[ANTIMICROBIAL DRESSINGS FOR INFECTED ULCER AND CLINICAL COMPREHENSION OF BIOFILM]. / ANTIMIKROBNE OBLOGE ZA INFICIRANI VRIJED I KLINICKE SPOZNAJE O BIOFILMU.

Current knowledge and proofs of biofilm, interactions between various bacterial species and overall virulence of microbes play a role in delayed healing of wound and development of infection. High quality description of clinical symptoms and current knowledge of microbes provide an excellent guideline for creating the strategy of wound treatment. Owing to better understanding of the role of biofilm in prolongation of healing time and facts about biofilm system and structure, scientists have developed the Ag+ technology. This technology has strong synergistic effects of the general and antimicrobial activity of ionic silver and specific compounds, which have proved efficient in biofilm obstruction and removal.

[140 years of CMA--53 years of AMSC]. / 140 godina HLZ-A--53 godine AMZH.

Croatian Academy of Medical Sciences was established in 1961 as the Commission for Scientific Research of the Croatian Medical Association Main Committee. In 1983 was separated from the Croatian Medical Association and became an independent organization--Croatian Academy of Medical Sciences. The Academy is a society of chosen scientists dealing with promotion of medical sciences to improve public health. To introduce Croatian medicine to the world the Academy publishes journals Acta Medica Croatica, Socijalna psihijatrija and Croatian Medical Journal.

Differences between keratoacanthoma and squamous cell carcinoma using TGF-alpha.

Squamous cell carcinoma (SCC) and keratoacanthoma (KA) are skin neoplasms of epithelial origin. In contrast to clearly malignant skin neoplasm SCC, KA is an unusual cutaneous neoplasm with a tendency to regression. The distinction between these two neoplasms, on histological grounds only, is still a challenge. In order to investigate further and to assess the possible differences in transforming growth factor-alpha (TGF-alpha) expression between SCC and KA, 40 of skin tumor specimens, 20 cases of each SCC and KA were analyzed immunohystochemicaly. We have found a significant difference in staining patterns between KA and SCC. In KAs we have detected TGF-alpha staining mainly diffusely (90% of cases) and without peripheral staining of cells in 1-2 layers (60% of cases). Contrary, there was a mostly patchy staining (55% of cases) with peripheral staining of cells in 1-2 layers (100% of cases) in SCCs. Generally, differentiation between KA and SCC can be based on clinical and histological ground, but the distinction between these two skin tumors could sometimes be difficult. We have shown that these skin neoplasms could be differentiated based on staining patterns of TGF-alpha expression, thus this method could aid in differentiation between these two closely related entities in clinical practice.

Definitions and outcome measures for bullous pemphigoid: recommendations by an international panel of experts.

Our scientific knowledge of bullous pemphigoid (BP) has dramatically progressed in recent years. However, despite the availability of various therapeutic options for the treatment of inflammatory diseases, only a few multicenter controlled trials have helped to define effective therapies in BP. A major obstacle in sharing multicenter-based evidences for therapeutic efforts is the lack of generally accepted definitions for the clinical evaluation of patients with BP. Common terms and end points of BP are needed so that experts in the field can accurately measure and assess disease extent, activity, severity, and therapeutic response, and thus facilitate and advance clinical trials. These recommendations from the International Pemphigoid Committee represent 2 years of collaborative efforts to attain mutually acceptable common definitions for BP and proposes a disease extent score, the BP Disease Area Index. These items should assist in the development of consistent reporting of outcomes in future BP reports and studies.

Descriptive epidemiology of cutaneous squamous cell carcinoma in Croatia.

The aim of the study was to investigate the squamous cell carcinoma (SCC) incidence in Croatia in the 2003-2005 period. The cases of SCC were retrospectively studied. Data were collected from University Department of Dermatology and Venereology, Zagreb University Hospital Center and National Cancer Registry. In the study period, there were 1,860 cases of SCC (934 men and 926 women). The crude incidence rate for the Croatian population of 100,000 was 14.6 for men and 13.4 for women. The age-standardized incidence rate (adjusted for the world standard population) was 8.9 for men and 5.2 for women. The head was almost exclusive localization of SCC in both sexes. The highest SCC incidence was recorded in Zadar County. These results will serve for the SCC trend monitoring in Croatia and Europe in the forthcoming years.

Polymorphisms of vitamin D receptor gene in the population of eastern Croatia with psoriasis vulgaris and diabetes mellitus.

The aim of this study was to evaluate the possible association between polymorphisms in the Vitamin D receptor gene (VDR gene) and tendency for development of psoriasis vulgaris and diabetes mellitus in the population of Slavonia, which is a region in the Eastern Croatia. In order to conduct the mentioned evaluation the restriction fragment length polymorphisms (ApaI, BsmI and TaqI) in the Vitamin D receptor gene were researched in three groups of patients: patients suffering only from psoriasis vulgaris, patients suffering only from diabetes mellitus, and patients suffering at the same time from both diseases. Four most common genotypes were found in all standardized control patients: triple heterozygotes BbAaTt (in 29.3% of the studied patients), bbAaTT (in 18.6% of the studied patients), bbaaTT (in 12.9% of the studied patients) and BbAATt (in 8.6% of the studied patients). Three most common VDR 3'-RFLP haplotypes determined in this study were: three-component baT, Bat and bAT haplotype. Results of the Hardy-Weinberg equilibrium showed presence of BsmI polymorphism genotype frequencies disequilibrium in the group of patients suffering from psoriasis and ApaI polymorphism in the group of patients suffering from both diseases. According to the same statistical test all conditions for TaqI polymorphism genotype frequency were fulfilled in all groups of studied patients. There was no significant difference in distribution of BsmI, ApaI or TaqI polymorphism genotype frequencies between control patients and any of the subgroup of studied patients. In studied population none of analysed polymorphisms individually was associated with the risk of development of psoriasis, diabetes or combined phenotype.

[Wounds in autoimmune bullous dermatoses and systemic connective tissue diseases]. / Rane kod autoimunih buloznih dermatoza i sistemskih bolesti vezivnog tkiva.

Autoimmune bullous dermatoses are a group of skin and/or mucous membrane diseases characterized by blisters and erosions, which are the results of autoantibodies directed to structural components of desmosomes and structural proteins of the basement membrane zone. In this group of diseases, the diagnosis is based on history, clinical presentation, histopathologic findings, findings of direct and indirect immunofluorescence, and specific evidence of circulating antibodies by the enzyme linked immunosorbent assay (ELISA) method. Connective tissue diseases are a heterogeneous group of diseases with some common pathogenetic mechanisms and frequent involvement of the skin. This group of diseases commonly includes lupus erythematosus, dermatomyositis/polymyositis, localized and systemic scleroderma. As most of the diseases in this group have positive one of the antinuclear antibodies, in clinical practice these diseases are often called autoimmune connective tissue diseases. In the group of autoimmune bullous dermatoses, wounds occur as the result of breaking of blisters, and consequently affect the epidermis alone or epidermis and upper dermis, while in the group of systemic diseases of connective tissue, wounds occur in advanced stages of disease as a result of vascular tissue damage, causing necrosis of tissue and wounds. When wounds in these diseases last for a longer period (longer than 3 months), they are considered as chronic wounds and in these cases it is necessary to determine the reason for slow healing. In patients with wounds as a symptom of disease, besides systemic therapy, special attention should be paid to local therapy in order to prevent superinfection and accelerate epithelialization and wound healing.

Collision Lesions: Genuine Collision (Conflict) or not?

By definition, the term "collision lesion" refers to two or more tumors coinciding in the same anatomic position or visceral organ. Collision lesions coexisting on the same skin location are defined as collision skin lesions (CSLs). Although this term implies a conflict between the tumors, this is not the case. CSLs appear to be rare, but still pose a significant diagnostic problem in everyday clinical practice and clinicians should be aware of their existence. The aim of this study was to elucidate the problem of CSLs in clinical practice, with an emphasis on classification of CSLs according to position dependence, tumor histogenesis, etiology, and possible lesion combinations in CSLs, as well as diagnostic possibilities. According to our results, accurate clinical diagnosis could be only rarely reached, requiring lesion excision and pathohistological confirmation of CSLs. Considering the fact that tumors in CSLs can be partially or completely overlying or can even be positioned one within the other, the existence of two or more tumors is extremely difficult to detect.

Contact allergy caused by fragrance mix and Myroxylon pereirae (balsam of Peru)--a retrospective study.

Because of their widespread use, fragrances are among the most common causes of contact allergic dermatitis, second only to nickel. During a five-year period 3,065 patients with contact dermatitis were patch tested using a specific mix of fragrances. 509 (16.6%) patients were allergic to the fragrance mix, while 258 (8.4%) patients exhibited an allergic reaction to Myroxylon pereirae (balsam of Peru). Between those 509 patients, 157 were patch tested with eight individual substances contained in the fragrance mix: cinnamal, cinnamyl alcohol, eugenol, isoeugenol, geraniol, hydroxycitronellal, alpha-amyl cinnamal and Evernia prunastri (oak moss). The most frequent allergens were isoeugenol 57.9% (91/157), eugenol 55.4% (87/157), cinnamyl alcohol 34.4% (54/157) and Evernia prunastri (oak moss) 24.2% (38/157). There were 62 patients (39.5%) who exhibited an allergic reaction to both the fragrance mix and Myroxylon pereirae (balsam of Peru). The results prove the importance of avoiding allergens in daily life, especially in industrial and cosmetic products. In order to prevent ACD, better cooperation between industry and dermatologists is needed.

[Atopy patch test--when is it useful?]. / Atopijski patch test--kada je koristan?

The aim of the article is to introduce the atopy patch test (APT) as a model of cellular immunity reaction. APT is epicutaneous test performed with food and aeroallergens, and represents a good model for T lymphocyte hypersensitivity. It is compared with skin prick test (SPT). Its value is supported by the fact that atopic dermatitis is the result of complex immune interactions and involves both Coombs and Gell reactions type IV and I. In this review, we shortly discuss the etiopathogenesis of atopic dermatitis, distinction of extrinsic and intrinsic issues, and compare the value of APT with SPT and IgE determination. APT includes epicutaneous application of type I allergens known to elicit IgE mediated reactions, followed by evaluation of eczematous skin reaction after 48 and 72 hours. The limitations of ATP include the lack of test standardization, but there also are comparative advantages over SPT and specific IgE determination. We also briefly discuss the most important food and aeroallergens. APT has been recognized as a diagnostic tool in the evaluation of food allergy and aeroallergens such as house dust mite, pollen and animal dander. APT is a useful diagnostic procedure in patients with atopic dermatitis allergic to inhalant allergens and in children with food allergy younger than 2 years. The sensitivity and specificity of the test greatly depend on the allergen tested and patient age.

[Photoallergic drug reactions]. / Fotoalergijske reakcije na lijekove.

Drug-induced hypersensitivity reactions include phototoxic and photoallergic reactions. Photoallergic reactions, which develop as cell-mediated immune responses to a light-activated compound, are described in this review article. The main topics include photobiology, list of common drugs inducing photoallergic reactions, immune response, clinical features, diagnostic and therapeutic approach. Photoallergic drug reactions can be avoided in most cases if the potential photoallergens are known and appropriate photoprotection is used.

[Reactions to insect stings and bites]. / Reakcije na ubode i ugrize insekata.

Reaction to insect sting and bite may be local, such as erythema, edema and pruritus, or systemic, such as anaphylactic reaction. Diagnosis can be made by patient history, clinical picture, skin testing, total and specific IgE level, and provocation test. Local reactions are treated with cold compresses, topical corticosteroids and oral antihistamines. Oral and intramuscular antihistamines and corticosteroids are used for the treatment of mild systemic reactions, and in severe reaction epinephrine injections are added. Hyposensitization is indicated in patients with severe systemic reaction, positive skin tests and high level of specific IgE antibodies.

[Management of allergic diseases]. / Lijecenje alergijskih bolesti.

Treatment of allergic diseases is based on the direct impact of the three main target areas: mast cell stabilization, preventing the release of mediators, and specific immune response. It is essential to prevent exposure to the causative allergen. Treatment is applied systemically or topically. Local treatment is preferred in many allergic skin diseases and asthma, when it is effective. Associated inflammatory components must also be treated, especially in the treatment of asthma, and not just with symptomatic agents. There is also anti-inflammatory and symptomatic treatment. Corticosteroids and antihistamines are the most commonly used drugs. Some subchapters list the benefits of individual drugs for organ systems, by their generic names. Mast cell stabilizers, beta-agonists, antihistamines, leukotriene antagonists, quinine antagonists, immunotherapy and omalizumab (anti-IgE antibody) are essential in the treatment of allergy.

[Atopic dermatitis in children and adults]. / Atopijski dermatitis u djece i odraslih.

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease characterized by itching and typical clinical features, depending on patient age. It is often associated with other atopic diseases such as asthma or allergic rhinitis, resulting from the complex etiology and pathogenesis. It occurs more frequently in people with genetic predisposition for atopic diseases. The intensity and extent of skin lesions (Scoring of Atopic Dermatitis, SCORAD Index) vary significantly among AD patients, depending on whether it is acute or chronic, and there are variations in laboratory parameters, especially immune. In the future, it will be necessary to reach consensus on the new criteria for defining AD instead of the old ones (brought by Hanifin and Rajka 31 years ago). What is needed is effective and safe treatment, and control of the early stages of AD as well as maintaining AD remission. The new therapeutic approach in AD has greatly improved the quality of life of AD patients. As the prevalence of the disease continues to increase, we emphasize the importance of prevention, prompt recognition and optimal treatment of the many patients with AD.

[Allergologic emergencies in dermatology--diagnostic and therapeutic procedures]. / Hitna stanja u alergologiji i dermatovenerologiji--dijagnosticki i terapijski postupci.

Emergencies in allergology and clinical immunology are quite common and pose a public health problem in Croatia and worldwide. Allergic reactions ranging from mild symptoms such as pruritus to generalized skin eruptions, gastrointestinal and respiratory symptoms to anaphylaxis with cardiovascular emergencies are very common. Reaction develops to inhalant substances, food and food ingredients, various foreign substances (blood, latex, etc.) and many other well known antigens and drugs which are frequent causes of anaphylactic reactions, asthma, generalized urticaria, angioedema. There are 35 different skin reactions induced by drugs through immune complexes, complement mediated reactions and direct histamine liberation (by opiates or dextran) and modulators of arachidonic acid metabolism (such as NSAID). Along with painful infiltrates, insect venom allergy manifests with disseminated exanthema and angioedema. Current diagnostic methods, especially therapeutic procedures for emergencies in concordance with the international consensus of the European Allergy White Paper, require the same procedure in clinical practice. Many patients with different allergic skin diseases are treated inappropriately, some are tested in active phase of the disease, during anti-allergic therapy, and some are administered corticosteroids and antihistamines longer than necessary. Sometimes, the treatment of emergencies requires a person experienced in intensive care medicine. However, any physician might be responsible for the treatment of acute symptoms in his office, and thus has to know the modalities and relevant drugs and treatment essentials. Anaphylactic reactions are rare, but every physician should be prepared for the worst. Due knowledge of the correct management should be a must for all of us. The most common emergencies require emergency treatment and diagnostic procedures upon disease regression.

[Chronologic annotation on the development of allergology and clinical immunology in Croatia]. / Kronoloski osvrt na razvoj alergologije i klinicke imunologije u Hrvatskoj.

This issue of Acta Medica Croatica is dedicated to historical development and role of allergology and clinical immunology in Croatia. Also listed are the names of experts who have historically marked allergology and contributed to its development. Understanding the origin of allergies as immune phenomena occurred in Croatia simultaneously to many other European countries. The origin and development of institutions established in the early 1920s constituted the backbone of a solid vertical line, crucial for the development of allergology and immunology in Croatia during the past century. Interest of allergology experts from various medical specialties has resulted in the establishment of Allergy Section at the Croatian Medical Association in 1952, now Croatian Society of Allergology and Clinical Immunology of the Croatian Medical Association. It turned out that the work of institutions and physicians, as well as cooperation with the Croatian Immunological Society and other scientific institutions during the second half of the 20th century provided solid foundation for contemporary research, design and development of allergy subspecialty centers and units at various medical institutions all over Croatia. Members of the Croatian Society of Allergology and Clinical Immunology have played an important role in educating new generations of physicians and in the organization of numerous research projects, symposia, congresses and seminars. Continuous, scientific and professional work has resulted in active Society membership in the European Academy of Clinical Immunology and Allergology.

Melanoma Controls the Metastatic Process only in Terms of Metastatic Cell Dissemination - What Is Responsible for Metastatic Cell Proliferation?

The process of melanoma metastasis can be divided into two stages of metastatic cell dissemination and proliferation. The whole process should be observed and distinguished through the variable or prism of time. The fact that melanoma metastases are detected in visceral organs at the stage when they are macroscopically visible does not imply that their onset has occurred much earlier. Additionally, it is quite obvious that the entire process is not driven by melanoma but rather only the initial stage of metastatic cell dissemination, whereas the later stage of metastatic cell proliferation is driven by other factors, firstly by mutated genes in the presence of melanoma or without it. Dissemination of metastatic cells occurs at approximately the same time in all melanomas, at MIS transition to MM, but is not immediately followed by metastatic cell proliferation; instead, some time has to elapse for a particular gene mutation to occur, and this timing varies among melanomas. Following dissemination of metastatic cells to visceral organs, they remain inactive, and in this period the presence of melanoma is not necessary anymore for metastatic cell proliferation, as they are waiting for a signal to start multiplying. This is clearly discernible from the fact that melanoma is today detected and removed frequently and early, but visible metastases then develop in the absence of melanoma, which may also regress spontaneously. Accordingly, MM is no longer necessary for metastasis later on. Finally, let me rephrase the title: melanoma is only responsible for initial dissemination of metastatic cells, whereas subsequent proliferation of metastatic cells is driven by other factors, most probably mutated genes.

Skin cancers in Croatia, 2003-2005: epidemiological study.

This study presents the incidence of major nonmelanoma skin cancers (major NMSCs), other nonmelanoma skin cancers (other NMSCs) and malignant melanoma (MM) in Croatia. The skin cancers recorded between 1 January 2003 and 31 December 2005 were retrospectively analyzed. Until 2003, the incidence of major NMSCs and other NMSCs was not estimated in Croatia. Incident cases of NMSCs were identified by the use of a questionnaire distributed to dermatology departments in Croatia and then collected at the University Department of Dermatology and Venereology, Zagreb University Hospital Center, and from the records kept at the National Cancer Registry. Incident cases of MM were extracted from the National Cancer Registry. During the 3-year period, 9,479 cases of major NMSCs are recorded, 4,622 (49%) in male and 4,857 (51%) in female patients. The crude incidence rate was 72.1/100,000 for males and 70.3/100,000 for females. Basal cell carcinoma (BCC) was the most common major NMSC in both sexes. In the total number of major NMSCs, there were 7,244 cases of BCC. Squamous cell carcinoma (SCC) was the second most common major NMSC. There were 1,860 SCC cases. The crude incidence rate was 54.9/100,000 for BCC in males, 53.9/100,000 in females, and 14.6/100,000 for SCC in male and 13.4/100,000 in female patients. Other NMSCs were registered in 119 cases (53% male and 47% female). The crude incidence rate was 0.9/100,000 for male and 0.8/100,000 for female patients. MM was registered in 1,427 cases (48% male and 52% female.) The crude incidence rate was 10.7/100,000 for males and females. These results will serve as reference for studying the patterns of descriptive epidemiology of major NMSCs, other NMSCs and MM in Croatia and Europe in the forthcoming years.

Molecular variants of human papilloma viruses type 16 and 6 in women with different cytological results detected by RFLP analysis.

HPV infections are common and the presence of the same high-risk type in cervical specimens can be due to reinfection or persistence. Persistent infection is the most important predictor for development of cervical carcinoma. The aim of this study was to validate PCR-RFLP with two sets of primers: MY09/MY11 that amplify a fragment of L1 and P1/P2 that amplify a fragment of E1 ORF. PCR product of MY09/MY11 was digested with a set of 6 restriction enzymes (RE) and PCR product of P1/P2 with a set of 12 RE. Cervical samples from 110 women patients of the University Gynecologic Clinic CHC Zagreb were analyzed. There were 98 (89.1%) PCR positive samples detected with P1/P2 primers, and 94 (85.5%) PCR positive samples detected with MY09/MY11 primers. Seven HPV types were detected with P1/P2-RFLP technique and 17 with MY09/MY11-RFLP PCR positive samples amplified with both primer pairs agreed with each other in 82 samples; 16 samples were only positive with P1/P2 and 12 samples were only positive by MY09/MY11. HPV 16 was detected in 39 samples with MY09/11-RFLP, out of these two variants (two different patterns) were found with P1/P2 using Dde I, Hae III and Eco I. HPV 6 was detected in 9 samples with MY09/11-RFLP, out of these two variants were found with P1/P2 using HinfI. Combining these two PCR-RFLP methods subtypes of HPV 16 and HPV 6 were detected.

Oxidative stress and ferritin expression in the skin of patients with rosacea.

BACKGROUND: Rosacea is a common chronic light-sensitive inflammatory skin disease of unknown origin. The purpose of this work was to determine the parameters of oxidative stress, antioxidative capacity, and the pathophysiologic role of ferritin expression in skin cells of patients with rosacea. OBJECTIVES: The investigation consisted of measurements of serum peroxide levels, serum total antioxidative potential levels, and immunohistochemical analyses of ferritin in skin tissue samples. RESULTS: Serum peroxide levels were significantly higher and serum total antioxidative potential levels were significantly lower in patients with rosacea than in healthy control subjects (P < .05). Compared with control subjects, the number of ferritin-positive cells was significantly higher (P < .001) in skin samples from patients with rosacea, especially those with severe disease. LIMITATIONS: Patients with rosacea in the study were aged 30 to 70 years (average age was 56 years). Younger patients with flushing only were not included according to the request of the ethics committee, limiting the use of diagnostic biopsies only to the necessary cases. CONCLUSION: The statistically significant differences in the expression of ferritin, higher peroxide levels, and lower antioxidative potential support the onset of systemic oxidative stress in patients with rosacea.