Pentoxifylline--efficient in the treatment of venous ulcers in the absence of compression?

The aim of the study was to test the efficacy and tolerability of pentoxifylline on the healing of venous ulcers in the absence of standard limb compression. The study used a prospective randomized, open, controlled, comparative, parallel group design. The study included 80 eligible patients with confirmed venous ulcers (with clinical and photoplethysmography findings). The patients received either pentoxifylline 1200 mg per day (3 x 400 mg) orally in addition of local therapy, or the same local therapy alone. The main outcome measures were complete healing of ulcers, change in the ulcer area over the six-month observation period, and tolerability of the drug. The results showed that complete healing occurred in 23 (57.5%) patients receiving pentoxifylline and 11 (27.5%) patients without pentoxifylline (log rank test =2.49, p=0.013). Unwanted effects of pentoxifylline occurred in 11/40 (27.5%) patients but were mild. Pentoxifylline is concluded to be efficacious in healing of venous ulcers in patients unable to tolerate compression therapy.     

Success in the use of oral propranolol in the treatment of infantile hemangioma in nasal tip – Report of two cases

Infantile hemangioma is the most common pediatric vascular tumor, with the following risk factors: low birth weight, prematurity, white skin, female gender, multiparity and advanced maternal age. The use of oral and topical beta-blockers, although recent, has emerged as the first line of treatment, with superior safety and efficacy to previously used therapies, such as corticosteroids and surgeries. This report describes two cases of nasal tip infantile hemangioma, treated with oral propranolol. Both presented excellent therapeutic responses.     

Delay in the diagnosis of leprosy in the Metropolitan Region of Vitória, Brazil

This paper reports on the time between the onset of the first lesion and diagnosis, defined as delay, and is based on results obtained by interviewers from a survey carried out amongst 450 leprosy patients in a leprosy endemic area in the Metropolitan Region of Vitória (MRV), state of Espirito Santo, Brazil. The mean age at diagnosis in all cases was 41.47 years and the median was 42.5 years. The mean age at diagnosis in MB (42.9 years) was greater than in PB (38.5 years). The mean of the delay in all cases was 25.25 months, median 12 months and range 0-360 months. The mean of the delay in MB (27.2 months) was greater than in PB (21.3 months). The results of this study suggest that although the delay in leprosy diagnosis in this region of Brazil was not too long when it was compared with other studies in endemic countries, it is still a problem: 65.4% of patients were diagnosed after a delay of 6 months. The Leprosy Control Programme in this state needs more effective health education in order to reduce the current period of delay before diagnosis.     

Relevance of the low-affinity type of the Fcγ-receptor IIIa-polymorphism in bullous pemphigoid

Bullous pemphigoid (BP) is mediated by autoantibodies directed against molecules of the basement membrane zone. The biological function of antibodies involves binding to Fc-receptors expressed on human leucocytes. Recent studies suggested that a functional single-nucleotide-polymorphism of the Fcγ-receptor IIIa (FcγRIIIa = CD16) at nucleotide 559 might predispose to the development of antibody-associated autoimmune disorders. This allelic difference affects the level of receptor affinity by predicting either a phenylalanine (F 158, low-affinity) or valine (V 158, high-affinity). We investigated if inherited frequencies of the high- and low-affinity FcγRIIIa polymorphism differed between patients with BP and healthy subjects. Genomic DNA from peripheral white blood cells was analyzed regarding FcγRIIIa polymorphism at nucleotide 559 by an established polymerase chain reaction. Sixty-seven Caucasian patients with BP and 88 healthy controls were included into the study. There was no significant difference in the distribution of the homozygous high-affinity FcγRIIIa-allotype (V/V) between BP-patients (14.9%) and healthy control subjects (20.5%). In contrast, 58.2% of the BP-patients were homozygous for the low-affinity FcγRIIIa-allotype (F/F), compared to 28.4% of the healthy controls (P = 0.001, OR 3.51). The frequencies of the polymorphism in the control group were in range of formerly published frequencies for healthy Caucasian subjects. Thus, the FcγRIIIa (158 F/V) polymorphism may modulate the susceptibility to acquire BP.     

Association of TGFβ1 and SMAD4 variants in the etiology of keloid scar in the Malay population

Keloid is a complex condition with environmental and genetic risk-contributing factors. Two candidate genes, TGFβ1 and SMAD4, located in the same signaling pathway are highly expressed in the keloid fibroblast cells. In a case-control design, TGFβ1 haplotypes showed association with the risk of keloid in the present study. The CC haplotype, composed of both c.29C>T and -509T>C variants, was observed more frequently among cases (Corrected p?=?0.037, OR?=?2.07, 95?% CI?=?0.87-4.93), showing a 4.5-fold increased risk for keloid. The AG genotype of the SMAD4 c.5131A>G variant showed a trend of significance (p?=?0.0573, OR?=?1.75, 95?% CI?=?0.99-3.13). Taken together, either of these variants is most probably causative at the expression level or is in linkage disequilibrium with other causative variants in a complex pattern together with the environmental factors that contribute to the condition. To the best of our knowledge, there is only one documented report on a relationship between TGFβ1 and keloid with no association within the Caucasian population, while there have not been any reports for SMAD4. Therefore, the present study is likely the first research showing a significant association between TGFβ1 variants and keloids in the Malay population.     

Alteration of the β-catenin pathway in spiradenoma

Background: Although skin carcinogenesis has been widely investigated, only limited information is available for epidermal tumors, while even less is known about other skin structures. Alterations in the β‐catenin pathway have been reported in several epidermal tumors, while little is known about in adnexal tumors. This study was performed to assess alterations in the β‐catenin pathway associated with adnexal tumors, and to investigate the mechanisms underlying these alterations. Methods: β‐Catenin expression in 48 adnexal tumors (trichoepithelioma, trichofolliculoma, pilomatricoma, syringoma, eccrine poroma, spiradenoma, sebaceous hyperplasia and nevus sebaceus) was assessed using immunohistochemistry. The tumors showing intense nuclear reactivity for β‐catenin were further evaluated by immunohistochemistry for β‐catenin degradation complex such as adenomatosis polyposis coli (APC), Axin and glycogen synthase kinase 3β (GSK‐3β). Results: Intense nuclear immunoreactivity for β‐catenin was observed in pilomatricoma and spiradenoma. Among 12 eccrine spiradenomas, APC was downregulated in 2 (16.7%) cases, and Axin and GSK‐3β were downregulated in 11 (91.7%) and 10 (83.3%) cases, respectively. Conclusions: This is the first reported analysis of the role of alterations in the β‐catenin pathway in spiradenoma. We suggest that downregulation of Axin and GSK‐3β in the β‐catenin pathway may be an important signaling alteration in the development of spiradenoma. Im M, Kim DH, Park JS, Chung H, Lee Y, Kim CD, Seo YH, Lee JH. Alteration of the β‐catenin pathway in spiradenoma.     

Immunocytochemical localization of lysozyme and β-defensin in the apocrine glands of the equine scrotum

The present study revealed in detail the subcellular localization of lysozyme and β-defensin in the apocrine glands of the equine scrotal skin, a specific body region. The apocrine glandular cells were equipped with a varying number of secretory granules, a well-developed Golgi apparatus and abundant cisternae of the rough endoplasmic reticulum within their cytoplasm. In these cells, reactive gold particles representing lysozyme were detectable in the secretory granules as well as the Golgi apparatus and elements of the rough endoplasmic reticulum. Additionally, the antimicrobial peptide group of β-defensin was also localized in the above-mentioned ultrastructures of the secretory cells. The presence and secretion of such substances that may serve as a non-specific defense against microorganisms are suggestive of the protective effect of the secretory production elaborated by the apocrine glands.     

Novel mutations in the BHD gene and absence of loss of heterozygosity in fibrofolliculomas of Birt-Hogg-Dubé patients

Birt-Hogg-Dubé (BHD) syndrome is an autosomal-dominantly inherited cancer syndrome characterized by fibrofolliculomas, lung cysts leading to pneumothorax, and chromophobic/oncocytic renal cell carcinoma. The disease is caused by heterozygous mutations in the BHD gene encoding folliculin and all mutations reported putatively lead to protein truncation. Although the function of folliculin is unknown, it is thought to be a tumor suppressor, with loss of heterozygosity (LOH) initiating tumor formation. Here, we report on four novel BHD gene mutations, including two splice-site mutations, in patients presenting with skin lesions only. We further show that LOH cannot be detected in fibrofolliculomas from three patients, suggesting that for the manifestation of cutaneous tumors in BHD syndrome haplo-insufficiency of folliculin is sufficient to initiate uncontrolled growth. Renal microscopic oncocytosis in BHD is considered as a precursor to malignant kidney tumors and may likewise be the result of haplo-insufficiency, with somatic second-hit mutations or LOH giving rise to malignancy later in life.     

How useful is the Mantoux test in the diagnosis of doubtful cases of cutaneous tuberculosis?

Background Diagnostic tests are critical to management when the clinical picture is unclear. We analyzed the records of patients in whom the initial diagnosis of cutaneous tuberculosis was doubtful to evaluate the utility of the Mantoux test in this setting. Materials and methods Of 375 patients with cutaneous tuberculosis seen in our department, the initial clinical diagnosis was doubtful in 90 patients. A Mantoux test was performed with 5 TU of purified protein derivative using standard techniques and read after two days. Patients also underwent skin biopsy and other laboratory tests and received treatment with antitubercular drugs. Patients who had case notes recording satisfactory improvement following antitubercular therapy were classified as having cutaneous tuberculosis; those with evidence of another diagnosis based on the laboratory tests and response to therapy were categorized as non‐tuberculosis cases. Patients with inadequate evidence for a diagnosis of either cutaneous tuberculosis or another disorder were classified as unresolved diagnosis. Results Readings were available in 79 patients: 39 were categorized as tuberculosis; 16 as non‐tuberculosis; while a final diagnosis could not be reached in 24 cases. Readings ranged from 0 to 40 mm in the cases and from 0 to 30 mm in non‐cases. The area under the receiver‐operating characteristic curve was 0.66 (95% CI 0.55–0.81). Using a cut‐off of 10 mm, the sensitivity and specificity of the tests were 58.97 and 62.50%, respectively. Conclusion The Mantoux test is of low accuracy in the diagnosis of doubtful cases of cutaneous tuberculosis.     

Molecular diagnosis of leishmaniosis in the Paraná state of southern Brazil

The objective of the present study was to establish a polymerase chain reaction (PCR) technique for the diagnosis of cutaneous and mucocutaneous leishmaniosis from autochthonous cases in the state of Paraná in southern Brazil as well as imported cases. We sought to determine its utility and accuracy compared with smears and present culture methods. To standardize PCR samples, skin and mucosal punch biopsies from human lesions were performed on patients living in different regions of the Paraná state (76 cases) and other endemic areas of Brazil and Argentina (7 cases). For PCR standardization, two pairs of primers (MP1L/MP3H and B1/B2) were utilized for amplification of the conserved sequences in the minicircle of kinetoplast DNA (kDNA) for the Leishmania braziliensis complex. Two other primer pairs (b1/b2 and a1/a2) were species-specific for L. (V.) braziliensis and L. (V.) amazonensis, respectively. After differential diagnosis, eight patients had clinical diagnosis of the cutaneous ulcer changed to others pathologies such as syphilis, baso-cellular carcinoma, varicose ulcer, ecthyma and paracoccidioidomycosis. Of the 75 patients with cutaneous (CL) and mucocutaneous (MCL) lesions who provided samples, 47 (46 CL + 1 MCL) were diagnosed with leishmaniosis by smear and 57 (52 LC + 5 MCL) were diagnosed by culture methods. In contrast, our PCR technique presented higher accuracy when compared to the direct examination and culture of parasites. PCR is applicable both for CL where all 61 lesions were diagnosed, and MCL where 12 of 14 lesions were diagnosed. This molecular biology technique is also a faster and more specific diagnostic method compared with present parasitological procedures.