Description of trunk neural crest migration and peripheral nervous system formation in the Egyptian cobra Naja haje haje.

The neural crest is a stem cell population that forms in the neurectoderm of all vertebrates and gives rise to a diverse set of cells such as sensory neurons, Schwann cells and melanocytes. Neural crest development in snakes is still poorly understood. From the point of view of evolutionary and comparative anatomy is an interesting topic given the unique anatomy of snakes. The aim of the study was to characterize how trunk neural crest cells (TNCC) migrate in the developing elapid snake Naja haje haje and consequently, look at the beginnings of development of neural crest derived sensory ganglia (DRG) and spinal nerves. We found that trunk neural crest and DRG development in Naja haje haje is like what has been described in other vertebrates and the colubrid snake strengthening our knowledge on the conserved mechanisms of neural crest development across species. Here we use the marker HNK1 to follow the migratory behavior of TNCC in the elapid snake Naja haje haje through stages 1-6 (1-9 days postoviposition). We observed that the TNCC of both snake species migrate through the rostral portion of the somite, a pattern also conserved in birds and mammals. The development of cobra peripheral nervous system, using neuronal and glial markers, showed the presence of spectrin in Schwann cell precursors and of axonal plexus along the length of the cobra embryos. In conclusion, cobra embryos show strong conserved patterns in TNCC and PNS development among vertebrates.

Long-term outcome of antineutrophil cytoplasmic antibody-associated small vessel vasculitis after renal transplantation.

The survival after renal transplantation of patients with antineutrophil cytoplasmic antibody (ANCA)-associated to systemic vasculitis is as good as in other diseases, although most of the reports are based on small numbers of patients. Furthermore, it is not known whether comorbidities (cardiovascular [CV] disease and cancer) are more frequent than in general population. We report our experience and the analysis of the published data on this topic. The outcome after transplantation in 49 patients with ANCA-associated small vessel vasculitis was compared with a control group. The relapse rate of vasculitis was 0.01 per patient per year. Comparison with the control patients revealed no difference in long-term outcome, CV mortality or incidence of malignancies. In the published literature, patients with ANCA at transplantation and with Wegener's granulomatosis are at greater risk of relapse. Taking our own results together with the review of the literature, we conclude that patient and graft survival rates compare favorably with those in control group that the recurrence rate is very low and that there is no increase in the incidence of cancer or in CV mortality. Patients with ANCA at transplantation and with Wegener's granulomatosis have a higher relapse rate.

Low-dose sirolimus combined with angiotensin-converting enzyme inhibitor and statin stabilizes renal function and reduces glomerular proliferation in poor prognosis IgA nephropathy.

BACKGROUND: There is a lack of new therapeutic strategies for IgA nephropathy. Low-dose sirolimus inhibits mesangial cell proliferation and renal fibrosis in animal models. METHODS: We performed a pilot, randomized controlled trial to evaluate the efficacy and safety of low-dose sirolimus in patients with a high-risk IgA nephropathy. Twenty-three patients with a glomerular filtration rate (GFR) within 30-60 mL/min and/or proteinuria >1 g/day were randomly assigned to low-dose sirolimus plus enalapril and atorvastatin (SRL group, n = 14) or enalapril plus atorvastatin (CONTROL group, n = 9). Primary composite end point was variation of haematuria, proteinuria and blood pressure. Secondary end points were isotopic GFR, renal histology evaluated by Oxford classification and safety parameters evaluated at 6 and 12 months. RESULTS: Primary end point improved significantly in the SRL group at 12 months. Regarding isotopic GFR, patients included in the CONTROL group lost 8 mL/min/1.73 m(2), whereas those in the SRL arm improved 5 mL/min/1.73 m(2) (P = 0.03). Proteinuria decreased similarly in both study groups. At 1 year, SRL treatment was associated with a significant reduction of mesangial and endocapillary proliferation, whereas glomerular sclerosis, tubular atrophy and interstitial fibrosis were similar. Sirolimus was well tolerated; all patients remained on therapy at 12 months. CONCLUSION: The addition of low-dose sirolimus to enalapril and statin is safe, stabilizes renal function and reduces glomerular proliferative lesions in patients with poor prognosis IgA nephropathy.

Aroma-active compounds, sensory profile, and phenolic composition of Fondillón.

The Fondillón is a wine made from overripe grapes of the Monastrell variety, which is characterized by a high alcohol content and a minimum barrel ageing of 10 years. The objective of this study was to analyze the Fondillón volatile composition, key aroma-active compounds, sensory profile and phenolic composition. Fifty-four volatile compounds were identified, quantified and classified as alcohols, esters, acids, aldehydes, lactones, phenols, hydrocarbons and ketone. From these compounds, 22 aroma-active compounds were identified, with phenylethyl alcohol, diethyl succinate and ethyl lactate having the highest flavor dilution factor. The Fondillón wines were characterized by having high intensity of alcohol, fruity and toasted odor and flavor notes, and long aftertaste. Besides, 25 phenolic compounds were also identified and quantified; the phenolic acids (gallic, protocatechuic and syringic acids) were the predominant phenolic compounds.

TRPC6 mutational analysis in a large cohort of patients with focal segmental glomerulosclerosis.

BACKGROUND: Mutations in the TRPC6 gene have been reported in six families with adult-onset (17-57 years) autosomal dominant focal segmental glomerulosclerosis (FSGS). Electrophysiology studies confirmed augmented calcium influx only in three of these six TRPC6 mutations. To date, the role of TRPC6 in childhood and adulthood non-familial forms is unknown. METHODS: TRPC6 mutation analysis was performed by direct sequencing in 130 Spanish patients from 115 unrelated families with FSGS. An in silico scoring matrix was developed to evaluate the pathogenicity of amino acid substitutions, by using the bio-physical and bio-chemical differences between wild-type and mutant amino acid, the evolutionary conservation of the amino acid residue in orthologues, homologues and defined domains, with the addition of contextual information. RESULTS: Three new missense substitutions were identified in two clinically non-familial cases and in one familial case. The analysis by means of this scoring system allowed us to classify these variants as likely pathogenic mutations. One of them was detected in a female patient with unusual clinical features: mesangial proliferative FSGS in childhood (7 years) and partial response to immunosupressive therapy (CsA + MMF). Asymptomatic carriers of this likely mutation were found within her family. CONCLUSIONS: We describe for the first time TRPC6 mutations in children and adults with non-familial FSGS. It seems that TRPC6 is a gene with a very variable penetrance that may contribute to glomerular diseases in a multi-hit setting.

Sjögren's syndrome of the oral cavity. Review and update.

Sjögren's syndrome is one of the most frequent autoimmune diseases. It is a chronic and systemic disorder predominantly found in women, and is characterized by the appearance of a lymphocytic inflammatory infiltrate, with dryness of the oral cavity and eyes, secondary to involvement of the salivary and lacrimal glands. The underlying causal mechanism involves a number of factors and has not been clearly established, though an autoimmune response is known to be triggered, with the accumulation of immune complexes in the gland acini that interfere with gland function. In the oral cavity, xerostomia or hyposialia is the most disabling manifestation for patients, and is accompanied by rapidly progressing caries, candidiasis and an important worsening of buccodental health. The most important complication is a 44-fold increase in the risk of developing non-Hodgkin lymphoma, compared with the general population. The treatment of Sjögren's syndrome is limited to symptomatic management, and involves the use of solutions to replace salivary secretion and afford a measure of hydration, cholinergic agents such as pilocarpine to stimulate the unaffected gland tissue and, recently, the administration of substances that act against surface antigens of the B lymphocytes, such as anti-CD20 and anti-CD22 antibodies. The present study provides an update on this disease, placing special emphasis on its odontologic implications.

Osteonecrosis of the jaws by intravenous bisphosphonates and osteoradionecrosis: a comparative study.

AIMS: We analyze the possible clinical differences between bone jaw exposed areas in ONJ (osteonecrosis of the jaws) and ORN (osteoradionecrosis). PATIENTS AND METHOD: Group 1 was composed with 53 ONJ cases and group 2 with 20 ORN cases. In both groups we analyzed, the major size of the exposed bone areas, the number of exposed areas, the location on the jaws and the presence of others associated and severe complications, such as skin fistulas and jaw fractures. We also investigated the possible local aetiology or trigger factor of the lesions. RESULTS: The major size of the bone exposed areas was 2.29+/-2.02(mean +/- std.dev) in group 1 and 2.7+/-2.9 (mean +/- std.dev) in group 2 (p>0.05). The number of exposed areas was 1.8+/-1.34 (mean +/- std.dev) in group 1 and 1.2+/-0.55 (mean +/- std.dev) in group 2 (p>0.05). There were more fractures in the second group (20%) (p<0.05), and skin fistulas (35%) (p<0.05). We found more patients in group 1 in which the dental extraction was the local aetiology of the bone necrosis (35 cases, 66.03%), while in group 2 there were 8 (40%) (p<0.05). CONCLUSIONS: In our study with ONJ there were not differences in the major size of the bone exposed areas, but there were more lesions per patient than in group with ORN. The severity of the complications, such as jaw fractures and skin fistulas were higher in ORN, and in this group it was more frequent the spontaneous lesions than in the ONJ where it is more frequent following dental extractions.

Mental neuropathy as a manifestation associated with malignant processes: its significance in relation to patient survival.

PURPOSE: Mental neuropathy (MN) is characterized by the presence of a sensory defect in the form of paresthesias or dysesthesias in the territory innervated by the mental nerve. MN may be the first manifestation of systemic cancer, a symptom of spread of an established tumor, or a sign of infiltration in an intraoral lesion. In any of these cases, the symptom is indicative of a very poor patient prognosis. MATERIALS AND METHODS: A total of 22 cancer patients with chin paresthesia were studied. Group 1 comprised patients with chin paresthesia who had a primary tumor in some other region at a distance from the oral cavity or maxillofacial zone. Group 2 in turn comprised patients with primary malignancies of the oral and/or maxillofacial territory and who likewise presented with chin paresthesia. Data were collected relating to patient age, gender, primary intraoral lesion (location, size, histologic diagnosis), primary systemic tumor, and mean patient survival. RESULTS: Group 1 consisted of 11 patients (8 men and 3 women), aged between 36 and 81 years (mean, 58.09 +/- 14.99 years), with different systemic cancers. The mean survival after the diagnosis of chin paresthesia was 14.8 +/- 16.5 months, and only 1 patient was still alive after 9 months. Group 2 consisted of 11 patients (8 men and 3 women), aged between 33 and 72 years (mean, 56.18 +/- 15.69 years). All presented with oral squamous cell carcinoma, with the single exception of 1 case of fibrosarcoma. In this group the mean survival of the 8 patients who died was 28.2 +/- 29.6 months. Three patients survived for a mean of 17 months. CONCLUSIONS: Chin paresthesia is a very important prognostic symptom determining the degree of infiltration of intraoral lesions, and in some cases it may be indicative of the existence of a primary tumor (identified or otherwise), with poor short-term survival--given that 81.9% of the patients studied (18 cases) had died before a mean of 20 months. Although mean survival was shorter (14.8 months) among the patients in group 1 than in group 2 (28.2 months), the difference was not statistically significant.

An update on the management of anticoagulated patients programmed for dental extractions and surgery.

Oral anticoagulants (OACs) antagonizing vitamin K - fundamentally sodium warfarin and acenocoumarol - are widely used for preventing arterial thromboembolism in patients with atrial fibrillation and/or heart valve prostheses, and for the treatment and prevention of deep venous thrombosis and pulmonary embolism. The handling of these drugs requires correct monitorization and dose adjustment to obtain the desired therapeutic effect while minimizing the adverse effects associated both with excessive anticoagulation (which leads to bleeding) and with insufficient antithrombotic action (which can produce thrombosis). This is particularly important when patients must be subjected to surgical procedures such as tooth extractions. In this context, a number of management recommendations are available. The present study offers an update on the recommendations for the management of anticoagulated patients programmed for tooth extractions. In recent years, most studies do not recommend reducing or interrupting anticoagulation, or replacing it with heparin, prior to tooth extraction - provided therapeutic international normalized ration (INR) levels are maintained, with emphasis on the application of local measures such as antifibrinolytic agents, for the control of hemostasia.

Pediatric dental care in a tertiary public hospital. Four years of experience in the Service of Stomatology of Valencia University General Hospital (Valencia, Spain).

UNLABELLED: A study is made of the experience gained with the Child Oral Care Program (Plan de Atención Dental Infantil, PADI) in the Service of Stomatology of Valencia University General Hospital (Valencia, Spain) after four years in operation (July 2003 - July 2007). STUDY DESIGN: The sample comprised 2626 children between 5-14 years of age, pertaining to department 9 of the Valencian public health system. A clinical history was compiled in each case, a radiological study was made, and a treatment plan was elaborated including fillings, extractions, and control visits. RESULTS: Of the 2626 designated children, 2369 visited our Service - mostly referred from the Preventive Dental Care Units. A total of 5784 fillings were carried out (93.3% with silver amalgam, 5.6% with composites and the rest as provisional fillings). The permanent first molars were the teeth with the largest number of fillings (70.2% of the total). These were followed in order of frequency by the second molars (19.1%). As regards composite resin fillings, most involved the upper central incisors, followed by the upper lateral incisors. A total of 644 extractions were performed, corresponding to 110 permanent teeth and 534 temporary teeth. In the case of the permanent dentition, the first molars were the most commonly removed teeth. In the temporary dentition, the most frequently removed teeth were the second molars. CONCLUSIONS: The response of the population to this program has been very good, and reinforces the preventive measures already in place, with the provision of restorative treatments to improve the oral and dental health of the pediatric population, and yielding good results in terms of the program quality indicators. The Service of Stomatology (Valencia University General Hospital) is able to address the demand and offers the public health network integrated and continuous patient care.

Epstein-Barr virus in oral proliferative verrucous leukoplakia and squamous cell carcinoma: A preliminary study.

The aim of this study was to analyze proliferative verrucous leukoplakia (PVL) and oral squamous cell carcinoma (OSCC) for the possible presence of Epstein-Barr virus (EBV). We studied three groups: Sub-Group 1 was composed of 10 patients with PVL, (6 of whom had developed OSCC); Sub-Group 2 comprised 5 patients with OSCC but no preceding PVL; and Sub-Group 3 were 5 controls with clinically normal oral mucosa. Oral biopsies from all cases were examined for Epstein-Barr virus (EBV) by nested PCR. EBV was detected in 60% of Sub-Group 1 patients (PVL ) and in 40% of Sub-Group 2 (OSCC), but in 0% of Sub-Group 3 (controls).

Benign tumors of the oral mucosa: a study of 300 patients.

OBJECTIVES: To analyze the frequency and type of the most common benign tumors of the oral mucosa found at the Hospital Stomatology Service, and to study the clinical characteristics and possible etiological factors. MATERIAL AND METHODS: This is a retrospective study of 300 patients with histologically diagnosed benign tumors of the oral mucosa. Data was compiled for each case, documenting information relating to age, gender, medication, habits (smoking, oral hygiene), anamnesis (reason for consultation, symptomatology, evolution), and the characteristics of the lesion (site, color, size, surface, consistency, and base). RESULTS: Of all the tumors studied, 53% were histologically diagnosed as fibroma. In the study of prevalence of benign tumors of the oral mucosa, no differences were found for age; however there were differences according to gender, finding a greater prevalence of fibromas, pyogenic granulomas, and giant cell granulomas in women, at a ratio of 2:1. The group of tumors studied showed a significantly asymptomatic behaviour, and self-limiting and slow growth. With respect to the possible etiologic agents, we found no statistically significant differences between them. CONCLUSIONS: Following the study of 300 patients histologically diagnosed with benign tumor of the oral mucosa, we can state that with regard to prevalence, we found significant differences with respect to gender, being more frequent in women. The fibroma is the most frequent benign tumor of the oral cavity.

Efficacy of mycophenolate treatment in adults with steroid-dependent/frequently relapsing idiopathic nephrotic syndrome.

BACKGROUND: This study assessed the efficacy of therapy with mycophenolate (MF) and reduced doses of steroids in adults with steroid-dependent/frequently relapsing idiopathic nephrotic syndrome (SD/FR-INS). METHODS: Twenty-nine nephrotic patients (including 16 males and 13 females; mean age: 40 years, range: 18-74) were treated. Starting doses of MF were 2000 mg/day for mofetil MF (1500 mg/day in one patient) or 1440 mg/day for sodium MF. The initial prednisone (PDN) dose was 10 mg/day in 14 patients, 5 mg/day in two patients and no steroids in one patient. In the remaining 12 patients, moderate initial doses of PDN were administered (mean: 23.7 mg/day, range: 15-40), tapering to 10 mg/day after 1 month. RESULTS: Nephrotic syndrome remission was achieved in 27/29 cases (93.1%) (25 complete, 2 partial). Two patients showed resistance to the prescribed schedule. The first cycle of MF therapy was concluded in 20 patients after a mean (range) of 16.9 months (12-49). Maintenance of remission was observed in 11 of these 20 cases (55%) after a mean follow-up of 32.8 months (12-108). In nine patients with nephrotic syndrome relapse after tapering of MF (MF dependency), the same MF-PDN schedule was restarted, leading again to remission in all nine. The remaining seven MF-sensitive patients are still receiving their first therapeutic cycle. To date, the mean time under therapy in the 27 MF-sensitive patients is 38 months (4-216). Regarding complications, only minor digestive disorders and a slight decrease in blood haemoglobin levels were observed in a few patients. CONCLUSIONS: MF plus reduced doses of PDN is an effective and well-tolerated therapy for adult SD/FR-INS. Though MF dependence is observed, its low toxicity could allow long periods of therapy if it is required to maintain nephrotic syndrome remission.

Psychological assessment of patients with temporomandibular disorders: confirmatory analysis of the dimensional structure of the Brief Symptoms Inventory 18.

OBJECTIVE: This article analyzes the psychometric and structural properties of the Brief Symptoms Inventory 18 in a sample of patients with temporomandibular disorders (TMDs), given the convenience of a brief evaluation of distress in these patients. METHODS: Confirmatory factor analysis was carried out in a sample of 114 patients with TMDs. Two models were tested: the theoretical model with the original structure proposed--which considers three dimensions--and the empirical model obtained through the exploratory factor analysis initially carried out by Leonard R. Derogatis--which consists of the four-factor structure. RESULTS: Both models reached satisfactory indexes in confirmatory factor analysis. Empirical and theoretical reasons led us to prefer the original proposal of three dimensions: somatization, depression and anxiety, and general distress. CONCLUSION: The Brief Symptoms Inventory 18 has been demonstrated to be a reliable and valid tool for the assessment of distress in patients with TMDs, with the advantage of its simplicity and ease of application.

Granulomatous facial reaction to injected cosmetic fillers--a presentation of five cases.

The use of substances to augment soft tissues as aesthetic purpose is associated with, among other undesirable effects, the appearance of foreign body granulomas. The improvements made to these substances have reduced the incidence of adverse reactions, but not eliminated them. We present five cases of foreign body reactions to three different products, dimethylpolysiloxane (silicone), bovine collagen, and polylactic acid, which were injected into the subcutaneous cellular tissue of the patients (all five were women), between two and sixteen years before the appearance of the foreign body reaction. All five presented painless, diffuse facial tumefaction, of firm, elastic consistency. The magnetic resonance image (MRI) studies showed signs of intense inflammatory reaction in the affected areas. The histology revealed the presence of foreign body granulomas with giant multi-nucleated cells. The patients were treated with systemically administered corticoids, except in one case which did not require pharmacological treatment.

Multiple sclerosis as first manifestation in oral and facial area: presentation of four cases.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, whose etiology is unknown, and which is characteristic by the appearance of a diverse neurological symptomatology consisting of outbreaks or gradual deterioration and lesions in any location of the brain s white matter which may provoke the after-effect of a definitive demyelination of the area. The disease affects young people, with its appearance being most frequent between 20 and 40 years of age, in temperate and cold climates, and with a man-woman rate of 0.46/0.67. The magnitude of this disease lies in the fact that it is the primary cause for permanent disablement among young adults. We are presenting 4 cases of MS whose initial symptom of the disease was the appearance of paraesthesia in the maxillofacial area, affecting one or more ramifications of the trigeminal nerve, and a progression time varying from 15 days to one year. All the patients were clinically diagnosed, with their diagnostics being confirmed both with magnetic resonance imaging as well as through the study of their cerebrospinal fluid (CSF) and the evoked potentials (EPs). Manifestations in the oral and facial area were the first manifestation of the disease in all cases.

Goodpasture syndrome during the course of a Schönlein-Henoch purpura.

Two months after surgical resection of a bronchogenic carcinoma, a 69-year-old patient presented with Schönlein-Henoch purpura with kidney involvement followed by pulmonary hemorrhage. The presence of an IgA linear pattern on the kidney biopsy specimen and circulating anti-glomerular basement membrane (GBM) IgA antibodies led to the diagnosis of Goodpasture syndrome, which implies the possibility that the well-known pulmonary involvement during the course of Schönlein-Henoch purpura could be caused by Goodpasture syndrome in certain cases. In cases of glomerulonephropathy with lung involvement, clinicians should not limit their investigations to anti-GBM IgG.

Proliferative verrucous leukoplakia: unusual locations of oral squamous cell carcinomas, and field cancerization as shown by the appearance of multiple OSCCs.

Proliferative verrucous leukoplakia (PVL) is an uncommon entity with a high tendency to develop oral squamous cell carcinomas (OSCCs). The objective of this study was to analyse the presence of various OSCCs in the same patient with PVL. We studied 19 patients with PVL who had developed at least one OSCC. We analysed how many of these developed more than one OSCC over a period between 24 and a maximum of 130 months, indicating the location of their OSCC, clinical type and the time lapse between the appearance of each of the different OSCCs in the same patient. Of the 19 patients, 10 presented more than one of these cancers, one of whom even went on to develop five different cancers. The most frequent location of OSCC was the gingiva and the palate; the least common was the tongue/floor of mouth. Ninety percent were women and 20% were smokers. The average time elapsed between the detection of the first tumour and the appearance of the second was 19.20 months (SD 13.41). Our patients with PVL developed a high frequency of OSCCs, on many occasions manifesting several cancers at different oral locations, thus demonstrating the field cancerization of this entity. The OSCC in PVL patients were at sites quite uncommonly affected in patients who develop OSCC in the absence of PVL.

Psychological variables and temporomandibular disorders: distress, coping, and personality.

OBJECTIVE: This study analyzes the psychological variables of distress, personality, and coping that are related to the diagnosis based on the Research Diagnostic Criteria for temporomandibular disorder. Study design An age and sex-matched controlled study conducted with a convenience sample (n=89) in a tertiary care facility. RESULTS: The MANCOVA between the muscular (n=47), articular (n=42), and control groups (n=100) showed that the muscular group differed from the control group, obtaining higher levels of distress, anxiety, and depression, and minor use of positive reinterpretation and humor as coping strategies; the articular group also showed higher distress, less positive reinterpretation, and a lower interest in the search of instrumental social support than the control group. The coping predictor of distress in both temporomandibular groups was behavioral disengagement; however, the personality predictors differed. Neuroticism and depression were present in the muscular group, whereas conscientiousness and self-discipline were in the articular group. CONCLUSION: Temporomandibular disorder patients have different psychological features than control subjects. There are also some differences between the diagnostic groups that should be considered to address the treatment of these patients.

Enhancing the efficacy of treatment for temporomandibular patients with muscular diagnosis through cognitive-behavioral intervention, including hypnosis: a randomized study.

OBJECTIVE: This study evaluated the efficacy of a cognitive-behavioral therapy (CBT), including hypnosis, in patients with temporomandibular disorders (TMDs) with muscular diagnosis. STUDY DESIGN: Seventy-two patients (65 women and 7 men with an average age of 39 years) were selected according to the Research Diagnostic Criteria for TMD, and assigned to the experimental group (n = 41), receiving the 6-session CBT program, and the control group (n = 31). All patients received conservative standard treatment for TMD. The assessment included pain variables and psychologic distress. RESULTS: There were significant differences between the groups, the experimental group showing a higher improvement in the variables evaluated. Specifically, 90% of the patients under CBT reported a significant reduction in frequency of pain and 70% in emotional distress. The improvement was stable over time, with no significant differences between posttreatment and 9-month follow-up. CONCLUSIONS: CBT, including hypnosis, significantly improved conservative standard treatment outcome in TMD patients.