Addition of magnesium sulfate to bupivacaine improves analgesic efficacy after tonsillectomy: A randomized trial and a CONSORT analysis.

OBJECTIVES: The main objective of this study was to compare the wound infiltration (peritonsillar fossa) of magnesium sulphate combined with bupivacaine, bupivacaine alone and saline solution on post-tonsillectomy pain in children. The accessory objectives were to evaluate the effect of magnesium sulphate infiltration on prevention of laryngospasm and occurrence of nausea/vomiting. METHODS: This study is a prospective; double blinded and randomized clinical trial. Seventy-five children undergoing tonsillectomy were enrolled. Patients were randomized into three groups using closed envelop technique. Group 1 (N=24) received saline solution (NaCl), group 2 (N=25) received 0.25% bupivacaine (1mg/kg) and group 3 received magnesium sulphate (5mg/kg) and 0.25% bupivacaine (1mg/kg) after tonsillectomy using three-point technique. Pain was evaluated using mCHEOPS scale. The occurrence of laryngospasm, nausea and vomiting was monitored. RESULTS: The mCHEOPS scores of the group 3 were significantly lower than those of the group 2 and 1 (P<0.001). Time to first analgesic administration was longer for the group 3 than for the groups 2 and 1 (P<0.001). The mean consumption of additional analgesic drugs was lower for the group 3 than the other groups (P<0.001). There were no episodes of laryngospasm in the group 3 in comparison with the other groups. The difference of the incidence of nausea and vomiting was not statistically significant (P=0.628). CONCLUSION: The adjunction of magnesium sulphate to bupivacaine proved to provide more efficient pain control than bupivacaine alone. However, the small number of participants and the absence of sampling at the P level of 0.005 do not allow to conclude with absolute certainty.

[Parathyromatosis: An uncommon cause of recurrent hyperparathyroidism]. / Parathyromatose : une cause rare d'hyperparathyroïdie récidivante.

INTRODUCTION: Parathyromatosis is a rare cause of recurrent hyperparathyroidism. It results from hyperfunctioning parathyroid tissue scattered throughout the thyroid bed region. CASE REPORT: A 51-year-old man with a history of parathyroidectomy, presented 18 years later with recurrent primary hyperparathyroidism. Surgical exploration identified a single parathyroid gland. The act was completed by a central compartment dissection and ipsilateral lobectomy. The patient was free of recurrence after a one-year follow-up. CONCLUSION: Parathyromatosis a rare cause of recurrent hyperparathyroidism. Its management is challenging. Extensive surgery is required with clearance of the central neck compartment and homolateral lobectomy. Medical therapy could be used to decrease parathormone level in recurrent parathyromatosis.

Biomechanisms of Comorbidity: Reviewing Integrative Analyses of Multi-omics Datasets and Electronic Health Records.

OBJECTIVES: Disease comorbidity is a pervasive phenomenon impacting patients' health outcomes, disease management, and clinical decisions. This review presents past, current and future research directions leveraging both phenotypic and molecular information to uncover disease similarity underpinning the biology and etiology of disease comorbidity. METHODS: We retrieved ~130 publications and retained 59, ranging from 2006 to 2015, that comprise a minimum number of five diseases and at least one type of biomolecule. We surveyed their methods, disease similarity metrics, and calculation of comorbidities in the electronic health records, if present. RESULTS: Among the surveyed studies, 44% generated or validated disease similarity metrics in context of comorbidity, with 60% being published in the last two years. As inputs, 87% of studies utilized intragenic loci and proteins while 13% employed RNA (mRNA, LncRNA or miRNA). Network modeling was predominantly used (35%) followed by statistics (28%) to impute similarity between these biomolecules and diseases. Studies with large numbers of biomolecules and diseases used network models or naïve overlap of disease-molecule associations, while machine learning, statistics, and information retrieval were utilized in smaller and moderate sized studies. Multiscale computations comprising shared function, network topology, and phenotypes were performed exclusively on proteins. CONCLUSION: This review highlighted the growing methods for identifying the molecular mechanisms underpinning comorbidities that leverage multiscale molecular information and patterns from electronic health records. The survey unveiled that intergenic polymorphisms have been overlooked for similarity imputation compared to their intragenic counterparts, offering new opportunities to bridge the mechanistic and similarity gaps of comorbidity.

Cryptocrine signaling in the thymus network and T cell education to neuroendocrine self-antigens.

Both during phylogeny and ontogeny the thymus appears as a nodal point between the two major systems of cell-to-cell signaling, the neuroendocrine and immune systems. This review presents the experimental observations which support a dual role in T cell selection played by the thymic repertoire of neuroendocrine polypeptide precursors. Through the mode of cryptocrine intercellular signaling thymic neuroendocrine-related precursors synthesized in thymic epithelial cells have been shown to influence the early steps in T cell differentiation. In addition, thymic neuroendocrine-related polypeptides are a source of self-antigens which are presented by the major histocompatibility system of the thymic epithelium. Preliminary data also suggest that the intrathymic T cell education to neuroendocrine self-antigens is not strictly superimposible to the antigen presentation by dedicated presenting cells. Insulin-like growth factor-II (IGF-II) was identified as one dominant member of the insulin family expressed by thymic epithelial and nurse cells. The intrathymic presentation of IGF-II or IGF-II derived self-antigens is under current investigation. If further confirmed, the central tolerogenic properties of IGF-II could be considered in the elaboration of a strategy for an efficient and safe prevention of insulin-dependent diabetes.

[Surgery of pleomorphic adenoma of the parotid gland]. / Chirurgie de l'adénome pléomorphe de la parotide.

INTRODUCTION: Pleomorphic adenoma is the most common benign tumor of the parotid gland. It has a tendency of recurrence and malignant transformation. The surgical excision of this lesion continues to be the subject of a major debate. In this study, we discuss optimal surgical options for pleomorphic adenoma. MATERIALS AND METHODS: We reviewed clinical records of 82 patients who underwent surgery. RESULTS: The tumor was localized in the superficial lobe in 81.7% of cases. Tumors of the deep lobe were removed by total parotidectomy. Those of the superficial lobe underwent partial exofacial parotidectomy (7 cases), exofacial parotidectomy (44 cases), or total parotidectomy (16 cases). Transitory facial paralysis was higher after total parotidectomy. Only one patient developed a recurrence, his tumor showed capsule infiltration. DISCUSSION: Conventional or partial superficial parotidectomy may be a good compromise with fewer complications and low incidence of recurrence.

[Idiopathic facial paralysis in children]. / Paralysie faciale idiopathique de l'enfant.

BACKGROUND: Idiopathic facial palsy is the most common cause of facial nerve palsy in children. Controversy exists regarding treatment options. The objectives of this study were to review the epidemiological and clinical characteristics as well as the outcome of idiopathic facial palsy in children to suggest appropriate treatment. PATIENTS AND METHODS: A retrospective study was conducted on children with a diagnosis of idiopathic facial palsy from 2007 to 2012. RESULTS: A total of 37 cases (13 males, 24 females) with a mean age of 13.9 years were included in this analysis. The mean duration between onset of Bell's palsy and consultation was 3 days. Of these patients, 78.3% had moderately severe (grade IV) or severe paralysis (grade V on the House and Brackmann grading). Twenty-seven patients were treated in an outpatient context, three patients were hospitalized, and seven patients were treated as outpatients and subsequently hospitalized. All patients received corticosteroids. Eight of them also received antiviral treatment. The complete recovery rate was 94.6% (35/37). The duration of complete recovery was 7.4 weeks. DISCUSSION: Children with idiopathic facial palsy have a very good prognosis. The complete recovery rate exceeds 90%. However, controversy exists regarding treatment options. High-quality studies have been conducted on adult populations. Medical treatment based on corticosteroids alone or combined with antiviral treatment is certainly effective in improving facial function outcomes in adults. In children, the recommendation for prescription of steroids and antiviral drugs based on adult treatment appears to be justified. CONCLUSION: Randomized controlled trials in the pediatric population are recommended to define a strategy for management of idiopathic facial paralysis.

Characterization of the insulin-like growth factor axis in the human thymus.

The components of the insulin-like growth factor (IGF) axis have been investigated in the normal human thymus. Using ribonuclease protection assays (RPA), IGF-II transcripts were detected in the normal human thymus. By reverse transcriptase polymerase chain reaction (RT-PCR) analyses, promoters P3 and P4 were found to be active in the transcription of IGF2 gene within human thymic epithelial cells (TEC). No IGF-II mRNA could be detected in human lymphoid Jurkat T cells with 30 cycles of RT-PCR. By Northern blot analyses, IGFBP-2 to -6 (but not IGFBP-1) were found to be expressed in TEC with a predominance of IGFBP-4. Interestingly, Jurkat T cells only express IGFBP-2 but at high levels. The type 1 IGF receptor was detected in Jurkat T cells but not in human TEC. The identification of the components of the IGF axis within separate compartments of the human thymus adds further evidence for a role of this axis in the control of T-cell development. The precise influence of thymic IGF axis upon T-cell differentiation and immunological self-tolerance however needs to be further investigated.

Cellular and molecular aspects of thymic T-cell education in neuroendocrine self principles. Implications for autoimmunity.

Thymic epithelial and nurse cells from different species express a repertoire of neuroendocrine polypeptide precursors. This repertoire exerts a dual role in T-lymphocyte selection according to their status either as cryptocrine signals or as neuroendocrine self-antigens of the peptide sequences that are processed from those precursors then presented to pre-T cells. Thymic neuroendocrine self-antigens correspond to peptide sequences highly conserved throughout evolution of their family. Though thymic MHC class I molecules are involved in the processing of thymic neuroendocrine self-antigens, preliminary data show that their presentation to pre-T cells is not allelically restricted. Thymic T-cell education in neuroendocrine families also implies that the structure of a given family may be presented to pre-T cells. Our studies have evidenced the homology between thymic neuroendocrine-related self-antigens and dominant T-cell epitopes of peripheral neuroendocrine signals (neuroendocrine autoantigens). The biochemical difference between neuroendocrine autoantigens and homologous thymic self-antigens might explain the opposite immune responses evoked by those two types of antigens (activation and memory induction vs. tolerogenic effect). Altogether, these studies support the therapeutic use of thymic neuroendocrine self-antigens in reprogramming the immunological self-tolerance that is broken in autoimmune endocrine diseases like insulin-dependent diabetes type I. As recently stated by P. M. Allen in an important review, the fate of developing T lymphocytes in the thymus is influenced by the numerous types of peptidic interactions within the thymic cellular environment. To define the precise nature of thymic cells and naturally occurring biochemical peptide signals involved in positive and negative selection of immature T cells has become a prominent objective for the future research efforts in thymic physiology. This paper will try to show how thymic neuroendocrine-related peptides synthesized and processed within the thymic microenvironment indeed can play a role both in the development of the peripheral T-cell repertoire and in the death of randomly rearranged, self-reactive T cells.

[Low-grade adenocarcinoma of nasal cavities: a case report]. / Adénocarcinome de bas grade des fosses nasales : à propos d'un cas.

Low-grade sinonasal adenocarcinomas are uncommon and recently described entities. Its histologic diagnosis is challenging. This tumour is characterized by a tendency to local invasion, and rare distant metastases. Well treated, the prognosis is excellent. We describe a case of low-grade nasal cavity adenocarcinoma and discuss the anatomoclinical, therapeutic and evolutionary characteristics of this malignant tumour. A 54-year-old female patient presented with a 10 years history of right-sided nasal obstruction and recurrent epistaxis. On examination the patient had a large, firm mass in the right nasal cavity. Endoscopic sinonasal surgery was performed. The lesion was found to originate from the posteriolateral wall of the right nasal cavity. Histopathology analysis identified a low-grade sinonasal adenocarcinoma. Upon follow-up 4 years after surgery, the patient exhibited no clinical evidence of recurrence. Low-grade sinonasal adenocarcinomas are poorly defined neoplasms, accounting for 4 to 20% of all sinonasal malignancies. The nasal cavity is the most frequently involved site. Low-grade sinonasal adenocarcinomas pose a diagnostic challenge for the pathologist because they must be distinguished from benign tumours, especially adenomas. The primary treatment of sinonasal adenocarcinoma is complete surgical excision.

Unusual form of cutaneous leishmaniasis: erysipeloid form.

UNLABELLED: We report the epidemiological and clinical characteristics of the erysipeloid form of cutaneous leishmaniasis as well as its diagnostic and therapeutic challenges. CASE REPORT: A 63-year-old woman, with no medical history, presented with a one-month history of erythematous nasal swelling. The lesion appeared after an accidental trauma. Erythematous infiltrative plaque was noted on the center of the face. There were also crust formations on the traumatic region. Despite local treatment and oral antibiotherapy, there was no improvement. The diagnosis of cutaneous leishmaniasis was confirmed by positive skin smears. Histopathological examinations of a skin biopsy showed no malignancy. The patient was treated intramuscularly with 10mg/kg per day systemic meglumine antimoniate with partial regression of symptoms. CONCLUSION: The erysipeloid type is a rare and unusual presentation of cutaneous leishmaniasis that often causes late diagnosis. Diagnosis is confirmed by the demonstration of the parasite by skin smear, histopathological examination and polymerase chain reaction. There are various therapeutic options. The evolution is generally favourable.

[Post-radiation mucocele in two patients treated for nasopharyngeal cancer]. / Mucocèle après radiothérapie chez deux patients traités pour cancer du nasopharynx.

A 30-year-old woman, with a history of nasopharyngeal carcinoma, which was treated by radiotherapy nine years previously, presented with occasional diplopia and recent headaches. A nasopharyngeal biopsy showed no recurrence. The imaging revealed a sphenoidal sinus mucocele. Endoscopic marsupialization of the mucocele allowed clinical improvement. A 56-year-old woman presented, five years after radiotherapy for nasopharyngeal carcinoma, with a fronto-orbital mass. CT-scan revealed a fronto-ethmoidal mucocele. Nasopharyngeal biopsy showed tumour recurrence. Marsupialization of mucocele was performed. Recurrence of the carcinoma was treated by radiotherapy and chemotherapy. Sphenoidal sinus mucocele developing after radiotherapy for nasopharyngeal carcinoma has rarely been reported. CT scan and MRI are useful tools in making the diagnosis. Biopsy is required to diagnose recurrence or associated radio-induced tumor. Endoscopic approach gives good results.

Association of squamous cell carcinoma of the larynx and chronic lymphoid leukemia.

INTRODUCTION: The association of squamous cell carcinoma of the larynx and chronic lymphocytic leukemia (CLL) is exceptional. We report an observation of this association and present the therapeutic problems as well as the effects on prognosis. OBSERVATION: Direct laryngoscopy showed a tumor of the right hemilarynx, with the biopsy concluding in moderately differentiated keratinizing squamous cell carcinoma. The patient had a total laryngectomy, with bilateral lymph node evidement. The anatomopathological examination of the operative specimen demonstrated infiltration of the larynx and squamous cell carcinoma adenopathies and CLL. It was decided to monitor the chronic lymphoid leukemia, classified as Binet stage B. The synchronous or metachronous onset of a second cancer in a patient with CLL is more frequent than in the general population. The synchronous association of squamous cell carcinoma of the larynx and CLL has been described only rarely. The therapeutic strategy should focus first on the cancer with the shortest survival rate. The prognosis is more negative in an association of cervicofacial squamous cell carcinoma and leukemia than in a single cervicofacial cancer.

Cholesteatoma of the frontal sinus.

PURPOSE OF STUDY: Cholesteatoma of the paranasal sinuses is a rare pathology. A review of the literature reported less than 30 cases. These lesions mainly involve the frontal sinus. CASE REPORT: A 25-year-old man presented with a right painful fronto-orbital mass associated with an ipsilateral eyelid oedema and a fever as high as 40°C. He experienced a general epileptic seizure requiring his admission in an intensive care unit. CT-Scan with iodine injection evidenced the opacification of the right frontal sinus with bone lysis of the posterior wall. Complete surgical resection of a cystic structure containing keratin material was performed via eyebrow incision. The pathological examination confirmed the diagnosis of sinus cholesteatoma. Neurological signs entirely disappeared after surgery. Craniofacial MRI realized 2 months later showed no sign of recurrence. Obliteration of the right frontal sinus was performed 4 months later. CONCLUSION: Although benign, cholesteatoma can spread to the surrounding structures leading to several complications including infections that can be life-threatening for the patient. CT-scan and MRI are useful examinations for diagnosis and follow-up. Complete surgical resection is required in order to avoid recurrence.

Development and evolutionary aspects of thymic T cell education to neuroendocrine self.

Thymic epithelial cells, including nurse cells (TECs/TNCs), from various species synthesize neuroendocrine-related precursors belonging to neurohypophysial, tachykinin and insulin hormone families. The thymic repertoire of neuroendocrine-related polypeptides illustrates at the molecular level the paradoxical role of the thymus in both T cell positive and negative selection. On the one hand, these precursors are a source of signals which interact with neuroendocrine-type receptors expressed by target pre-T cells according to the cryptocrine type of cell-to-cell signaling. On the other hand, the same precursors constitute a source of self-antigens which are presented to pre-T cells by the thymic major histocompatibility complex system. Basically, the model of thymic T cell education to neuroendocrine self was established by the identification in TECs/TNCs of immunoreactive (ir) oxytocin as the self-antigen of the neurohypophysial family. Nevertheless, through the expression in TECs/TNCs of ir-neurokinin A and ir-insulin-like growth factor-II, the model also applies to the tachykinin and insulin hormone families.

Thymic expression of insulin-related genes in an animal model of autoimmune type 1 diabetes.

BACKGROUND: Insulin and multiple other autoantigens have been implicated in the pathogenesis of autoimmune type 1 diabetes, but the origin of immunological self-reactivity specifically oriented against insulin-secreting islet beta-cells remains obscure. The primary objective of the present study was to investigate the hypothesis that a defect in thymic central T-cell self-tolerance of the insulin hormone family could contribute to the pathophysiology of type 1 diabetes. This hypothesis was investigated in a classic animal model of type 1 diabetes, the Bio-Breeding (BB) rat. METHODS: The expression of the mammalian insulin-related genes (Ins, Igf1 and Igf2) was analysed in the thymus of inbred Wistar Furth rats (WF), diabetes-resistant BB (BBDR) and diabetes-prone BB (BBDP) rats. RESULTS: RT-PCR analyses of total RNA from WF, BBDP and BBDR thymi revealed that Igf1 and Ins mRNAs are present in 15/15 thymi from 2-day-old, 5-day-old and 5-week-old WF, BBDR and BBDP rats. In contrast, a complete absence of Igf2 mRNA was observed in more than 80% of BBDP thymi. The absence of detectable Igf2 transcripts in the thymus of BBDP rats is tissue-specific, since Igf2 mRNAs were detected in all BBDP brains and livers examined. Using a specific immunoradiometric assay, the concentration of thymic IGF-2 protein was significantly lower in BBDP than in BBDR rats (p<0.01). CONCLUSIONS: The present study suggests an association between the emergence of autoimmune diabetes and a defect in Igf2 expression in the thymus of BBDP rats. This tissue-specific defect in gene expression could contribute both to the lymphopenia of these rats (by impaired T-cell development) and the absence of central T-cell self-tolerance of the insulin hormone family (by defective negative selection of self-reactive T-cells).

Evidence that insulin-like growth factor 2 (IGF2) is the dominant thymic peptide of the insulin superfamily.

The central T-cell tolerance of neuroendocrine functions has been proposed to be primarily induced by the thymic repertoire of neuroendocrine self antigens. The present study aimed at characterizing the human thymic insulin-related autoantigen able to represent the pancreatic B-cell function in face of the developing T-cells. Immunofluorescence studies were performed on human and rat thymic sections, as well as on the rat IT-45R1 thymic epithelial cell line using several antibodies to epitopes of the insulin peptide superfamily. These studies identify beyond any doubt that insulin-like growth factor 2 (IGF2) is the dominant thymic peptide of the insulin family. The sequence of an insulin-derived autoantigen is proposed. This autoantigen is a nonamer and has a hydrophobic residue leucine (L) at position 9. In the human species, this autoantigen would primarily be tolerogenic for the pancreatic B-cell endocrine function during fetal development.