Effect of compression therapy on a pseudo-Kaposi sarcoma.
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Biomedical subjects
Publications and source records attributed to R G Panizzon.
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Glutathione (GSH) and cysteine (CysH) have both been implicated in the biogenesis of the pheomelanin precursor 5-S-cysteinyldopa (5-S-CD). However, recent studies have shown that only CysH is transported across the membrane of isolated melanosomes, and that the positive regulation of CysH in pigment cells leads to an increased production of 5-S-CD. In the present study, the question was examined as to whether melanin precursors and tyrosinase could be coregulated by cellular thiols. To address this issue, the levels of CysH and GSH were varied in normal melanocytes and melanoma cells using buthionine sulfoximine (BSO), an inhibitor of GSH biosynthesis. Treatment with 50-100 microM BSO decreased GSH levels to less than 10% of control, and increased CysH levels between two- and five-fold in both cell types. Concomitant with this, an increase in the ratio of 5-S-CD to DOPA and a decrease in the pigment content of the cells were observed. The decrease in cell pigmentation was associated with strong decreases in tyrosine hydroxylase activity and 14C-melanin production. Only melanoma cells showed a modified tyrosinase isozyme pattern on Western immunoblots in response to BSO, while the mRNA expression of tyrosinase and TRP-1 were unchanged in both cell types. These results suggest that the balance between CysH and GSH, which is partly determined by the rate of utilization of CysH for GSH biosynthesis, regulates not only the levels of 5-S-CD and DOPA but also the melanogenic activity of pigment cells. Since DOPA functions as a cofactor in the monophenolase reaction of tyrosinase, it is proposed that the ratio of 5-S-CD to DOPA may be an important factor in the regulation of tyrosinase activity in situ.
DNA damage by UV radiation plays an essential role in skin cancer induction. We report that even sub-erythemal doses of solar simulating radiation, are capable of inducing substantial nuclear damage, namely pyrimidine dimers and p53 induction in human skin in situ. The quantity and distribution of p53 induced in human skin by UV radiation depended highly on the waveband and dose of UV used. Solar simulating radiation induced very high levels of p53 throughout all layers in epidermal keratinocytes 24 hr following an erythemal dose (230+/-15.9/1000 cells), and the induction followed a dose response. Following UVA I + II and UVA I radiations, p53 expression was approximately half of that seen with equivalent biological doses of solar simulating radiation (63.5+/-28.5 and 103+/-15.9, respectively). Expression of p53 was seen in basal cell keratinocytes at lower doses of UVA, but all layers of the epidermis were affected at higher doses. Pyrimidine dimer induction, however, was seen to be the same for equivalent biological doses of UVA I, UVA I + II and solar simulating radiations, which coincides with previous findings that pyrimidine dimers initiate the erythemal response and are implicated in skin carcinogenesis. When equivalent biological doses of pure UVA are used with no UVB contamination, significant nuclear alterations occur in human skin in situ, which can approach those seen with UVB radiation. Our results suggest that DNA damage assessed in vivo by immunohistochemistry could provide a very sensitive endpoint for determining the efficacy of protective measures, such as sunscreens or protective clothing, against both UVB- and UVA-induced damage in human skin.
The diagnosis of lymphoproliferative and melanocytic skin lesions is one of the most vexing problems in dermatopathology, a problem that is compounded by the far-reaching therapeutic and psychosocial consequences of the diagnosis for both patient and physician. On the occasion of a self-assessment slide seminar held during a dermatopathology meeting, 30 unusual lymphoproliferative and melanocytic lesions, each provided with four differential diagnoses, were evaluated by "expert pathologists" and other participants ("nonexperts") of the slide seminar. The final diagnosis was pinpointed by the majority of the experts in 16 of 30 cases (56%). The group of experts returned an unanimous decision on the diagnosis in only 2 of the 30 cases (7%). In contrast to the expert group, the preferred diagnoses given by the nonexperts showed a wider range. In 20 of 30 cases (66%), the final diagnosis could only be established after consideration of clinical, histologic, immunophenotypic, and molecular features. Our findings agree with the results of recent studies indicating quite a high degree of discordance among expert pathologists. The discordance between experts and, to a higher extent, nonexperts may have some crucial consequences for dermatopathology. Full agreement on diagnosis, particularly in unusual skin lesions, cannot be achieved only by an accumulation of expertises. Instead of relying on one single finding or diagnostic procedure ("gold standard") as the main criterion upon which to base a diagnosis, the diagnoses become more reliable if based on the integration of several factors including an evaluation of clinical and histomorphologic features and immunophenotypic and molecular findings ("diagnostic elements"), particularly in the field of lymphoproliferative and melanocytic lesions. In addition, a continuous retrospective work-up of difficult or unusual cases is recommended to ensure a long-term improvement in diagnostic reliability.
The term Spitz's nevus refers to a large spectrum of nevi composed of spindle and/or epithelioid cells. We report on a hitherto undescribed tubular variant of a dermal epithelioid nevus, characterized by aggregates composed exclusively of cuboidal cells with the prominent feature of tubular or microcystic structures. Immunohistochemically, the epithelioid cells expressed melanocytic markers (S-100, NKI/C3) lacking markers for cytokeratin or carcinoembryonic antigen. The three-dimensional analysis of the lesions by confocal laser scanning microscopy revealed the structural configuration of tubular or microcystic empty spaces bordered by cuboidal nevus cells. This rare variant of epithelioid nevus is another example for the remarkable diversity of Spitz's nevi.
BACKGROUND AND OBJECTIVE: Local PUVA (psoralen plus UVA light) is an effective outpatient treatment for patients with palmoplantar eczema or psoriasis. In this study, the efficacy, applicability and patient acceptance of two local forms of 8-methoxypsoralen (8-MOP) PUVA therapy were compared. METHODS: The study design was a left-right comparison (n = 37): the left hand or foot was treated with (aqueous) 8-MOP bath PUVA whereas the right received (ethanolic) 8-MOP lotion PUVA. After 1 month, the more successful treatment was continued on both sides until lesions cleared. RESULTS: Both therapies were effective and both useful for particular clinical applications: patients with erosive lesions and rhagades appreciated the gentleness of bath PUVA. Those with pustules or hyperkeratotic lesions appreciated the greater effectiveness of 8-MOP lotion PUVA. The total UVA dose and number of sessions to clearance were smaller with 8-MOP lotion. There was no difference in the length of the relapse-free period. Therapy nonresponders usually became apparent within the first 12 sessions. CONCLUSIONS: The difference between bath PUVA and lotion PUVA can be described as 'gentle' versus 'strong' therapy. The better therapy depends on clinical indication.
BACKGROUND: Photodynamic therapy (PDT) of superficial basal cell carcinomas using endogenous protoporphyrin IX generated by topically applied 5-aminolevulinic acid (5-ALA) is an innovative and clinically encouraging approach. OBJECTIVE: This paper reports on the first results of an ongoing clinical study on photodynamic therapy of 55 basal cell carcinomas in 19 patients. METHODS: Because of the chemical instability of 5-ALA, a novel nanocolloid lotion was developed. This formulation was applied to the lesions under occlusive dressing 6 h before irradiation with visible light from an unfiltered halogen lamp. Light-induced fluorescence was used to ascertain the superficial extension of the tumors. The response to the therapy was assessed by visual inspection and in 13 patients also by biopsies. RESULTS: After a single treatment, 47 (85%) basal cell carcinomas showed a complete response at a follow-up time of at least 6 months. For the remaining 8 (15%) lesions, a partial response was observed, indicated by a marked reduction of the tumor size. The treatment modality without local anesthetics was well tolerated by all patients, with only slight discomfort during light irradiation. CONCLUSION: Our results indicate that 5-ALA-PDT with our novel formulation, a nanocolloid lotion, is a highly effective and convenient therapy for the treatment of superficial basal cell carcinomas. Its use in the treatment of nodular tumors needs further investigations.
We report the case of a 17-year-old student from Cameroon who presented an atypical, mono-symptomatic form of Loa loa infection, characterized only by rare subcutaneous movements of adult worms.
We report the case of a 42-year-old man with symptomatic HIV infection (C3 CDC stage) who presented widespread hyperkeratotic skin lesions diagnosed as Norwegian scabies. The CD4 count was 87 cells/mm3. The patient has been the source of a nosocomial outbreak (20 individuals affected). He was treated successfully with combined topical treatment (permethrin 5% cream plus keratolytic agents) and oral ivermectin.
BACKGROUND: Tinea capitis is a worldwide-spread infection of the scalp caused by dermatophytes and is predominantly seen in children. The clinical manifestations range from mild scaling lesions to widespread alopecia or highly inflammatory suppurating lesions. Terbinafine and itraconazole seem to be promising therapies with shorter treatment durations than griseofulvin. OBJECTIVE: The objective of the present study was to test the sensitivity of different species of dermatophytes towards terbinafine and itraconazole, and to compare the results with a retrospective study on 35 immunocompetent patients with tinea capitis who were treated with terbinafine (Lamisil(R)). METHODS: Minimal inhibitory concentrations (MIC) were measured with an agar dilution method. RESULTS: Each tested species of dermatophyte was sensitive to terbinafine and itraconazole at different concentration ranges. The MIC for terbinafine ranged from 0.005 to 0.5 microg/ml and for itraconazole from 40 to 80 microg/ml. Microsporum canis was the dermatophyte least sensitive to terbinafine. Our retrospective study showed that the cure rate was excellent for Trichophyton violaceum and T. soudanense, variable for T. mentagrophytes and poor for M. canis and M. langeronii. CONCLUSIONS: (i) Regarding the results of susceptibility tests obtained with species involved in tinea capitis, clinical efficacy is not related to MIC measured in vitro; (ii) identification of the isolated dermatophyte from tinea capitis seems to be important for choosing the appropriate treatment.
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BACKGROUND: Peripheral and tissue eosinophilia are associated with a group of idiopathic inflammatory syndromes. The idiopathic hypereosinophilic syndrome represents a spectrum of disorders characterized by prolonged eosinophilia of an undetectable cause and significant organ dysfunction. The pathogenic role of the eosinophil in these conditions is attested to by evidence of eosinophil activation and degranulation at sites of tissue injury. Recently, an overlapping range of idiopathic eosinophilic muscle disease with an overall good prognosis has been described. RESULTS: We describe a patient with a syndrome of idiopathic myositis with eosinophilia and eosinophilic cellulitislike cutaneous manifestations. Histopathological studies of the skin and muscle revealed eosinophilic infiltration. Elevated serum levels of eosinophilic cationic protein and interleukin-5 paralleling disease activity were detected. CONCLUSIONS: This patient demonstrates clinical and laboratory features of eosinophilic myositis with eosinophilic cellulitislike skin lesions. The elevated serum levels of interleukin-5 and eosinophilic cationic protein may be responsible for the eosinophilia and tissue injury, respectively. With the advances in our understanding of cytokine-dependent regulatory mechanisms governing the eosinophil reaction, more targeted ways of manipulating eosinophilia as well as the entry and activation of eosinophils within specific tissues can be expected.
Vulvar melanomas are seen in about 3% of all melanomas. The percentage reaches 10% of all malignant tumors of the vulva. The mean age of the patients is approximately 55 years. The first symptoms noticed by the patients are bleeding, pruritus, or a mass in the groin. Vulvar melanomas are mostly located at the labia minora. The differential diagnosis comprises different pigmented lesions, such as seborrheic keratosis, nevocellular nevus, lentigo, or hyperpigmentations of different origin. There is no typical histopathological pattern, but mostly melanomas of this site are of the mucosal-lentiginous type. As treatment modalities, most investigators propose a complete excision for melanomas thinner than 1 mm, and for thicker melanomas a wide excision. Recent investigations have shown that hemivulvectomies or vulvectomies do not show a better survival. The question of a prophylactic ipsilateral lymph node dissection is not answered yet. The survival rates depend on the tumor thickness and/or the infiltration level. The importance of an early diagnosis should be stressed in vulvar melanomas, especially through an accurate inspection of the vulva at the time of a genital examination. In addition, vulvar self examinations are an excellent possibility for early diagnosis. This allows a definite treatment and vulvar conservation.
Steatocystoma multiplex (SM) and eruptive vellus hair cyst (EVHC) are known as clinically similar but histologically distinct entities, first described by Jamieson in 1873 and Esterly et al. in 1977, respectively. Herein we describe a 24-year-old female patient with both lesions on the anterior chest wall. The biopsy showed portions of two cysts close together with features of SM in one part and features of EVHC in the other part. Our case gives further evidence that these two conditions are closely related. To the best of our knowledge this is the first case where such an anatomically close relationship between these two types of cysts has been described.
BACKGROUND: Verrucous carcinoma is a slowly growing, well-differentiated neoplasm with a predilection for the oral cavity. OBJECTIVE: Data on the association of human papillomavirus (HPV) with oral verrucous carcinoma are very scarce. We searched for the presence of HPV in different stages of the tumour in a patient repeatedly treated by means of surgery, cryotherapy, radiotherapy and chemotherapy over a decade. METHODS: HPV DNA was detected in archival tumour tissue by nested PCR. HPV types were identified based on restriction fragment analysis. RESULTS: HPV type 11 was found in 1 early-stage and HPV 16 in 2 late-stage biopsy specimens of the tumour. CONCLUSION: Our findings provide further evidence for a role of HPV in oral verrucous carcinoma. The case history emphasizes the importance of a joint clinicopathological approach to this tumour.
Idiopathic middermal elastolysis (IMDE) is a rare disorder with two different clinical presentations: type I lesions, with tiny wrinkles along skin cleavage lines in large confluent areas, and type II lesions, with small perifollicular papular protrusions. The histopathological picture is characteristic. IMDE is mainly seen in healthy young or middle-aged women. We describe a 60-year-old male patient with this disorder. The special interest of this case report is that there was no photosensitivity and no exacerbation with PUV therapy. IMDE is probably a special sort of elastolytic disorder, for which immunologic mechanisms seem possible.
Patients with anti-SSA(Ro)-positive Sjögren's syndrome (SS)/lupus erythematosus (LE) overlap are a immunogenetically, serologically and clinically homogeneous group; what they have in common is an increased frequency of the HLA-DR3 phenotype, demonstrating SSA(Ro) antibody activity and the typical annular, polycyclic, erythematous lesions of subacute cutaneous LE. The sicca symptoms of SS may develop long after the cutaneous lesions of LE have been present, or vice versa, as well as vasculitic, purpuric, and Sweet's syndrome-like lesions. The elderly, predominantly female patients are at enhanced risk for pulmonary and neurological disease, but glomerulonephritis occurs infrequently. We present an 81-year-old, SSA(Ro) antibody-positive and HLA-DR3-positive woman with SS/LE overlap syndrome, who had cutaneous LE for 30 years, developing sicca symptoms, vasculitic and Sweet's syndrome-like skin lesions only years after the LE symptoms. Although there is still some discussion as to whether phenotypical SS/LE overlap represents a distinct disease or is secondary SS in SLE or systemic SS with cutaneous involvement, the SS/LE overlap syndrome seems well enough delineated to be considered as a disease entity with separate implications for therapy and prognosis. Its position in the spectrum of anti-SSA(Ro) antibody- and HLA-DR3-positive diseases and its relationship to SS and to anti-SSA(Ro) antibody-positive LE are discussed.
Minor nail trauma may cause bluish discoloration of the nail, while tangential skin trauma on the heel can result in a so-called black heel. To rule out melanoma in such clinical situations, a biopsy is needed to reveal homogeneous eosinophilic masses deposited under the nail plate or within it (transepidermal elimination). Most dermatopathologists attempt to demonstrate the presence of hemoglobin in these eosinophilic masses with Prussian blue stain, which typically remains negative. In our experience, these traumatically induced blood deposits are always situated in avascular spaces, devoid of degrading phagocytes. Consequently, a histochemical stain for these deposits should be directed specifically toward hemoglobin, not hemosiderin. In the dermatopathologic literature, the various techniques to detect hemoglobin deposits in tissue sections are not well-known. We would like to emphasize benzidine stain, a highly selective and efficient method to demonstrate the presence of hemoglobin deposits in histologic sections. To date, benzidine stain has not been utilized to characterize splinter hemorrhage (subungual hematoma). Of concern, the use of benzidine in histopathology laboratories is restricted because this agent is a known carcinogen, while the non-mutagenic derivative, 3,3',5,5'-tetramethylbenzidine, does not stain histologic sections. Patent blue V, a completely different and less specific agent, stains hemoglobin an intense blue-green.