Lingual fasciculation: A point of call for the diagnosis of amyotrophic lateral sclerosis.

A 60-year-old female patient, with no notable medical history, was referred by the internal medicine department for a dry mouth workup. The clinical examination revealed an absence of dryness, and the presence of lingual fasciculations, associated with difficulties in mastication and phonation. These symptoms appeared spontaneously 9 months before the consultation, after leaving confinement. Given the presence of lingual fasciculations, the diagnostic hypothesis of a neurological pathology, in particular amyotrophic lateral sclerosis (ALS), was suspected. After performing an electromyogram (EMG), the diagnosis of ALS was retained. Riluzole treatment was then started, and physical therapy sessions were scheduled. Riluzole allows an average gain of 4 to 6 months of life expectancy. Speech therapy and physical therapy allow to maintain the functions as long as possible and to improve the end-of-life conditions. The interest of early detection of ALS allows delaying the progression of the disease.

Oral giant cell tumor or giant cell granuloma: How to know?

Introduction: The distinction between giant cell tumors and giant cell granulomas is challenging, as both entities have overlapping diagnostic criteria, especially in oral locations. The two entities have similar clinical and radiological presentations, but they differ in their prognoses. Objective: The main objective of this study was to list the clinical, radiological, histological, and prognostic features of maxillomandibular giant cell tumors and giant cell granulomas cases n order to assess their value as a diagnostic referral factor that may allow the distinction between maxillo-mandibular giant cell granuloma and giant cell tumor. Study design: Data of maxillomandibular giant cell granulomas and giant cell tumors were assessed through a scoping review and a pre-existing systematic review of literature. We have also realized a bicentric retrospective study. Results: Various criteria facilitate the differential diagnosis like age, size, locularity and presence of necrosis zone but not the gender. The most discriminating factors was symptomatology (reported in 72% of GCTs while only 15% of GCGs) and the distribution pattern of giant cells in the stroma (homogeneously dispersed in 80% of GCTs versus grouped in clusters in 86.7% of GCGs). Recurrences were most described for giant cell tumors than giant cell granulomas. Malignant transformation and pulmonary metastasis were exclusively reported for giant cell tumors. Conclusion: As clinical and radiological elements are not sufficient to distinguish between these two entities, immunohistochemistry and molecular genetics can be represent diagnostic biomarkers to distinguish giant cell granulomas and giant cell tumors in oral cavity. We have attempted to define the main criteria for the differentiation of giant cell tumor and giant cell granuloma and propose a decision tree for the management of single maxillomandibular giant cell lesions.

French guidelines for the management of oral lichen planus (excluding pharmacological therapy).

INTRODUCTION: Oral lichen is a chronic inflammatory disease for which diagnostic management and follow-up are heterogeneous given the absence of specific guidelines in France. Our objective was to develop French multidisciplinary guidelines for the management of oral lichen. MATERIALS AND METHODS: Working groups from the Groupe d'Etude de la Muqueuse Buccale (GEMUB) formulated a list of research questions and the corresponding recommendations according to the "formal consensus" method for developing practice guidelines. These recommendations were submitted to a group of experts and the degree of agreement for each recommendation was assessed by a scoring group. RESULTS: Twenty-two research questions, divided into 3 themes (nosological classification and initial assessment, induced oral lichenoid lesions, and follow-up) resulted in 22 recommendations. Initial biopsy for histology is recommended in the absence of reticulated lesions. Biopsy for direct immunofluorescence is recommended for ulcerated, erosive, bullous types and for diffuse erythematous gingivitis. Management should include a periodontal and dental check-up, and investigation for extra-oral lesions. Hepatitis C testing is recommended only if risk factors are present. Definitions, triggering factors and the management of "induced oral lichenoid lesions" were clarified. Oral lichen must be monitored by a practitioner familiar with the disease at least once a year, using objective tools. CONCLUSION: This formalised consensus of multidisciplinary experts provides clinical practice guidelines on the management and monitoring of oral lichen.

Preclinical evaluation of mRNA trimannosylated lipopolyplexes as therapeutic cancer vaccines targeting dendritic cells.

Clinical trials with direct administration of synthetic mRNAs encoding tumor antigens demonstrated safety and induction of tumor-specific immune responses. Their proper delivery to dendritic cells (DCs) requires their protection against RNase degradation and more specificity for dose reduction. Lipid-Polymer-RNA lipopolyplexes (LPR) are attractive mRNA delivery systems and their equipment with mannose containing glycolipid, specific of endocytic receptors present on the membrane of DCs is a valuable strategy. In this present work, we evaluated the capacity of LPR functionalized with a tri-antenna of α-d-mannopyranoside (triMN-LPR) concerning (i) their binding to CD209/DC-SIGN and CD207/Langerin expressing cell lines, human and mouse DCs and other hematopoietic cell populations, (ii) the nature of induced immune response after in vivo immunization and (iii) their therapeutic anti-cancer vaccine efficiency. We demonstrated that triMN-LPR provided high induction of a local inflammatory response two days after intradermal injection to C57BL/6 mice, followed by the recruitment and activation of DCs in the corresponding draining lymph nodes. This was associated with skin production of CCR7 and CXCR4 at vaccination sites driving DC migration. High number of E7-specific T cells was detected after E7-encoded mRNA triMN-LPR vaccination. When evaluated in three therapeutic pre-clinical murine tumor models such as E7-expressing TC1 cells, OVA-expressing EG7 cells and MART-1-expressing B16F0 cells, triMN-LPR carrying mRNA encoding the respective antigens significantly exert curative responses in mice vaccinated seven days after initial tumor inoculation. These results provide evidence that triMN-LPR give rise to an efficient stimulatory immune response allowing for therapeutic anti-cancer vaccination in mice. This mRNA formulation should be considered for anti-cancer vaccination in Humans.

A hair on the tongue.

INTRODUCTION: Human hairs are generally localized on the cutaneous part of the head, neck, torso, armpits, pubis and limbs. Sometimes it can be found in an unusual localization and is then called heterotopic. OBSERVATION: A 30-year-old man presented with a hair in the middle of the dorsum of the tongue. It was decided to perform an excision under local anesthesia. DISCUSSION: Few reports exist that describe hair growing on mucosa. Only one other case has been published concerning the tongue.

High hepatitis C virus prevalence and incidence among Canadian intravenous drug users.

We used data and leftover samples collected through the SurvUDI network to describe the epidemiology of hepatitis C virus (HCV) infection among injection drug users (IDUs) in Eastern Central Canada. Among the 1380 selected IDUs, having participated twice or more between 1997 and 2003, the overall HCV prevalence rate was 60.4% (95% confidence interval [CI]: 57.7-63.0%). Among the 543 initially uninfected participants, the HCV incidence rate was 27.1 per 100 person-years (95% CI: 23.4-30.9 per 100 person-years). Independent predictors of seroconversion, identified among 359 participants, were age, injecting for a year or less, injecting with a syringe previously used by someone else, injecting most often cocaine, engaging in prostitution, and being recruited in a major urban centre. The HCV epidemic severely affects IDUs in this area. Actions to prevent HCV transmission, such as distribution of sterile injection equipment, have to be reinforced. Special efforts have to be targeted towards starting IDUs.

Fibrous encapsulation of single polymer microfibers depends on their vertical dimension in subcutaneous tissue.

The purpose of this research was to investigate possible explanations for why small-diameter microfiber implants do not experience encapsulation in subcutaneous tissue as do large-diameter fiber implants. Single polypropylene microfibers of approximately rectangular cross-section with rounded edges were twisted about their longitudinal axes and affixed at their ends to polycarbonate frames. The frames were implanted in rat subcutaneous dorsum for a 5-week period, then removed and processed for light microscopy analysis. Fibrous capsule presence/absence and thickness around the implants were assessed, and their relationships to geometric features of the fibers investigated. A logistic regression analysis between presence/absence of a fibrous capsule and geometric features of interest demonstrated strong predictive ability (92.4% correct predictions) for implant height and a well-defined threshold separating the presence and absence of a fibrous capsule at 5.9 microm (p < 0.001). Implant height was defined as the vertical distance between the most superficial and deepest level of the implant. This 5.9-microm threshold value of implant height is comparable to the 6.0-microm diameter threshold for capsule presence/absence in fibers of circular cross-section [Sanders et al. J Biomed Mater Res 2000; 52(1):231-237]. Fiber major axis length, minor axis length, aspect ratio, surface area per unit length, implant width, and implant angle did not show similar predictive ability or a well-defined threshold separating the presence and absence of a fibrous capsule. It is reasoned that for fibers greater than the threshold height of 5.9 microm, separation of collagen fibers in the extracellular matrix creates dead space regions adjacent to the fibers that attract inflammatory cells and stimulate fibrous capsule formation.

Short-term effect on growth of two doses of GRF 1-44 in children with growth hormone deficiency: comparison with growth induced by methionyl-GH administration.

In a double-blind study 12 prepubertal children with idiopathic growth hormone (GH) deficiency were treated with growth hormone releasing factor (GRF) 1-44 in a dosage of 7.5 or 15 micrograms/kg body weight, administered once a day subcutaneously. With 7.5 micrograms/kg the average growth velocity increased from 2.5 to 4.6 cm/year, an insufficient response. With the higher dosage the average growth velocity increased from 2.7 to 7.0 cm/year, a similar increase as observed with GH therapy in subsequent periods. In 3 of the 6 children treated with the higher dose appropriate catch-up growth was observed. The growth response of the lower leg length was not always consistent with the statural growth response.

[Efficacy and kinetics of chlorazepate administered to anxious patients in a single daily dose]. / Efficacité et cinétique du clorazepate administré en une dose unique quotidienne chez des anxieux.

Twelve patients of both sexes (5 women, 7 men; mean age = 39,9) suffering from marked anxiety as defined by DSM III for generalised anxiety (score greater than 20 on the Hamilton-A scale) but in good physical health, were given 15 mg of clorazepate daily at 8 p.m. for a period of 28 days. Desmethyldiazepam, the active metabolite of clorazepate was measured in blood samples on day 1, 14 and 28 of the experiment as well as the level of anxiety on the Hamilton scale. Anxiety decreased significantly between day 1 and day 14 (mean score declining from 33,9 to 18,4) and from day 14 to day 28 (mean score 18,4 to 14,7). Desmethyldiazepam reached its maximum blood concentration 2 hours after the first intake of clorazepate. A plateau had been reached at day 14 and remained stable up until day 28, indicating the absence of cumulating effects. The dosage remained the same for all patients during the 28 days of the experiment. There were no drop outs and no undesirable effects.

Pemoline pharmacokinetics and long term therapy in children with attention deficit disorder and hyperactivity.

The pharmacokinetic behaviour of pemoline was studied in 28 children, aged 5 to 12 years, diagnosed as having the attention deficit disorder with hyperactivity. The mean elimination half-life of pemoline in these children was approximately 7 hours, which is considerably shorter than the half-life of 11 to 13 hours previously reported in adults. The tendency of the half-life to increase with age may be explained by the statistically significant decrease in total body clearance with age. The increasing half-life of pemoline with age should be considered during long term drug therapy. In this study no tolerance to the beneficial effects of pemoline was observed over 6 months. The apparent therapeutic serum concentration range for these children was attained after doses of 37.5 to 131.25 mg pemoline daily. Since the optimum serum concentration shows wide variation, the dosing regimen must be determined individually. Routine monitoring of the pemoline serum concentrations is not useful because of this apparent variation in optimum serum concentration and because of the linear relationship between dose and concentration.

Plasma estrone sulfate levels in postmenopausal women.

Estrone sulfate levels were measured in the plasma of 63 postmenopausal women. The assay method involved prior extraction of the free estrogens, enzyme hydrolysis of the estrone sulfate with sulfatase and radioimmunoassay of the estrone liberated. The plasma levels ranged from 37 to 320 pg/ml (expressed as free estrone) with a mean value of 178 +/- 79 pg/ml. As observed in premenopause, estrone sulfate is quantitatively the most important circulating estrogen in postmenopausal women.

Analysis of pemoline in serum by high performance liquid chromatography: clinical application to optimize treatment of hyperactive children.

The analysis of pemoline (2-imino-5-phenyl-4-oxazolidine) by a rapid, sensitive, and specific high performance liquid chromatographic assay using ultraviolet detection is described. Only 100 microliters of plasma or serum is required. Analytical recoveries of 88% for pemoline and 93% for the internal standard (4-methylprimidone) are obtained by this procedure. Between-day precision studies of serum controls containing 10.2, 2.0, and 0.5 mg pemoline/liter produce coefficients of variation of 6.2, 9.4, and 16.2%, respectively. A clinical study of 28 children treated with pemoline demonstrated a linear relationship between drug dose and serum concentrations with an apparent therapeutic range falling between 1.7 and 7.0 mg/liter. These serum concentrations were achieved at drug dosages between 37.5 and 112.5 mg/day.

The responses to synthetic luteinizing hormone-releasing hormone in patients with primary selective pituitary deficiency in gonadotropins.

Fifteen patients, 11 female and four male, with primary selective pituitary deficiency in gonadotropins were submitted to the subcutaneous administration of 100 to 400 mcg. of luteinizing hormone-releasing hormone (LH-RH). When compared to the effect of LH-RH in eight normal female subjects, two types of responses were observed: there were either small increments in both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) or increases comparable to those observed in normal subjects. Five patients received 100 mcg. of LH-RH daily over four consecutive days. No additive nor depleting effects could be observed. The responses in seven patients given 400 mcg. were not significantly different from those obtained with 100 mcg. Our results indicate two possible etiologies of primary hypogonadotropic hypogonadism. A normal response in LH and FSH after administration of LH-RH assesses a selective hypothalamic deficit in releasing hormones, whereas a negative or low response suggests a dysfunction of the pituitary gonadotropic cell.

Pituitary responsiveness to gonadotrophin releasing factor (GnRH) in puerperium.

Administration of a single dose of Gondotrophin Releasing Factor (GnRF) failed to induce an increase in serum FSH immediately postpartum suggesting pituitary refractoriness. However, multiple injection of GnRF resulted in significant FSH increments but these were less than the FSH responses to a single injection of GnRF in normal menstruating women.