Cutaneous melanoma in Iceland: changing Breslow's tumour thickness.

BACKGROUND: The incidence of cutaneous melanoma increased dramatically in Iceland during the last two decades of the 20th century. OBJECTIVE: The aim of this study was to investigate the trend in Breslow's tumour thickness during the years 1980-2009. METHODS: The population-based Icelandic Cancer Registry provided information on all cutaneous melanomas diagnosed in the country during the study period, a total of 854 cases. Incidence rates were stratified according to gender, age at diagnosis, year of diagnosis and Breslow's tumour thickness. RESULTS: When stratified by gender and age, the incidence of thin (≤1.0 mm) melanomas increased dramatically in all subgroups. The increase in thin (≤1.0 mm) melanomas was more apparent in women or 2.6 per 100,000 in 1980-1989 to 13.3 in 2000-2009 and especially in young (<50 years) women or from 1.6 to 12.2 per 100,000 during the same period compared to an increase from 0.2 to 3.4 per 100,000 for young (<50 years) men (P < 0.05). In intermediate thickness (1.01-4.0 mm) tumours, the incidence increased only in men over the age of 50 from 2.1 in 1980-1989 to 11.3 per 100,000 in 2000-2009 (P < 0.05). The incidence of thick melanomas (>4 mm) did not increase. The median Breslow's thickness declined from 2.15 mm in 1980-1989 to 0.9 mm in 2000-2009 in males and from 1.0 to 0.6 mm in females for the same period (P < 0.001). CONCLUSION: The rise in melanoma incidence in individuals under 50 years and in women over 50 years was confined to thin tumours. However, among older males there was also an increased incidence of tumours of an intermediate thickness. This could indicate that future melanoma educational campaigns in Iceland should be directed at older individuals, and that older men may need special attention regarding suspicious nevi.

The role of Th17/Tc17 peripheral blood T cells in psoriasis and their positive therapeutic response.

It is known that NB-UVB therapy can suppress a broad range of immune cells, but the additional effect of bathing in geothermal seawater still remains unclear. To study the influence of treatment on the expression of circulating immune cells contributing to the pathogenesis of psoriasis, six patients with psoriasis were treated with bathing in geothermal seawater two times daily combined with NB-UVB five times/week for 2 weeks and six patients were treated with NB-UVB therapy three times/week for 8 weeks. Disease severity (Psoriasis Area and Severity Index, PASI), chemokines, inflammatory cytokines, T cells and Toll-like receptors in the blood and skin samples were evaluated on enrolment (W0) and at 1 (W1), 3 (W3) and 8 (W8) weeks. Compared with healthy controls, psoriasis patients with active disease had significantly higher proportion of peripheral CLA+ T cells expressing CCR10 and CD103 and T cells with both Th1/Tc1 (CD4+/CD8+ IFN-γ+ or TNF-α+ cells) and Th17/Tc17 (CD4+CD45R0+IL-23R+, CD4+/CD8+ IL-17A+ or IL-22+ cells) phenotypes. Both treatments gave a significant clinical effect; however, bathing in geothermal seawater combined with NB-UVB therapy was more effective than NB-UVB therapy alone. This clinical improvement was reflected by a reduction in circulating CLA+ peripheral blood T cells and by a decreased Th1/Th17 and Tc1/Tc17 inflammatory response. These findings suggest that the inflammatory response in psoriasis is predominantly driven by both CD4+ and CD8+ skin-homing tissue retaining T cells of the Th17/Tc17 lineages.

Efficacy of amorolfine nail lacquer for the prophylaxis of onychomycosis over 3 years.

BACKGROUND: Standard treatment for onychomycosis often results in less than half of subjects achieving disease-free nails. Onychomycosis is even more challenging to treat as relapses and re-infections are common. OBJECTIVE: To determine if a prophylactic effect exists when a treatment with amorolfine nail lacquer (ANL), with half the frequency of the standard regimen, is instituted following successful treatment of dermatophytic toenail onychomycosis with matrix involvement. METHODS: Efficacy and safety of a group treated with ANL (once every 2 weeks) were compared with that of an untreated group in a 36-month (3 years), single-centre, randomized, open-label, comparison study. Subjects to be included in the study were required to be cured of confirmed onychomycosis with matrix involvement after an initial treatment with either ANL + oral terbinafine or oral terbinafine alone in a previous study. Prophylaxis of onychomycosis was assessed by global recurrence rate, confirmed onychomycosis, clinical recurrence and mycological recurrence. RESULTS: A total of 52 subjects were enrolled (26 in each group) in the study. Throughout the study, recurrences occurred more quickly in the untreated group compared with that in the ANL group. Statistically significant differences were observed at month 12 (ANL, 8.3%; untreated, 31.8%; P = 0.047). At endpoint, 70.8% of the subjects treated with ANL remained cured compared to 50% in the untreated group (P = 0.153). Recurrence was delayed by nearly 200 days for the ANL group compared with that of the untreated group. Amorolfine was safe and well tolerated during the study, with no treatment-related adverse events. CONCLUSION: These results suggest that amorolfine nail lacquer may be effective and is safe for use as a prophylactic treatment for the recurrence of onychomycosis.

CDKN2A mutations and melanoma risk in the Icelandic population.

BACKGROUND: Germline CDKN2A mutations have been observed in 20-40% of high risk, melanoma prone families; however, little is known about their prevalence in population based series of melanoma cases and controls. METHODS: We resequenced the CDKN2A gene, including the p14ARF variant and promoter regions, in approximately 703 registry ascertained melanoma cases and 691 population based controls from Iceland, a country in which the incidence of melanoma has increased rapidly. RESULTS: We identified a novel germline variant, G89D, that was strongly associated with increased melanoma risk and appeared to be an Icelandic founder mutation. The G89D variant was present in about 2% of Icelandic invasive cutaneous malignant melanoma cases. Relatives of affected G89D carriers were at significantly increased risk of melanoma, head and neck cancers, and pancreatic carcinoma compared to relatives of other melanoma patients. Nineteen other germline variants were identified, but none conferred an unequivocal risk of melanoma. CONCLUSIONS: This population based study of Icelandic melanoma cases and controls showed a frequency of disease related CDKN2A mutant alleles ranging from 0.7% to 1.0%, thus expanding our knowledge about the frequency of CDKN2A mutations in different populations. In contrast to North America and Australia where a broad spectrum of mutations was observed at a similar frequency, in Iceland, functional CDKN2A mutations consist of only one or two different variants. Additional genetic and/or environmental factors are likely critical for explaining the high incidence rates for melanoma in Iceland. This study adds to the geographic regions for which population based estimates of CDKN2A mutation frequencies are available.

Evaluation of a rapid Gram stain interpretation method for diagnosis of bacterial vaginosis.

A simple Gram stain evaluation for the diagnosis of bacterial vaginosis was assessed in comparison to Nugent's method. The sensitivity (90%), specificity (94%), positive and negative predictive values (90% and 94%), and good interobserver agreement obtained indicate that the test method can be performed reliably in the routine clinical microbiology laboratory.

Nordic Occupational Skin Questionnaire (NOSQ-2002): a new tool for surveying occupational skin diseases and exposure.

Occupational skin diseases are among the most frequent work-related diseases in industrialized countries. Good occupational skin disease statistics exist in few countries. Questionnaire studies are needed to get more data on the epidemiology of occupational skin diseases. The Nordic Occupational Skin Questionnaire Group has developed a new questionnaire tool - Nordic Occupational Skin Questionnaire (NOSQ-2002) - for surveys on work-related skin disease and exposures to environmental factors. The 2 NOSQ-2002 questionnaires have been compiled by using existing questionnaires and experience. NOSQ-2002/SHORT is a ready-to-use 4-page questionnaire for screening and monitoring occupational skin diseases, e.g. in a population or workplace. All the questions in the short questionnaire (NOSQ-2002/SHORT) are included in the long version, NOSQ-2002/LONG, which contains a pool of questions to be chosen according to research needs and tailored to specific populations. The NOSQ-2002 report includes, in addition to the questionnaires, a comprehensive manual for researchers on planning and conducting a questionnaire survey on hand eczema and relevant exposures. NOSQ-2002 questionnaires have been compiled in English and translated into Danish, Swedish, Finnish and Icelandic. The use of NOSQ-2002 will benefit research on occupational skin diseases by providing more standardized data, which can be compared between studies and countries.

Combination therapy for onychomycosis.

Combination therapy is one way of improving the cure rate of onychomycosis. The LION Study examined the efficacies of terbinafine and itraconazole. The Icelandic cohort of the study reported that after 5 years only 46% of the terbinafine-treated patients and 13% of the itraconazole-treated patients were still disease-free, suggesting that relapses and reinfections were common in the long term treatment of onychomycosis with monotherapy. Combination therapy is a well-established principle in mycology; the current strategy involves the combination of oral and topical antifungal treatments. A number of specific drug combinations have proved to be useful in the treatment of onychomycosis: tioconazole and griseofulvin, amorolfine and griseofulvin, amorolfine and terbinafine, and amorolfine and itraconazole. However, comparison of the combination trials can be difficult because of the short duration of some of the studies and variation in global cure rates. Although it is necessary to consider these factors it is clear that combination therapy offers advantages when compared with monotherapy. Combination therapy can be administered sequentially or in parallel. Parallel therapy is recommended for patients who are likely to fail therapy (e.g. patients with diabetes), whereas sequential therapy is recommended for patients who show a poor response to initial treatment.

Comparison of Roche Cobas Amplicor and Abbott LCx for the rapid detection of Chlamydia trachomatis in specimens from high-risk patients.

OBJECTIVE: To evaluate two automated amplification systems for the detection of Chlamydia trachomatis in urogenital specimens, the Cobas Amplicor (Roche Diagnostic Systems, Branchburg, NJ) and the LCx (Abbott Laboratories, Abbott Park, IL). STUDY DESIGN: The two systems were compared testing specimens from 302 high-risk patients, including 98 female cervical swab specimens and 204 male urine specimens. The patients attended the state STD clinic in Reykjavik, Iceland, either because of symptoms or as a result of contract tracing. RESULTS: The prevalence of C. trachomatis infection was 15.3% in women and 13.2% in men. For the male urine specimens, the sensitivity and specificity were 100% and 99.4% for the Cobas Amplicor and 74.1% and 100% for the LCx. In the cervical swabs, both systems detected all 15 true-positive specimens. The internal control used with the Cobas Amplicor detected inhibition in 2% of the male urine and 20% female cervical swabs, respectively. CONCLUSION: The Cobas Amplicor demonstrated slightly better sensitivity than LCx in male urine specimens. Both systems offer the benefits of automation for routine diagnostic testing.

Unsaturated glycerol monoethers as novel skin penetration enhancers.

A mixture of glycerol monoethers was extracted from the liver oil of deep sea shark (Centroporus squamosus). It consisted mainly of monoethers of glycerol and linear monounsaturated octadecanol, and glycerol and linear monounsaturated hexadecanol. Only about 11% of the extract consisted of glycerol monoethers derived from linear saturated fatty alcohols. The glycerol monoether extract was somewhat less effective as skin penetration enhancer than oleic acid and other potent fatty acid penetration enhancers, but it was still a very effective enhancer in the hairless mouse skin model used in this study.

Reduced prevalence of cervical Chlamydia infection among women requesting termination.

BACKGROUND: The prevalence and pattern of Chlamydia trachomatis infection among women requesting induced abortion in the three year period 1992-95 was evaluated and compared to the results of a previous study in 1982-84, where the prevalence of chlamydial infection had been 13.5%. METHODS: A total of 1995 women requested termination, 1855 (93%) of whom were tested for Chlamydia and were included in the study. Two types of tests for chlamydial infection, ELISA and PCR, were used in two consecutive periods. In addition cultures for gonorrhea were done in each case. Information on age, marital status, parity, gestational age and the results of chlamydia and gonorrhea tests of the women and sexual partners were recorded. RESULTS: Chlamydia trachomatis positive women were 149 (8.0%), a significant reduction from the previous 1982-84 study (p<0.001). Women with positive tests were significantly younger (80% < or = 25 years of age; p<0.001) and more frequently single (86.6%; p<0.001), than those with negative tests, as in the previous period. Of the partners, 80.4% were contacted, and 52.1% presented for investigation. Of those tested 42.1% were Chlamydia positive. Four women (0.2%) had Neisseria gonorrhea but none of the partners. CONCLUSIONS: The prevalence of Chlamydia trachomatis is receding among women coming for termination of pregnancy. As treatment before or at operation has repeatedly been shown to be of benefit and since the prevalence is still considerable, continued screening of these women is justified.

Oral terbinafine in toenail dermatophytosis. A double-blind, placebo-controlled multicenter study with 12 months' follow-up.

The treatment of onychomycosis has previously often been protracted and unsuccessful. Terbinafine has been shown to be effective in short-term regimens. In this double-blind, placebo-controlled study, 148 patients with toenail dermatophytosis were randomized to treatment with either 250 mg terbinafine daily or placebo for 3 months. An additional treatment was given for 3 months to patients whose infection had not responded. The patients were followed clinically and mycologically through 12 months. After 3 months 82% of the terbinafine-treated group, versus 5% of the placebo group, showed significant improvement, i.e. negative culture and growth of unaffected nail more than 2 mm (p = < 0.0001). After 12 months clinical and mycological cure was seen in 40% of the patients treated with terbinafine for 3 or 6 months, while 67-81% were clinically cured, but with positive microscopy. Side-effects occurred in 13.5% of the terbinafine group, versus 5.4% of the placebo group, and were mild. 250 mg terbinafine daily for 3 months was significantly more effective than placebo. The efficacy did not appear to improve with additional treatment for 3 months.

[Cutaneous leishmaniasis. A case report.].

Cutaneous leishmaniasis is a common infection in South America and the Middle East. A 20 year Icelander was infected with leishmaniasis while travelling in South America. Treatment with the antimonial sodium stibogluconate was successful. With increased travelling to tropical and subtropical countries a rising incidence of tropical infectious diseases can be expected in Iceland.

[Dermatitis in cats and humans caused by Cheyletiella mites reported in Iceland.].

Cheyletiella mites (Acarina) are ectoparasites that infest cats, dogs and rabbits in many countries of the world. Upon contact with infested animals the mites may temporarily produce grouped, erythematous macules on the skin of humans which rapidly develop a central, vesicular papule. These signs are most often found on the arms and the trunk. Recently these typical signs were observed on the skin of the members of two different Icelandic families which both kept a Persian cat. An examination for ectoparasites on the cats revealed that both were infested by Cheyletiellaparasitovorax. It is unknown how and when the parasite was transmitted to Iceland.

Effect of various marine lipids on transdermal drug delivery--in vitro evaluation.

The effects of several marine lipids on the penetration of hydrocortisone and nitroglycerin through excised hairless mouse skin have been studied. Fatty acid extracts obtained by hydrolysis of Portuguese dog-fish-liver-oil or by hydrolysis of cod-liver-oil were shown to be effective skin penetration enhancers. Phospholipid obtained from squid was also shown to be effective enhancer. However, the enhancing effect of the marine products could generally be associated with their content of free unsaturated fatty acids. The fatty acid extract obtained from cod-liver-oil caused insignificant skin irritation when incorporated into an ointment base and applied to human skin.

Diagnosis of Chlamydia trachomatis infection in high-risk females with PCR on first void urine.

Recently the polymerase chain reaction (PCR) has been shown to be more sensitive than older methods in detecting Chlamydia trachomatis, when performed on endocervical swabs. A total of 203 high-risk females were enrolled in a comparative study of 3 methods for diagnosing C. trachomatis infections: McCoy cell culture and Amplicor PCR on endocervical swabs, and urine. Thirty-four had positive cultures, 38 positive PCR from cervix and 37 had positive PCR on urine specimens. When discrepancy occurred, the leftover Amplicor specimen was retested by Roche with Amplicor and a primer for the major outer membrane protein (MOMP) gene. In all three tests, 32 were positive. The sensitivity of culture was 87%, 92% in cervical PCR and 95% in urinary PCR. The specificity was 100% in both culture and urinary PCR but 98% in cervical PCR. Amplicor PCR performed on female urine is at least as sensitive and specific as cell culture.

Psoriasis treatment: bathing in a thermal lagoon combined with UVB, versus UVB treatment only.

We have compared bathing in a thermal lagoon in Iceland, combined with UVB treatment, to UVB treatment only in an open comparative study. Twenty-three psoriasis patients bathed 3 times daily and were treated with UVB 5 times a week for 4 weeks. The control group was only treated with UVB 5 times a week for 4 weeks. Psoriasis Area and Severity Index (PSAI) was used to estimate the severity of the disease. The mean PASI score in the bathing group decreased from 20.8 to 2.8 (p < 0.01). In the control UVB group, the PASI score decreased from 16. 7 to 6.9. The percentage difference between the groups was significant after 1, 2, 2 and 4 weeks. Bathing in the lagoon combined with UVB was found to be a very effective treatment and better than UVB treatment in our control group.

[Diagnosis of chlamydia trachomatis infections in women: urinary PCR compared to cervical culture and PCR on cervical swabs in high risk females.].

Diagnosis of Chlamydia trachomatis infections in women has traditionally depended on cell culture or enzyme linked immunoassay. Recently Polymerase Chain Reaction (PCR) has been shown to be more sensitive than these methods when performed on endocervical swabs. A total of 203 high risk females were enrolled in a comparative study of three methods for diagnosing C. trachomatis infections: McCoy cell culture and Amplicor(R) PCR on endocervical swabs and urine. Thirty four had positive cultures, 38 positive PCR from cervix and 37 had positive PCR on urine specimens. When discrepancy occurred, the leftover Amplicor(R) specimen was retested by Roche with Amplicor(R) and a primer for the Major Outer Membrane Protein (MOMP) gene. None was false positive in cell culture or in urinary PCR but two were false positive in cervical PCR. In all three tests, 32 were positive. The sensitivity of culture was 87%, 92% in cervical PCR and 95% in urinary PCR. The specificity was 100% in both culture and urinary PCR but 98% in cervical PCR. The results show that Amplicor(R) PCR performed on female urine is more sensitive and as specific as cell culture.