Impact of VDR and RXR expression in non-melanoma skin cancer pathogenesis.

1,25(OH)2 D3 , the active form of vitamin D, has been extensively studied for its putative protective activities against tumors. It does biological work by connecting to a nuclear receptor called VDR, which heterodimerizes itself to another nuclear receptor, RXR. The study observed differences in VDR and RXR expression in non-melanoma skin cancer a actinic keratosis and compared it with normal skin. We performed VDR and RXR immunohistochemistry of 76 controls (normal skin), 49 actinic keratosis, 99 basal cell carcinomas and 96 squamous cell carcinomas from formalin-fixed paraffin-embedded, resulting from surgical procedures. There was a clear pattern in the control group (p < 0.001), with the positivity of both receptors, VDR and RXR. Actinic keratosis differed from the basal cell carcinoma and control groups concerning RXR expression (p < 0.001). SCC was negative for both receptors, differing in all groups (p < 0.001). The site of positivity (nuclear, cytoplasmatic or both) of VDR differed between all groups (p < 0.001). To date, our series is the largest of VDR and RXR immunohistochemistry concerning non-melanoma skin cancer. Our findings reinforce the need to understand the pathways involving VDR and RXR to direct therapies and prevention manoeuvres.

Indeterminate thyroid cytology: detecting malignancy using analysis of nuclear images.

BACKGROUND: Thyroid nodules diagnosed as 'atypia of undetermined significance/follicular lesion of undetermined significance' (AUS/FLUS) or 'follicular neoplasm/suspected follicular neoplasm' (FN/SFN), according to Bethesda's classification, represent a challenge in clinical practice. Computerized analysis of nuclear images (CANI) could be a useful tool for these cases. Our aim was to evaluate the ability of CANI to correctly classify AUS/FLUS and FN/SFN thyroid nodules for malignancy. METHODS: We studied 101 nodules cytologically classified as AUS/FLUS (n = 68) or FN/SFN (n = 33) from 97 thyroidectomy patients. Slides with cytological material were submitted for manual selection and analysis of the follicular cell nuclei for morphometric and texture parameters using ImageJ software. The histologically benign and malignant lesions were compared for such parameters which were then evaluated for the capacity to predict malignancy using the classification and regression trees gini model. The intraclass coefficient of correlation was used to evaluate method reproducibility. RESULTS: In AUS/FLUS nodule analysis, the benign and malignant nodules differed for entropy (P < 0.05), while the FN/SFN nodules differed for fractal analysis, coefficient of variation (CV) of roughness, and CV-entropy (P < 0.05). Considering the AUS/FLUS and FN/SFN nodules separately, it correctly classified 90.0 and 100.0% malignant nodules, with a correct global classification of 94.1 and 97%, respectively. We observed that reproducibility was substantially or nearly complete (0.61-0.93) in 10 of the 12 nuclear parameters evaluated. CONCLUSION: CANI demonstrated a high capacity for correctly classifying AUS/FLUS and FN/SFN thyroid nodules for malignancy. This could be a useful method to help increase diagnostic accuracy in the indeterminate thyroid cytology.

Cellulose biomembrane versus collagenase dressing for the treatment of chronic venous ulcers: a randomized, controlled clinical trial.

Cellulose biomembranes may be used for difficult-to-treat ulcers. To assess the efficacy and safety of cellulose biomembranes compared to a collagenase dressing for the treatment of chronic venous ulcers. A randomized, controlled clinical trial was performed using two groups: one treated with collagenase dressing and the other with cellulose biomembrane over a 90-day (T90) period. Both groups received compression therapy. The primary outcome was reduction in ulcer area at T90. Secondary outcomes were healing status, decrease in devitalized tissue and exudate, vascular fraction, change in quality of life, and safety. We randomized 46 participants with 73 venous ulcers (21 with 36 ulcers in the collagenase group and 25 with 37 ulcers in the biomembrane group). A decrease in ulcer area occurred at T90 in both groups, but the difference was not significant. Complete healing before T90 occurred for seven ulcers in the collagenase group and 12 ulcers in the biomembrane group, without significant difference. However, the biomembrane promoted increased precocious healing (p = 0.02). Improved bed vitality and quality of life was observed as a function of time (p < 0.01), but this was not significant between the groups. Immunohistochemical analysis of CD34 showed an increase in vascular fraction in both groups (p < 0.01), with a higher level in the biomembrane group (p < 0.05). No adverse events were considered related to the products. Cellulose biomembranes, in combination with compressive therapy, are effective and safe for the treatment of venous ulcers and provide results similar to those with collagenase treatment.

Follicular thyroid lesions: is there a discriminatory potential in the computerized nuclear analysis?

BACKGROUND: Computerized image analysis seems to represent a promising diagnostic possibility for thyroid tumors. Our aim was to evaluate the discriminatory diagnostic efficiency of computerized image analysis of cell nuclei from histological materials of follicular tumors. METHODS: We studied paraffin-embedded materials from 42 follicular adenomas (FA), 47 follicular variants of papillary carcinomas (FVPC) and 20 follicular carcinomas (FC) by the software ImageJ. Based on the nuclear morphometry and chromatin texture, the samples were classified as FA, FC or FVPC using the Classification and Regression Trees method. RESULTS: We observed high diagnostic sensitivity and specificity rates (FVPC: 89.4% and 100%; FC: 95.0% and 92.1%; FA: 90.5 and 95.5%, respectively). When the tumors were compared by pairs (FC vs FA, FVPC vs FA), 100% of the cases were classified correctly. CONCLUSION: The computerized image analysis of nuclear features showed to be a useful diagnostic support tool for the histological differentiation between follicular adenomas, follicular variants of papillary carcinomas and follicular carcinomas.

Cohesive silicone gel implants with smooth, textured or polyurethane-coated surface to restore volume in eviscerated sockets.

The purpose of this article is to evaluate the three different surface coating on cohesive silicone gel implants in eviscerated rabbit eye sockets. Forty-five albino rabbits underwent right eye evisceration and received hemisphere-shaped cohesive silicone gel implants with smooth (Group 1), textured (Group 2), or polyurethane-coated surface (Group 3) in the socket. The animals were euthanized at 7, 30, and 90 days postoperatively. Computed tomography of the orbits was performed prior to euthanasia. Subsequently, the orbital contents were removed and underwent histologic and morphometric examination. Data were statistically analyzed. There were no adverse effects throughout the study. The majority of implants in the Group 1 exhibited 180° rotation. The Group 3 experienced an intense inflammatory reaction around the implant and implant deformation probably due to pseudocapsule contraction. Cohesive silicone gel implants had good integration into the scleral socket. Optimal results were obtained with cohesive silicone gel textured implants (Group 2). Smooth implants (Group 1) rotated significantly, whereas polyurethane (Group 3) coated implants precipitated an intense inflammatory reaction and were deformed postoperatively.

Three Adult Cases of Orbital Hidrocystoma Presenting with Blepharoptosis.

PURPOSE: To report adult cases of superior orbital apocrine hidrocystoma. METHODS: Retrospective case series of three patients with superior orbital apocrine hidrocystoma and blepharoptosis with review of the clinical aspects of each of the cases. RESULTS: All three cases presented with blepharoptosis. Two of the cases had occult hidrocystoma, and one was visibly subcutaneous at presentation. CONCLUSIONS: Although rare and more common along the eyelid margin, apocrine hidrocystomas may occur in the orbit leading to secondary blepharoptosis and should be included within the differential diagnosis of orbital cysts. Physicians should therefore be aware of this possibility.

Síndrome de Gorlin

Contexto: A síndrome de Gorlin ou síndrome do nevo basocelular é desordem autossômica dominante causada por mutação no gene Patched, que faz parte da via de sinalização Hedgehog.Descrição do caso: O paciente descrito tem 67 anos, apresenta múltiplos carcinomas basocelulares com início desde os 17 anos, além de cistos odontogênicos, escoliose dorsal, pits palmoplantares, hipertelorismo e macrocefalia.Discussão: A síndrome é manifestada pela tríade de múltiplos carcinomas basocelulares, tumores odontogênicos ceratocísticos e anomalias esqueléticas. Outras alterações orgânicas podem estar presentes, sendo o meduloblastoma, tumor maligno da fossa posterior, causa potencial de morte.Conclusão: O diagnóstico precoce é importante para que terapias menos agressivas sejam realizadas. O tratamento envolve equipe multidisciplinar e o aconselhamento genético é mandatório.

Primary cutaneous cryptococcosis in Brazil: report of 11 cases in immunocompetent and immunosuppressed patients.

BACKGROUND: Primary cutaneous cryptococcosis is an uncommon infectious disease caused by Cryptococcus neoformans or Cryptococcus gattii affecting immunosuppressed as well as immunocompetent patients. It is often misdiagnosed as it may mimic other cutaneous diseases. MATERIALS AND METHODS: We report a series of cases diagnosed from 2005 to 2010 in two general hospitals. The diagnosis in all patients was made on the basis of histopathology and culture. Phenoloxidase and canavanine-glycine-bromothymol blue tests were used in order to identify the Cryptococcus species. Systematic investigation ruled out the systemic involvement in every case. RESULTS: Eleven patients, 81.8% male, were diagnosed during this study. The immunosuppression status was identified in 54.5% of patients, and all of them were under corticosteroid therapy due to a variable set of diseases. All patients presented with circumscribed lesions on their upper limbs. Most lesions showed an infiltrative or tumoral aspect with up to 40 cm diameter. Fluconazole, up to 400 mg/daily, was the main therapeutic regimen and proved to be efficient. CONCLUSIONS: Primary cutaneous cryptococcosis has been diagnosed in both immunosuppressed and immunocompetent patients. Its peculiar clinical aspect could facilitate early diagnosis. Culture and biochemical tests should be performed in order to define the species involved.

Clinical and histological effects of the intrathecal administration of methylprednisolone in dogs.

BACKGROUND: Methylprednisolone is one of the most commonly used steroids for management of chronic back pain via epidural injection. Its inadvertent injection into the intrathecal space is associated with complications such as adhesive arachnoiditis. OBJECTIVE: The present study aimed to assess the clinical and histological changes associated with the injection of methylprednisolone into the intrathecal space of dogs. STUDY DESIGN: A randomized, double blind, controlled animal trial. METHODS: After approval by the animal research ethics committee, 14 dogs were studied in a randomized double blind controlled trial. They were assigned to one of 2 groups: Group I received 1 mL of 0.9% normal saline; Group II received 1 mL (1.15mg/kg) of methylprednisolone into the intrathecal space. Animals were clinically evaluated for 21 days, and then sacrificed. The lumbar and sacral portions of their spinal cords were removed for histological examination. RESULTS: In Group I, there were no clinical or histological changes. All animals in Group II showed no clinical changes but all exhibited histological changes in the spinal cord. The main histological changes consisted of meningeal thickening and lymphocytic infiltrates in the blood vessels. In 3 animals, adhesion of pia, arachnoid, and dura matter was noted and the nerve roots were surrounded by fibrosis. In one animal, necrosis of the spinal cord was evident. LIMITATIONS: The limitations of the present study include: small sample of animals (n=14), relative short clinical follow-up (21 days), and use of a commercially available drug solution, which is not preservative free. CONCLUSION: The present study demonstrated that the intrathecal administration of commercially available methylprednisolone was responsible for causing histological changes in the spinal cord and meninges of the animals studied.

Paracoccidioidomycosis: an unusual presentation in a young girl disclosing an unnoted HIV-infection.

The association of paracoccidioidomycosis with AIDS is apparently less frequent than expected. The authors present an unusual case of paracoccidioidomycosis in a 13-year-old female student which was later found to be the first opportunistic infection in the course of the patient's HIV-infection. The clinical presentation followed an accidental incised wound on the palmar region initially described as a 'sporotrichotic-chancre'. After good response under sulfamethoxazole-trimethoprin, the patient relapsed and presented an associated oral candidiasis. HIV-infection was documented and additional investigation showed CD4(+) T-cells=22/mm(3), CD8(+)=280 cell/mm(3) and viral load=4,043 log. This case report presents an uncommon dermatological-clinical picture in the youngest patient in which such association has been reported to date.

Oral stomatitis induced by endogenous progesterone: Case report.

Oral stomatitis induced by endogenous progesterone is a rare clinical condition which may be associated with cutaneous involvement. That is probably due to the peak of progesterone production during the luteal phase of the menstrual cycle. In the present case report, a 21-year-old patient displayed recurrent ulcerative lesions located on the buccal mucosa or the upper lip, on a monthly basis since the age of 15. Such lesions would always manifest themselves on the second day until the end of the menstrual cycle.

The neuraxial effects of intraspinal amitriptyline at low concentrations.

BACKGROUND: As a result of amitriptyline's vast array of actions, it could potentially be used as an intraspinal adjuvant in neuraxial anesthesia and/or in the treatment of refractory neuropathic pain. None of the previous studies examining the safety profile of intraspinal single doses of amitriptyline found signs of toxicity at concentrations below 15.4 mM/L (0.5%) and the current hypothesis regarding the pathophysiology of amitriptyline toxicity suggests it might be safe at low concentrations while still having relevant clinical effects. Hence, we conducted this study to assess the clinical and histological toxicity of intraspinal amitriptyline at the lowest dosages previously known to be effective. METHODS: Twenty-one dogs were randomized to receive a 1-mL single intraspinal dose of one of the three solutions: saline (0.9%), amitriptyline (0.15%), or amitriptyline (0.3%). The dogs were evaluated clinically 1 h after awakening from anesthesia and 21 days later. At 21 days, all animals were killed, and histological sections of the spinal cord and surrounding meninges were retrieved for analysis. RESULTS: All dogs recovered motor function, anal sphincter tone and sensibility. With the exception of one dog in the 0.15% amitriptyline group, all animals in both amitriptyline groups had marked adhesive arachnoiditis, which was absent in the control group. No evidence of direct neural damage was found on histological sections stained by glial fibrillary acidic protein technique in any of the study animals. CONCLUSION: The intraspinal administration of amitriptyline to dogs even in low concentrations is strongly associated with the development of intense meningeal adhesive arachnoiditis and is not safe even at low concentrations for which there was no previous evidence of toxicity.

Prevalence of precancerous skin lesions and non-melanoma skin cancer in Japanese-Brazilians in Bauru, São Paulo State, Brazil.

Precancerous lesions and skin cancer are infrequent in Asians, and have received little documentation in the literature. Brazil has the world's largest contingent of Japanese immigrants and their descendants, and 70% live in the State of São Paulo. The prevalence of such skin lesions in Japanese-Brazilians is unknown. This study aimed to assess the prevalence of actinic keratoses and non-melanoma skin cancer in first and second-generation Japanese-Brazilians over 30 years of age, without miscegenation, living in the city of Bauru, São Paulo State, in 2006. Of the 567 Japanese-Brazilians that underwent dermatological examination, actinic keratosis was diagnosed in 76, with a mean age of 68.9 years, and a single case of basal cell carcinoma was detected in a 39-year-old female patient. In Japan, prevalence of actinic keratosis varies from 0.76% to 5%, and the incidence of non-melanoma skin cancer is 1.2 to 5.4/100 thousand. Japanese-Brazilians from Bauru showed a 13.4% prevalence of actinic keratoses and earlier age at onset. Proximity to the Equator and a history of farming contribute to these higher rates. Presence of solar melanosis was associated with a 1.9-fold risk of developing actinic keratosis.