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Biomedical subjects

W Bergman

Publications and source records attributed to W Bergman.

72 records · Page 4Linked to original sources

Systemic cancer and the FAMMM syndrome.

The FAMMM syndrome consists of the familial occurrence of cutaneous malignant melanoma and atypical nevi (dysplastic nevi), and is inherited as an autosomal dominant trait. Conflicting results have been reported on the question of whether the syndrome includes increased susceptibility to non-melanoma cancers. We have studied cancer of all anatomic sites and histologies in nine FAMMM families which were ascertained in a pigmented lesions clinic in the Netherlands. We evaluated two hypotheses: that the number of systemic cancers observed in the families was excessive, compared to expected incidence, based on Dutch incidence data, and that there was variation (or heterogeneity) among families in the frequency of systemic cancer. A significant excess of systemic cancer (especially digestive tract cancer) was observed. Significant heterogeneity was also found among the families; three of the nine families had marked excess in numbers of systemic cancers, and the remaining families had normal numbers of cancers among the known FAMMM gene carriers and their first degree relatives. Thus, we provide evidence of increased susceptibility to systemic cancer occurring in conjunction with the FAMMM syndrome in a subset of this resource.

Adult↗

The familial dysplastic nevus syndrome. Natural history and the impact of screening on prognosis. A study of nine families in the Netherlands.

Since 1982, nine families with the dysplastic nevus syndrome have been identified in the Leiden area (The Netherlands). A total of 50 primary melanomas were diagnosed in 38 persons. Nineteen of these melanomas had been diagnosed before the start of the screening programme (category I), 11 were detected at the initial examination of the families (category II), and 20 were found during the course of follow-up (category III). To assess the effect of screening, we compared these categories with respect to the developmental stage of the melanomas. One of the 19 melanomas in category I, two of the 11 in category II and seven of the 20 in category III were melanoma in situ. The average thickness of the invasive melanomas in categories I, II and III was 1.75, 0.80 and 0.54 mm respectively. Sixteen of the 19 melanomas in category I (84%) were Clark III or IV, whereas 15 of the 20 melanomas in category III (75%) were Clark I or II. From these findings it may be concluded that screening can lead to the detection of melanomas at an earlier stage, which in turn can permit curative treatment and improvement of both prognosis and life expectancy. The need for supervision based on central registration of affected families to guarantee the continuity of screening is discussed.

Adolescent↗

Exclusion of the dysplastic nevus syndrome (DNS) locus from the short arm of chromosome 1 by linkage studies in Dutch families.

Familial dysplastic nevus syndrome (DNS) is an autosomal dominant premalignant condition characterized by multiple large moles of variable size and color and a strongly increased risk for cutaneous malignant melanoma. In order to determine the chromosomal localization of the DNS gene, linkage studies were initiated in six large Dutch families. No support was obtained for linkage between the loci for DNS and the rhesus blood group on chromosome 1. Data from additional markers (DNF15S1, D1Z2, FUCA1, D1S17, D1S57, and PGM1) make it possible to exclude the DNS gene from the short arm of chromosome 1 in these Dutch families.

Chromosomes, Human, Pair 1↗

Melanocytic atypia in dysplastic nevi. Immunohistochemical and cytophotometrical analysis.

In a double-blind study a correlation was found between the histologically assessed degree of nevomelanocytic atypia in 58 dysplastic nevi (DN) and the presence of two markers associated with malignant transformation. The markers included a marked expression of histocompatibility locus Class I antigens on nevomelanocytes (P less than 0.01) and abnormalities in the nuclear DNA content as measured by DNA cytophotometry (P = 0.01). Both markers were present in most of the markedly atypical DN, in about half of the moderately atypical DN, and in less than 30% of the mildly atypical DN. These findings suggest that a DN with marked or moderate melanocytic atypia indicates a premalignant condition and identifies a patient at risk for melanoma.

Antigens, Neoplasm↗

The efficacy of histopathological criteria required for diagnosing dysplastic naevi.

The efficacy of specific histopathological features for diagnosing dysplastic naevi was established by comparing their frequency in 62 dysplastic naevi, from 36 patients with the dysplastic naevus syndrome, with those in 326 ostensibly benign naevocellular naevi derived from a group of 67 autopsy cases. Individual diagnostic features had a low sensitivity, a low specificity or low predictive values. Discriminant analysis showed that the presence of dust-like melanin, irregular naevoid nests, markedly increased junctional activity and melanocytic nuclei equal or larger in size than overlying keratinocyte nuclei were the most discriminating features. Using two or more of these criteria plus a lymphocytic infiltrate as an obligatory diagnostic criterion, a reasonable efficacy could be reached for dysplastic naevi. Based on these combinations of criteria the prevalence of histologically proven dysplastic naevi in the autopsy group would be 10%. Lesions with all these four discriminating features were found in half of the patients from the dysplastic naevus syndrome group, but were absent in the autopsy group. We suggest that such severely atypical dysplastic naevi may be indicative of patients at high risk for developing malignant melanoma.

Adolescent↗

The role of MR imaging in evaluating metastatic spinal disease.

Fifty-eight patients with suspected epidural metastases were evaluated with MR imaging. Six patients were examined on two separate occasions. MR was judged to be diagnostic in 60 of the 64 examinations. Twenty-two patients also underwent myelography. MR was as diagnostic as myelography in all cases of epidural metastases. In addition, MR offered several advantages over myelography in the evaluation of metastatic spinal disease, including demonstration of paravertebral tumor extension, identification of additional osseous metastatic lesions, and visualization of areas of spinal cord compression occurring between areas of myelographic blocks. We conclude that MR imaging is the examination of choice for evaluating suspected metastatic spinal disease.

Adolescent↗

Clinical and genetic studies in six Dutch kindreds with the dysplastic naevus syndrome.

In an ancient fishing village in the neighbourhood of Leiden a cluster of melanoma-prone families was detected. In these families atypical precursor naevi were recognizable in many melanoma patients and in their relatives. This combination of symptoms is called the Dysplastic Naevus Syndrome (DNS). The spectrum of clinical signs characterizing the phenotype of the DNS ranged from apparent lack of gene-expression through minimal to obvious manifestations. Genetic analysis of six pedigrees revealed an autosomal dominant mode of inheritance, with a very variable expressivity of the gene, which is also rather frequently non-penetrant. The total number of family members (affected or at risk) was 314, 243 of which were alive and were personally examined by us. In the six pedigrees a total of 33 patients with melanoma occurred. In thirty patients with multiple atypical naevi, the clinical diagnosis of DNS was histologically verified. A further thirty-six patients with several atypical naevi were also regarded as gene carriers. Fifteen 'normal' individuals had to be gene-carriers on the basis of their position in the pedigree.

Adolescent↗

Reticular erythematous mucinosis syndrome in a patient with polyarthritis.

A patient with seronegative oligoarthritis who developed the reticular erythematous mucinosis (REM) syndrome is described. This syndrome is considered to be a dermatological entity unrelated to systemic disorders. Aggravation of the rash by exposure to sunlight and a good response to anti-malarial agents suggest a relationship with rheumatological disorders, e.g. rheumatoid arthritis and systemic lupus erythematosus. Dermatologists consulted by a patient with the REM syndrome should be aware of the possibility of an associated rheumatological disease.

Adult↗

Monoclonal antibodies selected to discriminate between malignant melanomas and nevocellular nevi.

Two monoclonal antibodies (MoAbs), PAL-M1 and PAL-M2, are described that were selected to discriminate between melanomas and nevocellular nevi (NN) in frozen sections. MoAb PAL-M1 reacted with all 15 melanoma metastases (MM), with 14 of 19 primary cutaneous melanomas (PCM), 9 of 35 dysplastic nevi (DN), and 2 of 26 NN. The 2 NN stained were removed from patients with the dysplastic nevus syndrome. MoAb PAL-M2 reacted with 9 of 15 MM, 5 of 19 PCM, 3 of 35 DN, and did not react with 26 NN after usual staining conditions. The proportion of melanocytic cells stained was low in DN and much higher in PCM and especially in MM. Staining in DN was restricted to intraepidermal or subepidermal nests of atypical melanocytes. In PCM, staining with PAL-M2 was observed only in tumors with a Breslow thickness of 0.76 mm or higher. PAL-M1 and PAL-M2 may be immunohistochemical markers for tumor progression in melanocytic proliferations.

Adolescent↗

Analysis of major histocompatibility antigens and the mononuclear cell infiltrate in halo nevi.

A series of monoclonal antibodies was used to characterize the nevomelanocytes and the inflammatory infiltrate of 11 halo nevi in different stages of resolution, employing an immunoperoxidase technique. Three of the 11 halo nevi histologically showed signs of mild or moderate nevomelanocytic atypia. It was found that the vast majority of the nevomelanocytes in halo nevi with a dense inflammatory infiltrate markedly expressed HLA-A,B,C antigens, while expression was not demonstrable in nevocellular nests not adjacent to the mononuclear infiltrate. No difference in expression of HLA-A,B,C antigens was found between the 3 cases with mild or moderate nevomelanocytic atypia and the other cases lacking atypia. Expression of HLA-DR (Ia-like) antigens was found on few nevomelanocytes in only 2 of 11 lesions. The cellular composition of the mononuclear inflammatory infiltrate showed a predominance of T cells (80% or more) with a relatively high proportion of cytotoxic/suppressor T cells. Most of the T cells showed signs of activation as judged by staining for HLA-DR antigens. These results demonstrate that the expression of HLA-A,B,C antigens on the nevomelanocytes and the cellular composition of the mononuclear inflammatory infiltrate in halo nevi are very similar to that in malignant melanomas and dysplastic neiv. These findings also indicate the expression of HLA-A,B,C antigens on nevomelanocytes is primarily dependent on the presence of T-cell immune response and not necessarily related to the presence of nevomelanocytic atypia.

Adolescent↗

An evaluation of the time-dependent dimensional stability of eleven elastomeric impression materials.

The dimensional stability of three polysulfides, one condensation-cured silicone, six addition-cured silicones, and one polyether, was evaluated when poured immediately and after storage for 1, 4, and 24 hours. Dimensional stability was determined by measuring the amount of gap width developed by a master coping when seated on the die that had been poured in the impression. The greatest accuracy occurred when the impressions were poured immediately. All the addition-cured silicone materials exhibited excellent dimensional stability for all storage times. Delayed pouring of artificial stone in the impressions made in these materials should result in very little change in die accuracy. The condensation-cured silicone material Polytrans has good accuracy if poured immediately. Delayed pouring results in a rapid loss of accuracy. The polysulfides have good accuracy only if poured immediately, with the exception of Omniflex, which can be stored up to 4 hours with only a minimum loss of accuracy. The polyether material Impregum expanded during storage. Since the dimensional change of the impression during storage is a characteristic of the material, a reduction in its bulk should lead to a desired amount of dimensional change. To achieve this desirable state, custom trays that will provide for the minimum recommended bulk of material should be fabricated. The complex geometry of the cavity preparation makes any prediction of the desirability of impression material expansion or contraction difficult, because a change in impression material dimensions may be beneficial to the fit in one portion of the casting but have an extremely adverse effect in another.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Phenomena↗

Immunohistochemical analysis of malignant melanomas and nevocellular nevi with monoclonal antibodies to distinct monomorphic determinants of HLA antigens.

Using an indirect immunoperoxidase technique, 20 nevocellular nevi, 5 dysplastic nevi, 14 primary cutaneous melanomas, and 24 metastatic melanomas were tested with a panel of monoclonal antibodies to monomorphic determinants of Class I (HLA-A,B,C) and Class II (la-like) major histocompatibility complex antigens. Class I HLA and beta 2-microglobulins were not detected on the majority of nevus cells but were expressed by 3 of 5 dysplastic nevi, by the majority of tumor cells in 12 of 14 primary cutaneous melanomas, and in 13 of 24 metastases. The different expression of Class I HLA and beta 2-microglobulins in primary and metastatic lesions suggests that loss of these antigens may be associated with progression of malignancy. Class II HLA were not detected in common nevi but were locally present in 1 of 5 dysplastic nevi, 7 of 14 cases of primary cutaneous melanoma, and all 24 cases of metastatic lesions tested. These findings suggest that increase in Class II HLA expression may be associated with progression of malignancy. The staining patterns obtained with monoclonal antibodies to distinct determinants of Class I HLA and Class II HLA were superimposable within each type of antigen. Therefore, the discrepancies in the literature about the expression of histocompatibility antigens by lesions of melanocytic origin are not likely to reflect the different specificity of the antibodies used by the various investigators.

Adolescent↗

Enhancement of air filtration using electric fields.

Although polarized electrostatic air filters are efficient air filtrating devices, their main disadvantages are difficulty in collecting conductive particles or in operating at relative humidities above 70%. We describe here a new filter design that eliminates these problems. A nonconductive media, normally a glass fiber mat, is placed between two insulated conductive screens. As the voltage across the screens is increased, the penetration of particles decreases exponentially. Increasing the electric field from 0 to 10 kV/cm will decrease the mass penetration from 60% to less than 10% of a polydispersed 0.8 micrometer ammd(sigma g = 2.0) sodium chloride aerosol. The experimental effects of face velocity, particle charge and size, packing density, fiber size, and screen insulation mirror the theoretical effects of these variables on particle penetration.

Air Conditioning↗