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Biomedical subjects

W Bergman

Publications and source records attributed to W Bergman.

At least 55 records · Page 3Linked to original sources

A comparative study of atypical and melanocytic naevi on the tropical island Curaçao and in The Netherlands.

A cross-sectional study was undertaken in 270 inhabitants of The Netherlands (moderate maritime climate, latitude 51 degrees 5' N-53 degrees 3' N) with skin types I-III and 757 inhabitants of the tropical island Curaçao (latitude 12 degrees 2' N-12 degrees 23' N). The latter group consisted of 282 White individuals (mostly Dutch immigrants) and 475 people with non-White skin types IV, V and VI. All participants underwent total skin examination and melanocytic naevi (MN) and clinically atypical naevi (AN) were noted. There was no statistical difference in the mean number of naevi > or = 2 mm or > or = 5 mm between the Curaçao and The Netherlands White groups, but the mean number of naevi > or = 2 mm and > or = 5 mm was significantly lower in the Curaçao non-White group. We found no obvious differences in mean naevus counts between genders and the various comparable age groups. Furthermore, we found no significant difference in mean crude and mean age-standardized prevalence of (one or more) AN between Whites in The Netherlands and on Curaçao. The Mantel-Haenszel prevalence ratio weighted for age and gender differences of Curaçao Whites vs non-Whites was 5.93 (95% confidence interval 3.9-12.0), demonstrating that AN are significantly less prevalent in darker skin types. In all groups, people with AN had significantly more MN than people without AN. We found a generation-dependent difference in the expression of AN among White inhabitants of The Netherlands and on Curaçao, with a higher prevalence of AN in the younger generation.

Adolescent↗

CDKN2 explains part of the clinical phenotype in Dutch familial atypical multiple-mole melanoma (FAMMM) syndrome families.

Combined multi-point linkage analysis in seven Dutch families with FAMMM syndrome confirmed the location of a melanoma susceptibility (MLM) gene in the 9p21 area. The occurrence of a shared high-risk haplotype in six of the families strongly suggests a founder effect in the Leiden region. No indication for locus heterogeneity was observed. Recently, the CDKN2 (p16) gene, an important regulator of the cell cycle, was isolated from the 9p21 region. A 19-bp germline deletion in the CDKN2 gene was detected in the high-risk haplotype, suggesting CDKN2 to be identical to MLM. Loss of heterozygosity studies in melanoma and pancreatic carcinoma from gene carriers strongly support the view that CDKN2 is a general tumour suppressor gene predisposing not only to melanoma but also to other malignancies. Interestingly, the occurrence of apparent clinical FAMMM cases with melanoma but without the high-risk deletion haplotype suggests the necessity of additional (naevus) genes to explain the complete FAMMM phenotype.

Adolescent↗

[Oral treatment of onychomycosis of the toe nails; comparison of cost-effectiveness of griseofulvin, itraconazole, ketoconazole and terbinafine].

OBJECTIVE: Determination of the most cost-effective oral drug treatment of onychomycosis of the toenails in the Dutch situation, by comparing griseofulvin, itraconazole, ketoconazole and terbinafine. DESIGN: Calculation of cost prices using a published meta-analysis. SETTING: The Netherlands. METHOD: Published efficacy and adverse reactions of treatment with griseofulvin, itraconazole, ketoconazole or terbinafine were related to 1993 Dutch cost prices of treatment. RESULTS: Itraconazole and terbinafine offered similar chances of success, but itroconazole treatment had to be repeated more often. On average, the costs of the treatment with itraconazole were 1.5 times as high as those of treatment with terbinafine. Griseofulvin treatment was cheapest but required the longest treatment course. CONCLUSION: A treatment with terbinafine is the most cost-effective, provided that onychomycosis has actually been established mycologically and all possible measures have been taken to prevent recurrence. It remains to be seen whether this drug treatment should be offered to all people affected by this essentially cosmetic problem.

Administration, Oral↗

Are atypical nevi a risk factor for uveal melanoma? A case-control study.

Atypical nevi and other potential risk factors for uveal melanoma were studied in 109 uveal melanoma patients and 149 controls. Information concerning employment, medical history, drug use, family history of cancer, excess sun exposure, and blistering sunburn before and after the age of 15 was obtained. A total skin examination was performed and skin type, hair color, eye color, freckles, actinic damage, the total number of common acquired nevi, and the number of clinically atypical nevi were noted. More atypical nevi were found in uveal melanoma patients than in controls (age- and sex-adjusted odds ratio of 2.9 [95% confidence interval 1.2-6.3] for one or two atypical nevi versus none; odds ratio of 5.1 [95% CI 1.3-20.0] for three or more atypical nevi versus none). Light skin types and freckling also prevailed in uveal melanoma cases. In our study, atypical nevi are more common in uveal melanoma patients than in controls. Further studies will have to indicate whether risk factors comparable to those for cutaneous melanoma really exist for uveal melanoma.

Adult↗

Genetics of seven Dutch familial atypical multiple mole-melanoma syndrome families: a review of linkage results including chromosomes 1 and 9.

Familial atypical multiple mole-melanoma syndrome is characterized by the familial occurrence of malignant melanoma of the skin in combination with multiple atypical precursor nevi; its pattern shows a dominant inheritance in pedigrees. During the last 5 years we have performed linkage analysis in seven Dutch familial atypical multiple mole-melanoma families to define the locus of the underlying gene defect. In 1989 it was reported that in familial melanoma families in the USA a disease-gene was located on chromosome 1p. However, in the Dutch families we could exclude this chromosome from harboring the Dutch familial atypical multiple mole-melanoma gene. Very recently a new candidate locus was found on chromosome 9p, which could be confirmed in our family material. A melanoma-associated gene was linked to several markers on chromosome 9p21. In a linkage analysis in which only melanoma patients were considered as affected, marker D9S171 showed a maximum lod score of 3.11 (theta 0.0). After introducing family members with 10 or more, or five or more, atypical nevi as affected in addition to the melanoma patients, the maximum lod score rose to 4.88 (theta 0.05) and 3.79 (theta 0.07), respectively. Interestingly, the sharing of a unique chromosome 9p21 haplotype among most melanoma patients in the families from two different villages suggests that an old common mutation is present in the Leiden region.

Adolescent↗

UV induction of cyclobutane thymine dimers in the DNA of cultured melanocytes from foreskin, common melanocytic nevi and dysplastic nevi.

We compared the induction of cyclobutane thymine dimers after exposure to 302 nm UV in foreskin-derived melanocytes and melanocytes from nevocellular nevi, as well as in melanocytes cultured from dysplastic nevi, precursor lesions of melanoma, derived from four, three and four individuals, respectively. Cyclobutane thymine dimers were quantified in situ by means of an immunofluorescence assay with a specific monoclonal antibody. A method was developed to compare separately performed experiments in a standardized manner. For melanocytes from each source, we demonstrated a linear relationship between UV dose and immunofluorescence. In nevocellular and dysplastic nevi, two subpopulations could be detected, distinguished by their nuclear size. Large nucleated nevocellular nevus cells were most susceptible to the induction of thymine dimers (49% higher induction compared to induction in foreskin melanocytes), while in normal-sized nuclei of these nevus cells the same induction of thymine dimers was found as in nuclei from foreskin melanocytes. In contrast, large nucleated dysplastic nevus melanocytes did not differ from the foreskin melanocytes, while normal-sized nuclei of dysplastic nevus cells showed a lower induction (32% lower induction than in foreskin melanocytes).

Cells, Cultured↗

Effect of fluoride on overdenture abutments.

This study evaluated the caries preventive effects of high concentrations of fluoride on overdenture abutment teeth. Twenty-four extracted caries-free teeth were randomly selected from a pool of patients aged 50-70 and prepared as for overdenture abutments. The teeth were sectioned mesiodistally into two halves. All surfaces on the teeth were painted with a protective varnish except for a window on the root surface and one on the cut dentin of the occlusal. The 48 root halves were randomly divided into four groups of 12 specimens. Each group received a different 4-minute treatment prior to being placed in a demineralizing solution for 6 hours. The treatment groups were (1) distilled H2O only; (2) 1,000 ppm F-; (3) 5,000 ppm F-; and (4) 10,000 ppm F-. The teeth were cycled for 6 hours in the demineralizing solution and 17 hours in a fluoride-free remineralizing solution for 17 days. Sections were cut at 100 +/- 10 microns through the windows. Standardized photomicrographs were made under polarized light using distilled H2O and quinoline as the imbibing media. Microradiographs were made of the same specimens and these were also photographed at the same magnification. The depths of the lesions were measured from drawings of the lesions projected on a digitizer screen. The amount of demineralization was calculated by subtracting the width of the mineralizing bands from the depth of the lesion. The conclusions were: (1) Lesions on the root surface were much shallower than on the occlusal; (2) A dose response to the fluoride concentration of the topical application was evident.

Aged↗

On naevi and melanomas in dysplastic naevus syndrome patients.

Cutaneous melanoma may occur as isolated, so-called 'sporadic' cases or in association with multiple atypical naevi and in familial clusters, in which case it is referred to as the familial dysplastic naevus syndrome (DNS). In this retrospective study (a) the number and body distribution of naevocytic naevi and (b) the body distribution of malignant melanoma (MM) in individuals with familial DNS were compared in order to study their association. In 45 patients with familial DNS aged 20-39 years naevus counts on trunk and lower extremities were compared with melanoma data and distributions from a second group of 43 patients from the same DNS families aged 12-66 years. Men had significantly more naevi of a size > or = 2 mm or > or = 5 mm on the back than women (P = 0.02). Women showed a tendency towards a greater number of naevi on the lower extremities than men, but in women no significant difference in naevi between the lower extremities and the back was found. The total number of naevi on the trunk and lower extremities in familial DNS patients was higher than that in the general population. In conclusion, it was found that predilection sites for melanoma in familial DNS patients of both sexes correspond with the distribution of naevi; in males naevi and melanoma counts and percentage distributions were higher on the back, in females both the back and the lower extremities were affected. These findings strongly suggest an association between naevus distribution and melanoma occurrence and site in familial DNS, analogous to earlier reports on sporadic melanoma.

Adolescent↗

Linkage analysis in Dutch familial atypical multiple mole-melanoma (FAMMM) syndrome families. Effect of naevus count.

Familial atypical multiple mole-melanoma (FAMMM) syndrome is characterized by the familial occurrence of malignant melanoma of the skin in combination with multiple atypical precursor naevi. In the present study we performed linkage analysis in seven Dutch FAMMM families to define the relationship between the ultimate phenotype melanoma and the postulated precursors, atypical (dysplastic) naevi. Various models were defined, varying from melanoma only to various combinations of melanoma and atypical naevi, reflecting the FAMMM phenotype. Using 124 microsatellite markers spread across all autosomes, hints for linkage were obtained between several chromosome 9p markers and a melanoma locus (D9S171; odds for linkage, 275:1). In a model including melanoma and a florid manifestation of atypical naevi a considerably higher lod score was obtained with D9S171 (odds for linkage, 4365:1); models including milder manifestations yielded less support. We conclude that, also in the Dutch FAMMM families, a melanoma gene is located on the short arm of chromosome 9 and that multiple atypical naevi, at least in certain cases, seems to be a component of the FAMMM phenotype.

Adult↗

PUVA keratosis. A clinical and histopathologic entity associated with an increased risk of nonmelanoma skin cancer.

BACKGROUND: Various types of hyperkeratotic lesions can be observed in patients with psoriasis treated with PUVA. Clinically it can be difficult to classify them and to differentiate benign from malignant hyperkeratotic lesions. Recently, we introduced the term PUVA keratosis, which we regard as a distinct entity. OBJECTIVE: The purpose of the study was to describe in more detail the clinical and histopathologic features of PUVA keratoses and to investigate a possible relation with nonmelanoma skin cancer. METHODS: A group of 13 psoriasis patients with PUVA keratoses was studied and compared with 247 psoriasis patients without these keratoses, who had also received long-term therapy with PUVA. RESULTS: The presence of PUVA keratoses was associated with an increased risk of nonmelanoma skin cancer. The estimated relative risk for skin cancer in patients with PUVA keratoses, adjusted for age, sex, and UVA dose, as compared with psoriasis patients without these keratoses, who had also received long-term PUVA treatment, was 6.5 (95% confidence interval, 1.3 to 32.1). Squamous cell carcinomas contributed the most to this increased risk. CONCLUSION: PUVA keratoses are associated with an increased risk of nonmelanoma skin cancer. Therefore careful clinical follow-up of psoriasis patients with PUVA keratoses is necessary, and cessation of PUVA treatment should be considered.

Adult↗

Multiple primary melanomas in a patient with familial-type DNS during clomiphene-induced pregnancy.

A 35-year old woman developed six primary cutaneous melanomas during her third pregnancy. She had received clomiphene treatment for nearly 2 years previously. She developed two more primary melanomas 15 and 21 months after giving birth. All melanomas were histologically associated with preexisting dysplastic naevi. The patient showed the characteristic phenotype of the dysplastic naevus syndrome; a cousin and an aunt were treated for malignant melanoma and the patient's brother had histologically confirmed dysplastic naevi. The course of her first two pregnancies was not complicated by the development of melanomas. We suggest that clomiphene may have played a role in the activation or progression of these 'precursor lesions' into malignant melanoma.

Adult↗

Dysplastic nevi. Occurrence in first- and second-degree relatives of patients with 'sporadic' dysplastic nevus syndrome.

In this study a cross-sectional survey was undertaken among 156 living family members of 31 probands originally classified as having sporadic (histologically verified) dysplastic nevus syndrome (DNS). Seven (13.2%) of 53 parents had clinically recognizable DNS. Twenty-six (36.1%) of the 72 sibs showed dysplastic nevi. The diagnosis of DNS in family members was based on mainly clinical examination; in eight family members--those with only mild manifestation of DNS--a nevus was removed for histologic confirmation. After correction for pedigree size, we found that 60% of patients with "type A sporadic" DNS actually had one or more relatives with a DNS phenotype. Only 25% (8/30) of the probands were ultimately true sporadic cases without a DNS-affected first- or second-degree relative. In 15% (5/31) of the probands no conclusions concerning the type of DNS could be made because the pedigree size did not allow such a conclusion. We also found a higher prevalence of dysplastic nevi among the younger generation as compared with the older generation in our probands with DNS and their families as well as in a general population study of 400 individuals. This generation-dependent difference in expression of the DNS phenotype suggests that besides a genetic factor, other factors may play a role in the development of the characteristic phenotype.

Adolescent↗

'High single-dose' European PUVA regimen also causes an excess of non-melanoma skin cancer.

We report the results of a long-term (12.8 years) follow-up study of the detection of malignant and benign skin tumours in patients with psoriasis, who were treated with PUVA according to the European, 'high single-dose' regimen. A total of 13 squamous cell carcinomas (SCC) and 24 basal cell carcinomas (BCC) were diagnosed in 11 of 260 patients. The incidence of both SCC and BCC was increased in comparison with the general Dutch population. The ratio of SCC to BCC in the general population was 1:8 but was 1:2.5 in our study group. A positive correlation was observed between the development of SCC and the total UVA dosage, the age of the patient at the start of the PUVA treatment and a history of arsenic use. This dose-related increase in the incidence of SCC, reported in studies from the U.S.A., has not been found in earlier European studies. The average time period between the start of PUVA therapy and the diagnosis of the first malignant skin tumour was 6.0 years for SCC and 4.7 years for BCC. Among the 49 benign skin tumours were actinic keratoses, a keratoacanthoma and 'PUVA keratoses', a newly described hyperkeratotic lesion, especially found in PUVA-treated patients.

Age Factors↗

Ocular melanoma in families with dysplastic nevus syndrome.

Five families with the dysplastic nevus syndrome, in each of which one member had ocular melanoma, are reported. These five families were examined within a 3-year period in one medical center. To date only five other families with such a combination have been reported. We suggest a causal relation between ocular melanoma and the familial dysplastic nevus syndrome.

Adolescent↗