bluuebunny/crossref_metadata_2025 huggingface dataset:
FGFR3 Gene Mutations in Chinese Cases of Thanatophoric Dysplasia Type 1
Authors: Yang Yu , Li Dong-Zhi
Published: October 2009

Objective: Thanatophoric dysplasia type 1 (TD 1) is typically a lethal dwarfism. We report our findings of fibroblast growth factor receptor 3 (FGFR3) mutations in Chinese cases of TD 1. Methods: Ten cases of TD 1 were identified prenatally by ultrasound. The FGFR3 gene was analyzed using direct DNA sequencing of the selected regions (exons 7, 10, 15, and 19) previously reported to contain mutations for TD 1. Results: A heterozygous C742T (R248C) mutation was found in 9 of the 10 cases. The remaining case was negative for mutations involved in exons 7, 10, 15 and 19. Conclusion: The results suggest that the R248C mutation may serve as the primarily targeted one of the FGFR3 gene for rapid molecular diagnosis of TD 1.
Role of Cyclooxygenase and Derived Reactive Oxygen Species in ρ-Kinase-Mediated Impairment of Endothelium-Dependent Vasodilation and Blood Flow after Ischemia-Reperfusion of the Rat Kidney
Authors: Versteilen Amanda M.G. , Korstjens Iolente J.M. , Musters René J.P. , Groeneveld A.B. Johan , Sipkema Pieter
Published: October 2009

Background/Aims: Decreased endothelium-dependent vasodilation and blood flow in renal ischemia-reperfusion (IR) may result in part from ρ-kinase activation, and cyclooxygenase (COX) activation, and resultant reactive oxygen species (ROS) may be involved. Methods: We tested this hypothesis in male Wistar rats, subjected to 60 min of bilateral clamping of the renal arteries and 60 min of reperfusion or a sham procedure, and treated by the ρ-kinase inhibitor Y27632 (1 mg/kg) and/or the nonspecific COX inhibitor diclofenac (10 mg/kg). Renal blood flow was measured by fluorescent microspheres, and ROS in the arterial endothelium was quantified by dihydroethidium staining. Endothelium-dependent vasodilation was determined by an acetylcholine concentration-response curve in the presence or absence of diclofenac (10 µM). Results: Y27632 increased renal blood flow and reduced ROS in vivo, and improved endothelium-dependent vasodilation in vitro, following IR with or without diclofenac. Following IR, diclofenac had no effect on renal blood flow and ROS in vivo, but improved endothelium-dependent vasodilation in vitro. Conclusion: Activation of ρ-kinase impairs endothelium-dependent vasodilation and perfusion following renal IR, independently of COX and resultant ROS. In contrast, the vasodilatory effect of ρ-kinase inhibition may be partly mediated by decreasing ROS, unrelated to COX and resultant vasoconstricting prostanoids.
Multi-Glycoside of Tripterygium wilfordii Hook f. Ameliorates Prolonged Mesangial Lesions in Experimental Progressive Glomerulonephritis
Authors: Wan Yigang , Sun Wei , Zhang Huilan , Yan Qiaojing , Chen Ping , Dou Chenhui , Yang Haiming , Ge Ming
Published: October 2009

Background/Aims: Multi-glycoside from Tripterygium wilfordii Hook f. (GTW) is used for treatment of progressive glomerulonephritis (GN) in China. We have previously reported the beneficial effects of GTW on acute GN induced by an anti-Thy-1.1 monoclonal antibody (mAb). In the present study, the effect and potential mechanisms of GTW on the chronic irreversible model of GN were investigated. Methods: Progressive GN was induced in rats by two intravenous injections of anti-Thy-1.1 mAb 1-22-3. Daily oral administration of GTW was started before the second injection of mAb until the day of sacrifice. Ten rats were randomly divided into a control (vehicle-treated) and a GTW-treated group, and sacrificed on day 45 after the first injection of mAb 1-22-3. Proteinuria was determined on days 0, 1, 3, 5, 7, 10, 14, 20, 25, 30, 35, 40, and 45. Blood biochemical parameters, morphological changes of mesangium, glomerular infiltration of macrophage and T lymphocyte, and glomerular mRNA expression of cytokines (TGF-β, IL-2, and IFN-γ) were examined from the samples taken at terminal sacrifice. Results: GTW treatment significantly ameliorated proteinuria, renal function, prolonged mesangial lesions and inflammatory cell accumulation in glomerulus. In addition, it significantly reduced the glomerular mRNA expression for TGF-β, IL-2, and IFN-γ. Conclusion: GTW ameliorates prolonged glomerular lesions presumably through suppression of cytokine production (TGF-β, IL-2, and IFN-γ). GTW could be an effective therapeutic agent for treatment of chronic renal diseases.
Report of a Brazilian Multicenter Study on Nephropathic Cystinosis
Authors: Vaisbich Maria Helena , Koch Vera H.
Published: October 2009

Introduction: The Brazilian Multicenter Nephropathic Study Group, founded in 1999, is currently composed of 16 pediatric nephrology units, which are coordinated by the Pediatric Nephrology Unit of Instituto da Criança – HCFMUSP. This Study Group intends to better know our patients, their special characteristics and facilitates the treatment. Objective: To present an update on the demographics of the ongoing study participants with interest on renal function status, response to therapy, and extra-renal complications. Methods: Patient recruitment to the study is based on informed consent and has been supported by the Brazilian Society of Nephrology, by the creation of an electronic homepage and by the participation in medical meetings and publications in medical periodicals. Our study protocol involves the initial and follow-up questionnaire, the measurement of intraleukocyte cystine content, initiation and follow-up therapy with cysteamine, and clinical patient follow-up based on a protocol of subsidiary exams. Results: We identified 102 patients (42 females) with nephropathic cystinosis in Brazil since 1999. Forty-six children are followed at the Instituto da Criança/SP, 15 at the Hospital Pequeno Príncipe/PR, 12 at the UNICAMP/SP, 10 at the Unidade de Transplante Renal – HCFMUSP/SP and 3 at the Santa Casa/SP; the remaining patients are followed at the Instituto da Criança and at their respective doctors’ offices in different nephrology services in Brazil. Of these patients, 23/102 (22.5%) have normal renal function, 19/102 (18.6%) are in chronic renal failure with conservative treatment, 26/102 are on dialysis (18 on peritoneal dialysis and 8 on hemodialysis), and 34/102 received a renal transplant. The extra-renal involvement diagnosed was: hypothyroidism in 63 patients, diabetes mellitus in 8 patients, muscular involvement in 7 patients, a compromised central nervous system in 5 patients, hepatic complications in 5 patients, and deglutition dysfunction in 2 patients. During this period, 10/102 patients died. Cysteamine has been used by 81/102 patients (20 children started the therapy under 2 years of age). Growth parameters were improved by cysteamine, mainly in the youngest patients. We used recombinant growth hormone in 15 patients with persistent low growth velocity and stature z score under 2.5%. We could also observe a delay in appearance of extra-renal complications in patients receiving cysteamine. Conclusion: Our study demonstrates the importance of a multi-center study for recruitment, diagnosis and management of rare diseases. This study promotes access to the adequate treatment with profound impact on the quality of life.
Improving the Management of Chronic Kidney Disease in Uruguay: A National Renal Healthcare Program
Authors: Schwedt Emma , Solá Laura , Ríos Pablo G. , Mazzuchi Nelson
Published: October 2009

Background: Uruguay has implemented a chronic kidney disease (CKD) prevention program. Aims: The objectives of the study are to assess the results of the National Renal Healthcare Program (NRHP). Methods: This study is a cohort study of nondialysis-registered patients from October 2004 to March 2008. We made a comparison between patients under nephrology care (NC) or the care of a primary care physician (PCP; prereferral). In the outcome analysis, the primary endpoint was end-stage renal disease (ESRD) and the secondary endpoints were progression of CKD, compliance with the therapeutic goals and death. ESRD/mortality predictors were determined by Cox analysis. Results: The study comprised 2,219 patients aged 67.4 ± 13.5 years, of whom 52.5% were male, 42.1% hypertensive, 16.9% had diabetic nephropathy, and 61.3 and 21.4% were in CKD stages III and IV, respectively. At baseline, NC patients showed a better control than patients under the care of a PCP: systolic blood pressure ≧160 mm Hg (22.4 vs. 31.1%); total cholesterol <5.8 mmol/l (56.6 vs. 42.5%); and low-density lipoprotein cholesterol <2.9 mmol/l (41.2 vs. 29.1%). Control improved in patients under the care of a PCP according to years of enrollment. Outcome analysis (1,188 patients) showed a significant improvement in targets, with 56% of the patients stabilizing. CKD stage IV, diabetic nephropathy, proteinuria and hypertension increased the risk of ESRD; angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and age <65 years decreased the risk. Conclusions: Our results highlight the best management of CKD patients in both groups and the impact of the NC and renin-angiotensin-aldosterone system blockers.
Visuospatial Dysfunction May Be a Key in the Differentiation between Alzheimer’s Disease and Subcortical Cognitive Impairment in Moderate to Severe Stages
Authors: Fukui T. , Lee E. , Kitamura M. , Hosoda H. , Bokui C. , Ikusu K. , Okita K.
Published: October 2009

Aims: Recent studies have suggested that subcortical cognitive impairment (SubCI) and Alzheimer’s disease (AD) can be differentiated by visuospatial tasks. We addressed at what severity stage these differences become apparent and what components in visuospatial processes are subject to impairment. Methods: Sixty patients with AD, 22 with vascular cognitive impairment and 63 with extrapyramidal diseases with cognitive impairment were assessed using the revised Hasegawa Dementia Scale (HDSR), clock drawing/reading/matching tests (CDT, CRT, CMT), figure copying (FIG) and Frontal Assessment Battery (FAB). Patients were categorized according to the HDSR scores in order to control for the severity of global cognitive impairment. Raw scores were converted to Z-scores for comparisons. Results: In the mild stage, results of all measures were comparable between AD and SubCI. In the moderate-severe stage, scores of CDT, CRT, CMT, FIG and FAB were significantly lower in SubCI. The results suggest that (given that global cognition is controlled for) visuo-perception, visuo-construction and semantic-numerical analyses of visual information may be more impaired in SubCI than AD. Conclusions: AD and SubCI may be difficult to be differentiated in the mild stages, and the visuospatial cognitive system may be extensively defective in SubCI.
Cytokines Involved in Interferon-γ Production by Human Macrophages
Authors: Robinson Cory M. , O’Dee Dawn , Hamilton Travis , Nau Gerard J.
Published: October 2009

Interferon (IFN)-γ is important to the immune defense against intracellular pathogens and specifically the ability of macrophages to control Mycobacterium tuberculosis (MTB). Increasing evidence has accumulated to support the idea that macrophages produce IFN-γ. We describe here the cytokine interactions that determine IFN-γ expression and secretion during MTB infection of human macrophages. Detection of biologically important IFN-γ levels in culture supernatants of MTB-infected human macrophages requires the addition of interleukin (IL)-12. IL-18 augmented IFN-γ production from human macrophages in response to the combination of MTB and supplemental IL-12. Although IL-18 gene expression was generally unchanged, IL-18 protein secretion was enhanced by the combination of MTB and IL-12, and functioned primarily to stimulate IFN-γ release. Importantly, IL-27 induced by MTB infection opposed IFN-γ production by antagonizing IL-18 activity in human macrophages. Neutralization of IL-27 increased the expression of the IL-18 receptor β-chain. Additionally, IL-27 blocked NF-ĸB activation in response to IL-18. These results define the signals required for IFN-γ production by human macrophages and highlight the interactions between cytokines produced during MTB infection. Together, they identify a novel role for IL-27 in regulating macrophage function by disrupting IL-18 activity.
Protective Role of Complement C5a in an Experimental Model of Staphylococcus aureus Bacteremia
Authors: von Köckritz-Blickwede Maren , Konrad Stephanie , Foster Simon , Gessner J. Engelbert , Medina Eva
Published: October 2009

The complement system is a key component of the innate immune response. Here, we have examined the role of complement anaphylatoxin C5a in an experimental model of Staphylococcus aureus bacteremia. Our data provide compelling evidence for a protective role of C5a during staphylococcal bloodstream infection.
Follicular Mucinosis Associated with Mycosis Fungoides
Authors: Büchner S.A. , Meier M. , Rufli T.
Published: October 2009

We report a patient who developed erythematous indurated plaques with alopecia on the face and multiple well-demarcated infiltrated scaling lesions on the trunk and extremities. Skin biopsy showed a mucinous degeneration of the follicular outer root sheaths and sebaceous glands consistent with the diagnosis of follicular mucinosis. A histologic examination of a specimen from the left forearm showed microscopic changes of mycosis fungoides. The present case confirms the need of multiple skin biopsies in the evaluation of patients with follicular mucinosis.
Elevated Glucocorticoid Receptor Concentrations before and after Glucocorticoid Therapy in Peripheral Mononuclear Leukocytes of Patients with Atopic Dermatitis
Authors: Rupprecht M. , Rupprecht R. , Kornhuber J. , Wodarz N. , Koch H.U. , Riederer P. , Hornstein O.P.
Published: October 2009

The number and affinity of glucocorticoid binding sites in peripheral mononuclear leukocytes of patients with atopic dermatitis (AD) and healthy controls were determined under baseline conditions and after a defined oral glucocorticoid treatment. Patients with AD (n = 15) exhibited significantly more glucocorticoid receptors (GR) per cell than the control group (n = 22), while the GR affinity did not differ. Methylprednisolone treatment resulted in a significant reduction of the GR sites per cell in the steroid-treated control group (n = 10) in contrast to the patients. The dissociation constant was not affected by methylprednisolone treatment in either group. In view of the therapeutic efficiency of glucocorticoids in AD and findings of abnormal cAMP and cAMP-phosphodiesterase activity, the elevated GR concentrations in AD lend support to the hypothesis of a compensatory GR upregulation due to an insufficient action of endogenous cortisol or to altered cAMP-induced GR expression.
Lack of Pancreatic Maldigestion in Atopic Dermatitis
Authors: Barba A. , Cavallini G. , Brocco G. , Schena D. , De Agostini F. , Scuro L.A. , Bovo P. , Chieregato G.C.
Published: October 2009

Twenty adult patients affected by atopic dermatitis (AD) were submitted to the p-aminobenzoic acid (PABA) test in order to evaluate the proteolytic pancreatic function. All but one showed a normal PABA test. These results seem to exclude a proteolytic maldigestion as a pathogenetic factor in AD.
Topical Tretinoin Decreases Healing Times of Electroepilation-Induced Wounds
Authors: Anthony J. , Miller L. , Dinehart S.M.
Published: October 2009

There is evidence that topical tretinoin promotes wound healing, especially when the wound area is pretreated. In our study, 5 patients were pretreated for 2 weeks with 0.05% tretinoin cream to one groin or axilla, followed by electroepilation to both sides. Electroepilation created small, superficial wounds. Healing was defined as complete re-epithelialization. In all patients the pretreated side showed a significantly decreased healing time as compared to the nonpretreated side. Pretreatment of skin with topical tretinoin may be useful in reducing healing times of patients undergoing electroepilation.
Nucleolar Organizer Regions Argyrophilic Associated Proteins in Cutaneous Melanocytic Lesions
Authors: Reis J.P. , Tellechea O. , Poiares Baptista A.
Published: October 2009

We applied a simple silver staining technique to visualize nucleolar organizer regions associated proteins (AgNORs) for the study of 47 melanocytic lesions (20 malignant melanomas, 5 dysplastic nevi, 4 Spitz nevi, 2 Reed and Gartman’s fusiform nevi and 16 melanocytic nevi). A statistically significant difference existed between the numbers of AgNORs per cell in benign and malignant lesions as a group. However, some overlapping counts were found, limiting the usefulness of the technique in differentiating benign from malignant lesions in individual cases.
Seborrheic Skin and Acne vulgaris as Protective Factors against the Development of Basal Cell Epithelioma
Authors: Friedman-Birnbaum R. , Linn S. , Eidlitz-Markus T. , Harth Y. , Cohen E.
Published: October 2009

This study was conducted in order to evaluate a possible protective role of seborrheic complexion and a history of acne on the development of basal cell epithelioma (BCE). For this purpose, 77 patients with this tumor were examined and asked to fill out a questionnaire. The questionnaire included demographic data and questions about skin type, eye and hair colors, sun exposure habits and a past history of acne. The nature, number and location of tumors, the texture of skin and acne scars were noted by a physician. A group of 93 age-, sex- and skin-color-matched patients served as controls. The results show a clear relationship between seborrheic features and a lower risk of developing BCE, after controlling for solar exposure using the Mantel-Haenszel summary measure. The same trend was found in patients with a history of acne. Whether ultraviolet light absorption by sebum, an anticancer activity of Propionibacterium acnes or other factors play a protective role against the development of BCE is as yet unclear.
Early Detection of Scleroderma Spectrum Disorders in Patients with Raynaud’s Phenomenon
Authors: Takehara K. , Soma Y. , Ishibashi Y.
Published: October 2009

Fifty patients with the chief complaint of Raynaud’s phenomenon (RP) presented at our scleroderma clinic from March to December 1990. Physical examination, routine laboratory tests (blood, urine and chest X-ray), determination of the pattern of RP, antinuclear antibody (ANA) tests and examination for nailfold bleeding were performed. Three patients were diagnosed as having systemic sclerosis sine scleroderma, 15 patients as having RP with positive anticentromere antibody and 6 patients as having an incomplete form of mixed connective tissue disease. Thus a total of at least 24 patients out of 50 (48%) were shown to have a scleroderma spectrum disorder. A definite RP pattern (triphasic or biphasic and bilateral), positive ANA and positive nailfold bleeding were strongly correlated statistically, suggesting that these are simple useful findings for the early detection of scleroderma spectrum disorders in patients with RP. We expect that there are many undiagnosed patients with an early-stage scleroderma spectrum disorder in the general population.
A New Classification of Ota’s Nevus Based on Histopathological Features
Authors: Hirayama T. , Suzuki T.
Published: October 2009

According to the distribution of the dermal melanocytes, Ota’s nevus was classified into 5 types: superficial (type S), superficial dominant (type SD), diffuse (type Di), deep dominant (type DD), and deep (type De). The histological types were, as expected, relatively well-correlated with the color of the nevus: the most brownish lesions represented type S or type SD while the most bluish lesions showed types Di DD or De. Furthermore these types were strongly correlated with the location of the nevus: types S and SD were more frequent on cheeks whereas types Di DD and De more frequently occurred on eyelid, temple and forehead. When combining both colorations and locations of the nevus, our classification appeared much more significant. Our new histological classification of Ota’s nevus may be very useful in making a therapeutic prognosis of the disease.
Immunophenotyping of Skin Cells during Healing of Suction Blister Injury
Authors: Reusch M.K. , Mansbridge J.N. , Nickoloff B.J. , Morhenn V.B.
Published: October 2009

The time course of appearance and the dynamic changes of immunocompetent cells were assessed in human skin following sterile suction blister wound healing. During epidermal regeneration, a local increase in Langerhans cells (LC) and the appearance of a mononuclear cell infiltrate were observed. Initially, T cells were exclusively of the T helper/inducer subtype, whereas during the later stages of the healing process an increasing number of cytotoxic/suppressor T cells (up to 30%) was observed. Keratinocytes of neither the adjacent nor the newly formed epidermis expressed HLA-DR over the course of the wound-healing process. Our results suggest that immune-competent cells such as T cells and LC may play an important role in the regulation of the wound-healing process.
Palmar Skin is Not Involved in Severe Atopic Eczema
Authors: Bonvén T.F. , Hansen L. , Thestrup-Pedersen K.
Published: October 2009

Irritant hand eczema is a well-known risk in adults, who have suffered from severe atopic dermatitis during childhood. We therefore studied the involvement of the skin on the hands in 29 consecutive patients admitted for severe atopic dermatitis. Only 5 of the 29 patients had eczema in the palmar skin (p < 0.01; sign test). There was no correlation with the existence of hyperlinearity, extent of disease, concomittant asthma, total serum IgE or work.
Argyrophilic Nucleolar Organizer Region Counts in Malignant Melanoma Associated with Benign Intradermal Nevus
Authors: Pich A. , Aloi F. , Margaria E. , Tomasini C.
Published: October 2009

A silver colloidal technique to demonstrate argyrophilic proteins of the nucleolar organizer regions (AgNORs) was performed on sections of 20 cases of malignant melanoma (MM) associated with underlying benign nevus (BN). In these cases, significant different AgNOR counts were found for MM and BN. In addition, this technique permitted the identification of melanocytic cells located between malignant and benign cells showing AgNOR scores intermediate (5.51) between BN (2.6) and MM (7.71) with a more complex and bizarre morphology than that observed in BN. The AgNOR technique can be suitable in the identification of residual nevus cells in MM, especially when their number is minimal and the common histologic criteria are unsatisfactory; it can also increase the understanding of the natural history of MM.
Cutaneous Manifestations of Neutrophilic Disease
Authors: Vignon-Pennamen M.-D. , Wallach D.
Published: October 2009

Seven patients with a complex form of neutrophilic dermatosis are reported. Clinically, they had variable associations of four types of lesions: blisters/pustules, plaques, nodules and ulcerations. Histologically, a neutrophilic infiltrate was observed at variable levels in the epidermis, dermis and subcutis. Systemic manifestations were present in all cases (general symptoms, joint, renal, ocular and lung involvements). Three patients had an associated disease (myelodysplasia, metastatic carcinoma, IgG gammopathy). Steroids were the most efficient treatment. These observations, as well as a review of the literature, support the opinion that the neutrophilic dermatosis represents a continuous spectrum encompassing four well-defined entities: subcorneal pustular dermatosis, Sweet’s syndrome, erythema elevatum diutinum and pyoderma gangrenosum. We propose that the different patterns of the neutrophilic dermatosis are the most obvious manifestations of a potentially multisystemic neutrophilic disease and allow its recognition.
Cutaneous Metastases from Follicular Thyroid Carcinoma: Histology, Immunohistology, and Electron Microscopy
Authors: Tronnier M. , Winzer M. , Wolff H.H.
Published: October 2009

Cutaneous metastases from thyroid carcinoma are extremely rare. We report 2 cases of skin metastases from a follicular thyroid carcinoma. A 53-year-old female patient underwent subtotal thyroidectomy because of the clinical suspicion of malignancy. Histological examination of the resected tissue did not clearly prove malignant features. Eight years later a cutaneous metastasis erupted next to the operation site at the neck. A 66-year-old female patient noticed a growing solitary skin nodule in the occipitoparietal region of her scalp 2 years before a follicular thyroid carcinoma was detected.
Variant of Hyper-IgE Syndrome: The Differentiation from Atopic Dermatitis Is Important because of Treatment and Prognosis
Authors: Hochreutener H. , Wüthrich B. , Huwyler T. , Schopfer K. , Seger R. , Baerlocher K.
Published: October 2009

The hyper-IgE syndrome is characterized clinically by recurrent staphylococcal abscesses of the skin, lungs and other sites from infancy. Affected patients also have a pruritic dermatitis that differs in character and distribution from lesions of atopic dermatitis. Most lack other signs of atopic disease, develop persistent pneumatoceles and have osteopenia. Laboratory abnormalities include the consistent presence of marked hyperimmunoglobulinemia E and eosinophilia of blood, sputum and tissues. They may have other inconsistent abnormalities of humoral and cellular immune responses and sometimes of phagocytic cell chemotactic responsiveness. Other clinical problems reported in such patients have included lymphomas, cryptococcal meningitis and cutaneous fungal disease. An 18-year-old male patient with a variant of the hyper-IgE syndrome which he had acquired after a measles attack at the age of 5 years suffered from recurrent ulcerative dermatitis and lymph node abscesses. Immunological investigation revealed an excessively elevated total serum IgE level (46,850 IU/ml), the presence of specific IgE to staphylococci, and quantitative and functional deficiency of IgG2. Skin and serological (radioallergosorbent) tests to inhalant and nutritive allergens were negative. Differentiation from atopic dermatitis should be made, because a long-term antistaphylococcal regime not only improves skin lesions but hinders the occurrence of lung abscesses and pneumatoceles.
Spontaneous Monitoring of Adverse Reactions to Drugs by Italian Dermatologists: A Pilot Study
Authors:   Gruppo Italiano Study Epidemiologici in Dermatologia
Published: October 2009

During 1988, the Gruppo Italiano Studi Epidemiologici in Dermatologia (GISED) coordinated a pilot study aimed at evaluating the feasibility of a system for spontaneous monitoring of adverse drug reactions in dermatological practice in Italy. Approximately 400 dermatologists were asked to collaborate, and 141 agreed to the study. Procedures similar to those well established in other surveillance programs (including the use of standard forms and standardized assessment procedure) were adopted. In a 2-month period 775 reports were collected, of which 711 were maintained after careful evaluation. The general profile of the adverse reactions reported was in accordance with the experience derived by other spontaneous surveillance programs. The main purpose of spontaneous reporting systems is the identification of new reactions, and a model analysis was proposed, in our study, with reference to skin reactions to bamifylline. The demonstration of the feasibility of a drug-monitoring program in Italy where little tradition exists in the area, is the most important result of our study.
Immunohistochemical Evidence of Skin Immune System Involvement in Vulvar Lichen sclerosus et atrophicus
Authors: Carli P. , Cattaneo A. , Pimpinelli N. , Cozza A. , Bracco G. , Giannotti B.
Published: October 2009

Biopsies taken from vulvar lesions in 12 women affected by vulvar lichen sclerosus et atrophicus (LSA) have been processed for immunohistological study. Activated (HLA-Dr+) T cells, associated with CD1a+ accessory cells, were found in the dermis in all cases, with architectural patterns varying in relation to the histological phase (early, well developed, old) of the lesion. Interestingly, the number of epidermal CD1a+ Langerhans cells (LCs) was increased in all cases, without any correlation with the amount of the dermal infiltrate and with the histological phase of the lesions. In fact, also in old lesions the number of epidermal CD1a+ LCs was increased, and the sparse dermal lymphoid cells showed a persistent HLA-Dr antigen expression. These data, indicating the persistent activation of epidermal antigen-presenting cells and lymphoid cells in all the evolutive phases of vulvar LSA, suggest a possible involvement of the skin immune system in the pathogenesis of LSA.
Topical Retinoic Acid Does Not Alter the Vasoconstrictive Properties of Topical Corticosteroids in Humans
Authors: Schmied C. , Saurat J.-H.
Published: October 2009

Dermo-epidermal atrophy is one of the main side effects of long-term treatment with topical corticosteroids. Retinoic acid may prevent and even reverse these effects in animals. Extension of this concept to therapy in humans implies that several studies have been performed; among others, it has to be established that treatment with topical retinoic acid does not interfere with the anti-inflammatory action of topical corticosteroids. The present study on the cutaneous vasoconstriction test comprised two different double-blind approaches: (i) vasoconstriction tests with betamethasone dipropionate (Diprolene®) and clobetasone butyrate (Emovate®) were carried out on skin that had previously been treated for 10 days with retinoic acid 0.01 0.025 or 0.05% (or excipient); (ii) vasoconstriction tests with a combination of triamcinolone acetonide 0.1% and retinoic acid 0.025% were compared with triamcinolone acetonide 0.1% alone. Pretreatment for 10 days with retinoic acid did not alter the vasoconstriction induced by corticosteroids: no decrease or increase in the vasoconstriction score was observed, whether the skin had been previously treated with retinoic acid or with excipient. The vasoconstriction scores obtained with a combination of retinoic acid and triamcinolone acetonide were identical with those obtained with the steroid alone. This study indicates that retinoic acid does not inhibit the vasoconstriction induced by topical corticosteroids and suggests that the anti-inflammatory effect of the latter should be maintained in association with retinoic acid.
Raynaud’s Phenomenon with Digital Necrosis as the First Manifestation of Undifferentiated Connective Tissue Syndrome
Authors: Sabán J. , Rodríguez-García J.L. , País J.R. , Mellado N. , Muñoz E.
Published: October 2009

A patient with severe Raynaud’s phenomenon (RP) associated with the presence of antibodies against extractable nuclear antigen (ribonucleoprotein) in the context of undifferentiated connective tissue syndrome is presented. The rapid course of digital necrosis in her case resulted in the surgical amputation of 9 of her fingers. We conclude that massive digital necrosis accompanied by severe RP could constitute the first manifestation of a connective tissue disease.
Vulvitis granulomatosa and Anoperineitis granulomatosa
Authors: Hackel H. , Hartmann A.A. , Burg G.
Published: October 2009

We present the case of a 77-year-old female with a rare genital and anoperineal granulomatous cutaneous manifestation resembling cheilitis granulomatosa Miescher. The typical histological findings of epithelioid cell granulomas were localized in the vulva and anoperineal region; the latter manifestation has not yet been described. Based on our personal observations and a review of the literature, the clinical and histological features of vulvitis granulomatosa are described.
Dermatophytosis Mimicking Kaposi’s Sarcoma in Human Immunodeficiency Virus Disease
Authors: Crosby D.L. , Berger T.G. , Woosley J.T. , Resnick S.D.
Published: October 2009

Kaposi’s sarcoma (KS) is an important finding in patients infected with human immunodeficiency virus (HIV), with a distinctive spectrum of clinical presentations. Three cases of dermatophytosis in HIV-infected patients are presented which clinically mimic the appearance of KS. This new observation underscores the importance of histopathologic examination in the evaluation of skin lesions suspicious for the diagnosis of KS. The other clinical mimickers of KS are reviewed.
HLA-DR Antigen Expression on Peripheral T Cell Subsets in Pityriasis rosea and Herpes zoster
Authors: Yoshiike T. , Aikawa Y. , Wongwaisayawan H. , Ogawa H.
Published: October 2009

Using 2-color fluorescein-activated cytometric analysis, HLA-DR antigen expression on peripheral blood T cell subsets was studied in patients with herpes zoster (HZ) pityriasis rosea (PR) and psoriasis. In HZ and PR, HLA-DR was found to be significantly expressed on T cell surfaces (CD3+ cells) when compared to that of the normal control (HZ: p < 0.001, PR: p < 0.05). Among T cell subsets, such HLA-DR antigen was predominantly expressed on suppressor/cytotoxic cells (CD8+) in HZ (vs. normal control, p < O.01). However, in the case of PR, it was predominantly expressed on helper cells (CD4+; vs. control, p < 0.05). On the other hand, activated T cell antigen (CD25+) was not significantly expressed on T cells (CD3+) in either HZ or PR. In the T cell subsets, HLA-DR antigen expression returned to normal levels during the recovery phases of HZ and PR.
Study of the Primary Crest ‘Pavement’ Structure in Healthy Skin
Authors: Hatzis J.
Published: October 2009

The primary crest surface of the healthy skin may have a smooth appearance or form a ‘pavement’-like picture because of the presence of circular or polygonal sub units. In this study, the primary crest pavement structure was examined in different sites of healthy skin. The pavement structure was found in 70–100% of the adjacent areas of the palms and soles and also on the skin of the elbows and knees. This pavement formation is absent on the skin surface of other areas or may be found in a small percentage of 5–20%. It is possible that the pavement structure could represent modified dermatoglyphics in the hairy skin.
Topical Treatment with 13-Cis-Retinoic Acid Improves Darier’s Disease and Induces the Expression of a Unique Keratin Pattern
Authors: Steijlen P.M. , Happle R. , van Muijen G.N.P. , van de Kerkhof P.C.M.
Published: October 2009

A patient with Darier’s disease was treated topically with either 13-cis-retinoic acid 0.1% all-trans-retinoic acid 0.05% or their cream base only. Both 13-cis-retinoic acid and all-trans-retinoic acid were effective. However, all-trans-retinoic acid had to be discontinued because of irritation. By contrast, 13-cis-retinoic acid was well tolerated and resulted in a complete remission. Both retinoids caused a marked change in the expression of cytokeratins. The most remarkable observation was the expression of cytokeratins 4,13 and 19 at retinoid-treated areas. These cytokeratins are absent in adult normal or diseased epidermis and hence provide a cell-biological tool to substantiate a retinoid effect.
Solar Urticaria and Disturbed Metabolism of Porphyrins
Authors: Beljaards R.C. , Bruynzeel D.P.
Published: October 2009

We report on a case of solar urticaria with elevated protoporphyrin in the stool. No other evidence for an erythropoietic protoporphyria could be found.
Nodular Prurigo Associated with Hodgkin’s Disease
Authors: Fina L. , Grimalt R. , Berti E. , Caputo R.
Published: October 2009

We report a case of prurigo nodularis of Hyde as the presenting sign of Hodgkin’s disease in a 22-year-old girl. Though pruritus is a common symptom of Hodgkin’s disease, prurigo nodularis has rarely been reported as a Hodgkin’s symptom.
Cutaneous Manifestations of Takayasu Arteritis
Authors: Francès C. , Boisnic S. , Blétry O. , Dallot A. , Thomas D. , Kieffer E. , Godeau P.
Published: October 2009

The aim of this retrospective study is to delineate in Europe the frequency and type of cutaneous manifestations associated with Takayasu arteritis (TA). Eighty patients with TA were analyzed. Symptoms suggestive of Raynaud’s syndrome were noted in 11 patients (14%) and could be directly related to large vessel involvement. Other skin lesions were observed in 10 patients (12.5%). Five had acute tender erythematous nodules on the legs with a clinical diagnosis of erythema nodosum; 2 had subacute ulcerated nodules of the legs; 1 had pyoderma-gangrenosum-like ulcerations of the four limbs which resulted from the breakdown of subcutaneous nodules; 1 had lupus-like malar flush, and the last one had urticarial lesions with livedo reticularis. Skin samples were obtained from 4 patients. Three of them agreed that reiterated biopsies be done on recurrent lesions. A granulomatous vasculitis was observed in 2 cases involving hypodermal arterioles in one case and veins in the other. The other pathological findings were septal and lobular panniculitis which can be associated with granulomatous vasculitis. Different histological findings on reiterated biopsies were frequently found. The absence of any other etiology and chronological arguments suggested a relationship between these skin lesions and TA. Tuberculosis was probable in 1 case but apparently was not related to the skin lesions.
Solitary Lichenoid Benign Keratosis: A Clinicopathological Investigation and Comparison to Lichen Planus
Authors: Panizzon R. , Skaria A.
Published: October 2009

The dermatopathologist is sometimes confronted with a single lesion biopsy showing the histopathology of a lichen planus (LP) taken from a patient having no further clinical signs of LP. This entity represents the ‘solitary lichenoid benign keratosis’ (SLBK). We report about 202 patients with 204 SLBK lesions which were diagnosed between 1981 and 1987. The mean age of these patients was 59 years, 62.4% were females. Only 2 of the 202 patients showed multiple lesions. In 30.6% the SLBK was located in the face and neck area. In the order of frequency the following clinical diagnoses were made: basal cell carcinoma, senile keratosis, Bowen’s disease or seborrheic wart among others. We were able to distinguish three clinical types: (1) an erythematous type, (2) a papulokeratotic type and (3) a plaque-like type. The histopathological difference between SLBK and LP is primarily quantitative. The SLBK shows the following pronounced criteria: parakeratosis, vacuolized keratinocytes in the basal layer, a spongiotic epidermis in the center of the lesion with exocytosis of lymphoid cells, edema in the papillary layer, elastosis and plasma cells. Regularly one can find ‘lentigo-senilis’-like lesions at the edge of an SLBK. Immunohistopathology showed no characteristic features in SLBK. The pathogenesis of this distinct entity is not yet clear.
Granulocyte-Macrophage Colony-Stimulating Factor in Psoriasis
Authors: Takematsu H. , Tagami H.
Published: October 2009

Granulocyte-macrophage colony-stimulating factor (GM-CSF), a product of activated T lymphocytes, macrophages, endothelial cells, fibroblasts, and keratinocytes, is thought to play an important role in inflammatory reactions by ‘priming’ or enhancing the functions of neutrophils and macrophages. The aim of this study was to determine whether GM-CSF is detectable in psoriatic lesions. No GM-CSF was detected by ELISA in the suction blister fluids raised on normal, psoriatic uninvolved or involved skin. In contrast, although we could not detect GM-CSF in most of the extracts from noninflammatory stratum corneum, it was readily detected in most of the scale extracts from psoriasis and sterile pustular dermatoses, and its level was significantly higher than that from the controls. These results suggest that in psoriasis GM-CSF may amplify and modulate inflammatory reactions and activated T cells.
Fumaric Acid Therapy in Psoriasis: A Double-Blind Comparison between Fumaric Acid Compound Therapy and Monotherapy with Dimethylfumaric Acid Ester
Authors: Nieboer C. , de Hoop D. , Langendijk P.N.J. , van Loenen A.C. , Gubbels J.
Published: October 2009

In a 4-month double-blind study the effects of dimethylfumaric acid esters (DMFAE-EC) and DMFAE plus salts of monoethylfumaric acid esters (fumaric acid combination, FAC-EC) in enteric-coated tablets were compared in 22 respectively 23 patients with psoriasis. In both groups about 50% showed a considerable improvement, i.e. the initial score was more than halved. The therapeutic effects showed no significant differences in both groups with respect to the total psoriasis score or the different parameters. In the FAC-EC group the effects were obtained more rapidly. Most frequently observed side effects in both groups were flushings, stomachache and diarrhea. Due to these complaints 3 respectively 8 patients discontinued therapy. Eosinophilia, leukopenia and lymphopenia were the most frequently observed differences in lab tests. It was concluded that FAC-EC had no significantly better effect than monotherapy with DMFAE-EC. Moreover, enteric coating of the tablets did not prevent stomach complaints. Until more information has been obtained about the pharmacokinetics, the toxicity and optimal composition of the drug, the fumaric acid therapy in psoriasis should be seen as experimental.
Frictional Properties of Human Forearm and Vulvar Skin: Influence of Age and Correlation with Transepidermal Water Loss and Capacitance
Authors: Eisner Peter , Wilhelm Dorothea , Maibach Howard I.
Published: October 2009

The dynamic friction coefficient between skin and a Teflon probe and its correlation with age, body weight, height, transepidermal water loss and skin capacitance was studied in vulvar and forearm skin of 44 healthy female volunteers. The friction coefficient of vulvar skin was 0.66 ± 0.03 (mean ± SEM) compared to that of forearm skin of 0.48 ± 0.01. The difference was highly significant (p < 0.001). Multiple-regression analysis showed that the vulvar skin friction coefficient was significantly correlated with capacitance as an indicator of stratum corneum hydration (p < 0.01) but not with age weight height or transepidermal water loss. It is concluded that the high friction coefficient of vulvar skin may be due to the increased hydration of vulvar skin. Age-related differences seem to exist for transepidermal water loss and friction coefficient in forearm but not in vulvar skin.
Dystrophic Epidermolysis bullosa inversa: A Case Report
Authors: Altomare G.F. , Polenghi M. , Pigatto P.D. , Nazzaro V. , Piattoni F.
Published: October 2009

The inverse form of recessive dystrophic epidermolysis bullosa is a rare genodermatosis characterized by a smouldering course of integumental blistering with improvement of lesions in adulthood, preferential localizations of lesions in flexural areas, severe oral and esophageal mucosal involvement and nail dystrophy. We describe a 41-year-old patient showing all the typical features of this form of epidermolysis bullosa. Ultrastructural findings in specimens obtained from perilesional and healthy skin were similar to those usually observed in the Hallopeau-Siemens form of epidermolysis bullosa. The patient has been treated with phenytoin for a period of 9 months with considerable improvement of the skin manifestations.
In vivo Evaluation of Unbound Water Accumulation in Stratum Corneum
Authors: Van Neste D.
Published: October 2009

In a series of previous experiments, we showed that the inflammatory response associated with skin barrier function damage induced by sodium laurylsulfate (SLS) was correlated with the concentration of SLS and with the duration of application under occlusion of the surfactant. In this experiment, we measured accumulation of unbound water that occurred when occlusive contact was maintained during a short period of time between the skin and the probe head of an electrometric device. Accumulation of unbound water was expressed as area under the curve (sum of increments of skin capacitance during a 45-second period of time; AUCC). For comparative purposes, we also measured transepidermal water loss (TEWL). Both skin function parameters were established for each individual skin site before and 24 h after removal of SLS patches (10, 5, 1 and 0% control solution under occlusion for 48 h). After SLS insult, AUCC and TEWL were increased, and changes were related to SLS concentration (p < 0.0002). There was a linear correlation between AUCc and log TEWL (p < 0.0002). On normal skin before application of SLS both parameters were also correlated (p < 0.04). The regression line between AUCC and log TEWL of normal skin differed however from that observed on SLS-pretreated sites. This indicates that electrometric data are able to simultaneously characterize changes in skin hydration, a rather static parameter, and changes in the amount of unbound water accumulation (AUCC), a dynamic parameter which proved to reflect TEWL.
Longitudinal Study of Patients with Anticentromere Antibody
Authors: Takehara K. , Soma Y. , Igarashi A. , Kikuchi K. , Tamaki T. , Ishibashi Y.
Published: October 2009

As has previously been reported by many investigators the anticentromere antibody is considered to be a useful serologic marker for the CREST (calcinosis, Raynaud’s phenomenon, esophageal involvement, sclerodactyly and telangiectasia) variant of systemic sclerosis. However, this antibody also appears in other conditions. By screening antinuclear antibody tests using HEp-2 cells as substrate, 39 patients were shown to have the anticentromere antibody. These patients were divided into 4 groups: group 1 = 17 patients with systemic sclerosis; group 2 = 9 patients with Raynaud’s phenomenon alone; group 3 = 7 patients with other connective-tissue diseases, and group 4 = 6 patients with conditions other than those present in groups 1–3. Follow-up over years revealed that some patients suffering solely from Raynaud’s phenomenon (group 2) developed the symptoms of systemic sclerosis. In contrast, of the patients who did not have Raynaud’s phenomenon (group 4), none developed any symptom suggesting systemic sclerosis. We suggest that the simultaneous presence of Raynaud’s phenomenon and the anticentromere antibody predicts the occurrence of systemic sclerosis. In contrast, the presence of the anticentromere antibody alone cannot necessarily be used to predict the development of systemic sclerosis.
Decreased Natural Killer Cell Function in Patients with Classical Kaposi’s Sarcoma
Authors: Weltfriend S. , Friedman-Birnbaum R. , Pollack S.
Published: October 2009

Natural killer (NK) cell activity of peripheral blood lymphocytes was evaluated in a group of 13 patients with classical Kaposi’s sarcoma (KS). All patients had a normal T4/T8 ratio, and the disease was confined to the skin of the lower extremities. A group of 5 healthy subjects served as controls. NK cell function was significantly decreased in patients as compared to controls. Our result is similar to that found in another group of patients with AIDS-related KS with lymphadenopathy and an abnormal T4/T8 ratio. This suggests that decreased NK cell function is not a result of a progressive process and might be directly involved in the development of KS.
A Case of Sweet’s Syndrome with Early Gastric Cancer
Authors: Uchida H. , Ikari Y. , Hashizume S. , Tokuhashi I. , Tadokoro M.
Published: October 2009

The case of a 49-year-old man with Sweet’s syndrome (acute febrile neutrophilic dermatosis) is described, who had coincidently gastric cancer. The therapeutic effectiveness of colchicine is also presented as one treatment for Sweet’s syndrome, because rapid regression of the lesions was noticed.
Extremely Extended Fournier’s Gangrene
Authors: Saijo S. , Kuramoto Y. , Yoshinari M. , Tagami H.
Published: October 2009

We describe a 19-year-old Japanese man with severe extensive necrotizing fasciitis that started as Fournier’s gangrene to involve the external genitalia, thigh and lower abdomen. High creatine phosphokinase, transient immunosuppression (reduced serum IgG level and negative tuberculin skin test reaction) and disseminated intravascular coagulation occurred during the necrotizing fasciitis.