[Primary extranodal ENT tuberculosis]. / La tuberculose primitive ORL extraganglionnaire.

OBJECTIVES: The aim of this sinusonasal study was to study several locations of ENT extranodal tuberculosis. MATERIAL AND METHODS: Our study focused on eight cases of tuberculosis in the cervicofacial region gathered in the ENT department of the Rabat Specialization Hospital (Morocco) between August 2004 and August 2006. They comprise two cases of rhinopharyngeal tuberculosis, two cases of tuberculosis, two cases of endobuccal tuberculosis (mandibular and lingual locations), and two cases of glandular tuberculosis (thyroid and parotid locations). RESULTS: These locations are rarely affected by tuberculosis. The clinical signs as well as radiology and endoscopy are not specific. The final diagnosis is based on histology. Bacillus cultures are necessary when caseum tuberculosis is not found, causing problems of differential diagnosis with granulomatous and malignant lesions. PCR provides quick bacterial antigen detection when cultures are negative. The treatment provides a quick and complete recovery while recurrences are infrequent. CONCLUSION: ENT tuberculosis is rare if excluding the nodal locations. It should be mentioned as a differential diagnosis, especially in endemic areas. Most often, this is a surprise diagnosis.

[Superior semicircular canal dehiscence mimicking otosclerosis: usefulness of imaging]. / Déhiscence du canal semi-circulaire antérieur mimant une otospongiose: intérêt de l'imagerie.

OBJECTIVES: To emphasize the role of computerized tomography (CT) in the etiologic work-up of stapes surgery failure. MATERIAL AND METHODS: Helical high resolution CT scan of the temporal bone with axial and coronal views and multiplanar reconstructions was performed in a patient who had undergone unsuccessful stapedectomy. RESULTS: CT scan demonstrated a well located prosthesis, the absence of the radiological hallmarks of otosclerosis, and revealed a superior semicircular canal dehiscence (SSCD). The diagnosis of SSCD was retrospectively considered accountable for the preoperative clinical and audiometric presentation that had mimicked otosclerosis. CONCLUSION: CT is the diagnostic test of choice in elucidating stapes surgery failure (with persistent or recurrent conductive hearing loss), whereas SSCD should be systematically considered among its causes.

Examinations of the Chemical Step in Enzyme Catalysis.

Advances in computational and experimental methods in enzymology have aided comprehension of enzyme-catalyzed chemical reactions. The main difficulty in comparing computational findings to rate measurements is that the first examines a single energy barrier, while the second frequently reflects a combination of many microscopic barriers. We present here intrinsic kinetic isotope effects and their temperature dependence as a useful experimental probe of a single chemical step in a complex kinetic cascade. Computational predictions are tested by this method for two model enzymes: dihydrofolate reductase and thymidylate synthase. The description highlights the significance of collaboration between experimentalists and theoreticians to develop a better understanding of enzyme-catalyzed chemical conversions.

Hydrogen tunneling in biology.

The mechanistic details of hydrogen transfer in biological systems are not fully understood. The traditional approach has been to use semiclassical transition-state theory. This theory cannot explain many experimental findings, however, so different approaches that emphasize the importance of quantum mechanics and dynamic effects should also be considered.

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): two case reports.

Sinus histiocytosis with massive lymphadenopathy or Destombes-Rosai-Dorfman's syndrome is a rare benign disease of unknown etiology, usually seen in younger patients. The cases reported concerned a 15-month old Caucasian boy and an 8 year old black boy with unilateral cervical enlargement, occasional fever and without any extranodal involvement. Diagnosis was performed by superficial lymph node biopsy. No immunodeficiency was found. The patients received no therapy and a complete spontaneous resolution was seen after a few months in the two cases. The clinical presentation, histologic characteristics, pathogenesis and treatment of the Destombes-Rosai-Dorfman's syndrome are discussed.

[Laryngeal neuroendocrine carcinoma: a case report]. / Carcinome neuroendocrine du larynx: a propos d'un cas.

Laryngeal neuroendocrine carcinomas are uncommon and not well known tumors. Three histological subtypes, each of them with a different prognosis and treatment, can be identified. We report a case of a large cell laryngeal neuroendocrine carcinoma in 32 old-year boy who presented a right glotto-subglottic tumoral process. The patient was treated by total laryngectomy associated with bilateral functional neck dissection but without postoperative chemotherapy. A disease recurrence occured three months after surgery consisting on a massive involvment of laterocervical and sus clavicular lymph nodes. The authors discussed the clinical features, the histological and immunohistochemical characteristics, the treatment and the prognosis of laryngeal neuroendocrine carcinoma, according to literature. (full article translated in English available on www.ent-review.com).

[Thyroid tuberculosis associated with papillary microcarcinoma of the thyroid gland: a case report]. / Tuberculose thyroïdienne associée à un microcarcinome papillaire thyroïdien: à propos d'un cas.

Tuberculosis of the thyroid gland is extremely uncommon. The infection may present first in the thyroid gland or appear secondary to a tuberculous process elsewhere in the body. The diagnosis is rarely made clinically because the different presentations of the disease often mimick malignancy or euthyroid nodular goitre. It is of interest to report a case of tuberculosis of the thyroid associated with papillary microcarcinoma of the gland. No tuberculous process elsewhere in the body has been found. The frequency of MCP on thyroidectomy specimens suggest that this association is incidental.

[Pleomorphic adenoma of the tongue base]. / Adénome pléomorphe de la base de langue.

INTRODUCTION: Pleomorphic adenoma is the most common lesion of minor salivary glands but is exceptional in the tongue base. REPORT CASE: We report the case of a 70-year-old woman with pleomorphic adenoma of the tongue base. The patient consulted for difficult swallowing, which developed over 4 months. Physical examination and computed tomography revealed a cystic tumour located in the right side of tongue base. The tumor was removed by transoral resection. The histological examination demonstrated a pleomorphic adenoma. DISCUSSION: We will discuss the diagnostic and therapeutically modalities of pleomorphic adenoma of the tongue base with a review of the literature.

[Post syphilitic oro-nasal communication]. / Communication bucco-nasale post-syphilitique.

INTRODUCTION: Oro-nasal communication occurs due to a lack of bone and mucous membranes between the oral cavity and the nasal fossae, rarely subsequent to tertiary syphilis. CASE REPORT: A 27 year-old woman with a history of an untreated genital chancre which developed 7 years earlier, presented hard palate necrosis surrounded with granulation tissue. Syphilitic gum of the hard palate was diagnosed. After antibiotic treatment, the palatine lesion healed with persistence of an oro-nasal fistula. Physical examination of the oral cavity demonstrated median oro-nasal communication of the hard palate measuring 0,5 cm in diameter. HIV and syphilitic serologies were negative. The treatment consisted in surgical closure of the oro-nasal communication by the refection of nasal and oral plans. The follow-up was good. DISCUSSION: Oro-nasal communication due to syphilis is exceptional, of easy diagnosis and generally needs surgical treatment.

Probing the superfluid velocity with a superconducting tip: the Doppler shift effect.

We address the question of probing the supercurrents in superconducting (SC) samples on a local scale by performing scanning tunneling spectroscopy (STS) experiments with a SC tip. In this configuration, we show that the tunneling conductance is highly sensitive to the Doppler shift term in the SC quasiparticle (QP) spectrum of the sample, thus allowing the local study of the superfluid velocity. Intrinsic screening currents, such as those surrounding the vortex cores in a type II SC in a magnetic field, are directly probed. With Nb tips, the STS mapping of the vortices, in single crystal 2H-NbSe(2), reveals both the vortex cores, on the scale of the SC coherence length xi, and the supercurrents, on the scale of the London penetration length lambda. A subtle interplay between the SC pair potential and the supercurrents at the vortex edge is observed. Our results open interesting prospects for the study of screening currents in any superconductor.

[Orbital osteoma: clinical evaluation of nine cases]. / Les ostéomes orbitaires: évaluation clinique de neuf cas.

INTRODUCTION: Osteoma of the nasosinus cavities, particularly the frontoethmoidal cavities, is often a fortuitous radiographic discovery. Potential complications include ophthalmological, sinusal, and endocranial disorders. MATERIAL AND METHODS: Nine patients (five men and four women), mean age 24.3 years (18-43) presenting orbital osteoma were managed from 1994 to 1999. RESULTS: Clinical signs were dominated by ophthalmological disorders, basically non-reducible exophthalmia (n = 8). Two patients had permanent unilateral nasal obstruction and one had acute sinusitis. The bony orbital tumefaction was located in the superior medial angle in five patients. Radiography (Blondeau view) demonstrated an opacity in the sinus with an orbital extension. Computed tomography, performed in all patients, identified the lesion location: ethmoidofrontal (n = 4), anterior ethmoidal (n = 2), frontal (n = 2), ethmoidomaxillary (n = 1). There were no endocranial extensions. Surgery was undertaken for eight patients generally via the transfacial approach (n = 7); a bicoronal approach was used for one patient. En bloc resection (n = 4) or fragmentation (n = 4) was performed. There was one postoperative complication: regressive diplopy. These patients have been followed regularly with clinical and radiographic explorations and have been free of relapse for 2 to 6 years. DISCUSSION: Frontoethmoidal osteoma is a relatively rare benign tumor. Severity depends on the orbital and endocranial extension. Imaging provides the positive diagnosis and guides the surgical approach. Therapeutic indications depend on the tumor size, its course, and the development of complications. We observed total relapse free outcome after complete resection.

[Ankylosis of the temporomandibular joint: a rare manifestation of ankylosing spondylitis]. / Ankylose de l'articulation temporo-mandibulaire: rare manifestation de la spondylarthrite ankylosante.

INTRODUCTION: The ankylosing spondylitis is a chronic inflammatory rheumatoid disease with predilection in the axial structures. The temporomandibular joint (TMJ) is involved in 10 to 24% of cases. Ankylosis of the TMJ is exceptional, only 11 cases being reported to date. OBSERVATION: A 48-year-old patient had been followed since 1987 for severe ankylosing spondylitis. The patient, known to be positive for tissue antigen HLA B27, was admitted for limitation of mouth opening. At physical examination, mouth opening was reduced to 1cm with no mandibular movements and a stiffness of the cervical spine in flexion. Computed tomography of the TMJs highlighted a bilateral lesion with ankylosis of the left joint and of C1-C2. Surgical treatment consisted in block resection of the two TMJs using a cartilaginous rib. With a follow up of 9 months, results have been satisfactory. DISCUSSION: Complementary explorations should be undertaken in ankylosing spondylitis patients with clinical symptoms suggestive of TMJ lesions in order to establish the diagnosis and initiate treatment and avoid the development of ankylosic forms.

Convex Arrhenius plots and their interpretation.

This paper draws attention to selected experiments on enzyme-catalyzed reactions that show convex Arrhenius plots, which are very rare, and points out that Tolman's interpretation of the activation energy places a fundamental model-independent constraint on any detailed explanation of these reactions. The analysis presented here shows that in such systems, the rate coefficient as a function of energy is not just increasing more slowly than expected, it is actually decreasing. This interpretation of the data provides a constraint on proposed microscopic models, i.e., it requires that any successful model of a reaction with a convex Arrhenius plot should be consistent with the microcanonical rate coefficient being a decreasing function of energy. The implications and limitations of this analysis to interpreting enzyme mechanisms are discussed. This model-independent conclusion has broad applicability to all fields of kinetics, and we also draw attention to an analogy with diffusion in metastable fluids and glasses.

Mechanistic studies of 3-deoxy-D-manno-2-octulosonate-8-phosphate synthase from Escherichia coli.

The anomeric specificity and the steady-state kinetic mechanism of homogeneous 3-deoxy-D-manno-2-octulosonate-8-phosphate (KDO8P) synthase were investigated. The open-chain 4-deoxy analogue of arabinose-5-phosphate (Ara5P), which is structurally prohibited from undergoing ring closure, was synthesized and tested as a substrate for the synthase. It was found that the analogue functions as a substrate with a similar kcat value to that of the original substrate. The kcat/Km value for the natural substrate is seven-times greater than that of the 4-deoxy analogue. However, taking into account the 9.5% and approximately 1% concentrations of the aldehyde forms of the 4-deoxy analogue and Ara5P in solution, then the 'true' Km values must be in the range 31.5 microM and 0.26 microM, respectively, requiring about a 3 kcal/mol contribution to the binding energy by the 4-hydroxyl group of Ara5P. The data provides evidence that the enzyme acts upon the acyclic form of the natural substrate. The steady-state kinetic study of KDO8P synthase was analyzed via inhibition using the products KDO8P and inorganic phosphate, and D-ribose-5-phosphate as a dead-end inhibitor. First, intersecting lines in double-reciprocal plots of initial-velocity data at substrate concentrations in the micromolar range suggest a sequential mechanism for the enzyme-catalyzed reaction. The inhibition by D-ribose-5-phosphate is competitive for Ara5P and uncompetitive for phosphoenolpyruvate (P-pyruvate). These inhibition patterns are consistent with the model wherein P-pyruvate binding precedes that of Ara5P binding. Furthermore, this order of substrate binding was supported by the observations that KDO8P is a competitive inhibitor for P-pyruvate binding, supporting the concept that KDO8P and P-pyruvate bind to the same enzyme form, and noncompetitively with respect to Ara5P. In addition, the inhibition by inorganic phosphate is noncompetitive with respect to both P-pyruvate and Ara5P, suggesting an apparent ordered release of products such that Pi first, followed by KDO8P. In conclusion, these data suggest a steady-state kinetic mechanism for KDO8P synthase where P-pyruvate binding precedes that of Ara5P, followed by the ordered release of inorganic phosphate and KDO8P.

Interactive effects of elevated CO(2) and mineral nutrition on growth and CO(2) exchange of sweet chestnut seedlings (Castanea sativa).

The effects of elevated atmospheric CO(2) (700 micro mol mol(-1)) and fertilization were investigated on 2-year-old sweet chestnut (Castanea sativa Mill.) seedlings grown outdoors in pots in constantly ventilated open-sided chambers. Plants were divided into four groups: fertilized controls (+F/-CO(2)), unfertilized controls (-F/-CO(2)), fertilized + CO(2)-treated plants (+F/+CO(2)) and unfertilized + CO(2)-treated plants (-F/+CO(2)). Dry matter accumulation and allocation were measured after one growing season and CO(2) exchange of whole shoots was measured throughout the growing season. Shoot growth and total leaf area of unfertilized plants were not affected by elevated CO(2), whereas both parameters were enhanced by elevated CO(2) in fertilized plants. Elevated CO(2) increased total biomass by about 20% in both fertilized and unfertilized plants; however, biomass partitioning differed. In unfertilized plants, elevated CO(2) caused an increase in root growth, whereas in fertilized plants, it stimulated aboveground growth. At the whole-shoot and leaf levels, photosynthetic activity of both fertilized and unfertilized plants increased in response to elevated CO(2), but the seasonal pattern of this enhancement varied with nutrient treatment. In unfertilized plants, a downward acclimation of photosynthesis was observed early in the season (June), and was related to reductions in nitrogen and chlorophyll content and to starch accumulation. The decrease in the slope of the A/C(i) curve suggested a decrease in Rubisco activity. In both fertilized and unfertilized plants, shoot respiration decreased during the night in response to elevated CO(2) until mid-July. The decrease was not related to changes in sugar concentration.

Andreev reflections on Y(1-x)Ca(x)Ba(2)Cu(3)O(7-delta): evidence for an unusual proximity effect.

We have measured Andreev reflections between an Au tip and Y(1-x)Ca(x)Ba(2)Cu(3)O(7-delta) thin films in the in-plane orientation. The conductance spectra are best fitted with a pair potential having the d(x2-y2)+is symmetry. We find that the amplitude of the is component is enhanced as the contact transparency is increased. This is an indication for an unusual proximity effect that modifies the pair potential in the superconductor near the surface with the normal metal.

Effects of protein glycosylation on catalysis: changes in hydrogen tunneling and enthalpy of activation in the glucose oxidase reaction.

Three glycoforms of glucose oxidase, which vary in their degree of glycosylation and resulting molecular weight, have been characterized with regard to catalytic properties. Focusing on 2-deoxyglucose to probe the chemical step, we have now measured the temperature dependence of competitive H/T and D/T kinetic isotope effects and the enthalpy of activation using [1-2H]-2-deoxyglucose. The D/T isotope effect on the Arrhenius preexponential factor (AD/AT) is 1.47 (+/-0.09), 1.30 (+/-0.10), and 0.89 (+/-0.04) for the 136, 155, and 205 kDa glycoforms, respectively. The value obtained for the 136 kDa glycoform is well above the range expected for semiclassical-classical (no tunneling) reactions (upper limit of 1.22). The abnormal A(D)/A(T) is rationalized by extensive tunneling. The enthalpies of activation are 8.1 (+/-0.4), 11.0 (+/-0.3), and 13.7 (+/-0.3) kcal/mol for the 136, 155, and 205 kDa glycoforms, respectively. Apparently, less glycosylation results in more tunneling and a lower enthalpy of activation. The crystal structure, kinetic analysis, and other studies suggest that the enzyme active site is not conformationally changed by the degree of glycosylation. Hence, the differences among the glycoforms, which indicate that changes in the enzyme polysaccharide envelope lead to a significant change in the nature of the hydrogen transfer step, suggest a dynamic transmission of protein surface effects to the active site.

Enzyme dynamics and hydrogen tunnelling in a thermophilic alcohol dehydrogenase.

Biological catalysts (enzymes) speed up reactions by many orders of magnitude using fundamental physical processes to increase chemical reactivity. Hydrogen tunnelling has increasingly been found to contribute to enzyme reactions at room temperature. Tunnelling is the phenomenon by which a particle transfers through a reaction barrier as a result of its wave-like property. In reactions involving small molecules, the relative importance of tunnelling increases as the temperature is reduced. We have now investigated whether hydrogen tunnelling occurs at elevated temperatures in a biological system that functions physiologically under such conditions. Using a thermophilic alcohol dehydrogenase (ADH), we find that hydrogen tunnelling makes a significant contribution at 65 degrees C; this is analogous to previous findings with mesophilic ADH at 25 degrees C. Contrary to predictions for tunnelling through a rigid barrier, the tunnelling with the thermophilic ADH decreases at and below room temperature. These findings provide experimental evidence for a role of thermally excited enzyme fluctuations in modulating enzyme-catalysed bond cleavage.

Catalytic mechanism of 3-deoxy-D-manno-2-octulosonate-8-phosphate synthase. The use of synthetic analogues to probe the structure of the putative reaction intermediate.

The proposed mechanistic pathway for the reaction catalyzed by 3-deoxy-D-manno-2-octulosonate-8-phosphate (Kdo8P) synthase was examined in terms of the structure of the putative bisphosphate intermediate. Two 2-deoxy analogues of the product Kdo8P, having been structurally prohibited from undergoing the ring-opening and possessing the stereochemistry of either the alpha-pyranase (compound 1) or the beta-pyranose form (compound 2) of the product, were synthesized and probed as inhibitors for the synthase. It was found that both analogues bind to the enzyme and are competitive inhibitors with respect to phosphoenolpyruvate binding, having Ki values of 470 microM and 303 microM, respectively. Comparison of this data to the Ki value of the tautomeric mixture of the product Kdo8P (Ki = 590 microM) suggests that both the alpha- and the beta-pyranose anomers (65.8% and 3.1%, respectively at neutral pH) bind to the enzyme with a slight (1.13 kJ/mol) preference for the beta-anomer, and that the C2 hydroxyl does not contribute to the binding. This uncertain stereochemical preference exhibited by the enzyme for the stereoisomers at the anomeric carbon suggests that the carboxylate binding site of the product is indistinct, while the hydroxyl and carboxylate binding sites may be interchangeable. More importantly, however, the isosteric phosphonate analogue 2,6-anhydro-3-deoxy-2 beta-phosphonylmethyl-8-phosphate-D-glycero-D-talo-octonate (3), which mimics the topological and electrostatic properties of the proposed cyclic intermediate, was found to be the most potent inhibitor of the enzyme with a Ki value of 5 microM. Two hitherto unrecognized aspects of the mechanism of the synthase were identified. First, the results showing that the cyclic analogues 1, 2 and 3 are inhibitors of the enzyme whereas the previously reported acyclic analogue, which contains no carbonyl group at C2 and may thus resemble the open-chain form of Kdo8P, is not an inhibitor, suggest that the pyranose form and not the open-chain acyclic form of the putative bisphosphate intermediate is handled by the enzyme. Second, since the overall stereochemical course of the transformation mediated by the synthase has been shown to involve si face addition of phosphoenolpyruvate to the re face of the carbonyl of arabinose 5-phosphate, the present observation involving analogue 3 suggest that the bisphosphate intermediate formed during the initial steps of synthesis may have the pyranose structure with the anomeric phosphate located in the beta-configuration.