Neurophysiological findings of the late-onset, dominant, proximal spinal muscular atrophies with dysautonomia because of the VAPB PR056SER mutation

The vesicle-associated membrane protein/synaptobrevin-associated membrane protein B (VAPB) Pro56Ser Mutation has been identified in Brazilian families showing various motor neuron syndromes. However, the neurophysiological characteristics of these patients have not been detailed, and some questions Still need to be solved, such as the possible presence of myotonia and the origin of the abdominal protrusion seen in most patients. The eventual finding of suggestive electrophysiological characteristics would be helpful not only for clinical diagnosis but also to selection of the appropriate DNA test. To clarify these questions we carried out sensory and motor conduction Studies, including symphatetic skin response, and needle examination in six genetically proven affected members. The electromyographic findings were those of a slowly progressive motor neuron disorder. Topographically, the abdominal muscles were severely affected, but the facial and laryngeal muscles were preserved or very mildly involved. Sensory conduction studies and sympathetic Skin responses were normal. No myotonic discharge was recorded. These findings are indistinguishable from those of other motor neuron disorders, although the predominant involvement of the proximal limbs and of the abdominal muscles may be of some help in the appropriate clinical setting.

Characterizing the phenotypic manifestations of MFN2 R104W mutation in Charcot-Marie-Tooth type 2

Mutations of the mitofusin 2 (MFN2) gene have been reported to be the most common cause of the axonal form of Charcot Marie Tooth disease (CMT). The aim of this study was to describe a de novo MFN2 p.R104W mutation and characterize the associated phenotype. We screened the entire coding region of MFN2 gene and characterized its clinical phenotype, nerve conduction studies and sural nerve biopsy. Neuropsychological tests and brain MRI were also performed. A de nova mutation was found in exon 4 (c.310C > T; p.R104W). In addition to a severe and early onset axonal neuropathy, the patient presented learning problems, obesity, glucose intolerance, leukoencephalopathy, brain atrophy and evidence of myelin involvement and mitochondrial structural changes on sural nerve biopsy. These results suggest that MFN2 p.R104W mutation is as a hot-spot for MFN2 gene associated to a large and complex range of phenotypes. (C) 2011 Elsevier B.V. All rights reserved.

Electrophysiologic Activity of the Vestibular Fold

Objectives: To assess the vestibular fold muscle after cordectomy and laryngeal reconstruction, the pattern of motor unit recruitment during sound emission, and the morphologic characteristics of motor unit action potentials. Design: Prospective analysis. Setting: Tertiary academic hospital. Patients: We evaluated 11 men (mean age, 65.7 years; age range, 53-82 years) who underwent laryngofissure, cordectomy, and laryngeal reconstruction with a vestibular fold flap. Interventions: Laryngeal electromyography with the insertion of a needle electrode for the assessment of the electrophysiologic activity of thyroartenoid muscle fibers and of the cricothyroid muscle on the operated on and nonoperated on sides. The thyroarytenoid muscle was evaluated by introducing a needle electrode through the thyroid cartilage and the cricothyroid membrane. Main Outcome Measures: Activities of needle insertion, spontaneous muscle activity during rest, and pattern of motor unit recruitment. Results: Seven patients (64%) had vestibular fold muscle fiber, all of whom showed motor unit recruitment in response to sound emission. No neurogenic muscle injuries were observed except in 1 patient with evidence of chronic injury. Conclusion: After cordectomy and laryngeal reconstruction, thyroarytenoid muscle fibers are present in the vestibular fold, with motor unit recruitment during sound emission.

NF-kappa b expression predicts clinical outcome for nasal polyposis

Objective: To correlate clinical prognosis of patients with nasal polyps to the expression of p65, c-Fos, GR alpha and GR beta. Methods: A biopsy was obtained at the first evaluation of patients with nasal polyps, and at rhinoplasty for control mucosa. Patients with nasal polyps were treated with glucocorticoids and followed for at least 60 months. The expression of p65, c-Fos, GR alpha and GR beta was determined by Real Time-PCR and correlated to clinical outcome. The end-point of resistance to glucocorticoid therapy was considered when surgery was indicated. Results: Patients with nasal polyps presented a higher expression of p65, a lower expression of GR alpha, and a lower GR alpha/GR beta ratio than control mucosa. The patients with nasal polyps who had a higher expression of p65 correlated with a poorer response to glucocorticoids, with a 3.5-fold higher risk for surgery. Conclusion: Patients with a higher p65 (NF-kappa B) expression at diagnosis were associated to a worse response to clinical treatment, suggesting one of the mechanisms of cell resistance to glucocorticoid treatment in patients with nasal polyps.

Expression of genes that encode the annexin-1 and galectin-1 proteins in nasal polyposis and their modulation by glucocorticoid

Rhinosinusal polyps physiopathology is not fully understand, despite numerous hypotheses regarding its inflammatory process. Aims: a prospective study regarding the gene expression of proteins: anexin-1 and galectin-1, which has an anti-inflammatory action and is modulated by steroids. Materials and Methods: eleven patients with rhinosinusal polyps suffered a biopsy of their polyps at two moments: in the absence of systemic steroids and during its use. In the two samples we assessed the expression of these genes and compared it to the normal nasal mucosa in the middle meatus. Results: We noticed that the mean expression of the genes which code anexin-1 and galectin-1 was predominantly increased, regardless of the use of steroids in relation to the control nasal mucosa. Notwithstanding, in polyps without the use of steroids, the mean gene expression of anexin-1 was significantly higher than in the polyps which were under the use of steroids. Regarding galectin-1, there was no significant difference between the expression mean values before and after the use of systemic steroids. Conclusion: The genes present an expression increase in the polyp mucosa, regardless of the use of steroids; nonetheless, the relationship of these two genes of anti-inflammatory proteins with steroids did not happen the same way.

Interieukin-17 and Kidney Allograft Outcome

Acute rejection episodes (ARE) are important complications that involve the interplay between mechanisms that maintain graft tolerance and promote rejection. The proinflammatory cytokine interieukin-17 (IL-17) has been implicated in many conditions in humans and mice. In kidney transplant patients, the evaluation IL-17 levels has been performed in only a few patients. We performed a cross-sectional study correlating quantitative IL-17 levels and clinical outcomes. Patients and methods. We studied 19 specimens from biopsies performed in patients (n = 19) who received isolated kidney grafts. ARE signs were present in 9 (47%) patients who provide specimens; whereas, 10 (53%) others showed no signs of rejection. Eighteen healthy control sample IL-17 underwent measurement, all of which were performed by an enzyme-linked immunosorbent assay method. We assessed other factors, such as the recipients demographic data, cold ischemia time, HLA mismatches, time elapsed from transplantation to the biopsy, posttransplantation status, antibody panel, donor type, and immunosuppressive treatment. Results. IL-17 levels were clearly increased among samples derived from patients with ongoing rejection (125.7 +/- 27.06 pg/mL) in contrast, to the nonrejection group, (30 +/- 13.32 pg/mL) (P < .05). Healthy controls showed no detectable IL-17 levels. Conclusions. These findings suggested that IL-17 was important in the pathophysiology of acute kidney rejection.

Superior oblique muscle amyloidosis mimicking myositis

A 47-year-old man presented with complaints of progressive diplopia in downgaze and a painful firm mass on the left medial superior canthus. On examination, there was marked hyperemia of the superior bulbar conjunctiva of the left eye. Systemic examination revealed erythematous papules on his trunk and pulmonary infiltrates. CT of the orbits revealed a fusiform enlargement of the left superior oblique muscle and diffuse infiltration of the left temporal region. Biopsy of the left superior oblique muscle and temporal muscle disclosed Congo red deposits that show apple-green birefringence under polarized light. A comprehensive systemic investigation failed to show any disease that could explain the amyloid deposits. The patient was then diagnosed as having primary systemic amyloidosis. We think that this case highlights the necessity of a biopsy in any atypical extraocular muscle enlargement before a diagnosis of myositis.

Advantages and Pitfalls of the Polymerase Chain Reaction in the Diagnosis of Esophageal Ulcers in AIDS Patients

HIV-1-infected patients frequently have opportunistic esophageal infections which, when associated with severe immunodeficiency, can be attributed to unusual pathogens. The clinical presentation of several esophageal diseases is similar and the best method for a specific diagnosis of these patients has not been well defined. To evaluate the role of the polymerase chain reaction (PCR) in the etiologic definition of esophageal ulcers in HIV-1-infected patients, 96 esophageal biopsies from 79 HIV-1-infected patients were processed by PCR using specific primers for cytomegalovirus (CMV), herpes virus (HSV), human papilloma virus (HPV), HIV-1, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Treponema pallidum, and Haemophilus ducreyi. The PCR results were compared to the histopathologic results. Seventy-nine patients were studied (mean age: 34 years; 62% men; median CD4 + T cell = 103.59 cells/mu l (range 1-795.2 cells/mu l). The most common endoscopic findings were as follows: esophageal candidiasis (37.1%), esophageal ulcers (24.7%), esophagitis (11.2%), and lugol-negative areas (10.1%). The histopathologic findings in the esophageal ulcers (22 biopsies) were non-specific inflammation (31.8%), HSV (36.4%), Candida (13.6%), CMV (13.6%), or HPV disease (4.5%). In the esophageal ulcer biopsies, the PCR results were negative in 27.6% of cases, and positive for HIV (65.5%), CMV (31%), HPV (20.7%), HSV (10.3%), and H. ducreyi (6.9%). The histopathologic examination did not identify a pathogen or identified only Candida in 15 biopsies of esophageal ulcers. PCR was positive in ten (66.7%) and negative in five (33.3%) of these biopsies (idiopathic ulcers). PCR detected: HIV (53.3%), CMV (20%), HPV (13.3%), and H. ducreyi (6,7%). PCR detected more etiologic agents in esophageal ulcers than histopathology and was able to detect unusual pathogens. On the other hand, sometimes more than one pathogen was detected in the esophageal ulcers, making it difficult to reach an accurate diagnosis. This finding indicates the need for more studies to evaluate the benefit of this method in the routine evaluation of esophageal ulcer biopsies in HIV-1-infected patients.

Magnetic Resonance Angiography in Extracranial Giant Cell Arteritis

Background: Noninvasive diagnosis of giant cell arteritis (GCA) remains challenging, particularly with regard to evaluation of extracranial arterial disease. Objectives: The objective of the study was to retrospectively review extracranial involvement in patients with GCA and/or polymyalgia rheumatica (PMR), evaluated with magnetic resonance imaging (MRI), especially 3-dimensional contrast-enhanced magnetic resonance angiography images of the aortic arch and its branches. Methods: Clinical information, biopsy status, and MRI examinations of 28 patients with GCA/PMR were reviewed. Patient images were mixed randomly with 20 normal control images and were independently reviewed by 2 radiologists. Interobserver agreement for detection of arterial stenosis was determined by the k coefficient. Results: Both readers described vascular alterations in keeping with extracranial GCA in 19 of 28 patients (67%) with good interobserver agreement (k = 0.73) and with even higher agreement on diagnosing nonocclusive versus occlusive disease (k = 1.00). The most common lesions were bilateral axillary stenosis or obstructions, observed by both readers in 8 patients (28%). Among the 19 patients with magnetic resonance angiography lesions in the subclavian/axillary arteries, 12 (75%) had biopsy-proven GCA, but only 5 (41%) of these patients had clinical features of large artery disease. Conclusions: In our series review, MRI could provide accurate information on involvement of the aortic arch and its branches in extracranial GCA, depicting different degrees of stenosis. Our analysis also illustrates that occult large artery vasculitis should be considered in patients without biopsy-proven GCA, patients with classic GCA but without clinical signs of large artery disease, and in patients initially diagnosed as having PMR.

The Impact of Preexisting Myocardial Remodeling on Ventricular Function Early after Tetralogy of Fallot Repair

Background: Twenty-three patients (median age 23 months) who underwent Fallot`s tetralogy repair were investigated prospectively to detect a possible association between histopathologic myocardial remodeling and echocardiographic findings of systolic or diastolic ventricular dysfunction. Methods: Intraoperatively resected infundibular bands and subendocardial biopsy samples from the right ventricle (RV) and left ventricle were obtained for histopathologic evaluation. Tissue Doppler echocardiographic interrogation of the ventricles was performed before surgery and in the postoperative period. Results: Histopathologic data revealed hypertrophy of the RV cardiomyocytes and increased interstitial collagen in both ventricles. Mean values of RV isovolumic acceleration decreased significantly at the third evaluation compared with the preoperative values (P = .006). RV myocardial fibrosis greater than 8.3% was associated with a probability of altered E` of at least 0.7 (odds ratio = 2.31). Conclusion: Preoperative histologic myocardial remodeling influenced the postoperative RV function in this group of patients with late repair. Further studies are necessary to evaluate the myocardium in younger patients and to define its influence in the long-term follow-up. (J Am Soc Echocardiogr 2010;23:912-8.)

Extramedullary plasmacytoma of the third eyelid gland in a dog

A case of extramedullary plasmacytoma of the third eyelid gland in a 7-year-old American Cocker Spaniel is reported. An enlargement of the third eyelid gland, abundant mucopurulent discharge, mild hyperemia and corneal pigmentation in the OD was present. Excisional biopsy of the mass revealed the gland was infiltrated and partially destroyed by a uniform population of neoplastic plasma cells. The neoplastic cells were positive for CD138, Ki-67 and lambda light chain. CD20, CD3, kappa light chain and cytokeratin were negative. Twelve months following surgery, no recurrence was observed. To the authors` knowledge, this is the first extramedullary plasmacytoma of the third eyelid gland reported in dogs.

Experimental infection of the rabbit tick, Haemaphysalis leporispalustris, with the bacterium Rickettsia rickettsii, and comparative biology of infected and uninfected tick lineages

The present study consisted of two experiments that evaluated experimental infections of Haemaphysalis leporispalustris ticks by a Brazilian strain of Rickettsia rickettsii, and their effect on tick biology. In experiment I, ticks were exposed to R. rickettsii during the larval, nymphal or adult stages by feeding on rabbits (Oryctolagus cuniculus) needle-inoculated with R. rickettsii, and thereafter reared on uninfected rabbits for the entire next tick generation. Regardless of the tick stage that acquired the infection, all subsequent tick stages were shown to be infected by PCR (infection rates varying from 1.3 to 41.7%), and were able to transmit R. rickettsii to uninfected rabbits, as demonstrated by rabbit seroconversion, guinea pig inoculation with rabbit blood, and PCR on rabbit blood. In Experiment II, ticks were exposed to R. rickettsii during the larval stage by feeding on rabbits co-infested with R. rickettsii-infected adult ticks, and thereafter reared on uninfected rabbits until the next generation of larvae. Again, all subsequent tick stages were shown to be infected by PCR (infection rates varying from 3.0 to 40.0%), and were able to transmit R. rickettsii to uninfected rabbits. Thus, it was demonstrated that larvae, nymphs, and adults of H. leporispalustris were able to acquire and maintain the R. rickettsii infection by transstadial and transovarial transmissions within the tick population, with active transmission of the bacterium to susceptible rabbits by all parasitic stages. Analyses of biological parameters of uninfected and R. rickettsii-infected tick lineages were performed in order to evaluate possible deleterious effects of R. rickettsii to the infected tick lineages. Surprisingly, all but one of the four R. rickettsii-experimental groups of the present study showed overall better biological performance than their sibling uninfected control ticks. Results of the present study showed that H. leporispalustris could support infection by a high virulent strain of R. rickettsii for at least two generations, in which infected tick lineages tended to have better performance than uninfected ticks. Our results support a possible role of H. leporispalustris in the enzootic maintenance of R. rickettsii in Latin America, as previously suggested by earlier works.

Use of laser phototherapy on a delayed wound healing of oral mucosa previously submitted to radiotherapy: case report

Radiotherapy produces both acute and delayed effects on mucosal tissues, disturbing their healing. This report shows a successful treatment with laser phototherapy (LPT) on a delayed wound healing in oral mucosa previously submitted to radiotherapy with a follow up of 3 years. A 47-year-old patient treated 6 months earlier for tongue squamous cell carcinoma by surgery and radiotherapy presented with a mass in the operated area. Biopsy showed chronic inflammatory infiltrate around a residual polyglactin suture. After 2 months there was a painful mucosal dehiscence on the biopsy site. LPT was performed using a semiconductor laser with 660-nm wavelength (InGaAlP) and spot size of 0.04 cm(2). The parameters applied were 40 mW, 4 Jcm(2)/point, 0.16 J/point, 2.4 J/session. The irradiation was performed punctually, through contact mode in 15 points (4 seconds/point), on top of and around the lesion, during ten sessions. The wound healed completely after ten sessions. This treatment proved to be conservative and effective, inducing healing of a chronic wound in a tissue previously submitted to radiotherapy.

Follicular lymphoma in the palate with clinical appearance similar to salivary gland tumors

Intraoral presentation of follicular lymphoma is rare, and only three cases in the palate have been reported to date. The present case report describes an uncommon case of follicular lymphoma affecting the palate. The clinical aspect was similar to salivary gland neoplasm, and an incisional biopsy was important to establish the correct diagnosis and consequently to plan the treatment. Also discussed is the differential diagnosis among follicular lymphoma, mucosa-associated lymphoid tissue lymphoma, and follicular lymphoid hyperplasia with regard to the histopathologic and immunohistochemical features. (Quintessence Int 2010; 41: 661-663)

Cheilitis glandularis: A clinicopathological study in 22 patients

Background: Cheilitis glandularis (CG) is a condition in which thick Saliva is secreted by minor labial salivary glands and adheres to a swollen lip causing discomfort to the patient. Most Publications refer to single case reports or small case series. Objective. We sought to report and to analyze clinical, pathological, and therapeutic data oil 22 patients with CG seen at the department of dermatology at our university. Method: Retrospective data about 22 patients with CG are reviewed and presented. Results: Seventeen patients were male and 5 were female. All were fair skinned, including 6 albino individuals. Several of them presented significant signs of photodamage on the lips. treatment was performed in 10 severely affected patients and consisted of I vermilionectomy followed by minor salivary gland removal. Histopathological Study revealed Various degrees of chronic sialadenitis and vermilion epithelial changes. Superficially invasive and in Situ squamous cell carcinoma of the vermilion was detected in 3 cases. Limitations: Biopsy and surgery were not performed in all patients. Conclusions: CG is strongly related to Sun sensitivity and may be more severe in albino patients. The swollen, sun-exposed lip may become more susceptible to the occurrence of squamous Cell carcinoma. (J Am Acad Dermatol 2010;62:233-8.)