Photodynamic therapy in actinic cheilitis: clinical and anatomopathological evaluation of 19 patients

BACKGROUND: Actinic cheilitis, a common disease caused by chronic solar exposure and tobacco use, is considered a premalignant lesion with potential to develop into squamous cell carcinoma. Some of the available treatments are invasive, have unaesthetic results and require multiple sessions. OBJECTIVE: To assess the efficacy of a therapy and its cosmetic results. METHODS: In this uncontrolled clinical trial a single photodynamic therapy (PDT) session using 16% methyl-aminolevulinate was performed on actinic cheilitis of the lower lip. A standardized questionnaire was applied in order to assess the clinical improvement from the patients' point of view and the satisfaction with the treatment. Anatomopathological evaluation was performed before the treatment and two months afterwards. RESULTS: The sample was composed of 19 patients (10 males and 9 females), phototypes I to III, with average age of 62 years. Main adverse effects were: sudden pain, scabs, herpes flare-up, and edema. The average score of pain during the procedure was 5,8+2,9. At the final assessment the patients reported improvement of 80% and satisfaction of 85% (p<0.01). Anatomopathological analysis showed a significant decrease of dysplasia (p=0.03) in spite of its presence in 84% of cases. There was no significant correlation between the level of dysplasia with either the subjective impression of clinical improvement (p=0.82) or with the patients' final satisfaction (p=0.96). CONCLUSION: PDT is effective in the treatment of actinic cheilitis, but it is associated with a significant level of pain. Due to the persistence of dysplasia, more research needs to be done in order to define the ideal number of sessions for the effective treatment of these lesions.

Haploinsufficiency of a Spliceosomal GTPase Encoded by EFTUD2 Causes Mandibulofacial Dysostosis with Microcephaly

Mandibulofacial dysostosis with microcephaly (MFDM) is a rare sporadic syndrome comprising craniofacial malformations, microcephaly, developmental delay, and a recognizable dysmorphic appearance. Major sequelae, including choanal atresia, sensorineural hearing loss, and cleft palate, each occur in a significant proportion of affected individuals. We present detailed clinical findings in 12 unrelated individuals with MFDM; these 12 individuals compose the largest reported cohort to date. To define the etiology of MFDM, we employed whole-exome sequencing of four unrelated affected individuals and identified heterozygous mutations or deletions of EFTUD2 in all four. Validation studies of eight additional individuals with MFDM demonstrated causative EFTUD2 mutations in all affected individuals tested. A range of EPTUD2-mutation types, including null alleles and frameshifts, is seen in MFDM, consistent with haploinsufficiency; segregation is de novo in all cases assessed to date. U5-116kD, the protein encoded by EFTUD2, is a highly conserved spliceosomal GTPase with a central regulatory role in catalytic splicing and post-splicing-complex disassembly. MFDM is the fast multiple-malformation syndrome attributed to a defect of the major spliceosome. Our findings significantly extend the range of reported spliceosomal phenotypes in humans and pave the way for further investigation in related conditions such as Treacher Collins syndrome.

Asymptomatic nodules of the upper lip: report of a canalicular adenoma with immunoprofile presentation

Canalicular adenoma is an uncommon benign tumour that generally arises in the minor salivary glands of individuals over 60 years old. This study illustrates a case of canalicular adenoma in a 70-year-old female, presenting as two distinct asymptomatic nodules in the upper lip. Immunohistochemistry analysis was performed. Clinical features, management, histology and immunoprofile from this case and from the literature are discussed.

Celecoxib treatment does not alter recruitment and activation of osteoclasts in the initial phase of experimental tooth movement

In a previous study, we reported that the short-term treatment with celecoxib, a nonsteroidal anti-inflammatory drug (NSAID) attenuates the activation of brain structures related to nociception and does not interfere with orthodontic incisor separation in rats. The conclusion was that celecoxib could possibly be prescribed for pain in orthodontic patients. However, we did not analyze the effects of this drug in periodontium. The aim of this follow-up study was to analyze effects of celecoxib treatment on recruitment and activation of osteoclasts and alveolar bone resorption after inserting an activated orthodontic appliance between the incisors in our rat model. Twenty rats (400420 g) were pretreated through oral gavage with celecoxib (50 mg/kg) or vehicle (carboxymethylcellulose 0.4%). After 30 min, they received an activated (30 g) orthodontic appliance, set not to cause any palate disjunction. In sham animals, the appliance was immediately removed after introduction. All animals received ground food and, every 12 h, celecoxib or vehicle. After 48 h, they were anesthetized and transcardiacally perfused through the aorta with 4% formaldehyde. Subsequently, maxillae were removed, post-fixed and processed for histomorphometry or immunohistochemical analyses. As expected, incisor distalization induced an inflammatory response with certain histological changes, including an increase in the number of active osteoclasts at the compression side in group treated with vehicle (appliance: 32.2 +/- 2.49 vs sham: 4.8 +/- 1.79, P<0.05) and celecoxib (appliance: 31.0 +/- 1.45 vs sham: 4.6 +/- 1.82, P<0.05). The treatment with celecoxib did not modify substantially the histological alterations and the number of active osteoclasts after activation of orthodontic appliance. Moreover, we did not see any difference between the groups with respect to percentage of bone resorption area. Taken together with our previous results we conclude that short-term treatment with celecoxib can indeed be a therapeutic alternative for pain relieve during orthodontic procedures.

Comparison of the Anesthetic Efficacy between Bupivacaine and Lidocaine in Patients with Irreversible Pulpitis of Mandibular Molar

Introduction: The purpose of this study was to compare the anesthetic efficacy of 0.5% bupivacaine with 1:200,000 epinephrine with that of 2% lidocaine with 1:100,000 epinephrine during pulpectomy in patients with irreversible pulpitis in mandibular posterior teeth. Methods: Seventy volunteers, patients with irreversible pulpitis admitted to the Emergency Center of the School of Dentistry at the University of Sao Paulo, randomly received a conventional inferior alveolar nerve block containing 3.6 mL of either 0.5% bupivacaine with 1:200,000 epinephrine or 2% lidocaine with 1:100,000 epinephrine. During the subsequent pulpectomy, we recorded the patients subjective assessments of lip anesthesia, the absence/presence of pulpal anesthesia through electric pulp stimulation, and the absence/presence of pain through a verbal analog scale. Results: All patients reported lip anesthesia after the application of either inferior alveolar nerve block. By measuring pulpal anesthesia success with the pulp tester, lidocaine had a higher success rate (42.9%) than bupivacaine (20%). For patients reporting none or mild pain during pulpectomy, the success rate of bupivacaine was 80% and lidocaine was 62.9%. There were only statistically significant differences to the success of pulpal anesthesia. Conclusions: Neither of the solutions resulted in an effective pain control during irreversible pulpitis treatments of mandibular molars. (J Endod 2012;38:594-597)

Taxonomic study on the molluscs collected in Marion-Dufresne expedition (MD55) to SE Brazil: Xenophoridae, Cypraeoidea, mitriforms and Terebridae (Caenogastropoda)

The deep-water molluscs collected during the expedition MD55 off SE Brazil have been gradually studied in some previous papers. The present one is focused on samples belonging to caenogastropod taxa Xenophoridae Troschel, 1852, Cypraeoidea Rafinesque, 1815, mitriforms and Terebridae Morch, 1852. Regarding the Xenophoridae, Onustus aquitanus n. sp. is a new species, collected off the littoral of Espirito Santo and Rio de Janeiro, Brazil, 430-637 m depth (continental slope). The main characters of the species include the small size (c. 20 mm), the proportionally wide shell, the white colour, the short peripheral flange, the oblique riblets weakly developed and a brown multispiral protoconch. This appears to be the smallest living species of the family, resembling in this aspect fossil species. In respect to the Cypraeoidea, the following results were obtained: family Cypraeidae Rafinesque, 1815: Erosaria acicularis (Gmelin, 1791) and Luria cinerea (Gmelin, 1791) had the deepest record, respectively 607-620 m and 295-940 m, although the samples were all dead, eroded shells. Family Lamellariidae d'Orbigny, 1841: a total of three lots were collected, provisionally identified as Lamellaria spp. as the samples consist of only vestigial shells; possibly each lot represents a different species. Family Pediculariidae Gray, 1853: a sample of Pedicularia tibia Simone, 2005 was found, expanding the range c. 1000 km southwards, from Ceara to Espirito Santo. Family Ovulidae Fleming, 1822: Pseudosimnia lacrima n. sp., collected off Espirito Santo, 607-620 m depth, is described here and is mainly characterised by its strong biconic outline, small size (c. 7 mm), and a thick peripheral callus. Family Triviidae Troschel, 1863: Cleotrivia antillarum (Schilder, 1922) is recorded for the first time as deep as 620 m, and its distribution expanded from Rio Grande do Norte to Espirito Santo; Dolichupis akangus n. sp. with rounded outline and c. 15 transverse ribs; D. pingius n. sp. with the outer lip expanded posteriorly and c. 10 ribs. In respect to the mitriform neogastropods, the following species are emphasised: family Costellariidae MacDonald, 1860: Vexillum sp., 607-620 m depth; Turricostellaria amphissa n. sp., 295 m depth; T. jukyry n. sp.; T. apyrahi n. sp., both 790-1575 m depth; T. ovir n. sp., 1200 m depth; Nodicostellaria crassa (Simone, 1995), 240-600 m depth, with extension northwards of the range up to Espirito Santo; Austromitra decresca n. sp., 60-105 m depth. Family Mitridae Swainson, 1829: Subcancilla joapyra n. sp., 295 m depth; S. cf. straminea (Adams, 1853), 607-620 m depth. Family Volutomitridae Gray, 1854: Microvoluta corona n. sp., 1500-1575 m depth. Family Mitromorphidae Casey, 1904: Mitromorpha sama n. sp., 607-940 m depth; M. mirim n. sp., 60105 m depth. Regarding the conoidean Terebridae, this paper is a complement of a previous study. It deals with a new species Terebra assu Simone n. sp., from the Abrolhos Bank, 295 m depth, characterised by its narrow outline, yellowish colour, weak sculpture on the last whorls, and a proportionally broad, paucispiral protoconch. A second finding of Terebra alagoensis Lima, Tenorio & Barros, 2007 expands the geographic range from Alagoas to north Espirito Santo. A discussion on the systematics of the "complex Terebra doellojuradoi" in South American coast is also provided, highlighting the improbability of synonymy between T. leptapsis Simone, 1999 and T doellojuradoi Carcelles, 1953. Differences in size, sculpture, spire angulation, aperture, and mainly in protoconch, indicate specific separations. The presently studied terebrids belong to the "complex Terebra doellojuradoi", which encompasses closely related, deep-water, small species, possessing a relatively high degree of endemicity.

A novel microdeletion syndrome at 3q13.31 characterised by developmental delay, postnatal overgrowth, hypoplastic male genitals, and characteristic facial features

Background Congenital deletions affecting 3q11q23 have rarely been reported and only five cases have been molecularly characterised. Genotype. phenotype correlation has been hampered by the variable sizes and breakpoints of the deletions. In this study, 14 novel patients with deletions in 3q11q23 were investigated and compared with 13 previously reported patients. Methods Clinical data were collected from 14 novel patients that had been investigated by high resolution microarray techniques. Molecular investigation and updated clinical information of one cytogenetically previously reported patient were also included. Results The molecular investigation identified deletions in the region 3q12.3q21.3 with different boundaries and variable sizes. The smallest studied deletion was 580 kb, located in 3q13.31. Genotype. phenotype comparison in 24 patients sharing this shortest region of overlapping deletion revealed several common major characteristics including significant developmental delay, muscular hypotonia, a high arched palate, and recognisable facial features including a short philtrum and protruding lips. Abnormal genitalia were found in the majority of males, several having micropenis. Finally, a postnatal growth pattern above the mean was apparent. The 580 kb deleted region includes five RefSeq genes and two of them are strong candidate genes for the developmental delay: DRD3 and ZBTB20. Conclusion A newly recognised 3q13.31 microdeletion syndrome is delineated which is of diagnostic and prognostic value. Furthermore, two genes are suggested to be responsible for the main phenotype.

Total Obturation of Velopharynx for Treatment of Velopharyngeal Hypodynamism: Case Report

A child with microdeletion at 22q11.21 was referred to a craniofacial center due to hypernasality, unintelligible speech, and bifid uvula. Velopharyngeal dysfunction remained after surgical repair of submucous cleft palate and speech therapy. A prosthetic-behavioral treatment approach involving total obturation of the velopharynx was successfully implemented for management of velopharyngeal hypodynamism.

RHYTHM-AF: design of an international registry on cardioversion of atrial fibrillation and characteristics of participating centers

Background: Atrial fibrillation is a serious public health problem posing a considerable burden to not only patients, but the healthcare environment due to high rates of morbidity, mortality, and medical resource utilization. There are limited data on the variation in treatment practice patterns across different countries, healthcare settings and the associated health outcomes. Methods/design: RHYTHM-AF was a prospective observational multinational study of management of recent onset atrial fibrillation patients considered for cardioversion designed to collect data on international treatment patterns and short term outcomes related to cardioversion. We present data collected in 10 countries between May 2010 and June 2011. Enrollment was ongoing in Italy and Brazil at the time of data analysis. Data were collected at the time of atrial fibrillation episode in all countries (Australia, Brazil, France, Germany, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom), and cumulative follow-up data were collected at day 60 (+/- 10) in all but Spain. Information on center characteristics, enrollment data, patient demographics, detail of atrial fibrillation episode, medical history, diagnostic procedures, acute treatment of atrial fibrillation, discharge information and the follow-up data on major events and rehospitalizations up to day 60 were collected. Discussion: A total of 3940 patients were enrolled from 175 acute care centers. 70.5% of the centers were either academic (44%) or teaching (26%) hospitals with an overall median capacity of 510 beds. The sites were mostly specialized with anticoagulation clinics (65.9%), heart failure (75.1%) and hypertension clinics (60.1%) available. The RHYTHM-AF registry will provide insight into regional variability of antiarrhythmic and antithrombotic treatment of atrial fibrillation, the appropriateness of such treatments with respect to outcomes, and their cost-efficacy. Observations will help inform strategies to improve cardiovascular outcomes in patients with atrial fibrillation.

Importance of early diagnosis of Stickler syndrome in newborns

Objective: The study aims to investigate a possible correlation between the main clinical and ophthalmological characteristics, age and Robin sequence in patients with the Stickler syndrome. Introduction: The Stickler syndrome is an autosomal dominant genetic disorder, characterised by ocular, orofacial and skeletal anomalies and/or auditory loss. Patients with Robin sequence features and respiratory complications are frequently diagnosed with the Stickler syndrome. The heterogeneous phenotypic manifestations may present a challenge for early clinical diagnosis. Methods: We performed a retrospective study of the 98 patients with the Stickler syndrome, between November 1995 and June 2009. The data were compared to investigate their ocular alterations and association with the Robin sequence. To be included, patients had to present with the following triad: cleft palate, facial features (hypoplastic midface, micrognathia and prominent eyes) and ocular anomalies (myopia and/or abnormalities of the retina). Results: Fifty-one percent of the patients presenting with Robin sequence features had been diagnosed with the Stickler syndrome. Ocular alterations were found in 50% of the patients. Discussion: The Robin sequence may appear as an isolated condition or associated with other features, or else as part of other known syndromes. Currently, the diagnosis of the Stickler syndrome is based on clinical signs. Affected individuals eventually develop hearing loss, retinal detachment and blindness. The ophthalmological complications associated are usually progressive and can lead to blindness.

Free Rhodium (II) citrate and rhodium (II) citrate magnetic carriers as potential strategies for breast cancer therapy

Abstract Background Rhodium (II) citrate (Rh2(H2cit)4) has significant antitumor, cytotoxic, and cytostatic activity on Ehrlich ascite tumor. Although toxic to normal cells, its lower toxicity when compared to carboxylate analogues of rhodium (II) indicates Rh2(H2cit)4 as a promising agent for chemotherapy. Nevertheless, few studies have been performed to explore this potential. Superparamagnetic particles of iron oxide (SPIOs) represent an attractive platform as carriers in drug delivery systems (DDS) because they can present greater specificity to tumor cells than normal cells. Thus, the association between Rh2(H2cit)4 and SPIOs can represent a strategy to enhance the former's therapeutic action. In this work, we report the cytotoxicity of free rhodium (II) citrate (Rh2(H2cit)4) and rhodium (II) citrate-loaded maghemite nanoparticles or magnetoliposomes, used as drug delivery systems, on both normal and carcinoma breast cell cultures. Results Treatment with free Rh2(H2cit)4 induced cytotoxicity that was dependent on dose, time, and cell line. The IC50 values showed that this effect was more intense on breast normal cells (MCF-10A) than on breast carcinoma cells (MCF-7 and 4T1). However, the treatment with 50 μM Rh2(H2cit)4-loaded maghemite nanoparticles (Magh-Rh2(H2cit)4) and Rh2(H2cit)4-loaded magnetoliposomes (Lip-Magh-Rh2(H2cit)4) induced a higher cytotoxicity on MCF-7 and 4T1 than on MCF-10A (p < 0.05). These treatments enhanced cytotoxicity up to 4.6 times. These cytotoxic effects, induced by free Rh2(H2cit)4, were evidenced by morphological alterations such as nuclear fragmentation, membrane blebbing and phosphatidylserine exposure, reduction of actin filaments, mitochondrial condensation and an increase in number of vacuoles, suggesting that Rh2(H2cit)4 induces cell death by apoptosis. Conclusions The treatment with rhodium (II) citrate-loaded maghemite nanoparticles and magnetoliposomes induced more specific cytotoxicity on breast carcinoma cells than on breast normal cells, which is the opposite of the results observed with free Rh2(H2cit)4 treatment. Thus, magnetic nanoparticles represent an attractive platform as carriers in Rh2(H2cit)4 delivery systems, since they can act preferentially in tumor cells. Therefore, these nanopaticulate systems may be explored as a potential tool for chemotherapy drug development.

Effects of intravenous furosemide on mucociliary transport and rheological properties of patients under mechanical ventilation

The use of intravenous (IV) furosemide is common practice in patients under mechanical ventilation (MV), but its effects on respiratory mucus are largely unknown. Furosemide can affect respiratory mucus either directly through inhibition of the NaK(Cl)2 co-transporter on the basolateral surface of airway epithelium or indirectly through increased diuresis and dehydration. We investigated the physical properties and transportability of respiratory mucus obtained from 26 patients under MV distributed in two groups, furosemide (n = 12) and control (n = 14). Mucus collection was done at 0, 1, 2, 3 and 4 hours. The rheological properties of mucus were studied with a microrheometer, and in vitro mucociliary transport (MCT) (frog palate), contact angle (CA) and cough clearance (CC) (simulated cough machine) were measured. After the administration of furosemide, MCT decreased by 17 ± 19%, 24 ± 11%, 18 ± 16% and 18 ± 13% at 1, 2, 3 and 4 hours respectively, P < 0.001 compared with control. In contrast, no significant changes were observed in the control group. The remaining parameters did not change significantly in either group. Our results support the hypothesis that IV furosemide might acutely impair MCT in patients under MV.

Morphological characterization of the nasopalatine region in human fetuses and its association to pathologies

The nasopalatine region is composed of structures such as the vomeronasal organ and nasopalatine duct. The nasopalatine duct may provide the communication of the mouth to the nasal cavity in human fetuses and can be obliterated in an adult human. Knowledge on the development of the nasopalatine region and nasopalatine duct in humans is necessary for understanding the morphology and etiopathogenesis of lesions that occur in this region. Objective: The aim of the present study was to describe the morphological aspects of the nasopalatine region in human fetuses and correlate these aspects with the development of pathologies in this region. Material and Methods: Five human fetuses with no facial or palatine abnormalities were used for the acquisition of specimens from the nasopalatine region. After demineralization, the specimens were histologically processed. Histological cuts were stained with methylene blue to orient the cutting plane and hematoxylin-eosin for the descriptive histological analysis. Results: The age of the fetuses was 8.00, 8.25, 9.00 and 9.25 weeks, and it was not possible to determine the age in the last one. The incisive canal was observed in all specimens as an opening delimited laterally by the periosteum and connecting oral and nasal cavity. The nasopalatine duct is an epithelial structure with the greatest morphological variation, with either unilateral or bilateral occurrence and total patent, partial patent and islet forms. The vomeronasal organ is a bilateral epithelized structure located alongside the nasal septum above the incisive canal in all the fetuses. Conclusions: The incisive canal, nasopalatine duct and vomeronasal organ are distinct anatomic structures. The development of nasopalatine duct cysts may occur in all forms of the nasopalatine duct.

Neurovascular anatomical variations in the anterior palate observed on CBCT images

Objective: This study aimed to assess the presence of additional foramina and canals in the anterior palate region, through cone beam computed tomography (CBCT) images, describing their location, direction, and diameter. Materials & Methods: CBCT exams of 178 subjects displaying the anterior maxilla were included and the following parameters were registered: gender; age group; presence of additional foramina in the anterior palate (AFP) with at least 1 mm in diameter; location and diameter of AFP; and direction of bony canals associated with AFP. Results: Twenty-eight patients (15.7%) presented AFP and in total 34 additional foramina were registered. No statistical differences between patients with or without AFP were found for gender or age. The average diameter of AFP was 1.4 mm (range from 1 to 1.9 mm). Their location was variable, with most of the cases occurring in the alveolar process near the incisors or canines (n = 27). In 18 cases, AFP was associated with bony canals with upward or oblique direction toward the anterior nasal cavity floor. In 14 cases, the canal presented as a direct extension of the canalis sinuosus, in an upward direction laterally to the nasal cavity aperture. In two cases, the canal was observed adjacent to the incisive and joined the nasopalatine canal superiorly. Discussion: CBCT images have a crucial role in the recognition of anatomical variations by allowing detailed tridimensional evaluations. Additional foramina and canals in the anterior region of the upper jaw are relatively frequent. Practitioners should be aware and trained to identify these variations. Conclusions: Over 15% of the population studied had additional foramina in the anterior palate, between 1 mm and 1.9 mm wide, with variable locations. In most cases the canals associated with these foramina either presented as a direct extension of the canalis sinuosus, or coursed towards the nasal cavity floor.

Taxonomical study on a sample of pulmonates from Santa Maria da Vitória, Bahia, Brazil, with description of a new genus and four new species (Mollusca: Orthalicidae and Megalobulimidae)

A sample of Pulmonata collected in Santa Maria da Vitória, interior of Bahia, Brazil, in Caatinga semi-arid environment, is studied taxonomically. From the five species, four are revealed as new, including a new genus. The new taxa are the Bulimulidae (1) Kora corallina gen. et sp. n. characterized by the elongated shell with aperture somewhat dislocated from the shell axis, and an oblique tooth in middle level of inner lip; (2) Spixia coltrorum, mainly characterized by an uneven spire, delicate sculpture and peristome with 4 equidistant teeth; (3) Anostoma tessa, mainly characterized by a broad spire and well-developed anal canal; and the Megalobulimidae (4) Megalobulimus amandus, mainly characterized by pointed protoconch sculptured by dense quantity of axial cords. Rhinus suturalis is the only previously known species, but its geographic distribution is expanded southwards to Bahia state. A discussion with respect to necessity for improving the study on the malacofauna from the interior region of the Brazilian Northeast and the importance for preservation of the Caatinga biome is also provided.