The usefulness of acetic acid wash and chemiluminescent illumination (Vizilite) in the visualization of oral mucosal white lesions

A diligent and careful examination of the mouth and oral structures has been historically deficient in revealing premalignant and malignant oral lesions. Conventional screening practice for oral neoplastic lesions involves visual scrutiny of the oral tissues with the naked eye under projected incandescent or halogen illumination. Visualization is the principal strategy used to find patients with lesions at risk for malignant transformation; hence, any procedure which highlights neoplastic lesions should aid the clinician. This pilot study examined the usefulness of acetic acid wash and chemiluminescent light (Vizilite) in enhancing visualization of oral mucosal white lesions, and its ability to highlight malignant and potentially malignant lesions. Fifty five patients referred for assessment of a white lesion, were prospectively screened with Vizilite, and an incisional biopsy performed for a definitive diagnosis. The age, sex, and smoking status of all patients were recorded, and all lesions were photographed. The visibility, location, size, border, and presence of satellite lesions, were also recorded. The Vizilite tool enhanced intraoral visualization of 26 white lesions, but it could not distinguish between epithelial hyperplasia, dysplasia, or carcinoma. Indeed, all lesions appeared ‘‘aceto-white’’, regardless of the definitive diagnosis. On one occasion, Vizilite aided in the identification of a satellite lesion that was not observed by routine visual inspection. Vizilite appears to be a useful visualization tool, but it does not aid in the identification of malignant and potentially malignant lesions of the oral mucosa.

High Frequency of Lamivudine Resistance Mutations in Brazilian Patients Co-Infected With HIV and Hepatitis B

This study analyzed the genotype distribution and frequency of lamivudine (LAM) and tenofovir (TDF) resistance mutations in a group of patients co-infected with HIV and hepatitis B virus (HBV). A cross-sectional study of 847 patients with HIV was conducted. Patients provided blood samples for HBsAg detection. The load of HBV was determined using an ""in-house"" real-time polymerase chain reaction. HBV genotypes/subgenotypes, antiviral resistance, basal core promoter (BCP), and precore mutations were detected by DNA sequencing. Twenty-eight patients with co-infection were identified. The distribution of HBV genotypes among these patients was A (n = 9; 50%), D (n = 4; 22.2%), G (n = 3; 16.7%), and F (n = 2; 11.1%). Eighteen patients were treated with LAM and six patients were treated with LAM plus TDF. The length of exposure to LAM and TDF varied from 4 to 216 months. LAM resistance substitutions (rtL180M + rtM204V) were detected in 10 (50%) of the 20 patients with viremia. This pattern and an accompanying rtV173L mutation was found in four patients. Three patients with the triple polymerase substitution pattern (rtV173L+ rtL180M + rtM204V) had associated changes in the envelope gene (sE164D + sl195M). Mutations in the BCP region (A1762T, G1764A) and in the precore region (G1896A, G1899A) were also found. No putative TDF resistance substitution was detected. The data suggest that prolonged LAM use is associated with the emergence of particular changes in the HBV genome, including substitutions that may elicit a vaccine escape phenotype. No putative TDF resistance change was detected after prolonged use of TDF. J. Med. Virol. 82:1481-1488, 2010. (C) 2010 Wiley-Liss, Inc.

Oral-Nasal-Ocular Cleft: The Greatest Challenge Among the Rare Clefts

Introduction: Number 3 cleft or oral-nasal-ocular cleft is a well-known entity that was described by Morian over a century ago. This malformation is a paranasal-medial orbitomaxillary cleft running across the lacrimal segment of the lower eyelid and over the lacrimal groove. The Tessier number 3 naso-ocular cleft represents one of the most difficult and challenging malformations to correct for the reconstructive surgeon. We have conducted a retrospective analysis of our series consisting of 21 cases. Objective: The objective was to review the functional outcome and aesthetic results of the different techniques applied for each case. Materials and Methods: From 1997 to 2007, 21 patients with a Tessier number 3 cleft were treated in our craniofacial units. The clinical findings, tomographic studies, and surgical procedures were reviewed and analyzed. We have discussed our protocol of the treatment. Results: We have treated facial malformation in 2 craniofacial centers. Fourteen patients were evaluated in the first year of their life, with an average age at presentation of 3 years. Twelve patients were female, and 9 were male; 6 patients had amniotic bands in limbs, 5 patients had an association with Tessier number 11 cleft, 3 patients with number 9 cleft, and 1 with number 7 cleft. Related to cleft lip, 10 patients had bilateral cleft lip, and 8 patients had unilateral cleft lip. Three patients did not have any involvement of the upper lip. The alar base was deviated upward in 19 patients, 11 cases had severe anatomic alteration with the lateral border of the ala above the medial canthus, and 8 cases had a mild dislocation. Nine cases of lacrimal duct obstruction and 8 cases of lacrimal duct extrophy were identified. Twelve patients had a lower eyelid coloboma of varying grades, and there were 2 cases of microblepharia. Aiming the soft tissue reconstruction, eyelid, nose, and upper lip were evaluated regarding their position, absence of tissue, and position of medial canthus and ala. Twelve of our patients underwent correction in the same moment, their medial canthus rotated upward and the ala downward, using the contralateral side as the reference. The lip was treated using a Millard-like technique. Neo-conjunctivorhinostomy was performed in the same moment in 2 patients or later in 1 case. Four patients had plagiocephaly due to the cranial involvement, and they were submitted to cranioplasty. Three had neurosurgical approach and advancement of the frontal bandeau. One adult patient received an acrylic plate to reshape the frontal area. Conclusions: Tessier number 3 cleft is one of the most difficult and challenging malformations to correct for the reconstructive surgeon. Besides the difficulties of its treatment, patients with Tessier number 3 cleft may achieve good results when the team has good skills.

Anatomic Landmarks for Localization of the Spinal Accessory Nerve

This anatomical study examines the anatomic topography and landmarks for localization of the spinal accessory nerve (SAN) during surgical dissections in 40 fresh human cadavers (2 females and 38 males; ages from 22 to 89 years with a mean of 60 years). In the submandibular region, the SAN was found anteriorly to the transverse process of the atlas in 77.5% of the dissections. When the SAN crossed the posterior belly of the digastric muscle, the mean distance from the point of crossing to the tendon of the muscle was 1.75 +/- 0.54 cm. Distally, the SAN crossed between the two heads of the SCM muscle in 45% of the dissections and deep to the muscle in 55%. The SAN exited the posterior border of the sternocleidomastoid muscle in a point superior to the nerve point with a mean distance between these two anatomic parameters of 0.97 +/- 0.46 cm. The mean overall extracranial length of the SAN was 12.02 +/- 2.32 cm, whereas the mean length of the SAN in the posterior triangle was 5.27 +/- 1.52 cm. There were 2-10 lymph nodes in the SAN chain. In conclusion, the nerve point is one of the most reliable anatomic landmarks for localization of the SAN in surgical neck dissections. Although other anatomic parameters including the transverse process of the atlas and the digastric muscle can also be used to localize the SAN, the surgeon should be aware of the possibility of anatomic variations of those parameters. Similar to previous investigations, our results suggest that the number of lymph nodes of the SAN chain greatly varies. Clin. Anat. 22:471-475, 2009. (c) 2009 Wiley-Liss, Inc.

Macroscopic test of quantum mechanics versus stochastic electrodynamics

We identify a test of quantum mechanics versus macroscopic local realism in the form of stochastic electrodynamics. The test uses the steady-state triple quadrature correlations of a parametric oscillator below threshold.

A Randomized Trial of a Skin Sealant to Reduce the Risk of Incision Contamination in Cardiac Surgery

Background. Immobilizing skin microbes is a rational approach to reducing contamination of surgical sites by endogenous microorganisms. Methods. This randomized, controlled, parallel-group, multicenter, open-label clinical trial (ClinicalTrials.gov NCT00467857) enrolled 300 adults scheduled for elective coronary artery bypass graft surgery. Patients received iodine-based skin preparations followed by a cyanoacrylate-based skin sealant or skin preparations alone. Microbiological samples collected from sternal and graft incision sites immediately before any skin preparation, at the wound border after skin incision, and at the incision after fascial closure were evaluated quantitatively. Results. In evaluable patients, mean microbial counts in collected samples increased at the sternal site after fascial closure compared with after skin incision by 0.37 log(10) colony-forming units (CFU)/mL in the skin sealant group (n = 120) and by 0.57 log10 CFU/mL in the control group (n = 132) (p = 0.047, Wilcoxon rank sum test). At the graft site, mean microbial counts increased by 0.09 (n = 119) and 0.27 (n = 127) log(10) CFU/mL, respectively (p = 0.037). There was a 35.3% relative risk reduction in surgical site infection (SSI) occurring in the skin sealant group (9 of 146 patients, 6.2%) versus the control group (14 of 147 patients, 9.5%). In obese patients (body mass index [BMI] > 30.0 to <= 37.0 kg/m(2)), the relative risk reduction for SSI associated with skin sealant was 83.3%. Conclusions. Pretreatment with skin sealant protects against contamination of the surgical incision by migration of skin microbes. Further data are needed to confirm the impact of this technology on SSI rates in clinical practice. (Ann Thorac Surg 2011;92:632-7) (C) 2011 by The Society of Thoracic Surgeons ADULT CARDIAC

Leprosy in transplant recipients: report of a case after liver transplantation and review of the literature

P>Leprosy still is an important public health problem in several parts of the world including Brazil. Unlike the diseases caused by other mycobacteria, the incidence and clinical presentation of leprosy seems little affected in immunosuppressed patients. We report the first case, to our knowledge, of a liver transplant patient who developed multi-bacillary leprosy. The patient presented with papules and infiltrated plaques with loss of sensation suggestive of leprosy 3.5 years after living-related liver transplantation for autoimmune hepatitis. A skin biopsy showing non-caseating macrophagic granulomas, neuritis, and intact acid-fast bacilli on Fite-Faraco stain, confirmed the diagnosis of borderline lepromatous leprosy. The donor of the liver did not show any evidence of leprosy. During follow-up, the patient presented 2 episodes of upgrading leprosy type I reactions, 1 mild before leprosy treatment, and 1 moderate 3 months after receiving standard multi-drug treatment (rifampicin, clofazimine, and dapsone). These reactions were accompanied by increase in liver function tests, especially of canalicular enzymes. This reaction occurred despite the patient`s triple immunosuppression regimen. The moderate reaction was successfully treated with further immunosuppression (prednisone, 0.5 mg/kg). Currently, the patient is asymptomatic, off leprosy medication, with routine liver transplant follow-up. The dilemmas in diagnosis and management of such a case are discussed and the literature on leprosy in transplant recipients is reviewed.

Use of multiple channel pH monitoring for evaluation of ultra-distal reflux in patients after fundoplication for treatment of Barrett`s esophagus

Dysplasia and esophageal adenocarcinoma may arise in patients with Barrett`s esophagus after fundoplication esophageal pH monitoring showing no acid in esophagus. This suggests the need to develop methodology to evaluate the occurrence of ultra-distal reflux (1 cm above the LES). The objective of the study was to compare acid exposition in three different levels: 5 cm above the upper border of the LES, 1 cm above the LES and in the intrasphincteric region. Eleven patients with Barrett`s esophagus after Nissen fundoplication with no clinical, endoscopic and radiologic evidence of reflux were selected. Four-channel pH monitoring took place: channel A, 5 cm above the upper border of the LES; channel B, 1 cm above the LES; channel C, intrasphincteric; channel D, intragastric. The results of channels A, B and C were compared. There was significant increase in number of reflux episodes and a higher fraction of time with pH <4.0 in channel B compared to channel A. There was significant decrease in fraction of time with pH <4.0 in channel B compared to channel C. Two cases of esophageal adenocarcinoma were diagnosed in the studied patients. The region 1 cm above the upper border of the LES is more exposed to acid than the region 5 cm above the upper border of the LES, although this exposure occurred in reduced levels. The region 1 cm above the upper border of the LES is less exposed to acid than the intrasphincteric region.

The structure of versutoxin (delta-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel

Background: Versutoxin (delta-ACTX-Hv1) is the major component of the venom of the Australian Blue Mountains funnel web spider, Hadronyche versuta. delta-ACTX-Hv1 produces potentially fatal neurotoxic symptoms in primates by slowing the inactivation of voltage-gated sodium channels; delta-ACTX-Hv1 is therefore a useful tool for studying sodium channel function. We have determined the three-dimensional structure of delta ACTX-Hv1 as the first step towards understanding the molecular basis of its interaction with these channels. Results: The solution structure of delta-ACTX-Hv1, determined using NMR spectroscopy, comprises a core beta region containing a triple-stranded antiparallel beta sheet, a thumb-like extension protruding from the beta region and a C-terminal 3(10) helix that is appended to the beta domain by virtue of a disulphide bond. The beta region contains a cystine knot motif similar to that seen in other neurotoxic polypeptides. The structure shows homology with mu-agatoxin-l, a spider toxin that also modifies the inactivation kinetics of vertebrate voltage-gated sodium channels. More surprisingly, delta-ACTX-Hv1 shows both sequence and structural homology with gurmarin, a plant polypeptide. This similarity leads us to suggest that the sweet-taste suppression elicited by gurmarin may result from an interaction with one of the downstream ion channels involved in sweet-taste transduction. Conclusions: delta-ACTX-Hv1 shows no structural homology with either sea anemone or alpha-scorpion toxins, both of which also modify the inactivation kinetics of voltage-gated sodium channels by interacting with channel recognition site 3. However, we have shown that delta-ACTX-Hv1 contains charged residues that are topologically related to those implicated in the binding of sea anemone and alpha-scorpion toxins to mammalian voltage-gated sodium channels, suggesting similarities in their mode of interaction with these channels.

Recessive COL6A2 C-globular Missense Mutations in Ullrich Congenital Muscular Dystrophy ROLE OF THE C2a SPLICE VARIANT

Ullrich congenital muscular dystrophy (UCMD) is a disabling and life-threatening disorder resulting from either recessive or dominant mutations in genes encoding collagen VI. Although the majority of the recessive UCMD cases have frameshift or nonsense mutations in COL6A1, COL6A2, or COL6A3, recessive structural mutations in the COL6A2 C-globular region are emerging also. However, the underlying molecular mechanisms have remained elusive. Here we identified a homozygous COL6A2 E624K mutation (C1 subdomain) and a homozygous COL6A2 R876S mutation (C2 subdomain) in two UCMD patients. The consequences of the mutations were investigated using fibroblasts from patients and cells stably transfected with the mutant constructs. In contrast to expectations based on the clinical severity of these two patients, secretion and assembly of collagen VI were moderately affected by the E624K mutation but severely impaired by the R876S substitution. The E624K substitution altered the electrostatic potential of the region surrounding the metal ion-dependent adhesion site, resulting in a collagen VI network containing thick fibrils and spots with densely packed microfibrils. The R876S mutation prevented the chain from assembling into triple-helical collagen VI molecules. The minute amount of collagen VI secreted by the R876S fibroblasts was solely composed of a faster migrating chain corresponding to the C2a splice variant with an alternative C2 subdomain. In transfected cells, the C2a splice variant was able to assemble into short microfibrils. Together, the results suggest that the C2a splice variant may functionally compensate for the loss of the normal COL6A2 chain when mutations occur in the C2 subdomain.

Anterior Selective Amygdalohippocampectomy: Technical Description and Microsurgical Anatomy

OBJECTIVE: We introduce a technique for performing a selective amygdalohippocampectomy (AH) through a minisupraorbital approach. METHODS: A minisupraorbital craniotomy and an anterior selective AH were performed in 8 cadaver heads (16 sides). The anatomic specimens were analyzed, and the extent of resection of the hippocampus and amygdala was evaluated. Surgically relevant measurements were performed using anatomic specimens. An image-guided system was used to document the extent of the anterior AH. Laboratory data were used to support the clinical application of the technique. RESULTS: The anterior route allowed removal of the amygdala and hippocampus, as confirmed by anatomic assessment. The image-guided system and anatomic evaluation confirmed that the amygdala and hippocampus can be accessed and removed through this route. The mean distance between the anterior aspect of the uncus and the tip of the temporal horn was 17.0 +/- 4.6 mm; the mean distance from the head of the hippocampus to the posterior border of the cerebral peduncles was 26.0 +/- 3.2 mm. Clinical application resulted in satisfactory removal of the amygdala and hippocampus. CONCLUSION: The anterior route for selective AH is a logical and straightforward approach to the mesial temporal lobe. Compared with other variations, it is less invasive and destructive, especially in terms of the fibers of the optic pathway, temporal stem, and lateral temporal neocortex.

Tenascin and fibronectin expression in carcinoma ex pleomorphic adenoma

This study was conducted to analyze the participation of tenascin and fibronectin, components of the extracellular matrix. in different types of carcinoma ex pleomorphic adenoma (CXPA). Seventeen cases of CXPA, classified according to the presence of epithelial and myoepithelial cells and the degree of invasion-intracapsular, minimally, and frankly invasive carcinoma-were immunohistochemically labeled for tenascin and fibronectin. Normal salivary gland included in the specimens showed tenascin only around the excretory duct, and fibronectin slightly expressed all over the stroma of the gland. In reminiscent pleomorphic adenoma, tenascin and fibronectin were observed around tubular structures and in the stroma. Both tenascin and fibronectin were expressed in all the CXPA studied. In areas of in situ carcinoma of the intracapsular type, the expression of these extracellular matrix proteins was enhanced compared with areas of residual pleomorphic adenoma. In intracapsular and minimally invasive types of CXPA, some areas of the tumor border presented tenascin and no fibronectin, pattern that may represent the real invasive front. In frankly invasive CXPA type with only epithelial component, fibronectin was strongly observed in a fibrillar network pattern, and tenascin was only focal. In frankly invasive type with myoepithelial component, tenascin staining was very strong and diffuse. This study showed different patterns of expression of tenascin and fibronectin along the process of tumorigenesis and tumor progression in CXPA, a fact that might play a role in invasion properties of these tumors.

Coordinated expression of ER, PR and HER2 define different prognostic subtypes among poorly differentiated breast carcinomas

Aims: Histological grade is one of the most important prognostic factors in breast carcinomas, but poorly differentiated neoplasms still have quite heterogeneous biological behaviour, since they can be genetically classified as basal-like, HER2+ or even luminal. The aim was to analyse the frequency of oestrogen receptor (ER), progesterone receptor (PR) and HER2 expression profiles among breast carcinomas with < 10% tubular formation, and their correlation with classic prognostic factors. Methods and results: One hundred and thirty-four samples of paraffin-embedded tumours were studied retrospectively. The tumours were classified in to four groups by their ER/PR/HER2 profile: (i) ER+ and/or PR+ but HER2-; (ii) ER+ and/or PR+ and HER2+; (iii) ER- and/or PR- but HER2+; and (iv) ER-, PR- and HER2- (triple-negative). The histological features of triple-negative and HER2+ carcinomas overlap. The only difference was the expression of basal cytokeratins (basal CK), which was more frequent among triple-negative carcinomas. Basal-CK expression defined a more aggressive group of tumours, according to the pathological features, regardless of the immunohistochemical profile. Conclusions: Group 1 and 2 tumours (ER+ and/or PR+ tumours with or without HER2 expression) were not statistically different, suggesting that poorly differentiated carcinomas with hormone receptors correspond to the luminal B type of tumour. Among poorly differentiated breast carcinomas, the classic profile associated with basal-CK identifies distinct subtypes equivalent to those seen by genetic classification.

Prognostic value of NDRG1 and SPARC protein expression in breast cancer patients

An increasing number of studies have shown altered expression of secreted protein acidic and rich in cysteine (SPARC) and N-myc down-regulated gene (NDRG1) in several malignancies, including breast carcinoma; however, the role of these potential biomarkers in tumor development and progression is controversial. In this study, NDRG1 and SPARC protein expression was evaluated by immunohistochemistry on tissue microarrays containing breast tumor specimens from patients with 10 years of follow-up. NDRG1 and SPARC protein expression was determined in 596 patients along with other prognostic markers, such as ER, PR, and HER2. The status of NDRG1 and SPARC protein expression was correlated with prognostic variables and patient clinical outcome. Immunostaining revealed that 272 of the 596 cases (45.6%) were positive for NDRG1 and 431 (72.3%) were positive for SPARC. Statistically significant differences were found between the presence of SPARC and NDRG1 protein expression and standard clinicopathological variables. Kaplan-Meier analysis showed that NDRG1 positivity was directly associated with shorter disease-free survival (DFS, P < 0.001) and overall survival (OS, P < 0.001). In contrast, patients expressing low levels of SPARC protein had worse DFS (P = 0.001) and OS (P = 0.001) compared to those expressing high levels. Combined analysis of the two markers indicated that DFS (P < 0.001) and OS rates (P < 0.001) were lowest for patients with NDRG1-positive and SPARC-negative tumors. Furthermore, NDRG1 over-expression and SPARC down-regulation correlated with poor prognosis in patients with luminal A or triple-negative subtype breast cancer. On multivariate analysis using a Cox proportional hazards model, NDRG1 and SPARC protein expression were independent prognostic factors for both DFS and OS of breast cancer patients. These data indicate that NDRG1 over-expression and SPARC down-regulation could play important roles in breast cancer progression and serve as useful biomarkers to better define breast cancer prognosis.

Posttranslational mechanisms associated with reduced NHE3 activity in adult vs. young prehypertensive SHR

Crajoinas RO, Lessa LMA, Carraro-Lacroix LR, Davel APC, Pacheco BPM, Rossoni LV, Malnic G, Girardi ACC. Posttranslational mechanisms associated with reduced NHE3 activity in adult vs. young prehypertensive SHR. Am J Physiol Renal Physiol 299:F872-F881, 2010. First published July 14, 2010; doi:10.1152/ajprenal.00654.2009.-Abnormalities in renal proximal tubular (PT) sodium transport play an important role in the pathophysiology of essential hypertension. The Na(+)/H(+) exchanger isoform 3 (NHE3) represents the major route for sodium entry across the apical membrane of renal PT cells. We therefore aimed to assess in vivo NHE3 transport activity and to define the molecular mechanisms underlying NHE3 regulation before and after development of hypertension in the spontaneously hypertensive rat (SHR). NHE3 function was measured as the rate of bicarbonate reabsorption by means of in vivo stationary microperfusion in PT from young prehypertensive SHR (Y-SHR; 5-wk-old), adult SHR (A-SHR; 14-wk-old), and age-matched Wistar Kyoto (WKY) rats. We found that NHE3-mediated PT bicarbonate reabsorption was reduced with age in the SHR (1.08 +/- 0.10 vs. 0.41 +/- 0.04 nmol/cm(2)xs), while it was increased in the transition from youth to adulthood in the WKY rat (0.59 +/- 0.05 vs. 1.26 +/- 0.11 nmol/cm(2)xs). Higher NHE3 activity in the Y-SHR compared with A-SHR was associated with a predominant microvilli confinement and a lower ratio of phosphorylated NHE3 at serine-552 to total NHE3 (P-NHE3/total). After development of hypertension, P-NHE3/total increased and NHE3 was retracted out of the microvillar microdomain along with the regulator dipeptidyl peptidase IV (DPPIV). Collectively, our data suggest that the PT is playing a role in adapting to the hypertension in the SHR. The molecular mechanisms of this adaptation possibly include an increase of P-NHE3/total and a redistribution of the NHE3-DPPIV complex from the body to the base of the PT microvilli, both predicted to decrease sodium reabsorption.