Publications (69)144.3 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: : Angiogenesis and vascularity are researched in melanocytic tumors for their importance in carcinogenesis. For the first time, to the best of our knowledge, the authors compared the microvascular characteristics between small/medium congenital nevocellular nevi (CN), common blue nevi (BN), common and dysplastic acquired melanocytic nevi (AMN), and melanomas. The authors collected 31 BN, 48 CN (≤5 cm), 35 AMN (14 common, 21 dysplastic), and 26 melanomas. Vessels were stained with factor VIII. Microvascular density (MVD) and total vascular area (TVA), where evaluated in high capillary density areas. Student t and Mann-Whitney tests were used. MVD (mean ± SD) was low in BN (3.52 ± 1.21) and significantly higher in CN (7.56 ± 2.47) (P < 0.001). TVA was low in BN and significantly higher in CN (Mann-Whitney U = 141, n1 = 48, n2 = 31, P < 0.001, 2-tailed). MVD was not significantly different between common and dysplastic AMN (20.64 ± 7.87 and 20.38 ± 9.54, respectively) (P > 0.05). TVA was not significantly different between common and dysplastic AMN (Mann-Whitney U = 164, n1 = 14, n2 = 21, P > 0.05, 2-tailed). MVD was significantly lower in CN (7.56 ± 2.47) compared with AMN (20.49 ± 8.79) (P < 0.001). TVA was significantly lower in CN compared with AMN (Mann-Whitney U = 1486, n1 = 48, n2 = 35, P < 0.001, 2-tailed). MVD was significantly lower in AMN (20.49 ± 8.79) compared with melanomas (33.77 ± 14.32) (P < 0.001). TVA (mean ± SD) was significantly smaller in AMN (18473.94 ± 7050.61) compared with melanomas (29308.50 ± 11307.22) (P < 0.001). Vascularity increased from BN to CN to AMN with melanomas being the most vascular. Common and dysplastic AMN had comparable vascularity. The implications of our results regarding melanoma transformation risk are considered.
- [Show abstract] [Hide abstract] ABSTRACT: Mediterranean Kaposi's sarcoma (MKS), HIV-related KS (HIV-KS) and immunosuppression-associated KS (IS-KS), caused by human herpes virus 8 (HHV-8), share similar histological features. The aim of this study was to investigate differences in epidermal nerve fibers (ENFs) between the three KS types and controls. Skin biopsies from 23 HIV-KS, 16 MKS, 28 IS-KS patients and 18 controls, age-gender matched, were immunostained with PGP 9.5; ENFs in upper epidermal layer (EL) and penetrating the basement membrane were measured. The mean number of nerve fibers penetrating ENFs was significantly lower in HIV-KS (p < 0.001) compared to all other groups. MKS and IS-KS had comparable ENFs but lower than controls (p < 0.00 1). In the upper EL all groups had comparable ENFs and lower than controls. In conclusion, HIV-KS can be distinguished histologically from other types, by counting ENFs. Moreover, KS is associated with decreased ENFs, which may be a histological reflection of nerve damage. This is even more pronounced in HIV-KS patients and could be explained by a neurotoxic action of HHV-8, HIV, and their co-existence.
- [Show abstract] [Hide abstract] ABSTRACT: Caspase-14 is a seemingly non-apoptotic caspase involved in keratinocyte differentiation and cornification of the skin. Keratin-19 is an epithelial marker and a potential marker of epidermal stem cells that is expressed during human fetal skin development. We examined the immunohistochemical expression of caspase-14 in relation to CK-19 in the human fetal skin during development and perinatally, to assess their role in human skin maturation. Skin samples were received at autopsy. In the fetal epidermis, caspase-14 was predominantly expressed in the more differentiated layers, gradually disappearing from the basal layer toward term. By contrast, keratin-19 expression gradually decreased with epidermal maturation through gestation (rho = -0.949; p = 0.0001) and was a marker of the germinative layers. Keratin-19 was preserved in scarce basal cell nests at term and postnatally. Caspase-14 and keratin-19 were inversely expressed in the differentiating epidermal layers through gestation (p < 0.0001). Concerning the appendages, in hair follicles and sebaceous glands, caspase-14 located preferentially in the more differentiated layers of the inner root sheath, whereas keratin-19 was expressed in the outer sheath. Eccrine sweat glands showed a variable pattern of caspase-14 and keratin-19 expression. In conclusion, caspase-14 emerged as a marker of human skin differentiation during development, while keratin-19 marked the germinative epithelial layers in the fetal epidermis and appendages and possibly the nests of epidermal stem cells.
- [Show abstract] [Hide abstract] ABSTRACT: The development and progression of squamous cell carcinoma (SCC) of the skin is characterized by an accumulation of molecular changes. The aim of this study was to investigate the association of the immunohistochemical expression of cyclooxygenase-2 (COX-2), enhancer of zeste homolog 2 (EZH-2), and p53 in actinic keratosis (AK) and SCC and detect any differences between invasive and preinvasive squamous epidermal lesions. Forty-three cases with AK, 38 with SCC, and 9 with SCC arising on AK (SCC/AK) were studied. For COX-2 immunostaining, weak or no reaction was associated with AK (58.10% of cases), whereas moderate or strong reaction with SCCs (34.2% and 39.5%, respectively). Furthermore, 88.9% of the "mixed" SCC/AK specimens demonstrated moderate reaction (χ = 29.924, P < 0.0001). For EZH-2 immunostaining, a weak or no reaction was observed in 62.8% of AK cases, whereas a moderate reaction was observed in 42.1% of SCCs and 77.8% of "mixed" SCC/AK cases (χ = 18.91, P = 0.001). Weak immunoreactivity of p53 was associated with AK (58.1%), moderate with SCC (44.7%), and strong with SCC/AK lesions (66.7%) (χ = 15.999, P = 0.003). COX-2, p53, but mainly EZH-2 immune expression seems to be strongly associated with the biological potential of squamous epidermal cells and seems to be differentiating SCC by comparison to AK of the skin. The value of the combined expression of these markers is worth being further investigated as an additional tool for diagnostic, prognostic, and possibly, therapeutic use.
- [Show abstract] [Hide abstract] ABSTRACT: OBJECTIVE: To investigate the underlying mechanisms of polyneuropathy induced by HIV infection or antiretroviral drugs. METHODS: We tested 100 HIV patients (59 with AIDS). Ninety-three patients received antiretroviral drugs. Forty-four were treated with neurotoxic compounds (ddI, ddC, d4T). Nerve conduction velocities and the sympathetic skin response (SSR) in palms and soles were measured in all patients. In skin biopsies (ankle and thigh), the intraepidermal nerve fiber density (IENFD) and the number of epidermal fibers without contact to the basal membrane (fragments) were quantified using PGP9.5 staining. RESULTS: Severity of the disease (CD4+count) correlated to conduction velocities of peroneal (p<0.01, Spearmans rank correlation), sural (p<0.01) and median nerves (p<0.05/p<0.001, sensory/motor). In contrast, the duration of neurotoxic treatment did not impair conduction velocities (p>0.3) but correlated to reduced IENFD in the ankle (r=-0.24, p<0.05). Despite their reduced IENFD, patients with long neurotoxic treatment had a high number of fragments irrespective of their CD4+count. CONCLUSIONS: Neurotoxic treatment appears to primarily impair thin fiber conduction, whereas HIV neuropathy is linked to large fiber impairment and reduction of fragments of nerve fibers. SIGNIFICANCE: These findings emphasize the differential pattern of polyneuropathy in HIV patients caused by the infection or induced by antiretroviral treatment.
- [Show abstract] [Hide abstract] ABSTRACT: Background: CHARTER study provided a method for quantifying penetration of antiretroviral (ARV) drugs in the CNS, developing the CNS penetration-effectiveness (CPE) rank by algorithmically combining the individual drug rankings. CPE was associated with CSF viral load. Nevertheless, its association with neurocognitive disorders is ambivalent. The present study aimed to investigate whether the CPE rank might also associate with HIV-related distal sensory polyneuropathy (DSP) Methods: A total of 102 consecutive HIV patients of an outpatient clinic were submitted to clinical examination, electrophysiology, and intraepidermal nerve fiber density (IENFD) evaluation by skin biopsy for the presence of DSP. The HIV status, surrogate markers and antiretroviral history was recorded and the CPE rank of the current ARV regimen was calculated. Statistical analysis was executed using SPSS 15.0 Results: Almost 16% presented with symptomatic DSP and another 36% demonstrated subclinical DSP, recognized by means of electrophysiology and/or IENFD determination. IENFD was associated with more advanced HIV disease, lower nadir CD4 count, and exposure to NRTIs. Mean CPE rank was 1.52±0.77. The CPE rank did not differ in patients with or without DSP. Using the cutoff value of CPE = 2, the regimen was characterized as CNS effective or not effective. Patients under CNS effective regimen were older (41.9±11.6 vs. 38.9±8.3 years, p=0.014), had lower values of IENFD in the calf (3.36±1.75 vs. 6.02±2.47, p=0.02) and worse DSP in terms of conduction velocity, vibration threshold and tendon reflexes. IENFD correlated with the CPE rank values (r=0.22, p=0.039) Conclusion: ARV therapy with increased CNS effectiveness was associated with worse measures of small and large fiber neuropathy, such as IENFD, electrophysiology and clinical findigs, probably attributed to increased age, ARV toxicity, metabolic complications or compartmentalization of HIN in the nervous system
- [Show abstract] [Hide abstract] ABSTRACT: We evaluated the role of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and hypoxia-inducible factor 1-a (HIF1-a) in melanoma angiogenesis and investigated their expression in dysplastic nevi, as potential melanoma precursors. In addition, we examined a possible correlation of VEGF expression with PlGF and HIF1-a. These factors were detected immunohistochemically in 95 melanomas of all types and stages and in 28 dysplastic nevi. We used 10 intradermal melanocytic nevi as controls. HIF1-a was expressed in 93 out of 95 (97.89%) melanomas and in none of the dysplastic or control nevi. HIF1-a expression was more intense in melanocytes around necrotic areas but did not correlate with melanoma type, the Clark staging or the Breslow thickness. A strong positive association was detected between HIF1-a and VEGF expression in all cases. VEGF was detected in 82 out of 95 (86.31%) melanomas and in 21 out of 28 (75%) dysplastic nevi, whereas it was expressed weakly in neoplastic cells of the controls. Its expression was more intense in melanomas, especially in nodular melanomas of elevated stage and thickness. PIGF was detected in 46 out of 95 (48.42%) melanomas and in none of the nevi. Expression did not correlate with melanoma staging nor thickness; however, it was more intense in superficial spreading melanomas, where a weak positive association between VEGF and PlGF was also detected. There was no association between HIF1-a and PlGF in any melanoma type. Hypoxia, through the expression of HIF1-a, plays a key role in melanoma progression; it activates VEGF secretion, which induces angiogenesis and metastasis. The role of PlGF seems to be limited.
- [Show abstract] [Hide abstract] ABSTRACT: The larger number of T-lymphocytes in the periphery of vitiligo lesions and their association with angiogenesis are reported. The objective of this study was to investigate angiogenesis, VEGF and mast cell in vitiligo lesions. Specimens of 30 patients' biopsies, from lesional and perilesional nondepigmented skin were stained for mast cells, CD34 and VEGF. The evaluation was made by image analysis and the measured variables were statistically analyzed. A significantly increased number of CD34 and VEGF positive vessels and mast cells were detected in the centre of the lesion than in the periphery (p < 0.0001, p < 0.0001 and p = 0.001). There was a positive correlation of CD34, VEGF and mast cell number between the centre and the periphery of the lesions (r = 0.877, p < 0.0001; r = 0.946, p < 0.0001 and r = 0.863, p < 0.0001, respectively). The increased angiogenesis and mast cell numbers in the area where lymphocyte number is lower may be explained with the stepwise inflammatory process in vitiligo.
- [Show abstract] [Hide abstract] ABSTRACT: Black yeasts are a rare cause of infections especially in Europe, yet their pathological significance is increasing, particularly in cases of immunosuppression. We report a 53-year-old immunocompetent woman with an extensive skin infection due to Aureobasidium pullulans, who responded well to treatment with liposomal amphotericin B.
- [Show abstract] [Hide abstract] ABSTRACT: A 48-year-old woman with a 10-month history of widespread, hyperpigmented, slightly pruritic macules, with a red border, involving the trunk and the proximal limbs (Fig. 1) was referred to our outpatient department. The oral mucosa, palms, soles, scalp, and nails were normal.Figure 1. Multiple hyperpigmented macules with an active border on the trunkLaboratory tests showed elevated liver enzymes [alanine aminotransferase (ALT), 68 IU/L (normal value, < 40 IU/L); aspartate aminotransferase (AST), 41 IU/L (normal value, < 40 IU/L)], the presence of antibodies to hepatitis C virus (anti-HCV) and HCV RNA (Amplicor Roche). In addition, cryoglobulinemia type III (IgMκ,λ, IgGκ,λ) was detected with a high cryocrit value, and there was detectable C-reactive protein, rheumatoid factor, and a low titer of antinuclear antibodies (1 : 80). A percutaneous liver biopsy showed changes compatible with mild chronic hepatitis (grade, 6; stage, 0). The possible source of infection was unknown, as the patient had no history of parenteral transmission (e.g. blood transfusions, intravenous illicit drug use). A skin biopsy specimen from the active border of a lesion showed hyperkeratosis, parakeratosis, and hydropic degeneration of the basal cell layer, with the formation of colloid bodies in the epidermis. A moderate perivascular lymphohistiocytic infiltrate with melanophages and free melanin granules was observed in the upper dermis (Fig. 2). Immunostaining of paraffin-embedded tissue sections with the TORDJT-22 IgG1 mouse monoclonal antibody to HCV (Biogenex, Son Ramon, USA), which is specific for the nonstructural region of HCV (NS3-NSH, C100 antigen) using the avidin–biotin–peroxidase complex (ABC) as well as the alkaline phosphatase antialkaline phosphatase (APAAP) methods, failed to detect HCV in the lesion of erythema dyschromicum perstans (EDP) (Nakopoulou L, Manolaki N, Lazaris A et al. Tissue immunodetection of C100 hepatitis C virus antigen in major thalassemic patients. Hepato-Gastroenterol 1999; 46: 2515–2520). Direct immunofluorescence showed IgG, IgM, IgA, and fibrinogen deposits on colloid bodies. EDP was diagnosed on the basis of these clinical and laboratory findings.Figure 2. Hydropic degeneration of the basal cell layer with colloid bodies in the epidermis. Moderate perivascular lymphohistiocytic infiltrate with melanophages and free melanin granules in the upper dermis (hematoxylin and eosin, × 200)The patient was treated with interferon-α2b (Intron-A, Schering Plough Athens, Greece), 3 MU thrice weekly subcutaneously for 12 months, with additional topical steroid application. There was no response to this treatment with new lesions appearing in previously unaffected areas of the trunk and extremities. HCV RNA remained persistently positive. Thus, a modified regimen with interferon-α2b, 6 MU thrice weekly for 6 months, was tried. At the end of the treatment course, the eruption of EDP had greatly improved. Liver enzymes were normal (ALT, 22 IU/L; AST, 24 IU/L) and HCV RNA had become negative. Four months later, however, cutaneous lesions reappeared and hepatitis C relapsed. At this time point, combination therapy of interferon-α2b, 3 MU thrice weekly, with ribavirin, 1000 mg daily, was given. Six months later, liver enzymes were normal (ALT, 42 IU/L; AST, 39 IU/L), HCV RNA was negative, and the lesions of EDP had resolved.
- [Show abstract] [Hide abstract] ABSTRACT: Vitiligo is probably the end result of different interacting processes. To determine the possible roles of neural and apoptotic mechanisms in the pathogenesis of vitiligo. Fifty-six biopsies from 28 patients with generalized vitiligo (28 from depigmented lesional areas and 28 from clinically nondepigmented skin at the periphery of the same areas) were examined; the panaxonal marker neuropeptide protein gene product 9.5 (PGP 9.5) and apoptosis were investigated using immunohistochemistry. Statistically significant differences were detected in the numbers of PGP 9.5-positive nerve fibers/axons in the papillary dermis between the center and periphery of the lesions (i.e. increased at the center in comparison with the periphery). A statistically significant inverse association was found between PGP 9.5 immunostaining in the dermis at the lesion center and the duration of the disease. When apoptosis and PGP 9.5 expression were compared, there was an identical distribution of PGP 9.5-positive nerve fibers/axons and apoptotic cells in the epidermis (i.e. basal in the lesion center; diffuse at the lesion periphery). There is a possible connection between the neural and apoptotic pathogenetic theories of vitiligo.
- [Show abstract] [Hide abstract] ABSTRACT: Systemic sclerosis (SSc) is a progressively evolving multisystemic disorder of unknown etiology. Beyond skin, several other organs can also be affected with a severity of involvement that is often heterogeneous. We describe a 53-year-old female patient who was admitted urgently to the hospital almost collapsed, because of numerous bleeding deep skin ulcers, located all over the body. Clinical findings and autoantibody screening were typical of SSc. Moreover, both histopathology and immunofluorescence findings were compatible with scleroderma and vasculitis as well. In addition, pituitary hormone investigation revealed severely damaged function of the gland. We assume that severe skin ulceration and serious hypopituitarism were both implications of underlying SSc-associated vasculitis. To the best of our knowledge, these peculiar clinical manifestations have not been described in the international literature to date.
- [Show abstract] [Hide abstract] ABSTRACT: In the present study we evaluated, in involved and clinically uninvolved skin of Rosacea, microvessels density (MVD) and total vascular area (TVA) in addition to multiple morphologic characteristics of microvessels and also mast cells (MCs) number. We examined also the relationship between angiogenesis, MCs number and disease clinicopathological data. The study included 69 patients with Rosacea. A skin biopsy with a 4-mm punch was performed from clinically involved skin in each case. In nine randomly selected patients, facial biopsy specimens were obtained from both involved and clinically uninvolved skin. Histological sections, immunostained for factor VIII, were evaluated by image analysis for the quantification of MVD, TVA and several morphometric parameters related to the vessel size or shape. MCs detection in the dermis was carried out using the chloracetate esterase method (Fast Blue RR) in parafin sections. Serum antibodies against H.pylori were detected. Statistically important differences concerning the factors of angiogenesis between lesional and clinically non-lesional skin were demonstrated. A statistical important correlation was found also between high vascular density, PPR clinical type and the presence of ocular manifestations. MVD or TVA showed no correlation with the degree of solar elastosis or inflammation and with the Demodex density as well. However, high MVD values were found to correlate with granuloma formation in the dermis. MCs number were significantly greater in lesional compared to clinically non-lesional skin. Statistical significance was shown between MCs density and disease duration. However, no correlation between MCs number and blood vessel density was found. Angiogenesis seems to play an important role in the pathogenesis especially of the more severe clinical form of Rosacea. MCs seem to participate in evolution to disease chronicity by contributing to inflammation, angiogenesis and tissue fibrosis.
- [Show abstract] [Hide abstract] ABSTRACT: The linear intraepidermal nerve fibre density (IENFD) and secondary branching were evaluated from skin biopsy of both the distal calf and the proximal thigh after staining with protein gene product 9.5 in 94 individuals of an HIV outpatient cohort. Possible correlations with clinical and electrophysiological evidence of distal sensory polyneuropathy (DSP), patients' demographics, antiretroviral history and HIV surrogate markers were analysed. Reduced IENFD was recognized in the majority of this population (mean +/- standard deviation [SD] IENFD in the calf and the thigh was 3.19 +/- 1.91 and 7.07 +/- 3.5 fibres/mm, respectively). One-third of the patients with low IENFD had no clinical or electrophysiological evidence of DSP. The level of prior immunosuppression as expressed by lower nadir CD4 count, more advanced HIV stage and prior exposure to combinations of neurotoxic antiretrovirals was associated with more decreased IENFD. Increased SB was associated with symptomatic DSP.
- [Show abstract] [Hide abstract] ABSTRACT: Angiogenesis seems to contribute to tumor growth and the development of metastases. There may be an association between the vascular density of individual tumors and their prognosis. In the present survey we studied 53 cases of renal cell carcinoma investigating possible relationship between histologic grade and microvessel density (MVD) measured by an image analysis system. According to our results MVD was significantly associated with the histologic grade, higher grades being accompanied with a higher MVD. Further studies are needed to investigate a possible connection of MVD with the prognostic role of grade in RCCs.
- [Show abstract] [Hide abstract] ABSTRACT: Injectable cutaneous microimplants may occasionally cause either persistent local irritation or late skin reactions in the form of foreign body granulomas at the injected areas. Permanent elimination of the latter is not easily achieved. The skin of a female patient developed nodules along the treated sites on her face a few months following the last session of intracutaneous injections. Intralesional steroids offered temporary and incomplete clearance. Colchicine was administered orally for better results.
National Technical University of AthensAthínai, Attica, Greece