Establishment of a cardiac biobank in a Department of Pathology and Laboratory Medicine.

Biobanks are considered to be important resources of Departments of Pathology and Laboratory Medicine allowing the clarification of relevant disease mechanisms and the improvement of the diagnosis, prognosis, and treatment of both pediatric and adult cardiovascular diseases. To successfully establish a cardiovascular biobank, it is important to consider the public opinion and views on it and the factors involved in the willingness of the public to participate in the donation of genetic material. The literature was systematically reviewed to identify the attitude and willingness of patients affected by congenital and acquired heart disease to participate in biobanking research. Six relevant studies were identified in which it was indicated that psychosocial and demographic characteristics, as well as the patient's medical condition, could influence patient and family members' attitudes and willingness to participate in research. In both congenital and acquired heart diseases, participation in biobank research activities was higher if patients and their families were approached when hospitalized, but not during the acute moment of their illness. Other quantitative and qualitative studies are required to improve patient and family participation in these research initiatives.

Polyurethane foam/nano hydroxyapatite composite as a suitable scaffold for bone tissue regeneration.

In bone tissue regeneration, the use of biomineralized scaffolds to create the 3D porous structure needed for well-fitting with defect size and appropriate cell interactions, is a promising alternative to autologous and heterologous bone grafts. Biomineralized polyurethane (PU) foams are here investigated as scaffold for bone tissue regeneration. Biomineralization of the foams was carried out by activation of PU surface by a two steps procedure performed for different times (1 to 4 weeks). Scaffolds were investigated for morphological, chemico-physical and mechanical properties, as well as for in vitro interaction with rat Bone Marrow Mesenchymal Stem Cells (BMSCs). Untreated and biomineralized PU samples showed a homogenous morphology and regular pore size (average Ø=407µm). Phase and structure of formed calcium phosphates (CaPs) layer onto the PU foam were analyzed by Fourier Transform Infrared spectroscopy and X-ray diffraction, proving the formation of bone-like nano hydroxyapatite. Biomineralization caused a significant increase of mechanical properties of treated foams compared to untreated ones. Biomineralization also affected the PU scaffold cytocompatibility providing a more appropriate surface for cell attachment and proliferation. Considering the obtained results, the proposed scaffold can be considered suitable for bone tissue regeneration.

Adnexal polyp in a newborn baby.

Birthmarks can frequently be seen in newborn babies, but their etiopathogenesis is often unclear. These lesions can be divided into three groups: vascular birthmarks, pigmented birthmarks, and birthmarks resulting in abnormal development. Some birthmarks may require further analysis and clinical follow-up in order to rule out underlying defects, malignant potential, or correlation with syndromic diseases. Presented here is the case of a newborn baby with two simultaneous birthmarks: an adnexal polyp and a nevus anemicus. Adnexal polyps are considered an uncommon clinical observation

Angles and geometric shapes, but not lines, in melanocytic lesions may be helpful in the clinical diagnosis of melanoma.

BACKGROUND: Geometric shapes have been suggested to be found in malignant melanomas. We have observed a number of melanomas presenting with linear and incomplete angulated figures. OBJECTIVE: To verify the assumption that geometric shapes, a linear border and/or incomplete angulated figures may indicate a potential melanoma. METHODS: Patients with surgically removed melanocytic lesions were admitted to the study. We evaluated the presence of a sharp linear demarcation, the presence of contiguous lines resulting in the formation of angle/s and the presence of complete geometric figure. We distinguished the obtained results into melanoma and benign melanocytic naevi. RESULTS: A total of 471 melanomas and 1979 melanocytic naevi were collected. Linear borders, angles and geometric figures were observed in 42 melanomas and in 75 benign melanocytic naevi. Angles with incomplete geometric configuration were observed in 21 melanomas and in 37 benign naevi (21/471 vs. 37/1979, 4.24% vs. 1.87%; P < 0.0016); complete even if irregular geometrical figures in 12 melanomas and 17 naevi (12/471 vs. 17/1979, 2.54% vs. 0.85%; P < 0.005). The presence of line(s) did not significantly differed in the two considered groups. CONCLUSIONS: Melanocytic lesions with angulated shapes and complete geometrical configurations might indicate a suspect melanoma. Only sharp linear demarcation of the lesion do not seem to be significantly associated with melanoma suspicion.

Clinically and/or histologically pigmented poromas in Caucasian patients.

AIM: Pigmented poromas are rarely reported and considered to be more common in non-white people and on non-acral sites. Objective of the present study was to report our cases of pigmented poromas with particular attention to the presence of clinical and/or microscopic evidence of pigmentation, their characteristics and the diagnostic pitfall with other pathologies. METHODS: All the histologically confirmed poromas observed from January 1994 to July 2012 were considered. Clinic-epidemiological data were collected. The presence of clinical pigmentation was recorded as well as the presence of melanin pigmentation or melanocytes in the histologic specimens. RESULTS: One hundred and one patients with poromas were collected. All the patients were Caucasians. All the lesions were solitary. Only three patients had a clinically visible pigmented poromas. In eight cases the presence of melanin and melanocytes did not produce a clinically visible pigmentation. All the poromas with pigmentation did not occur on palmo-plantar surfaces. CONCLUSION: Pigmented poromas may be observed even in Caucasian patients and their clinical aspect mimic basal cell carcinoma and/or melanoma. The presence of pigment visible at the histology may not be observed in the clinical expression. The absence of pigmentation on palmo-plantar location is confirmed in all the reported cases.

Observational study on the mitotic rate and other prognostic factors in cutaneous primary melanoma arising from naevi and from melanoma de novo.

BACKGROUND: Melanomas can arise from naevi or appear de novo. The frequency or the effect of their origin on prognosis is still debated. Mitotic rate (MR) and ulceration of melanomas have been proposed as further new prognostic indexes. AIM: To determine the different prognostic factors in melanomas de novo and melanomas from pre-existing naevi and whether these two melanoma groups have different MR or presence of ulceration. METHODS: All patients with confirmed primary melanomas observed in our clinic from 1996 to July 2013 were included. The distinction between the two groups of melanomas was histologically based. We compared Breslow's thickness, the number of mitosis/mm(2) and the presence of ulceration between the naevus-associated melanoma and de novo melanoma group. RESULTS: Of the 873 melanomas, 626 (71.8%) have a de novo melanoma, 247 (28.2%) a naevus-associated melanoma. Breslow's thickness was not significantly different in the two groups (0.77 ± 1.47 mm vs. 0.59 ± 1.35 mm). The number of patients with presence of ulceration and MR ≥1 mitosis/mm(2) was not significantly different in the two groups (19.6% vs. 16.3%). In thicker melanomas (Breslow's thickness ≥ 1 mm), the number of patients with ≥6 mitosis/mm(2) was significantly higher (26.6% vs. 7.9%; P < 0.05) in the de novo melanoma group. CONCLUSIONS: When mitosis ≥ 1 mm/mm(2) , the results obtained do not show a better or worse prognosis based on Breslow's thickness, ulceration and MR in melanomas associated with naevus vs. melanomas de novo. When ≥6 mitosis/mm(2) are considered, the number of patients in the de novo melanoma group with thick melanoma is highly more represented. The debate about the cut-off value of mitosis ≥1 mm(2) is open.

Unusual sites for poromas are not very unusual: a survey of 101 cases.

BACKGROUND: Poromas are benign adnexal tumours generally believed to be of eccrine origin, which usually develop on palmoplantar sites. However, it is thought that a percentage of poromas develop on non-palmoplantar or 'unusual' sites. AIM: To review cases of poromas with reference to their clinicoepidemiological characteristics, paying particular attention to the those located on sites other than the palms and soles. METHODS: All histologically confirmed poromas seen at our department between 1994 to 2012 were reviewed. The clinicoepidemiological data recorded included age at diagnosis, gender, location, size, colour, and preoperative and pathological diagnoses. RESULTS: In total, 101 poromas were reviewed, corresponding to 0.0058% of all the epithelial skin tumours biopsied in our department. The mean age was 65.05 years (range 30-100 years), and the male to female ratio was 1.52. All the lesions were solitary and asymptomatic, with no sign of bleeding. The most common presentation was a red or reddish lesion, particularly at palmoplantar sites, where 33 (32.7%) of the 101 poromas were located, Poromas found at other affected sites were more usually skin-coloured, and these lesions included 7 neoplasms located in the armpits and 18 on the head and neck. The correct preoperative diagnosis was made in 12 cases of 33 detected poromas (36%), all of which were localized to the palmoplantar surfaces. CONCLUSIONS: Based on our experience, we consider that there are no 'unusual' sites for poromas, and palmoplantar poromas were in fact in the minority. Furthermore, some localizations suggest derivation of these palmoplantar poromas from the folliculosebaceous apocrine unit.

Tinea capitis in the paediatric population in Milan, Italy: the emergence of Trichophyton violaceum.

Tinea capitis (TC) is the most common type of dermatophytosis in children. The epidemiology of TC depends on the geographical areas, and it changes over time. The aim of the study is to determine the incidence of TC and to identify the causative species in children observed at Dermatology Outpatient Department of the University of Milan, Italy, between January 2004 and December 2011. Four hundred and eighty-six children with suspected dermatomycosis were observed; TC was the most prevalent dermatomycoses with 86 cases. The most common isolated dermatophyte in scalp lesions was Trichophyton violaceum with 33 cases. The most recent epidemiological Italian studies still show zoophilic fungi as primary cause of TC. We are the first medical team in Italy to demonstrate a dominance of anthropophilic fungi, in particular T. violaceum.

Tinea corporis due to Trichophyton rubrum in a woman and Tinea capitis in her 15-day-old baby: molecular evidence of vertical transmission.

We report a case of a 40-year-old Caucasian woman who came under our observation with a 7-year history of a chronic erythematous scaly dermatitis, diagnosed as psoriasis, involving gluteal area and thighs, and treated with topical steroids without benefit. During pregnancy, a progressive worsening of her condition and an extension of cutaneous lesions were observed. Her newborn, a 15-day-old girl, presented a similar scaly and squamous lesion on her scalp. Mycological examination was positive for Trichophyton rubrum in both cases, and random amplified polymorphic DNA analysis confirmed the isogenicity of the two isolates. We performed a diagnosis of T. rubrum tinea corporis and tinea capitis. The case we describe illustrates an unusual clinical presentation of tinea corporis with remarkable extension of cutaneous lesions due to the diagnostic delay and the continuous use of local steroids, together with a rare tinea capitis in the newborn. Our experience highlights the possibility of mother-child transmission and the importance of an early diagnosis.

-308(G/A) TNF-alpha gene polymorphism and risk of depression late in the life.

The relationship between major depression (MD) and dementia in the elderly is still not clear, but it is certain that the immune system and in particular, pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, play a key role in the mechanisms underlying the two neuro-psychiatric disorders. In our experience, the -308(G/A) single nucleotide polymorphism (SNP) in the TNF-alpha gene is associated with earlier age at onset in patients affected by Alzheimer's disease (AD). The aim of this study was to investigate the association between the -308(G/A) SNP and late-life MD in elderly people without dementia. Blood samples were obtained from 50 subjects, after screening with the geriatric depression scale (GDS>or=15) and mini-mental state examination (MMSE>or=24). The -308 (G/A) SNP was genotyped by SSP-PCR amplification. Two-hundred-fourty age-matched healthy volunteers were taken as the control group. We identified different genotype and allele distributions of the SNP in old depressed patients and healthy controls (HC). Our results evidenced a significantly higher percentage of the GG genotype in depressed subjects (84.0% vs. 68.3%; p=0.007) and consequently of the G allele (92.0% vs. 81.9%; p=0.05). The presence of the GG genotype raised the risk of developing MD (odds ratio=OR=2.433, confidence interval=Cl=1.09-5.43). Our findings suggested that the investigated TNF-alpha SNP may: (1) affect MD susceptibility; (2) be involved both in AD and MD development, but probably with a distinct role in the two pathologies.

An unusual bilateral areolar dermatitis.

This article describes an uncommon clinical manifestation of contact dermatitis due to dyed tissues, showing bilateral plaque lesions on the mammary areolas. The clinical history, histological and patch testing examinations confirmed the diagnosis. The possible triggering factors related with this kind of contact dermatitis and possible differential diagnosis are briefly discussed.

[Dialysis and quality of life: identifying and managing critical aspects]. / Terapia dialitica e qualitá di vita: individuare le aree di criticitá per orientare alla metodica più idonea.

Living with a chronic disease is for the patient a ''disease experience'' that also affects the psychosocial sphere and has a negative impact on perceived quality of life. To estimate the effect of dialysis on the perceived quality of life and to identify by means of a specific questionnaire the aspects that are compromised most. From our results it emerged that the examined patients had a sufficiently good total perception of quality of life, even though about 30% of the patients reported critical aspects related to daily life and, in some age groups, also related to dialysis method. This study confirms the importance of developing educational and supportive predialysis programs in order to identify and reduce the critical aspects.

Seborrheic keratosis with compound nevus, junctional nevus and basal cell carcinoma in the same lesion.

Seborrheic keratosis can be associated with different neoplasms such as basal cell carcinomas, squamous cell carcinomas and melanomas. We describe an unusual case of a man who presented with a brown plaque on his back. The clinical diagnosis was melanoma. Histopathologic examination of the lesion revealed four neoplasms: a compound nevus, a junctional nevus, a superficial basal cell carcinoma and a seborrheic keratosis. Although this association most likely represents a chance phenomenon, we discuss the possibility that the seborrheic keratosis developed from the nevus, and that subsequently the junctional nevus and the basal cell carcinoma developed from the seborrheic keratosis.

17 alpha-O-(aminoalkyl)oxime derivatives of 3 beta,14 beta-dihydroxy-5 beta-androstane and 3 beta-hydroxy-14-oxoseco-D-5 beta-androstane as inhibitors of Na(+),K(+)-ATPase at the digitalis receptor.

The synthesis and binding affinities to the digitalis Na(+),K(+)-ATPase receptor of a series of 3 beta,14 beta-dihydroxy-5 beta-androstane and 3 beta-hydroxy-14-oxoseco-D-5 beta-androstane derivatives bearing a 17 alpha-(aminoalkoxy)imino chain are reported; some derivatives were also studied for their inotropic activity. Our recently proposed model of interaction of molecules with the digitalis receptor was used to design these compounds. On that basis, the possibility to design novel potent inhibitors of Na(+),K(+)-ATPase without being constrained by the stereochemistry of the classical digitalis skeleton in the D-ring region was predicted. The binding affinities of the most potent compounds in the two series, (EZ)-17 alpha-[2-[(2-aminoethoxy)imino]ethyl]-5 beta-androstane-3 beta,14 beta-diol (6f) and (EZ)-3 beta-hydroxy-17 alpha-[2-[(2-aminoethoxy)imino]ethyl]-14,15-seco-5 beta-androstan-14-one (24c) are higher than that of the potent natural compound digitoxigenin, despite the unusual alpha-exit of the substituent in position 17 of 6f or the disruption of the D-ring in 24c. These results further support the validity of our recently proposed model of binding at the digitalis receptor. Results of the inotropic tests on guinea pig atrium deserve further investigation on the pharmacological profile of these derivatives.

High sensitivity of human epidermal keratinocytes (HaCaT) to topoisomerase inhibitors.

In the panorama of the numerous established cell lines, the human keratinocyte line HaCaT has a very interesting feature, having a close similarity in functional competence to normal keratinocytes. This cell line has been used in many studies as a paradigm for epidermal cells and therefore we selected HaCaT as a cell model for investigating the activity of three antitopoisomerase drugs (Camptothecin, Doxorubicin, Ciprofloxacin) on in vitro cell growth. The effect was evaluated both by a 24-h cytotoxicity test and by a 7-day antiproliferation assay, in which the cell viability was assessed by an MTT (3-(4,5-dimethyl-2-thiazolyl) 2,5-diphenil-2-H-tetrazolium bromide) test. DNA topoisomerase I was also partially purified from a nuclear extract of HaCaT cells, the level of topo I catalytic activity was measured by a pBR322 DNA relaxation assay and then the in vitro effect of antitopoisomerase drugs on the target enzyme was also assessed. The results indicated that the in vitro sensitivity of human epidermal HaCaT cells to antitopoisomerase drugs is comparable to that of many human tumour cell lines. HaCaT cells express a high level of topoisomerase I activity that is significantly inhibited by both Camptothecin and Doxorubicin and to a minor degree by Ciprofloxacin. A high correlation between the cell sensitivity to the antitopoisomerase I drug measured by the MTT test and the in vitro direct inhibition of HaCaT topoisomerase I was observed, suggesting that HaCaT cells can represent a very interesting model both for studying cellular pharmacokinetics of antineoplastic drugs on keratinocytes and for predicting possible secondary effects, exerted by these drugs on cutaneous cells, during treatment with chemotherapy.

Usefulness of histological examination for the diagnosis of onychomycosis.

BACKGROUND: [corrected] Direct microscopy and culture tests currently used in the diagnosis of nail mycosis can yield false-negative results, and confirmation of the pathogenic agent, especially in non-dermatophyte infections, is often a lengthy process. OBJECTIVE: The aim of this study was to investigate the usefulness of the histological examination of nail clipping samples in supplementing the standard microscopic and culture techniques for the diagnosis of onychomycosis. PATIENTS AND METHODS: One hundred and seventy-two subjects affected by nail alterations suggestive of onychomycosis were evaluated. Nail specimens were studied with 3 different techniques: direct microscopic examination of a 40% KOH clarified preparation, fungal culture and histological examination. Patients positive for fungal infection were re-evaluated with the same techniques after treatment with oral terbinafine, fluconazole or itraconazole and topical application of bifonazole or ciclopirox for 2 months. RESULTS: Direct microscopy was positive in 102 (59.3%) nail specimens. The culture test was positive in 90 cases (52.9%), showing a dermatophyte in 45, a yeast in 23 and a mould in 22 samples. The histological examination was positive in 94 (54.6%) samples. In 4 cases, it was the only investigation confirming the clinical diagnosis of nail mycosis. In most of the cases, the morphological aspect of the hyphae and/or spores suggested also to which group of pathogens (dermatophytes, yeasts or moulds) the mycetes observed in the histological sections could be ascribed. The concurrent presence of a dermatophyte and a mould was evidenced in a few specimens. The control histological examination at the end of the treatment showed negative results or residual non-vital hyphae and/or spores. CONCLUSIONS: Results of the present study indicate that the histological examination of nail clipping specimens is a relatively inexpensive, rapid and easily performed procedure. It is useful to confirm or refute the results of routine microscopy and culture tests. Moreover, nail histopathological observation may help in ascribing a pathogenic role of non-dermatophyte isolates and evaluating the effectiveness of antifungal treatment.