Collagen deposition around polypropylene tapes implanted in the rectus fascia of female rats

OBJECTIVE: Implantation of the mesh induces a foreign-body reaction followed by the development of connective tissue that may alter tape property. The aim of our study was to evaluate the deposition of collagen in the vicinity of monofilament tension-free vaginal tape (TVT; Ethicon Inc., Johnson & Johnson) and multifilament intravaginal slingplasty (IVS; Tyco Healthcare) polypropylene tapes implanted in female rats. METHODS: The samples of the meshes (10 mg each) were implanted in the rectus fascia of 14 Wistar female rats and removed after 42 days. Collagen was extracted with 0.5 M acetic acid and subsequently with pepsin (1 mg/ml in 0.5 M acetic acid). Collagen concentration was measured using Sircol Collagen Assay (Biocolor Ltd.) and normalised for milligrams of tape weight. For histological examination, tape samples were stained with haematoxylin and eosin or with silver for type III collagen. RESULTS: The total amount of collagen extracted did not differ significantly between TVT and IVS samples. For both tapes, extraction with acetic acid yielded a higher amount of collagen (about 70%) than extraction with pepsin. On histological examination, less densely packed bundles of collagen fibres and a slightly more intense inflammatory reaction were observed with TVT compared with IVS mesh. CONCLUSION: The total amount of collagen deposited around the polypropylene mesh implanted in female rats was similar for TVT and IVS meshes, but differences were noted in the arrangement of the collagen fibres and the intensity of the inflammatory reaction.     

Limited significance of family history for presence of BRCA1 gene mutation in Polish breast and ovarian cancer cases

It is estimated that about 5–10% of ovarian and 2–5% of all breast cancer patients are carriers of a germline BRCA1 or BRCA2 gene mutation. Most families with detected BRCA1 or BRCA2 gene mutation are qualified for molecular testing on the basis of family history of breast or ovarian cancers. The purpose of our study was to establish the frequency of positive family history of cancer in a series of Polish consecutive breast and ovarian cancer patients in two groups, with and without the BRCA1 gene mutations. We analysed the prevalence of four of the most common BRCA1 mutations: 5382insC (c.5266dupC), 300T>G (p.181T>G), 185delAG (c.68_69delAG) and 3819del5 (c.3700_3704del5). The patient group consisted of 1,845 consecutive female breast and 363 ovarian cancer cases. 19 out of 37 (51%) of BRCA1-positive ovarian cancer patients and 21 out of 55 (39%) BRCA1-positive breast cancer had negative family history of breast and/or ovarian cancer among first- and second-degree relatives. In ovarian cancer patients, negative family history was more frequent in those with 300T>G BRCA1 gene mutation than in 5382insC carriers. This finding indicates the necessity of searching for 300T>G mutation in families with a single diagnosis of ovarian cancer in family. The high frequency of mutations detected in breast cancer patients lacking obvious family history shows that breast cancer patients should be qualified for genetic testing on the basis of wide clinical and pathological criteria.     

The frequency of NBN molecular variants in pediatric astrocytic tumors

Gliomas, particularly those of astrocytic origin, are the most frequent primary central nervous system tumors that develop in children. The majority of them are benign and slow growing, with relatively good prognosis. Several genomic and gene alterations are known to be involved in astrocytoma development, but the precise mechanisms remain poorly understood. The NBN gene, which participates in DNA double-strand break repair and maintenance of genome stability, has been postulated to be a susceptibility factor for a number of cancers. Here we report the results of NBN gene analyses performed in 127 children with various astrocytic tumors. PCR-SSCP analysis followed by DNA sequencing was used for molecular variant screening. Three carriers (2.37%) of different germline mutations on one NBN allele were found. The common Slavic deletion c.657_661del5 (p.K219fsX19) was detected in a patient with pilocytic astrocytoma; a known mutation, c.643C>T (p.R215W), and a new substitution, c.565C>G (p.Q189E), were identified in two patients with primary glioblastoma. The risk of developing astrocytic malignancies is estimated to be 1.33 times higher for c.657_661del5 and 3.2 times higher for c.643C>T than in the general Polish population (P > 0.05). Because of the low frequency of the mutations identified in the studied group, we were unable to determine the exact role of NBN in the development of astrocytoma in children. The presence of two potentially pathogenic NBN molecular variants among 16 glioblastoma cases (12.5%) could be a remarkable finding in our study. We thus cannot exclude a possible role of NBN in the tumorigenesis of a certain type of astrocytic tumors.     

Alterations in the Cerebral Microvascular Proteome Expression Profile After Transient Global Cerebral Ischemia in Rat

This study aimed at obtaining an in-depth mapping of expressional changes of the cerebral microvasculature after transient global cerebral ischemia (GCI) and the impact on these GCI-induced expressional changes of post-GCI treatment with a mitogen-activated protein kinase kinase (MEK1/2) inhibitor. GCI was induced in male Wistar rats followed by treatment with either vehicle or the MEK1/2 inhibitor U0126 every 12 h post-GCI. Seventy-two hours after GCI or sham surgery, the cerebral microvasculature was isolated and the protein content analysed with state-of-the-art mass spectrometry. The proteomic profile of the isolated cerebral microvasculature 72 h after GCI (compared to sham) indicated that the main expressional changes could be divided into nine categories: (1) cellular respiration, (2) remodelling of the extracellular matrix, (3) decreased contractile phenotype, (4) clathrin-mediated endocytosis, (5) ribosomal activity, (6) expression of chromatin structure-related proteins, (7) altered synaptic activity, (8) altered G-protein signalling and (9) instability of the membrane potential. Treatment with U0126 partly normalized the expression of one or more of the proteins in all nine categories. Flow cytometry confirmed key findings from the proteome such as upregulation of the extracellular proteins lamininβ2 and nidogen2 (p < 0.05) after GCI. These results provide valuable molecular insight into the broad and complex expressional changes in the cerebral microvasculature after GCI and the effect of early MEK1/2 inhibitor treatment on these changes.     

Psoriasis vulgaris and familial cancer risk- a population-based study

Background

Follow-up studies of psoriasis patients indicate an increased risk in the occurrence of malignancies at different sites of origin. Population stratification and/or complicated interpretation of evidence on the risk of cancer (due to the small number of patients included in most series) lead to inconsistent data. Herein we investigated the risk of occurrence of malignancies at different sites of origin in a series of 517 psoriasis patients and their 1st degree relatives.

Methods

We evaluated the tumour spectrum as well as the age of the patient at diagnosis of cancers in psoriasis families along with the observed and expected frequencies of malignancies. The distribution of 17 common mutations/polymorphisms in 10 known cancer susceptibility genes among psoriasis patients and 517 matched healthy controls were examined. No such study has been published to date.

Results

The statistical comparison of the observed and expected frequencies of cancers revealed a higher than expected occurrence of Hodgkin’s lymphoma among males in psoriasis families when compared to the general population (OR=1.8, 95%CI 1.6-2.1, p=0.002). There was a non-significant tendency towards a younger age of onset and overrepresentation of laryngeal cancer and leukaemia in psoriasis families. We found no major differences in the distribution of cancer susceptibility mutations among our cases and the healthy controls.

Conclusions

The results of our study suggest an increased risk of Hodgkin’s lymphoma for male members of psoriasis families. Further studies are needed to confirm the findings and to evaluate whether or not the application of cancer surveillance protocols for Hodgkin’s lymphoma, leukaemia and laryngeal cancer are justified in these families.

     

FC03.2Cumulative incidence of self reported skin disease in hydrotherapists working in swimming pools

Objective:  To assess the cumulative incidence and characteristics of self reported skin disease in hydrotherapists.
Methods:  Hydrotherapists, who had completed a hydrotherapy training course answered a questionnaire in reference to newly appeared skin disease. Data were analyzed statistically.
Results:  190 subjects presently working as hydrotherapists were studied. Of them 75.8% were female and 24.2% were male. 80% of the hydrotherapists worked up to 10 000 cumulative hours defined by the formula: working hours per weeks × number of weeks per year × years of work in the pool. 85 of the subjects (45%) reported on the development of skin disease for the first time after starting work at the swimming pool. 21 (11.8%) had a preexisting skin disease. The most frequent symptoms included pruritus, burning, stinging, erythematous patches and xerotic skin on the extremities, trunk and folds. A statistically significant relationship between the cumulative working time and the incidence of dermatological pathology compatible with contact dermatitis was found.
Conclusions:  The incidence of self reported skin diseases, developing for the first time or due to exacerbation of preexisting dermatological conditions, in hydrotherapists working in swimming pools is high. Statistically significant relationship between the cumulative hours of immersion in the pool and the incidence of the dermatological pathology was observed suggesting a dose response relationship between exposure and effect.     

Lupus Erythematosus-like Eruption due to D-Penicillamine in Progressive Systemic Sclerosis

A 58-year-old woman with progressive systemic sclerosis developed a butterfly erythematous eruption, hemorrhagic maculae, crusting, and erosions on the face 15 days following administration of D-penicillamine. This appeared to be a lupus erythematosus-like eruption due to an adverse drug reaction to D-penicillamine because of the rapid recovery from the general symptoms, the total involution of skin lesions with topical treatment only, the transient demonstration of autoantibodies and their fast negativation, negative ANA, and the histologic features of lupus erythematosus combined with marked exudative changes.