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ABSTRACT: Matrix metalloproteinases (MMPs) are implicated in the development of cancers including malignant melanoma (MM) and breast cancer. We tested the possible association of MMP1 and MMP8 gene variation with these two types of cancer. We genotyped 300 unselected patients with MM, 300 consecutive breast cancer cases, 300 controls for melanoma, and 300 controls for breast cancer (age-matched and sex-matched healthy adults with negative cancer family histories). Our study showed that the MMP8 gene rs11225395 polymorphism was associated with the risk of developing MM (odds ratio: 1.69; 95% confidence interval: 1.02-2.80; P=0.040) for the A/A genotype and 1.49 (95% confidence interval: 1.03-2.17; P=0.035) for the A/G genotype compared with the G/G genotype. The A allele was over-represented among MM cases compared with controls (odds ratio=1.54; P=0.017). In-vitro assays showed that the A allele had a higher promoter activity than the G allele in melanoma cells. No association was detected between this variant and breast cancer susceptibility. We found no strong association between MMP1 variation and the risk of MM or breast cancer. The finding of this study indicates an influence of MMP8 gene variation on melanoma susceptibility.
Melanoma research 06/2011; 21(5):464-8. · 2.06 Impact Factor
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ABSTRACT: Antimalarial drugs--chloroquine, hydroxychloroquine and quinacrine, initially devised for the treatment of malaria, have been used in the therapy of diverse skin diseases, including lupus erythematosus, dermatomyositis, porphyria cutanea tarda, and sarcoidosis. The mechanism of action of these drugs involves stabilization of lysosomal enzymes, inhibition of antigen-presenting cells and T lymphocyte stimulation, blocking of the pro-inflammatory cytokine cascade and endosomal toll-like receptor signaling. The understanding of potential mechanisms of action of antimalarials may extend their use to new areas in dermatology. This work describes the pharmacologic properties of antimalarial drugs and indications for their use in clinical practice. Moreover, the most important limitations of therapy with antimalarials and their adverse side effects are discussed.
Annales Academiae Medicae Stetinensis 01/2011; 57(1):38-44.
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ABSTRACT: Vitiligo is an idiopathic chronic skin disease that is notable for depigmented macules forming by destruction of melanocytes mediated by cells of the immune system. Vitiligo occurs in 1-2% of the population irrespective of race and without predilection to gender or age. The dynamics and extent of the disease vary widely, ranging from stable cases with isolated minor foci to states showing rapid progression and occupying large areas of the skin. For many patients, the disease represents a serious cosmetic defect which limits their activities in various spheres of life. There are many noninvasive methods of treatment but none of them offers a guarantee of complete therapeutic success. PUVA- and UVB-therapy are recognized as the most effective and most commonly used methods. The management of vitiligo should also include education, cosmetic correction options, and psychotherapy in some cases.
Annales Academiae Medicae Stetinensis 01/2011; 57(3):23-7.
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Melanoma research 04/2010; 20(2):159-60. · 2.06 Impact Factor
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ABSTRACT: Clinical symptoms attributed to the nail apparatus and observed in cosmetology include atrophic or hypertrophic lesions, pathologic nail coloration, abnormalities of the nail surface, and disorders of the nail plate and bed junction. These symptoms may reflect pathologic processes limited to the nail apparatus or may be the consequence of a dermal or systemic disease. Even though the etiology of nail lesions is variegated, diseases of the nails are simply classified as infectious or non-infectious. The aim of this work was to present the most common diseases of the nail apparatus encountered in cosmetology. Often, nail diseases worsen the quality of life of the patient. In addition, the variegated symptomatology demonstrates that nail lesions should be viewed in a wider perspective because they often are important signs of pathologic processes taking place in the organism of the patient.
Annales Academiae Medicae Stetinensis 01/2010; 56(1):57-64; discussion 64.
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ABSTRACT: Erythematotelangiectatic skin is a common cosmetic and medical problem. Flushing or persistent erythema, teleangiectasias, and occasionally other inflammatory skin lesions can be caused by internal or environmental factors. Certain physiologic reactions and systemic or dermatologic diseases represent internal conditions leading to visible skin flushing in the blush area. Erythematotelangiectatic skin is found in body areas which are particularly exposed to various environmental factors and perform important esthetic functions at the same time. Determination of the main etiopathologic factor responsible for flushing in the blush area precedes the selection of an adequate method of care, correction or treatment of the erythematotelangiectatic skin. The main aim of this study was to analyze fundamental mechanisms of flushing or persistent erythema and their sequellae basing on the literature. Another aim was to review current diagnostic options useful in examining the etiology and severity of erythematotelangiectatic skin symptoms.
Annales Academiae Medicae Stetinensis 01/2009; 55(1):58-65; discussion 65.
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Tadeusz Debniak,
Thierry van de Wetering,
Rodney Scott,
Leszek Nagay,
Cezary Cybulski,
Bohdan Górski,
Anna Jakubowska,
Jacek Gronwald,
Bartłomiej Masojć,
Tomasz Huzarski,
Tomasz Byrski,
Katarzyna Nej-Wołosiak,
Józef Kładny, Romuald Maleszka,
Jan Lubinski
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ABSTRACT: In this report the contribution of CDKN2A/ARF germline mutations to early-onset cancers of the breast, pancreas and malignant melanoma was examined. We screened 66 women with breast cancer diagnosed at age 30 and below, 72 melanoma patients with the median age at diagnosis < or = 40 years and 51 pancreatic cancer patients diagnosed under the age of 50 years. In the total set of 189 patients we found a novel change Pro48Arg (nt 143 c > g), a novel intronic change IVS1+36 g>c and two common variants A148T and IVS3+29 c>g. The results of this study revealed a paucity of mutations in CDKN2A/ARF suggesting that in the Polish population this gene does not contribute significantly to early-onset breast cancer, pancreatic cancer and malignant melanoma.
European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 11/2008; 17(5):389-91. · 2.21 Impact Factor
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ABSTRACT: Every adverse and undesirable event observed after administration of the therapeutic dose of the drug is defined as adverse drug reaction. The aim of the study was to evaluate the incidence frequency of cutaneous adverse drug reactions, to define the drugs inducing such reactions and to define the type of the most frequently found lesions in patients admitted to Department of Dermatology and Venereology of Pomeranian Medical University in Szczecin (PAM) in 1996-2006.
A retrospective analysis of medical files of the patients, who were hospitalized in the Department of Dermatology and Venereology of PAM in Szczecin in 1996-2006, was carried out. Due to cutaneous adverse drug reactions, 386 patients were hospitalized. They made 4.25% of all admitted to our Department.
These reactions were found more frequently in females (65.5%) than in males (34.5%). Non-steroidal anti-inflammatory drugs induced adverse events most frequently (37.6%), followed by aminopenicillin antibiotics, particularly amoxycillin-containing agents, responsible for 25.8% of these reactions. Other antibiotics were responsible for undesirable events less frequently--9.6%. Macular and maculopapular rashes were the most frequently observed adverse cutaneous drug reactions (42.0% of the cases), followed by acute urticaria and Quincke's oedema (39.1% of all reactions), whereas contact dermatitis after topical drugs was found in 8.0% of the cases.
Cutaneous adverse drug reactions were mainly induced by non-steroidal anti-inflammatory drugs and aminopenicillin antibiotics. The most frequent forms of cutaneous adverse drug reactions were maculopapular rashes, acute urticaria and Quincke's oedema.
Annales Academiae Medicae Stetinensis 02/2008; 54(2):52-8.
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ABSTRACT: The paper presents current opinions on aetiopathogenesis of dry skin including its occurrence in the course of certain dermatological disorders. A meaning of natural moisturizing factor, lipid barrier as well as epidermal differentiation processes in the maintenance of the proper skin moisturization is described. The importance of topical treatment is emphasized. Moreover, a survey of moisturizing factors applied in dry skin care is included.
Annales Academiae Medicae Stetinensis 01/2008; 54(3):54-7.
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Tadeusz Debniak,
Rodney Scott,
Bartłomiej Masojc,
Pablo Serrano-Fernández,
Tomasz Huzarski,
Tomasz Byrski,
Bogusław Debniak,
Bohdan Górski,
Cezary Cybulski,
Krzysztof Medrek,
Grzegorz Kurzawski,
Thierry van de Wetering, Romuald Maleszka,
Józef Kładny,
Jan Lubinski
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ABSTRACT: We sought to examine the association between MC1R variants and the risk of melanoma and breast cancer in Polish population. We also determined the prevalence of compound heterozygous carriers of MC1R and CDKN2A (A148T) variants. We examined 500 unselected melanoma cases, 511 consecutive invasive breast cancer patients, 800 newborns, 421 healthy adults matched for sex and age with the melanoma cases and 511 healthy women matched for sex and age with the breast cancer cases. A statistically significant association of all 4 MC1R variants with the melanoma risk was found. For the R151C variant p value was 0.000008 and odds ratio 2.9; for the V60L variant p value was 0.007 and OR 1.78; for the R160C p was 0.006 and OR 1.76; for the R163Q p was 0.015 and odds ratio 2.1. None of the compound heterozygotes were significantly over-represented among any of the melanoma cases, the highest OR (4.2) observed in patients harbouring the A148T variant in CDKN2A and the R151C variant in MC1R. Positive association was found between carrying any of the MC1R variants and (i) increased occurrence of melanoma among I degree relatives of the carriers; (ii) increased occurrence of melanoma on UV-non-exposed skin areas. We also observed a tendency of increased risk of multiple melanomas among carriers of MC1R variants. The haplotype analysis demonstrates that MC1R variants do not co-occur in cis, compound carriers have both alleles affected. We found no association with the MC1R variants and breast cancer risk. In conclusion, the results of this population-based study show herein that MC1R variants are associated with increased melanoma risk in the Polish population. The risk of disease seems to be increased additively for patients harbouring also the CDKN2A common variant A148T.
International Journal of Cancer 01/2007; 119(11):2597-602. · 5.44 Impact Factor
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ABSTRACT: Thermal imaging is a powerful tool for the study of temperature of the human body. Even though the skin lies superficially and as such is an ideal object for thermography, the method has not gained widespread acceptance as a diagnostic modality in dermatology. The aim of this study was to describe the methodology of thermography for applications in dermatology and to develop a method for computer processing ofthermograms. In addition, we searched for skin factors, which could be responsible for false results in thermography and errors during interpretation of thermal images.
Clinical trials were performed in 2001-2005. We enrolled 230 patients, including 70 who were hospitalized at the Department of Dermatology and Venereal Diseases, Pomeranian Medical University in Szczecin, and 160 who were referred from the Outpatient Dermatology Clinic. The control group consisted of 20 healthy volunteers. The skin was examined to disclose primary and secondary skin lesions. Thermography was performed according to recommendations of the European Association of Thermology. Therma CAM SC500 infrared camera was used and the thermograms were analyzed with Therma CAM 200 Professional software.
1. Areas of the skin with inflammatory reactions resulting from allergy, infection or other process causing local hyperthermia could be visualized. 2. Primary eruptions (papules, nodules) and secondary eruptions (scales) presenting as hypothermia in thermography were found in the skin of the patients and some individuals from the control group. 3. Interpretation of thermograms in dermatoses can be done using various colour scales, like "rain", "iron", "medical", "grey", "greyred" and the three-dimensional scale.
1. Thermography is a useful diagnostic method in dermatology. 2. The normal thermogram, as well as thermograms specific for various dermatoses need to be described. 3. Compliance is indispensable with rules and principles concerning the examination itself, as well as analysis and clinical interpretation of the results. 4. The person performing the examination and interpreting the thermograms should take part in history-taking and physical examination of the patient and should be familiar with photographic documentation of the examined regions of the skin.
Annales Academiae Medicae Stetinensis 02/2006; 52(3):91-7.
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ABSTRACT: Subacute cutaneous lupus erythematosus (SCLE) is a subset of lupus erythematosus that identifies patients with clinically recognized erythematous, nonscarring lesions, photosensitivity and serologic abnormalities. Anti-Ro (SS-A) antibodies are considered to be a typical immunopathologic marker of SCLE. Autoimmune diseases have been also characterized by the disturbances in the cytokine network. The aim of this study was to compare the concentrations of proinflammatory cytokines (IL-1beta, IL-6, IL-12, IL-18 and TNF-alpha) in serum of ANA-positive (antibody against nuclear antigen) and ANA-negative patients with SCLE. Sera samples were collected from 15 patients with SCLE (9 ANA-positive and 6 ANA-negative ones). The preliminary identification of autoantibodies as well as their titers was determined on HEp-2 cells using IIF method. Western blotting (EUROIMMUN) was applied to verify the results of IIF. Proinflammatory cytokine concentrations in the patients' sera samples were determined by enzyme-linked immunosorbent assay (ELISA) (Bender MedSystems). The levels of IL-12 were higher in ANA-positive patients than in ANA-negative subgroups [median (interquartile range), 330 pg/ml (128-708 pg/ml) versus 39.4 pg/ml (31.25-80 pg/ml)]. Similar differences were observed in the level of IL-18 [median (interquartile range), 508.4 pg/ml (180-1222 pg/ml) versus 100.5 pg/ml (78.1-154 pg/ml)]. The differences in TNF-alpha levels between the groups of ANA-positive and ANA-negative patients were at the verge of statistical significance, p<0.05. The sera levels of IL-1beta and IL-6 were low and of no significant difference concerning the ANA-positive and ANA-negative subgroups. Since serum levels of IL-12 and IL-18 were higher in ANA-positive patients than in ANA-negative patients, these cytokines might play an important role in the inflammatory process in SCLE.
Immunology Letters 02/2006; 102(1):79-82. · 2.53 Impact Factor
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Tadeusz Debniak,
Rodney J Scott,
Tomasz Huzarski,
Tomasz Byrski,
Andrzej Rozmiarek,
Bogusław Debniak,
Elzbieta Załuga, Romuald Maleszka,
Józef Kładny,
Bohdan Górski,
Cezary Cybulski,
Jacek Gronwald,
Grzegorz Kurzawski,
Jan Lubinski
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ABSTRACT: The population frequencies of the CDKN2A variants remain undetermined. In Poland there are three common variants of CDKN2A: an alanine to threonine substitution (A148T), Nt500c>g and Nt540c>t, which have been detected in other populations. To establish if they are associated with an increased malignant melanoma (MM) risk we did an association study based on genotyping 471 patients with MM and 1,210 random control subjects from the same Polish population. We found a significantly increased frequency of the A148T variant among patients with MM (7.0%) in comparison with the general population (2.9%). The incidence of the A148T variant remained greater in both unselected and familial melanoma subgroups. A statistically significant positive association was seen for unselected MM (odds ratio, 2.529; P = 0.0003), especially in patients diagnosed under 50 years of age (odds ratio, 3.4; P = 0.0002). The A148T carrier population (heterozygous G/A alleles) was more likely to have a relative with malignancy compared with the noncarrier population (57% versus 36%, respectively; P = 0.03). Further examination of the CDKN2A promoter sequence done in 20 melanoma patients with the A148T change (heterozygous G/A alleles) and 20 patients with MM without this alteration identified it was in linkage disequilibrium with a polymorphism in the promoter region at position P-493. We found no statistically significant overrepresentation of the Nt500c>g and the Nt540c>t polymorphisms in the Polish melanoma population. In conclusion, the A148T variant of the CDKN2A gene seems to be associated with an increased risk of development of MM. Additional studies are required to confirm whether this particular change is associated with increased risk of other nonmelanoma malignancies.
Cancer Research 02/2005; 65(3):835-9. · 7.86 Impact Factor
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Tadeusz Debniak,
Bohdan Górski,
Rodney J Scott,
Cezary Cybulski,
Krzysztof Medrek,
Elzbieta Zowocka,
Grzegorz Kurzawski,
Boguslaw Debniak,
Józef Kadny,
Stanislawa Bielecka-Grzela, Romuald Maleszka,
Jan Lubiński
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ABSTRACT: The CDKN2A/ARF genes have been associated with increased risk of malignant melanoma (MM) in families with multiple members affected by disease and in families characterized by the constellation of breast cancer and MM. The exact contribution of CDKN2A/ARF to disease risk remains poorly characterized, especially in diverse populations. In this report, the contribution of CDKN2A/ARF germline mutations and large rearrangements to disease in Polish familial MM (FMM) and aggregations of breast cancer and MM were assessed using a strategy that included genomic sequencing, restriction fragment length polymorphism and multiplex ligation-dependent probe amplification. We examined 16 FMM cases (group 1), 44 MM probands with a cancer family aggregation (CFA) that included at least one breast cancer (group 2) and 22 breast cancer probands with CFA and MM (group 3). The results revealed a paucity of mutations in CDKN2A/ARF, suggesting that in the Polish population this gene does not contribute significantly to either FMM or MM within the context of CFA.
International Journal of Cancer 08/2004; 110(4):558-62. · 5.44 Impact Factor
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ABSTRACT: Tuberous sclerosis (Bourneville-Pringle disease) is an inherited disease with a prevalence rate ranging from 1:10,000 to 1:23,000. It is inherited as an autosomal dominant with a variable gene penetrance. However about 60% of cases represent new mutations. This disease is characterized by a defect in cell migration, proliferation and differentiation in organs like skin, brain, kidneys, heart, lungs and eyes. The mechanism involves formation of hamartoma tumours responsible for the functional impairment of these organs.
Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego 07/2004; 16(96):589-91.
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ABSTRACT: Tuberous sclerosis (Bourneville-Pringle disease) is an genetic autosomal dominant disease, but in over 50% cases there are new spontaneous mutations. During this disease visceral hamartomas do tend to develop in various tissues. Earlier it was considered that in order to set a diagnosis the knowledge of Vogt's triade was required (angiofibroma, epilepsia, mental retardation). But new not typical forms occur, that do not contain all the above mentioned three elements. The phenomenon is connected with the appearance of a new mutations of the gene or with a variable gene penetrance. In these study case we present a 21-year old patient who shows the fully blown symptoms of Vogt's triad and her father who only has hypopigmented macules on his back.
Polskie archiwum medycyny wewnȩtrznej 09/2003; 110(2):877-84. · 1.37 Impact Factor
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Tadeusz Debniak,
Bohdan Górski,
Cezary Cybulski,
Anna Jakubowska,
Grzegorz Kurzawski,
Marcin Lener,
Marek Mierzejewski,
Bartosz Masojć,
Krzysztof Medrek,
Józef Kładny,
Elzbieta Załuga, Romuald Maleszka,
Maria Chosia,
Jan Lubiński
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ABSTRACT: In this study we determined in what proportion of consecutive malignant melanoma (MM) cases the 657del5 mutation of exon 6 of the NBS1 gene can be detected and whether it is associated with the occurrence of MM. Two groups of patients were studied: a series of 80 consecutive patients with histologically confirmed MM of the skin diagnosed in the city of Szczecin, Poland, and a series of 530 consecutive individuals selected at random by family doctors from the city of Szczecin. Molecular examination included an allele-specific polymerase chain reaction assay for the NBS1 founder mutation (657del5), genomic sequencing, loss of heterozygosity analysis using CA-repeat microsatellite markers, and haplotype analysis. The NBS1 founder mutation was detected in two of the 80 (2.5%) MM cases and in three of the 530 individuals (0.6%) from the general population. The difference was not statistically significant. However, examination of tumorous DNA from the patients with MM and NBS1 mutation revealed loss of heterozygosity in both cases. Haplotype analysis revealed that allellic loss affects wild-type alleles. Breast cancer was found in second-degree relatives of both MM probands with NBS1 mutations. One of these probands was simultaneously affected with breast cancer. It seems that the 657del5 mutation of exon 6 of NBS1 gene may be responsible for the occurrence of a small proportion of MM patients, characterized by the occurrence of breast cancer among their relatives.
Melanoma Research 09/2003; 13(4):365-70. · 2.19 Impact Factor
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ABSTRACT: Concentrations of trimethoprim and sulfamethoxazole in plasma, cantharidin-induced skin blister fluid and theoretical peripheral compartment were determined in twelve male subjects suffering from bacterial skin diseases after a single oral dose of 0.32 g of trimethoprim and 1.6 g of sulfamethoxazole. Maximum trimethoprim concentrations of 8.5 +/- 1.1 micromol/l in plasma, 5.6 +/- 0.8 micromol/l in blister fluid and 5.8 +/- 2.2 micromol/l in theoretical peripheral compartment were found after 3 +/- 1, 7 +/- 2 and 9 +/- 6 h, respectively. Degree of penetration into blister fluid and theoretical peripheral compartment was 0.94 +/- 0.23 and 1.05 +/- 0.09, respectively. The differences between respective pharmacokinetic parameters of trimethoprim in blister fluid and theoretical peripheral compartment were statistically insignificant. Maximum sulfamethoxazole concentrations of 295 +/- 47 micromol/l in plasma, 182 +/- 46 micromol/l in blister fluid and 239 +/- 58 micromol/l in theoretical peripheral compartment were found after 3 +/- 1, 8 +/- 2 and 7 +/- 4 h, respectively. Degree of penetration into blister fluid and theoretical peripheral compartment was 0.82 +/- 0.20 and 1.04 +/- 0.02, respectively. In contrast to trimethoprim, the differences between respective pharmacokinetic parameters of sulfamethoxazole in blister fluid and theoretical peripheral compartment, except time to maximum concentration, were statistically significant. Cantharidin-induced skin blister fluid method can be used to estimate drug penetration into skin. Due to differences between the respective pharmacokinetic parameters in experimental and theoretical peripheral compartment, in some cases evaluation of drug penetration into skin should not be replaced by the theoretical peripheral compartment calculation.
Polish journal of pharmacology 56(2):257-63.
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Indian journal of dermatology, venereology and leprology 77(2):253. · 0.98 Impact Factor
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ABSTRACT: Efficacy and safety of azithromycin and doxycycline for the treatment of moderate acne vulgaris were evaluated (240 patients) in both intention-to-treat and per-protocol populations. The evaluation of clinical efficacy was based on the change in the number of facial inflammatory lesions from baseline to the end of treatment, and noninferiority was defined by the upper 95% confidence limit of the difference between two treatments being less than 9. Reduction in the number of lesions was similar with both azithromycin and doxycycline treatments (27 +/- 12 and 30 +/- 12, respectively) in both groups. Also, the upper 95% confidence limit of 5 inflammatory lesions has satisfied the noninferiority criterion. The incidence of adverse events did not differ between the two treatment groups. The shorter and simpler treatment schedule of azithromycin had similar efficacy and safety as doxycycline in the treatment of moderate acne vulgaris, confirming noninferiority of azithromycin as compared with doxycycline.
SKINmed 9(2):86-94.
