Refractoriness to antivascular endothelial growth factor treatment: role of myeloid cells

CD11b+Gr1+ cells, which include neutrophils, macrophages, and myeloid-derived suppressor cells, have been shown to contribute to tumor angiogenesis. Recently, we found that accumulation of CD11b+Gr1+ in tumors renders them refractory to angiogenic blockade by vascular endothelial growth factor (VEGF) antibodies. This effect was traced to a pathway of CD11b+Gr1+-mediated angiogenesis that is, at least in part, driven by the secreted protein Bv8, which is up-regulated by the important myeloid growth factor granulocyte colony-stimulating factor (G-CSF). Thus, G-CSF may promote tumor angiogenesis through a Bv8-dependent pathway that bypasses VEGF and renders tumors refractory to anti-VEGF therapy.     

Skin manifestations with Rotavirus infections

Rotavirus infection is one the most frequent cause of diarrhea among infants and children. Although it is not associated to specific dermatologic clinical pictures, recently, different clinical manifestations have been reported in association with this infection. They include exanthema, Gianotti-Crosti syndrome, and Acute Infantile Hemorrhagic Edema. The condition can be diagnosed microbiologically with stool cultures. The prognosis is excellent in healthy, immunocompetent individuals.     

Newborn hearing screening project using transient evoked otoacoustic emissions: Western Sicily experience

OBJECTIVE: To study the incidence of congenital sensorineural hearing loss in all newborns introducing a screen test with a protocol no expensive, with a good "screen sensitivity" that could let an earlier identification of hearing impairment beginning early intervention by 2 months of age and increasing the probability of having language development within the normal range of development. METHODS: The study was conducted in Sciacca hospital from the beginning of 2003 to our days and was carried out with transient evoked otoacoustic emission using the criteria for PASS or RETEST and considering eventual prenatal and perinatal risk factors. All the newborns were divided into four groups each one with its personal secondary step program. RESULTS: In the years 2003-2004 the number of the newborns in Sciacca hospital was: 538 for 2003, 653 for 2004 with a total of 1191; all these infants were divided in three groups: resident in Sciacca, resident in the Sciacca borderlands and resident out of the district of Sciacca. The coverage (percentage of the target population who undergo the screen) was of 90% in the 2003 (483 newborns) and of 90% in the 2004 (585 newborns) with two cases of congenital sensorineural hearing loss identified. The incidence of sensorineural hearing loss, in the District of Sciacca, was estimated to be 2.07/1000 in 2003 and 1.70/1000 in 2004. CONCLUSIONS: The higher incidence of sensorineural hearing loss in our study is due to a high prevalence of consanguineous marriage in Sicily that was shown to be linked with hearing impairment. The "sensitivity value" was 95% at the first step but became 99% after the second step with a few number of false positive (0.74%). All the infants with a diagnosis of sensorineural hearing loss began a rehabilitation program before the age of 5 months and they have a good speech development and speech intelligibility.     

Fibrosis in regressing melanoma versus nonfibrosis in halo nevus upon melanocyte disappearance: Could it be related to a different cytokine microenvironment?

BACKGROUND: It is not clear why melanocyte disappearance occurs without fibrotic evolution in halo nevus and with fibrotic evolution in regressing melanoma. METHODS: Six halo nevi, seven regressing primary melanomas, and seven primary melanoma (PM) without regression were studied using immunohistochemistry for the phenotype of inflammatory infiltrate and the expression of cytokines involved in fibrogenesis or macrophage regulation. Melanocytes were also evaluated using electron microscopy. RESULTS: CD8(+) lymphocytes predominated in halo nevus, whereas CD4(+) lymphocytes prevailed in melanoma; a few macrophages were only found in melanoma. Fibrogenic cytokines, IL-6, platelet-derived growth factor, and transforming growth factor-beta were only expressed in melanoma, whereas basic fibroblastic growth factor was also expressed in halo nevus. Antifibrotic cytokine tumor necrosis factor (TNF)-alpha was expressed at a higher degree in halo nevus. Cytokines involved in macrophage regulation were only expressed in melanoma. CONCLUSIONS: Fibrogenic cytokines were more frequently expressed in melanoma than in halo nevus, irrespective of regression. At ultrastructural level, melanocytes showed a more activated status in regressing melanoma than in halo nevus, in compliance with a milieu richer in cytokines. Although the cytokine microenvironment does not completely justify the fibrotic evolution in regressing PM, the higher TNF-alpha expression in halo nevus suggests a possible role in nonfibrotic evolution of this lesion.     

Role of contact sensitization in chronic urticaria

We tested the hypothesis that contact allergy plays a role in chronic urticaria, and included the Italian series of patch tests in the diagnostic workup. Of 121 patients with chronic urticaria, 50 (41%) tested positive to contact allergens. In all patients, avoidance measures led to a complete remission within 1 month. We suggest that testing for contact sensitization can be helpful in the management of chronic urticaria.     

Semisolid formulations containing dimethyl sulfoxide and α-tocopherol for the treatment of extravasation of antiblastic agents

The topical treatment with dimethyl sulfoxide (DMSO) and/or α-tocopherol (α-T) is widely used in order to prevent the local complications of extravasation of cytostatic drugs and protect patients against skin ulceration. Till now, DMSO and α-T have been mainly used in solution. The goal of this study was to formulate semisolid preparations for cutaneous application differing in the hydrophilic and lipophilic properties and containing DMSO and α-T in combination. With respect to solutions, the use of semisolid preparations containing DMSO and α-T could be advantageous in patients having extravasation as DMSO and α-T can remain in contact with the skin over an extended period of time. As a consequence, the action of the active principles can be limited specifically on the injured skin area, reducing the cutaneous irritative effects of DMSO. The following types of semisolid formulations containing 50% m/m DMSO and 2.5% m/m α-T were prepared: hydrophilic ointment, o/w emulsion, hydrophilic gel and lipophilic gel. The ex vivo skin permeation of DMSO and α-T was evaluated by using modified Franz’s diffusion cells and human stratum corneum and epidermis (SCE) as a membrane. The permeated and retained amounts of DMSO and α-T were determined. The oleogel preparation, the hydrophilic gel and the o/w emulsion were uniform in colour and aspect, without any evidences of phase separation over the period of the study. Hydrophilic ointments were discarded as they showed phase separation after 12 h. All formulations had a different behaviour in terms of skin permeability. In particular, hydrogel and o/w emulsion showed the best control on the drug release considering the interactions of the vehicle components with the SCE and the drugs partition between the vehicle and the SCE. The DMSO permeated amount after 24 h was 4.1 mg/cm² for hydrogel and 2.5 mg/cm² for emulsion while the permeated amount of pure DMSO after 24 h was 47.5 mg/cm². Therefore, aiming to reduce side effects after the topical application of the antidotes DMSO and α-T, these results suggested that hydrogel and o/w emulsion could be considered the most promising formulations for further clinical evaluations in managing of extravasation of anthracyclines.