Doppler laser imaging predicts response to topical minoxidil in the treatment of female pattern hair loss.

Topical minoxidil is the only drug approved by the US FDA for the treatment of female pattern hair loss. Unfortunately, following 16 weeks of daily application, less than 40% of patients regrow hair. Several studies have demonstrated that sulfotransferase enzyme activity in plucked hair follicles predicts topical minoxidil response in female pattern hair loss patients. However, due to patients’ discomfort with the procedure, and the time required to perform the enzymatic assay it would be ideal to develop a rapid, non-invasive test for sulfotransferase enzyme activity. Minoxidil is a pro-drug converted to its active form, minoxidil sulfate, by sulfotransferase enzymes in the outer root sheath of hair. Minoxidil sulfate is the active form required for both the promotion of hair regrowth and the vasodilatory effects of minoxidil. We thus hypothesized that laser Doppler velocimetry measurement of scalp blood perfusion subsequent to the application of topical minoxidil would correlate with sulfotransferase enzyme activity in plucked hair follicles. In this study, plucked hair follicles from female pattern hair loss patients were analyzed for sulfotransferase enzyme activity. Additionally, laser Doppler velocimetry was used to measure the change in scalp perfusion at 15, 30, 45, and 60 minutes, after the application of minoxidil. In agreement with our hypothesis, we discovered a correlation (r=1.0) between the change in scalp perfusion within 60 minutes after topical minoxidil application and sulfotransferase enzyme activity in plucked hairs. To our knowledge, this is the first study demonstrating the feasibility of using laser Doppler imaging as a rapid, non-invasive diagnostic test to predict topical minoxidil response in the treatment of female pattern hair loss.

Use of biologics for psoriasis in Central and Eastern European countries.

OBJECTIVES: To evaluate the use of biological agents for the treatment of psoriasis and to explore country-specific differences within six Central and Eastern European (CEE) countries, namely Bulgaria, Croatia, the Czech Republic, Hungary, Poland and Romania. METHODS: A literature overview on the epidemiology and disease burden of psoriasis in CEE was conducted. The number of patients treated with biologics was obtained from patient registries, ministries of health, national professional societies and health insurance funds. Biological treatment rates were estimated by two different methods: (i) as a proportion of all psoriasis patients of a country (assuming a common prevalence of psoriasis 2%) and (ii) per 100,000 population. Moreover, we provide a detailed comparison of drug coverage policies and guidelines regulating the treatment with biologics in psoriasis. RESULTS: On average 0.25% of all psoriasis patients, or five psoriasis patients out of 100,000 inhabitants are treated with biologics embedding a 14.6-fold difference between the six countries. Bulgaria, Croatia and Poland lag behind the other three countries in the use of biologics. The significant differences among CEE countries cannot be explained by variations in prices of biologics, cost-effectiveness or budget impact of biologics. It seems that the time since coverage decision, the fewer number of covered biologics, the more restrictive criteria to be eligible for covered treatment in terms of baseline Psoriasis Area and Severity Index and Dermatology Life Quality Index scores, and the maximum duration of treatment allowed are responsible for the majority of the differences. CONCLUSIONS: There exists a disconnect between the European psoriasis treatment guidelines and the various CEE country-specific biologic coverage eligibilities. The cost of biologic therapy for psoriasis is not solely and directly responsible for the different use rates amongst the CEE countries. Psoriasis may not be perceived by all payers as a serious disease that can be successfully treated in a cost-effective manner.

Has psoriasis its own characteristic trichogram?

The aim of this study was to determine if there were characteristic trichogram changes in scalp psoriasis in patients without clinically evident effluvium or alopecia. A total of 45 patients (17 men and 28 women, aged from 15 to 73 years) with clinically and histologically confirmed psoriasis vulgaris with scalp involvement were included. The control group consisted of 60 volunteers (23 males and 37 females aged from 15 to 74 years) with no scalp involvement. Our results from the psoriatic group showed highly increased proportions of dysplastic hair roots. Median proportion was 50% with 95% confidence interval (CI) for median 30-60%, whereas telogen hair ratio was slightly increased-median proportion was 16% with 95% CI for median 15-20%. Within the psoriasis patients' group no statistically significant correlations were found between the proportion of dysplastic hairs and the patients' age, sex, and the intensity and duration of disease. According to the results of this study, the dysplastic hairs in scalp psoriasis are statistically significant much more frequently compared with the control group. Thus, the increased proportion of dysplastic hairs in scalp psoriasis without effluvium or alopecia might be its characteristic trichogram sign.

Leprosy in Croatia in the twentieth century.

Even today, leprosy is a relatively frequently occurring disease, especially in tropical regions of the world. From the eleventh to thirteenth century, leprosy pandemics affected Europe, including Croatia. Probably as a consequence of such history, one can still find endemic foci of leprosy in present-day Croatia. The aim of this study was to analyse all cases of leprosy registered in Croatia during the twentieth century; therefore, we studied thoroughly existing medical documentation and published reports on sporadic leprosy cases, and went on to collect the relevant data through on-site investigation in those parts of Croatia known as putative endemic foci of leprosy. In this way, we collected data concerning the number of leprosy cases, the probable sources of infection, and traced the possible paths of spread of the disease. During the twentieth century, 17 cases of leprosy were registered in Croatia. However, due to the loss of medical documentation concerning the cases from Metkovic, the total number was obviously slightly greater. Concerning the 17 analysed cases, 4 patients were most probably infected during their visits (as sailors or immigrant workers) to the Middle East, South America or Africa; 3 patients developed leprosy after prolonged close contact with previously infected family members, while the exact source of infection remains unsettled for the remaining 10. However, 2 of these patients originated from the area of Cazin in Bosnia and Herzegovina, which is known to be an endemic focus of leprosy. Furthermore, the remaining 8 came from the small area of the village of Blizna in the Croatian municipality of Trogir, and therefore it seems reasonable to conclude that Blizna represents the endemic focus of leprosy in Croatia. The last case of leprosy in Blizna was registered back in 1956. Nevertheless, it is clear that sporadic cases of leprosy can reappear in Croatia, originating either from this endemic focus of Blizna, or as an infected person returning to Croatia from abroad. So, we can conclude that, even today, Croatian medical doctors (and especially dermatovenereologists) should still be acquainted with the clinical diagnosis of leprosy and basic principles of its treatment.

Isolated cases of palmoplantar keratoderma, Unna-Thost type.

A study on the prevalence of hereditary palmoplantar keratoderma, Unna-Thost type, was carried out in Croatia. Altogether 205 cases were verified, and of these forty-eight were chosen for further studies. Six isolated cases of hereditary palmoplantar keratoderma, Unna-Thost type, were found. The following theories were considered to explain such a phenomenon: spontaneous mutation, reduced gene expression, incomplete penetration of the gene, late onset of the disease, unknown biological father of the proband, and involvement of genes in addition to the autosomal dominant one.

Markers for vitiligo related neuropeptides in human skin nerve fibers.

Skin distribution of substance P (SP)-, somatostatin (SOM)-, calcitonin-gene-related peptide (CGRP)- and neuropeptide-Y (NPY)-like immunoreactivity in vitiligo patients was studied by an indirect immunofluorescence technique. Immunocytochemical characteristics of the epidermis, dermoepidermal junction, papillary and reticular dermis, and skin appendages were analyzed in lesional and marginal vitiligo areas as well as in healthy skin. SP-, SOM-, CGRP-, and NPY-immunoreactive nerve fibers were observed in healthy pigmented skin, with patterns specific for immunoreactive distribution. Thin SP-containing fibers were observed in dermal papillae, extending into the epidermis, and SP-immunoreactive nerve fibers were seen around blood vessels and sweat glands. SOM-immunoreactive varicose nerve fibers were associated with Meissner's corpuscles in dermal papillae, while CGRP-like immunoreactivity was demonstrated in free subepidermal nerve terminals and sensory nerve fibers around blood vessels, hair follicles and sweat glands. Autonomic NPY-containing nerve fibers innervated eccrine sweat glands and blood vessels. The distribution of these neuropeptides was the same in healthy controls, except for an increased immunoreactivity to NPY and to a lesser extent to CGRP. These results suggest that NPY may serve as a neurochemical marker in the pathogenesis of the disease, thus supporting the neuronal theory of vitiligo.

A genome-wide association screen identifies regions on chromosomes 1q25 and 7p21 as risk loci for sporadic prostate cancer.

We conducted a genome-wide association study of 3090 sporadic prostate cancer patients and controls using the Affymetrix 10 000 SNP GeneChip. Initial screening of 40 prostate cancer cases and 40 non-cancer controls revealed 237 SNPs to be associated with prostate cancer (P<0.05). Among these SNPs, 33 were selected for further association analysis of 2069 men who had undergone a cancer-screening prostate biopsy. Results identified five loci as being significantly associated with increased prostate cancer risk in this larger sample (rs 1930293, OR=1.7, P=0.03; rs 717809-2p12, OR=1.3, P=0.03; rs 494770-4q34, OR=1.3, P=0.01; rs 2348763-7p21, OR=1.5, P=0.01; rs 1552895-9p22, OR=1.5, P=0.002). To validate these association data, 61 additional HapMap tagSNPs spanning the latter five loci were genotyped in this subject cohort and an additional 1021 men (total subject number=3090). This analysis revealed tag SNP rs 4568789 (chromosome 1q25) and tag SNP rs 13225697 (chromosome 7p21) to be significantly associated with prostate cancer (P-values 0.009 and 0.008, respectively). Haplotype analysis revealed significant associations of prostate cancer with two allele risk haplotypes on both chromosome 1q25 (adjusted OR of 2.7 for prostate cancer, P=0.0003) and chromosome 7p21 (adjusted OR of 1.3, P=0.0004). As linkage data have identified a putative prostate cancer gene on chromosome 1q25 (HPC1), and microarray data have revealed the ETV1 oncogene to be overexpressed in prostate cancer tissue, it appears that chromosome 1q25 and 7p21 may be sites of gene variants conferring risk for sporadic and inherited forms of prostate cancer.

Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer.

The prostate-specific gene, TMPRSS2 is fused with the gene for the transcription factor ERG in a large proportion of human prostate cancers. The prognostic significance of the presence of the TMPRSS2:ERG gene fusion product remains controversial. We examined prostate cancer specimens from 165 patients who underwent surgery for clinically localised prostate cancer between 1998 and 2006. We tested for the presence of TMPRSS2:ERG gene fusion product, using RT-PCR and direct sequencing. We conducted a survival analysis to determine the prognostic significance of the presence of the TMPRSS2:ERG fusion gene on the risk of prostate cancer recurrence, adjusting for the established prognostic factors. We discovered that the fusion gene was expressed within the prostate cancer cells in 81 of 165 (49.1%) patients. Of the 165 patients, 43 (26.1%) developed prostate-specific antigen (PSA) relapse after a mean follow-up of 28 months. The subgroup of patients with the fusion protein had a significantly higher risk of recurrence (58.4% at 5 years) than did patients who lacked the fusion protein (8.1%, P<0.0001). In a multivariable analysis, the presence of gene fusion was the single most important prognostic factor; the adjusted hazard ratio for disease recurrence for patients with the fusion protein was 8.6 (95% CI=3.6-20.6, P<0.0001) compared to patients without the fusion protein. Among prostate cancer patients treated with surgery, the expression of TMPRSS2:ERG fusion gene is a strong prognostic factor and is independent of grade, stage and PSA level.

Correlation between Bcl-2 and Bax in atrophic and hypertrophic type of actinic keratosis.

BACKGROUND: Recent investigations consider actinic keratosis (AK) as an earliest visible pattern of squamous cell carcinoma (SCC). We have analysed the expression of apoptosis-related proteins TP53, Bcl-2 and Bax in 30 atrophic and 30 hypertrophic AK cases. MATERIAL AND METHODS: Immunohistochemical analysis was performed following microwave streptavidin immunoperoxidase protocol on DAKO TechMate Horizon automated immunostainer (DAKO, Copenhagen, Denmark). Monoclonal antibody for TP53 and Bcl-2 and polyclonal antibody for Bax (DAKO, Copenhagen, Denmark) were used. RESULTS: Expression of TP53 showed no significant differences between two analysed groups (chi2-test, P = 0.35636) whereas expression of Bcl-2 and Bax protein was significantly higher in atrophic compared to hypertrophic AK (chi2-test, P = 0.01458 and P = 0.00358, respectively). Comparison of Bcl-2 : Bax ratio in two analysed AK showed significantly higher value in hypertrophic compared to atrophic AK (Mann-Whitney U test, P = 0.02272). Statistical analysis did not show any correlation between patient's sex and age, localization and size of the lesion with expression of investigated oncoproteins (anova, P > 0.05). CONCLUSIONS: Our results may indicate higher resistance of keratinocytes on apoptotic stimuli in hypertrophic compared to atrophic AK. Thus, we suppose that keratinocytes in hypertrophic AK live longer and probably have higher propensity for additional mutations and conversion to overt SCC.

Treatment of cutaneous leishmaniasis with 20% paromomycin ointment.

Cutaneous leishmaniasis is an infectious disease caused by flagellate protozoa of the genus Leishmania. In Mediterranean countries, the most common causative agents are Leishmania (L.) major, L. infantum and L. tropica. In Croatia, cutaneous leishmaniasis is a rare disease, the last case being reported in 1988. Our patient was a 5-year-old boy with a left cheek skin lesion in the form of papule with central exulceration, hyperkeratotic crust and erythema of a 6-month duration. The diagnosis of cutaneous leishmaniasis was based on history data (stay in the southernmost region of Croatia and multiple mosquito bites), light microscopic histology (dense infiltrates of large histiocytes with extracellular bodies), and positive Montenegro (leishmanin) test. A new therapy with aminosidine (paromomycin), an aminoglycoside antibiotic, in the form of ointment at a concentration of 20%, was for the first time used in Croatia. Four-week therapy resulted in complete regression of the skin lesions with residual hyperpigmentation. During therapy, no local or systemic side effects were observed. Thus, topical therapy with paromomycin could be considered an efficient therapeutic alternative in the management of cutaneous leishmaniasis.

Clinical evaluation of a more rapid and sensitive Psoriasis Assessment Severity Score (PASS), and its comparison with the classic method of Psoriasis Area and Severity Index (PASI), before and after climatotherapy at the Dead-Sea.

BACKGROUND: The Psoriasis Area and Severity Index (PASI) is used to quantify the extent of the disease, and to evaluate its improvement with treatment. It is considered to be a slow, rough, nonsensitive, and complex tool, with high interobserver variability and low reproducibility. OBJECTIVES AND METHODS: To develop a simpler, more sensitive, and more rapid end-point determination for evaluating the psoriatic condition, and to compare its sensitivity with that of the classic PASI score in psoriatic patients undergoing 4-week climatotherapy at the Dead-Sea (Israel). RESULTS: This study describes a new, rapid, and simple Psoriasis Assessment Severity Score (PASS), whose readings are spread over a longer scale, making the test more sensitive than PASI, and allow better differentiation. CONCLUSIONS: The comparison between the classic PASI and our new PASS emphasizes the weight of the "sensitivity to change" (responsivity) in selecting a better evaluation method for psoriatic patients.

Hereditary palmoplantar keratoderma, type papulosa, in Croatia.

BACKGROUND: Hereditary palmoplantar keratoderma (HPPK), type papulosa, is rare, and epidemiologic data are sporadic and inconsistent. An epidemiologic population study of this disease has not been performed previously. OBJECTIVE: We performed a large population study on prevalence of HPPK, type papulosa, in Croatia. METHODS: The data were collected from medical records of dermatology departments throughout Croatia; 14 patients and their relatives were examined. Histopathologic studies were performed in 11 of these 14 patients. RESULTS: Fifty-five patients were identified and the prevalence was 1.17 per 100,000 inhabitants. All 55 patients belonged to 20 different families. An autosomal dominant mode of inheritance was confirmed in 13 families. All 14 patients examined by the authors had both palmar and plantar lesions; the volar aspects of fingers were also involved. Thickened nails were observed in four patients, and no significant skin lesions were found elsewhere. CONCLUSION: HPPK, type papulosa, is rare, and its prevalence in Croatia is about four times lower than HPPK, Unna-Thost type. It should be considered a distinct entity.