Assessment of cryopreserved donor skin viability: the experience of the regional tissue bank of Siena.

Skin allografts from cadaver donors are an important resource for treating extensive burns, slow-healing wounds and chronic ulcers. A high level of cell viability of cryopreserved allografts is often required, especially in burn surgery, in Italy. Thus, we aimed to determine which conditions enable procurement of highly viable skin in our Regional Skin Bank of Siena. For this purpose, we assessed cell viability of cryopreserved skin allografts procured between 2011 and 2013 from 127 consecutive skin donors, before and after freezing (at day 15, 180, and 365). For each skin donor, we collected data concerning clinical history (age, sex, smoking, phototype, dyslipidemia, diabetes, cause of death), donation process (multi-tissue or multi-organ) and timing of skin procurement (assessment of intervals such as death-harvesting, harvesting-banking, death-banking). All these variables were analysed in the whole case study (127 donors) and in different groups (e.g. multi-organ donors, non refrigerated multi-tissue donors, refrigerated multi-tissue donors) for correlations with cell viability. Our results indicated that cryopreserved skin allografts with higher cell viability were obtained from female, non smoker, heartbeating donors died of cerebral haemorrhage, and were harvested within 2 h of aortic clamping and banked within 12 h of harvesting (13-14 h from clamping). Age, cause of death and dyslipidaemia or diabetes did not appear to influence cell viability. To maintain acceptable cell viability, our skin bank needs to reduce the time interval between harvesting and banking, especially for refrigerated donors.

Is osteopontin involved in cutaneous fibroblast activation? Its hypothetical role in scleroderma pathogenesis.

Osteopontin (OPN) is an extracellular matrix protein implicated in bone remodeling, but it presents also pro-inflammatory and pro-fibrotic properties. OPN expression also occurs upon exposure of cells to classical mediators of acute inflammation such as tumor necrosis growth factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta), as well as fibrogenic cytokines such as transforming growth factor beta (TGF-beta), although a detailed understanding of these regulatory pathways is still unknown. Plasma OPN levels in both limited and diffuse systemic sclerosis patients (lSSc and dSSc) were statistically higher compared to those of control subjects. Immunohistology demonstrated that high TGF-beta levels, alpha smooth muscle actin (alphaSMA) levels and consequently high OPN levels were found in the affected skin of sclerodermic patients (lSSc and dSSc) compared to levels found in healthy skin. In order to better understand how OPN interferes with the fibrotic process, healthy skin fibroblasts were treated for 24 and 48 hours with bleomycin and with endothelin-1 (ET-1) plus TGF-beta in order to induce the fibrogenesis. After 48 hours of stimulation, healthy treated fibroblasts showed statistically increased alphaSMA levels (index of differentiation into myofibroblasts) and simultaneously statistically increased OPN levels compared to healthy untreated ones. This study demonstrates that OPN levels increase simultaneously with the increasing of alphaSMA levels, therefore it is reasonable to hypothesize that OPN interferes in the pathogenesis of Systemic Sclerosis in the early stage of fibroblast differentiation process.

Mycosis fungoides: disease evolution of the "lion queen" revisited.

Mycosis fungoides (MF), which represents the most common subtype of primary cutaneous T-cell lymphoma (CTCL), is an epidermotropic lymphoma included as an indolent form in the recent WHO/EORTC classification. From a clinical point of view, the classic disease progression usually is slow and takes over years or even decades, and characterized by the evolution from patches to more infiltrated plaques and eventually to tumours or erythroderma. However, the analysis of the MF disease course has been greatly impaired by the rarity of the disease, thus data about the time course of disease progression and pattern of relapse during time are not well known. In this review, a summary of published data on MF large patients cohorts will be presented, together with the results obtained by a retrospective analysis of clinical features and follow-up data of 1,422 MF patients diagnosed and followed-up from 1975 to 2010 in 27 Italian Centres (Italian Study Group for Cutaneous Lymphoma). From a clinical perspective, the amount of data support the relevance of a stage-tailored, differentiated follow-up strategy, in as much as the TNMB staging appears not only to be associated with different progression rates, but also shows as a new finding a relationship with different patterns of disease progression. From a biological point of view, there is the need to understand the molecular basis of the different clinical pathways of disease progression, to be able to potentially identify at an earlier phase of disease evolution, the patients who are more likely to develop erythroderma or tumour-stage progression. In conclusion, if MF is indeed a true "lion queen", as dermatologists we need to be expert and wise tamers to keep it under control.

Nanocomposite thin films based on polyethylene vinyl acetate and piezoelectric nanomaterials.

This paper aims at describing the fabrication and characterization of nanocomposite thin films based on polyethylene vinyl acetate, at different content of vinyl acetate, and piezoelectric nanomaterials, namely zinc oxide and barium titanate. These membranes were prepared by casting, achieving a thickness in the order of 160-210 µm. The nanocomposites were characterized in terms of morphological, mechanical and chemical properties, finding a homogeneous distribution of nanomaterials, and the elastic modulus ranges from 2 to 25 MPa, while keeping an elongation break from 750 to 1500 % and tensile strength from 2.5 MPa up to 10 MPa. These results show the potential of these nanocomposite formulations as smart composite thin films for a series of biomedical applications, including the regeneration of osteoarticular tissues.

Dermatofibrosarcoma protuberans in childhood: two case reports and review of the literature.

Dermatofibrosarcoma protuberans (DFSP) is a rare skin cancer with intermediate malignancy, characterized by a progressive local growth and a propensity for local recurrence. DFSP is most frequent in adults; however, in recent years, DFSP in childhood emerged to be more common than previously believed. Unfortunately DFSP in children may be misdiagnosed, leading to a delay in the treatment. The authors report two cases of childhood DFSP with unusual clinical presentation: a congenital nodular variant and an atrophic variant developed at 2 years of age, both with acral localization. They highlight the importance of an early diagnosis by pediatricians and dermatologists to ensure an appropriate complete excision and reduce the risks of recurrences.

Experimental fossilization of mat-forming cyanobacteria in coarse-grained siliciclastic sediments.

Microbial fossils and textures are commonly preserved in Ediacaran and early Cambrian coarse-grained siliciclastic sediments that were deposited in tidal and intertidal marine settings. In contrast, the fossilization of micro-organisms in similar marine environments of post-Cambrian age is less frequently reported. Thus, temporal discrepancies in microbial preservation may have resulted from the opening and closing of a unique taphonomic window during the terminal Proterozoic and early Phanerozoic, respectively. Here, we expand upon previous work to identify environmental factors which may have facilitated the preservation of cyanobacteria growing on siliciclastic sand, by experimentally determining the ability of microbial mats to trap small, suspended mineral grains, and precipitate minerals from ions in solution. We show that (i) fine grains coat the sheaths of filamentous cyanobacteria (e.g., Nodosilinea sp.) residing within the mat, after less than 1 week of cell growth under aerobic conditions, (ii) clay minerals do not coat sterile cellulose fibers and rarely coat unsheathed cyanobacterial cells (e.g., Nostoc sp.), (iii) stronger disturbances (where culture jars were agitated at 170 rpm; 3 mm orbital diameter) produce the smoothest and most extensive mineral veneers around cells, compared with those agitated at slower rotational speeds (150 and 0 rpm), and (iv) mineral veneers coating cyanobacterial cells are ~1 µm in width. These new findings suggest that sheathed filamentous cyanobacteria may be preferentially preserved under conditions of high fluid energy. We integrate these results into a mechanistic model that explains the preservation of microbial fossils and textures in Ediacaran sandstones and siltstones, and in fine-grained siliciclastic deposits that contain exceptionally preserved microbial mats.

Molecular biosignatures reveal common benthic microbial sources of organic matter in ooids and grapestones from Pigeon Cay, The Bahamas.

Ooids are sedimentary grains that are distributed widely in the geologic record. Their formation is still actively debated, which limits our understanding of the significance and meaning of these grains in Earth's history. Central questions include the role played by microbes in the formation of ooids and the sources of ubiquitous organic matter within ooid cortices. To address these issues, we investigated the microbial community composition and associated lipids in modern oolitic sands at Pigeon Cay on Cat Island, The Bahamas. Surface samples were taken along a transect from the shallow, turbulent surf zone to calmer, deeper water. Grains transitioned from shiny and abraded ooids in the surf zone, to biofilm-coated ooids at about 3 m water depth. Further offshore, grapestones (cemented aggregates of ooids) dominated. Benthic diatoms and Proteobacteria dominated biofilms. Taxa that may promote carbonate precipitation were abundant, particularly those associated with sulfur cycling. Compared to the lipids associated with surface biofilms, relict lipids bound within carbonate exhibited remarkably similar profiles in all grain types. The enhanced abundance of methyl-branched fatty acids and ß-hydroxy fatty acids, 1-O-monoalkyl glycerol ethers and hopanoids bound within ooid and grapestone carbonate confirms a clear association of benthic sedimentary bacteria with these grains. Lipids bound within ooid cortices also contain molecular indicators of microbial heterotrophic degradation of organic matter, possibly in locally reducing conditions. These included the loss of labile unsaturated fatty acids, enhanced long-chain fatty acids/short-chain fatty acids, enriched stable carbon isotopes ratios of fatty acids, and very high stanol/stenol ratios. To what extent some of these molecular signals are derived from later heterotrophic endolithic activity remains to be fully resolved. We speculate that some ooid carbonate forms in microbial biofilms and that early diagenetic degradation of biofilms may also play a role in early stage carbonate precipitation around ooids.

Physical map of the malaria vector Anopheles gambiae.

Random cDNA clones, cosmid clones and RAPD polymorphic fragments have been localized by in situ hybridization to the ovarian nurse cell polytene chromosomes of the malaria vector Anopheles gambiae. We thus established 85 molecular markers for 110 sites within the whole A. gambiae polytene chromosome complement. The cDNA clones analyzed were isolated at random, and their exact localizations were determined by in situ hybridization. For 15 of the cDNA clones, a partial nucleotide sequence has been obtained; for nine of them sequence searches in the GenBank database revealed high degrees of similarity with published sequences. The cosmid clones analyzed were obtained as the result of screening with a few of the aforementioned cDNA clones of particular interest, or taken from a small set of randomly isolated cosmid clones. The RAPD clones are polymorphic fragments, potentially diagnostic for the various chromosomal forms of A. gambiae that are currently being analyzed.

Long-term prognostic impact of repeated measurements over 1 year of pulse pressure and systolic blood pressure in the elderly.

Systolic blood pressure (SBP) and pulse pressure (PP) have been identified in western industrialized countries as major predictors of cardiovascular events in the elderly on the basis of measurements taken at a single visit. Considering the wide variability of blood pressure (BP) in older people, this study set out to assess the prognostic significance of measurements of SBP and PP taken over several months according to a monitoring scheme mimicking routine care. A total of 444 Italian general practitioners enrolled a cohort of 3858 unselected elderly outpatients and followed them up for 10 years. BP was recorded at recruitment, 1 week later and at quarterly visits during the first year. The average BP of these six visits was used to define the patient's BP status. During the 10-year follow-up, 1561 participants died, 709 from cardiovascular diseases. Proportional hazard regression analysis, adjusted for all main prognostic factors including antihypertensive treatment, showed that for each 10-mmHg increment in SBP and PP there were, respectively, 5 and 9% increases in risk for total mortality (TM) and 9 and 13% increases in risk for cardiovascular mortality (CVM) (all P < 0.01). However, including both SBP and PP in the model, only PP showed an independent, significant relationship with TM and CVM. In conclusion, prognostic information based on repeated measurements of PP is stronger than that given by SBP and consequently should be recommended in the definition of cardiovascular risk in the elderly.

Assessment of ventricular function in arterial hypertension with radionuclide ventriculography.

Diastolic function of the left ventricle was assessed in 29 untreated patients with mild to moderate hypertension and in 21 normotensive control subjects using gated radionuclide ventriculography. In hypertensive patients, the time to peak filling rate was significantly longer (p less than 0.01) than that in control subjects, and first-third filling fraction and peak filling rate were significantly reduced (p less than 0.001). The ejection fraction and peak ejection rate were also significantly reduced in hypertensive patients (p less than 0.001). No relation was observed between diastolic functional impairment and age, cardiac hypertrophy, or severity of hypertension. Thus, early impairment of ventricular filling is present in hypertension, even in young patients without evidence of cardiac hypertrophy.

Long-term efficacy of screening for hypertension in a community.

Screening for hypertension in the community leads to the identification of hypertensive people not previously detected, and those detected but inadequately treated or not treated at all. The aim of the present study was to assess the long-term efficacy of screening for blood pressure control in a general population. During 1981, 2139 parents of high school students were invited to our institute for a blood pressure measurement; 1533 persons (71.7%) attended the screening; 239 of them (15.6%) were found to be hypertensive (diastolic blood pressure greater than or equal to 95 mmHg or already receiving antihypertensive treatment). Among the hypertensives, 42.3% did not know that they had high blood pressure, and only 7.5% had their blood pressure controlled by treatment. After being informed about the importance of lowering their blood pressure levels, all hypertensives were invited again to the institute for a further evaluation. Two hundred and two persons (84.5%) attended the re-examination. Of these, 154 (76.2%) were still hypertensive. Of the 202, 151 (74.7%) had contacted their physicians. The most common advice was to make further measurements of blood pressure over a period of time, followed by laboratory tests. The proportion of treated hypertensives rose from the initial 33.1% to 53.9%, but in about half the patients normalization of blood pressure was not achieved. Physicians tended to treat only people with moderate to severe hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypomelanosis of Ito associated with chromosomal translocation involving Xp11.

We report on a 3-year-old girl with hypomelanosis of Ito (HI). She has typical skin lesions and mild CNS involvement characterized by impaired walking and borderline mental retardation. Cytogenetic investigation showed a 18/X translocation with breakpoint on Xp11. This is the sixth case of HI in which this breakpoint has been reported, underlining that this event cannot be considered coincidental. Further studies are needed to understand the etiologic and pathogenetic meaning of this finding.

X-linked mental retardation, microcephaly, and growth delay associated with hereditary bullous dystrophy macular type: report of a second family.

We report on 2 patients with mental retardation and bullous dystrophy, macular type. The observation of the condition in a male and his maternal uncle is consistent with recessive X-linkage. Due to the rarity of the condition, nosologic definition was difficult before the birth of the propositus. The clinical picture in the two patients described, characterized by mental retardation, dwarfism, microcephaly, alopecia, bullous dystrophy macular type, hypogenitalism, is very much like the one observed in the patients, all males, belonging to the only other family reported to date. The recent localization of the bullous dystrophy gene in the Xq24-qter segment opens the possibility of prenatal diagnosis.

Effects of long-term treatment with prazosin on left ventricular diastolic function in mild to moderate hypertension.

It is not well established if blood pressure control is associated with an improvement in diastolic function, whose impairment represents an early marker of cardiac involvement in systemic hypertension. The purpose of this study was to evaluate whether a prolonged treatment with an alpha 1-blocking agent can lead to a reversal of the abnormalities of left ventricular filling. Eleven never-treated patients with mild to moderate essential hypertension were examined before and after at least six months of treatment with prazosin. Cardiac function and left ventricular mass were measured by means of radionuclide ventriculography and echocardiography. Average blood pressure values significantly decreased during the treatment period: from 163.54 +/- 17.80 mm Hg to 146.81 +/- 13.14 mm Hg for systolic blood pressure and from 106.09 +/- 6.96 mm Hg to 92.90 +/- 8.93 mm Hg for diastolic blood pressure. All the indices of left ventricular mass showed a trend toward reduction, but the differences with respect to the baseline values did not reach statistical significance. Average value of ejection fraction was normal before treatment and did not change significantly after treatment. All indices of diastolic function were significantly lower than normal controls' values at the beginning of the study and tended to worsen at the end of the study. Our findings suggest that diastolic function is not consistently affected by the therapy with alpha 1-adrenoreceptor antagonists despite good blood pressure control.

Antihypertensive treatment of the elderly in general practice.

In order to assess the antihypertensive care received by the elderly, where clear therapeutic guidelines are lacking, a population of 3,858 aged over 64 years was studied. Data were derived from a large Italian 'Study on Blood Pressure in the Elderly', carried out in general practice. Over 90% of the 2,059 known hypertensive patients were receiving drug treatment, with no age or sex-related differences. A single drug was prescribed to 50.2% of treated patients; only 5.5% were receiving three or more drugs. Diuretics and older sympatholytic agents were by far the most frequently prescribed categories, with four drugs (hydrochlorothiazide, amiloride, methyldopa and chlorthalidone) accounting for over 50% of all prescriptions. Low-dosage treatment schedules were frequently used, often associated with less-often-than-daily drug administration. Our study shows that physicians' attitudes to the treatment of arterial hypertension in the elderly are fairly uniform, with treatment of all subjects but with low drug dosages.

Left ventricular diastolic function in normotensive adolescents with different genetic risk of hypertension.

Abnormalities of the diastolic function of the left ventricle are the first sign of cardiac involvement in arterial hypertension. We have studied the diastolic function in a group of normotensive adolescents with confirmed family history of hypertension. M-mode echocardiography was performed in 86 normotensive males aged 14-19 years: 41 sons of at least one hypertensive parent (SHT) and 45 sons of normotensive parents (SNT). Cross-sectional area of the left ventricle and left ventricular (LV) mass index were significantly greater in the SHT than in the SNT group (10.05 +/- 1.84 vs. 8.9 +/- 1.56 cm/m2, p less than 0.01 and 129.3 +/- 296.3 vs. 109.23 +/- 25.7 g/m2, p less than 0.002, respectively). No significant difference between the two groups was observed in the indices of left ventricular diastolic function, except for mitral valve opening rate (463.51 +/- 90.45 in SHT vs. 416.71 +/- 78.84 mm/s in SNT; p less than 0.02). From the analysis of the subgroup of adolescents having left ventricular mass greater than the upper normal value, we observed that they showed mean time of rapid filling significantly longer than SNT: this could represent an early marker of the pathological character of such hypertrophy. Our results suggest that the higher LV mass observed in the SHT is not associated with chamber and myocardial stiffness abnormalities.

Arm position as a source of error in blood pressure measurement.

The present study was designed to assess the value of correct positioning of a patient's arm when measuring blood pressure (BP). A total of 181 subjects were examined, 141 hypertensives on treatment, 25 untreated hypertensives, 15 normotensives. All the subjects underwent three BP measurements after a 5-min resting period in supine position. Then two BP readings were recorded in standing position with the arm either positioned by the patient's side or supported passively at patient's heart level. Average systolic BP (SBP) in standing position were 144.6 +/- 20.2 mmHg with the arm at the side and 136.4 +/- 21.1 mmHg with the arm at the heart level (p less than 0.001); average diastolic pressures were 99.0 +/- 12.0 mmHg and 90.2 +/- 12.3 mmHg (p less than 0.001), respectively. A fall in SBP greater than or equal to 20 mmHg from the supine to the upright position was detected in 18.2% of cases when measurement was performed at heart level; such a reduction was inapparent in two-thirds of cases when the arm was placed at the patient's body side. Incorrect positioning of a patient's arm during BP measurements in standing position leads to overestimation of BP values and masks the presence of postural hypotension.

Awareness, treatment, and control of hypertension in the elderly in a general practice experience. Study Group on Hypertension in the Elderly.

In 3858 ambulatory elderly people (age greater than or equal to 65 years) prevalence of hypertension was 67.8%. The hypertensive status was unknown to both the doctor and the patient in 21.4% of cases. More than 90% of known hypertensives were treated, but hypertension could be considered as controlled in less than 30% of them.

[Penile metastasis from bladder cancer. A case report]. / Metastasi peniene da tumore vescicale. Un caso clinico.

Penile metastases from bladder cancer are unusual. A case of a man, 50 years old, with undifferentiated bladder carcinoma submitted to radical cystoprostatectomy and ileal conduit is presented. Twelve months after the primary diagnosis the patient presented metastases of the penis.