamacije.

Production of leukotrienes, lipooxygenase products of arachidonic acid metabolism, plays an important role in inflammatory reactions, particularly well studied in bronchial asthma. Lipooxigenase-5 and lipooxygenase-activating protein-5 are crucial in the production of leukotrienes with potent biological activities. Leukotriene B4 is a leukocytic chemoattractant and it induces aggregation and adherence of leukocytes to endothelial vasculature. Sulfidopeptid leukotrienes (C4, D4 and E4) are potent bronchoconstrictors, producing mucous secretion in the airways and increasing vascular permeability. Leukotrienes participate in the process of inflammation, as well as in early and late asthmatic responses. They are found in the blood, liquid obtained upon bronchoalveolar lavage as well as in the urine, irrespectively whether bronchospasm developed spontaneously or it was induced by an allergen. Administration of the specific leukotriene receptor antagonists or leukotriene synthesis inhibitors ameliorates the symptoms and signs of bronchial asthma.

[The role of prostaglandins in allergic inflammation]. / Uloga prostaglandina u alergijskoj inflamaciji.

Prostaglandins likewise leukotriens are proinflammatory mediators resulting from metabolic degradation of the arachidonic acid originating from membrane phospholipids. The most important products of enzyme cyclooxygenation of arachidonic acid are prostaglandins D2, E2, F2a, tromboxane A2 and prostacyclin. Prostaglandins express their tissue effects via the five basic receptor types. Within the allergic inflammation activated mast cell synthesizes prostaglandin D2 (first lipid mediator) which has bronchoconstrictive and vasodilating effects and attracts neutrophilic leukocytes. Moreover, it also participates in the late phase reactions, six hours subsequent to the exposure to the allergen. This mediator is also important in pathogenesis of urticaria, allergic rhinitis and allergic bronchial asthma. In addition to prostaglandin D2, prostaglandin F2a and tromboxane A2 also have bronchoconstrictive actions, while prostacyclin and prostaglandin E have bronchodilating effects. Inhalation of prostaglandin E prevents asthmatic attacks caused by allergens, strain, metabisulfite and ameliorates attacks of aspirin asthma, which confirms the hypothesis that aspirin asthma is based on cyclooxigenase inhibition and increased leukotriene production. In patients with atopic dermatitis, prostaglandin E has suppressive effects on Interferon gamma production by Th1 helper cells and increases production of Interleukin 4 by the Th2 cells. Tromboxane A2 plays a certain role in the development of bronchial hyperreactivity and late asthmatic response. Prostaglandins are also important mediators in the pathogenesis of allergic conjunctivitis. Most of nonsteroidal antiinflammatory drugs inhibit the enzyme cyclooxygenase and thus also prostaglandin biosynthesis and release.

[Hypersensitivity to mites and house dust]. / Preosetljivost na grinje i kucnu prasinu.

The paper deals with the current data on hypersensitivity to house dust allergens, particularly to house dust mite allergens. Hypersensitivity to house dust mites is more prevalent than hypersensitivity to any other allergen. Ecologic factors for mite survival are cited, particularly emphasizing the importance of air humidity. Over the last 50 years there have been several changes in construction and furnishing of houses in developed countries which fostered mite proliferation. Mite allergens are identified and cloned, monoclonal antibodies to these allergens are produced. There are methods for estimating mite allergen concentration in homes which made possible to investigate the relationship between mite allergen exposure and development of bronchial hyperreactivity. Various methods for mite allergen avoidance are developed and their efficacy is under investigation.

[The role of thrombocytes in allergic inflammation]. / Uloga trombocita u alergijskoj inflamaciji.

The platelet has traditionally been associated with haemostasis. Participation of platelets in defence mechanisms is presentiment by the knowledge that primary haemostasis may be phylogenetic vestige retained from the behaviour of primitive leukocytes. Platelets have the ability to undergo shape change with pseudopod formation, chemotaxis, diapedesis, and phagocytose. Platelets contain a wide range highly potent inflammatory factors that are capable of inducing or augmenting certain inflammatory responses. Different surface molecules have been detected on the plasma membrane, highlight the platelets ability to bind a variety of biologic surfaces, including those of other cells, resulting in close apposition of platelets and their targets. They can interact with parasites, viruses and bacteria. Studies from several groups suggest an important role of the platelet in allergic processes. Platelets possess receptor for immunoglobulin E. Numerous clinical reports are describing the modification of biologic activity of platelets from allergic patients as compared to healthy subjects. The incidence of abnormal platelet responsiveness is in higher among patients having high serum IgE titres. Platelet depletion decreased the anaphylactic response and protects against the lethal consequences of the antigen provocation. Evidence now exists in support of primary role of the platelet in the pathogenesis of bronchial asthma. Platelets can participate in allergic asthma by acting as inflammatory cells, by releasing spasmogens and by interacting with other inflammatory cells. Thrombocytopenia and the increased plasma levels of platelet-derived markers occurred in parallel with bronchoconstriction induced by antigen provocation of allergic astmatics. Platelet depletion inhibits the ability of antigen to induce late onset airways obstruction and airway hyperresponsiveness. Platelet apheresis in human resulted in a positive clinical effect. Platelets respond to aspirin or other NSAIDs in acetyl salicylic acid sensitive asthmatics and these findings provide further evidence for role of the platelet in this form of bronchial asthma.

[The role of mononuclear phagocytes and dendritic cells in allergic inflammation]. / Uloga mononuklearnih fagocita i dendriticnih celija u alergijskoj inflamaciji.

Mononuclear-phagocytic system is a diffuse network of cells which includes monoblasts and promonocytes of the bone marrow, blood monocytes, as well as free and fixed tissue macrophage cells. In different tissues and organs macrophages acquire different morphological and functional properties under the influence of the local tissue factors. Interaction of macrophages with other cells and molecules is performed via the large number of different receptors resulting in activation of the macrophage cell, accompanied by a series of morphological and metabolic changes which potentiate all its functions. Activated macrophage cells were found in certain diseases. Macrophages and dendritic cells are associated with all aspects of immunity. Owing to their capacity to undergo phagocytosis they are of the utmost importance for unspecific defense from microorganisms. As accessory cells they also participate in cellular and humoral immunity, being at the same time effector cells owing to their capacity of antigen presentation. Moreover, they also participate in immune response regulation owing to their influence on the function of other cells, including mast cells, basophilic leukocytes and T lymphocytes, in which they may influence differentiation toward Th1 or Th2 and cytokine milieu favorable for allergic reaction. Dendritic cells are the most important antigen-presenting cells and thus, they play a major role in activation of helper T lymphocytes, and mode of antigen presentation is significant for regulation of the nature and intensity of the immune response. Pulmonary macrophage cells have been most thoroughly studied, and the observed changeability of their functional and morphological characteristics is of the utmost importance for studying of the pathogenetic properties and regulation of the chronic inflammatory response in bronchial asthma.

[Laboratory diagnosis of allergic inflammation]. / Laboratorijska dijagnostika alergijske inflamacije.

Monitoring of allergic inflammation includes direct examination of biopsy specimens from mucosa and epithelium, and indirect study by sputum, bronchoalveolar and nasal lavage fluid and peripheral blood. Although, some of these detection assays are not applicable to clinical use, it is now possible to measure a number of inflammatory mediators released from cells participating in allergic disease. The release of performed histamine from peripheral blood basophils challenged with specific antigen remains a valuable in vitro correlate of immediate hypersensitivity reactions. However, other mediators such as LTC4 and IL-4 are also generated by basophils upon IgE dependent activation. Tryptase and PGD2 are released from mast cells upon activation. Eosinophils contain in their granules proteins that cause damage to the bronchial epithelium: MBP and ECP. It is possible to measure soluble markers from other cells (T cells, macrophages, platelets, endothelial cells) involved in allergic inflammation. Detection of mediators have produced data that have significantly added to our understanding of the mechanisms and allowed better pharmacological control of allergic inflammation.

[Liver damage caused by sensitivity to anti-inflammatory agents]. / Ostecenja jetre izazvana senzibilizacijom na antiinflamacione lekove.

Nonsteroidal antiinflammatory drugs may cause hepatic sensibilization and impairment. The incidence of these changes is low and referential data are scarce and related mainly to reaction which clinically corresponds to hepatic or cholestatic reaction. We present a patient who is sensitive to Diclofenac and has hepatic granuloma which developed after the use of the drug. History, clinical presentation, laboratory results, US examination of the liver and pathohistologic analysis of the hepatic biopsy sample enabled us to diagnose hepatitis with granulomatous impairment. Improvement of symptoms and signs of the disease was spontaneous and without administration of glucocorticoid drugs.

[Sjogren's syndrome]. / Segrenov sindrom.

Sjogren's syndrome is a chronic inflammatory disease of unknown aethiology. It is characterized by decreased secretion of salivary and lacrimal glands, which induces keratoconjunctivitis sicca and xerostomia. Sjogren's syndrome is a central autoimmune disease, and it has characteristics of both organ-specific and generalized autoimmune diseases. It can exist as a primary disease or is associated with other autoimmune diseases (most freyuently with systemic lupus erythematosus or rheumatoid arthritis) and is classified as a secondary Sjogren's syndrome. The aethiology is multifactorial, and it has not yet been completely explained. In the pathogenesis of the disease the important role have genetic predisposition, chronic oestrogen stimulation, end viral infections, especially of the herpes virus group (EBV, CMV, HHV6) and retroviruses. In the clinical picture xerostomia, xerophtalmia and non-erosive arthritis are the most common features, with the whole spectrum of extraglandular manifestations of respiratory, gastrointestinal, skin, and haematologic, neurologic and endocrinologic disturbances. Pathohistological findings of minor labial salivary gland lymphocyte infiltration is the most specific and the most sensitive diagnostic criterion of Sjogren's syndrome. The diagnosis of keratoconjunctivitis sicca is made by Schrimer's test, Rose bengal dye staining and by the "tear break up time". Differential diagnosis of Sjogren's syndrome includes an extremely large number of various pathologic states. The treatment of Sjogren's syndrome consists of symptomatic treatment of dry mucosas (artificial tears, etc.) and also of antiinflammatory drugs, glucocorticoids, immunosuppressive drugs. Plasmapheresis and intravenous administration of immunoglobulins are used for immunosuppression in these patients.