Photodegradation of irinotecan (CPT-11) in aqueous solutions: Identification of fluorescent products and influence of solution composition

The photodegradation of irinotecan (CPT-11), the semisynthetic derivative of the antitumor alkaloid 20(S)-camptothecin, has been investigated. The drug was exposed to laboratory light for up to 5 days in 0.9% saline solution (pH 8.5). Five significant photodegradation products were observed and a high-performance liquid chromatography (HPLC) assay was employed to isolate them from CPT-11 using gradient conditions. The structures were elucidated by nuclear magnetic resonance spectroscopy and tandem mass spectrometry and shown to be the result of extensive modifications of the lactone ring of CPT-11. Three of the compounds were found to belong to the mappicine group of alkaloids. In addition, the effect of light on the stability of CPT-11 in aqueous solutions and biological fluids was also assessed, Potassium phosphate buffers (0.05 M, pH 5.0-8.2) and saline, plasma, urine, and bile solutions containing 20 mu M CPT-11 were equilibrated in the dark for 24 h before being exposed to laboratory light for up to 171 h at ambient temperature. Four of the five identified photodegradation products were observed and quantitated by isocratic HPLC, using a different detection mode (fluorescence) than the one used for gradient elution, In general, CPT-11 was found to be unstable under neutral and alkaline conditions for all solutions investigated, with the exception of bile. We conclude that CPT-11 is photolabile and that care should be taken to protect samples, particularly those intended for the isolation and identification of novel metabolites of CPT-11.

Color Doppler imaging of the superior ophthalmic vein in different clinical forms of Graves` orbitopathy

To compare color Doppler imaging (CDI) parameters of the superior ophthalmic vein (SOV) in patients with Graves` orbitopathy (GO) and in normal controls. Forty-three GO patients and 14 normal controls underwent CDI of the SOV. Patients had either fibrotic (lipogenic or myogenic) or congestive orbitopathy. The findings for each group were compared. Fifty-eight orbits with fibrotic orbitopathy, 28 with congestive orbitopathy, and 28 from controls, were studied. In the congestive group, SOV flow was detected in 13, undetectable in 11, and reversed in four orbits; in the fibrotic group, it was present in 41 and undetectable in 17 orbits. In normal controls, SOV flow was detected in 25 and undetectable in three orbits. The differences among the three groups were significant. There was also a significant difference between controls and the congestive GO orbits but not between the fibrotic group and the other two groups. Fibrotic myogenic orbitopathy patients displayed a significantly smaller SOV flow than patients with lipogenic orbitopathy. SOV was significantly reduced in orbits with congestive GO or with myogenic fibrotic GO, but not in orbits with fibrotic lipogenic orbitopathy. SOV congestion may be a contributing pathogenic factor in both congestive and fibrotic myogenic Graves` orbitopathy.

Autoinflammatory diseases: Mimics of Autoimmunity or part of its spectrum? Case presentation

Introduction: Autoinflammatory diseases are very rare diseases presenting within a wide clinical spectrum. Recognition of the main clinical features are challenging due to overlapping or mimicking with autoimmune diseases. Discussion: A case series is reviewed to illustrate typical and atypical features and the difficulties of these diagnoses in the low prevalence areas-a typical unrecognized case of familial Mediterranean fever (FMF) in a youngster, an atypical adult case with overlapping of IMF with Behcet disease, and an early presentation of FMF in infant presenting with inflammatory colitis, as well as the overlapping features within the cryopirin diseases spectrum in an 8-year-old boy who presented with systemic onset arthritis. Conclusion: These cases may represent examples of a very puzzling relationship among disorders of innate and adaptive immune systems and inflammation.

Activation of the shoulder and arm muscles during axial load exercises on a stable base of support and on a medicine ball

The purpose of this study was to compare SEMG activities during axial load exercises on a stable base of support and on a medicine ball (relatively unstable). Twelve healthy male volunteers were tested (x = 23 +/- 7y). Surface EMG was recorded from the biceps brachii, anterior deltoid, clavicular portion of pectoralis major, upper trapezius and serratus anterior using surface differential electrodes. All SEMG data are reported as percentage of RMS mean values obtained in maximal voluntary contractions for each muscle studied. A 3-way within factor repeated measures analysis of variance was performed to compare RMS normalized values. The RMS normalized values of the deltoid were always greater during the exercises performed on a medicine ball in relation to those performed on a stable base of support. The trapezius showed greater mean electric activation amplitude values on the wall-press exercise on a medicine ball, and the pectoralis major on the push-up. The serratus and biceps did not show significant differences of electric activation amplitude in relation to both tested bases of support. Independent of the base of support, none of the studied muscles showed significant differences of electric activation amplitude during the bench-press exercise. The results contribute to the identification of the levels of muscular activation amplitude during exercises that are common in clinical practice of rehabilitation of the shoulder and the differences in terms of type of base of support used. (C) 2006 Elsevier Ltd. All rights reserved.

ELECTROMYOGRAPHIC AMPLITUDE RATIO OF SERRATUS ANTERIOR AND UPPER TRAPEZIUS MUSCLES DURING MODIFIED PUSH-UPS AND BENCH PRESS EXERCISES

Imbalance and weakness of the serratus anterior and upper trapezius force couple have been described in patients with shoulder dysfunction. There is interest in identifying exercises that selectively activate these muscles and including it in rehabilitation protocols. This study aims to verify the UT/SA electromyographic (EMG) amplitude ratio, performed in different upper limb exercises and on two bases of support. Twelve healthy men were tested (average age = 22.8 +/- 3.1 years), and surface EMG was recorded from the upper trapezius and serratus anterior using single differential surface electrodes. Volunteers performed isometric contractions over a stable base of support and on a Swiss ball during the wall push-up (WP), bench press (BP), and push-up (PU) exercises. All SEMG data are reported as a percentage of root mean square or integral of linear envelope from the maximal value obtained in one of three maximal voluntary contractions for each muscle studied. A linear mixed-effect model was performed to compare UT/SA ratio values. The WP, BP, and PU exercises showed UT/SA ratio mean +/- SD values of 0.69 +/- 0.72, 0.14 +/- 0.12, and 0.39 +/- 0.37 for stable surfaces, respectively, whereas for unstable surfaces, the values were 0.73 +/- 0.67, 0.43 +/- 0.39, and 0.32 +/- 0.30. The results demonstrate that UT/SA ratio was influenced by the exercises and by the upper limb base of support. The practical application is to show that BP on a stable surface is the exercise preferred over WP and PU on either surfaces for serratus anterior muscle training in patients with imbalance between the UT/SA force couple or serratus anterior weakness.

The relationship between two types of upper eyelid movements: Saccades and pursuit

PURPOSE. To establish the relationship between upper eyelid saccades and upper eyelid pursuit movements. METHODS. Upper eyelid saccades and periodic sinusoidal upper eyelid pursuit movements were recorded in a sample of controls and patients with Graves upper eyelid retraction. A video-computerized system was used to register both types of movements that accompanied 60 of eye rotation across the upper and lower hemifields. The forced harmonic oscillator model was used to fit saccadic and pursuit movements. RESULTS. Mean mid-pupil eyelid distance for the Graves patients (6.6 +/- 1.1 mm) was significantly higher than for the controls (4.6 +/- 0.8 mm; t = 7.18; P < 0.00001). Despite the difference in the upper eyelid resting position, saccades and pursuit eyelid movements of both groups were extremely well fitted by underdamped solutions and steady forced solutions of the harmonic oscillator model, respectively. For the controls, the amplitude of the pursuit movements was well correlated with the upward and downward saccades. The amplitude of the eyelid movements of the Graves patients (saccades and pursuit) was significantly reduced compared with that of the controls. CONCLUSIONS. Saccadic and pursuit movements of the upper eyelid can be described by the harmonic oscillator model. In healthy subjects and Graves patients, the amplitude of pursuit lid movements is correlated to the saccade amplitude. Pursuit eyelid movements are more difficult to register than saccades, and their measurements do not allow clear separation of the relaxation and contraction properties of the upper eyelid retractors.

Progressive bilateral enophthalmos associated with cerebrospinal shunting

A 22-year-old woman was examined for a complaint of bilateral progressive enophthalmos that had begun after the cerebrospinal fluid shunting procedure 9 years ago. Photographs and CT scans taken before surgery proved that the position of her eyes was normal before surgery. The enophthalmos was so severe that it induced a poor eyelid-globe apposition with trichiasis and superficial keratopathy. CT of the orbits showed that both orbital roofs were arched and displaced toward the anterior cranial fossa. The placement of porous polyethylene sheets on the orbital roofs through a coronal approach corrected the eye position. A literature review indicated that cerebrospinal shuntings are plagued by a variety of complications including bone changes and craniosynostosis. We believe that enophthalmos associated with cerebrospinal fluid shunting results from a rare acquired bony orbital anomaly.

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.

Effects of Recession versus Tenotomy Surgery without Recession in Adult Rabbit Extraocular Muscle

PURPOSE. Surgical recession of an extraocular muscle (EOM) posterior to its original insertion is a common form of strabismus surgery, weakening the rotational force exerted by the muscle on the globe and improving eye alignment. The purpose of this study was to assess myosin heavy chain (MyHC) isoform expression and satellite cell activity as defined by Pax7 expression in recessed EOMs of adult rabbits compared with that in muscles tenotomized but not recessed and with that in normal control muscles. METHODS. The scleral insertion of the superior rectus muscle was detached and sutured either 7 mm posterior to its original insertion site (recession surgery) or at the same site (tenotomy). One day before euthanatization, the rabbits received bromodeoxyuridine (BrdU) injections. After 7 and 14 days, selected EOMs from both orbits were examined for changes in fast, slow, neonatal, and developmental MyHC isoform expression, Pax7 expression, and BrdU incorporation. RESULTS. Recession and tenotomy surgery resulted in similar changes in the surgical EOMs. These included a decreased proportion of fast MyHC myofibers, an increased proportion of slow MyHC myofibers, and increased BrdU-positive satellite cells. Similar changes were seen in the non-operated contralateral superior rectus muscles. The ipsilateral inferior rectus showed reciprocal changes to the surgical superior rectus muscles. CONCLUSIONS. The EOMs are extremely adaptive to changes induced by recession and tenotomy surgery, responding with modulations in fiber remodeling and myosin expression. These adaptive responses could be manipulated to improve surgical success rates. (Invest Ophthalmol Vis Sci. 2010;51:5646-5656) DOI:10.1167/iovs.10-5523

Dilated cardiomyopathy in a case of Shwachman-Diamond syndrome

The Shwachman-Diamond syndrome is an autosomal recessive bone marrow failure syndrome with exocrine pancreatic insufficiency. Additional organ systems, such as the liver, heart and bone, may also be affected. We report a patient with a long history of cardiac failure and diagnosis of dilated cardiomyopathy with intermittent neutropenia. Periodic follow-up revealed progressive cardiac failure and pulmonary hypertension. A diagnosis of Shwachman-Diamond syndrome was made at the autopsy.

Glucose transporter protein 1 expression in mucoepidermoid carcinoma of salivary gland: correlation with grade of malignancy

P>Mucoepidermoid carcinoma (MEC), the most common primary salivary malignancy, shows great variability in clinical behaviour, thus demanding investigation to identify of prognostic markers. Since Warburg`s studies, unrestricted cell growth during tumorigenesis has been linked to altered metabolism, implying hypoxic stimulation of glycolysis and diminished contribution of mitochondrial oxidative phosphorylation to cellular ATP supply. Hypothesizing that the study of MEC metabolic status could lead to the discovery of prognostic markers, we investigated by immunohistochemistry the expression of glucose transporter 1 (Glut-1), mitochondrial antigen and peroxiredoxin I (Prx I) in samples of MEC from different histological grades. Our results showed that mitochondrial antigen and Prx I were expressed in the majority of the MEC cases independent of the histological grade. In contrast Glut-1 expression increased significantly as the tumours became more aggressive. These results suggested that oxidative phosphorylation may contribute to ATP supply in all stages of MEC progression, and that the relative contribution of glycolysis over mitochondria for cellular ATP supply increases during MEC progression, favouring growth under low oxygen concentration. In addition, the observed high Prx I protein levels could provide protection to tumour cells against reactive oxygen species generated as a consequence of mitochondrial function and hypoxia-reoxygenation cycling. Altogether our findings suggest that upregulation of Glut-1 and Prx I constitute successful adaptive strategies of MEC cells conferring a growth advantage over normal salivary gland cells in the unstable oxygenation tumour environment.

Elastic moduli of model random three-dimensional closed-cell cellular solids

Most cellular solids are random materials, while practically all theoretical structure-property results are for periodic models. To be able to generate theoretical results for random models, the finite element method (FEM) was used to study the elastic properties of solids with a closed-cell cellular structure. We have computed the density (rho) and microstructure dependence of the Young's modulus (E) and Poisson's ratio (PR) for several different isotropic random models based on Voronoi tessellations and level-cut Gaussian random fields. The effect of partially open cells is also considered. The results, which are best described by a power law E infinity rho (n) (1<n<2), show the influence of randomness and isotropy on the properties of closed-cell cellular materials, and are found to be in good agreement with experimental data. (C) 2001 Acta Materialia Inc. Published by Elsevier Science Ltd. All rights reserved.

Echinobothrium chisholmae n. sp (Cestoda, Diphyllidea) from the giant shovel-nose ray Rhinobatos typus from Australia, with observations on the ultrastructure of its scolex musculature and peduncular spines

Echinobothrium chisholmae n. sp. is described from Rhinobatos typus Bennett (Rhinobatidae), collected from Heron Island, Great Barrier Reef, Australia. E. chisholmae differs from all congeners in possessing 11 hooks in each dorsal and ventral group on the rostellum and groups of 3-6 hooklets on either side of the hooks. A single metacestode of E. chisholmae was collected from the decapod crustacean Penaeus longistylus Kubo. Yellow pigmentation of the cephalic peduncle in immature adults is caused by the accumulation of large vesicles in the distal cytoplasm of the tegument. The vesicles probably provide materials for spine formation. Ultrastructural examination of the rostellar musculature revealed that the muscles are stratified (striated-like), consisting of a periodic repetition of sarcomeres separated by perforated Z-like lines that are oblique to the long axes of the myofilaments.

On the Hopf bifurcation in control systems with a bounded nonlinearity asymptotically homogeneous at infinity

The paper studies existence, uniqueness, and stability of large-amplitude periodic cycles arising in Hopf bifurcation at infinity of autonomous control systems with bounded nonlinear feedback. We consider systems with functional nonlinearities of Landesman-Lazer type and a class of systems with hysteresis nonlinearities. The method is based on the technique of parameter functionalization and methods of monotone concave and convex operators. (C) 2001 Academic Press.

Caries-preventive Efficacy and Retention of a Resin-modified Glass lonomer Cement and a Resin-based Fissure Sealant: A 3-year Split-mouth Randomised Clinical Trial

Purpose: This prospective clinical trial compared the retention rate and caries-preventive efficacy of two types of sealant modalities over a 3-year period. Materials and Methods: Using a split-mouth randomised design, 1280 sealants were randomly applied on sound permanent second molars of 320 young patients aged between 12 and 16 years. Half of the teeth (n = 640) were sealed with a resin-modified glass ionomer cement (RMGIC) (Vitremer (TM), 3M ESPE) and the other half (n = 640) with a conventional light-cure, resin-based fissure sealant (LCRB) (Fluoroshield (R), Dentsply Caulk). Teeth were evaluated at baseline, 6-, 12-, 18-, 24-, 30- and 36-month intervals with regard to retention and new caries development. Results: On the sealed occlusal surfaces after 3 years, 5.10% of RMGIC and 91.08% of LCRB sealants were totally intact and 6.37% of RMGIC and 7.65% of LCRB sealants were partially intact. New caries lesions were found in 20.06% of RMGIC sealed occlusal surfaces, compared to 8.91% for LCRB sealants. Conclusions: The findings of the present clinical study suggest that RMGIC should be used only as a transitional sealant that can be applied to newly erupting teeth throughout the eruptive process, whereas LCRB sealants are used to successfully prevent occlusal caries lesions once an effective rubber dam can be achieved. It can be concluded that there are differences between the RMGIC and LCRB sealants over a 3-year period in terms of the retention rate and caries-preventive efficacy. RMGIC can serve as a simple and economic sealing solution, however provisional. Due to its poor retention rate, periodic recalls are necessary, even after 6 months, to eventually replace the lost sealant.