Securing injection laryngoplasty with anti-reflux valve.

BACKGROUND: Injection laryngoplasty (IL) is a common procedure performed by the laryngologist to treat glottal insufficiency. It can be performed under general anaesthesia (GA) or as an office-based procedure. One of the common problems faced during IL is the disconnection between the injection needle and injection material syringe due to high-pressure effect. This may lead to leakage of the injectates especially when injecting high-viscosity materials such as calcium hydroxylapatite (CaHa) or injecting through hard fibrotic scar of the vocal fold. PURPOSE: Due to this recurring issue, we propose anti-reflux valve as a connector to link up these two devices. The function of anti-reflux valve is to ensure secure connection between these two devices and overcome the problem. METHODS: The anti-reflux valve that can be used is NeutraClearTM needle-free connector EL-NC1000 or MicroClaveTM clear connector. In our practice, these anti-reflux valves are used together with Integra MicroFrance straight malleable injection needle (0.5 mm diameter, 250 mm length) for IL under GA. However, any other injection needle suitable for IL may also be used with these anti-reflux valves. RESULTS: Our 3 years' experience has shown good outcome with no reported incidence of device detachment or leakage of injectates during IL procedure. CONCLUSIONS: Anti-reflux valve is a readily available device in the operating theatre or clinic and only involve simple preparation prior to IL. It is beneficial as an added device in IL procedure.

Folate-equipped nanolipoplexes mediated efficient gene transfer into human epithelial cells.

Since recombinant viral vectors have been associated with serious side effects, such as immunogenicity and oncogenicity, synthetic delivery systems represent a realistic alternative for achieving efficacy in gene therapy. A major challenge for non-viral nanocarriers is the optimization of transgene expression in the targeted cells. This goal can be achieved by fine-tuning the chemical carriers and the adding specific motifs to promote cellular penetration. Our study focuses on the development of novel folate-based complexes that contain varying quantities of folate motifs. After controlling for their physical properties, neutral folate-modified lipid formulations were compared in vitro to lipoplexes leading to comparable expression levels. In addition, no cytotoxicity was detected, unlike what was observed in the cationic controls. Mechanistically, the delivery of the transgene appeared to be, in part, due to endocytosis mediated by folate receptor targeting. This mechanism was further validated by the observation that adding free folate into the medium decreased luciferase expression by 50%. In vivo transfection with the folate-modified MM18 lipid, containing the highest amount of FA-PEG(570)-diether co-lipid (w:w; 90:10), at a neutral charge ratio, gave luciferase transgene expression. These studies indicate that modification of lipids with folate residues could enhance non-toxic, cell-specific gene delivery.

A fast-initiating ionically tagged ruthenium complex: a robust supported pre-catalyst for batch-process and continuous-flow olefin metathesis.

In this study, a new pyridinium-tagged Ru complex was designed and anchored onto sulfonated silica, thereby forming a robust and highly active supported olefin-metathesis pre-catalyst for applications under batch and continuous-flow conditions. The involvement of an oxazine-benzylidene ligand allowed the reactivity of the formed Ru pre-catalyst to be efficiently controlled through both steric and electronic activation. The oxazine scaffold facilitated the introduction of the pyridinium tag, thereby affording the corresponding cationic pre-catalyst in good yield. Excellent activities in ring-closing (RCM), cross (CM), and enyne metathesis were observed with only 0.5 mol % loading of the pre-catalyst. When this powerful pre-catalyst was immobilized onto a silica-based cationic-exchange resin, a versatile catalytically active material for batch reactions was generated that also served as fixed-bed material for flow reactors. This system could be reused at 1 mol % loading to afford metathesis products in high purity with very low ruthenium contamination under batch conditions (below 5 ppm). Scavenging procedures for both batch and flow processes were conducted, which led to a lowering of the ruthenium content to as little as one tenth of the original values.

New oligo-beta-(1,3)-glucan derivatives as immunostimulating agents.

Oligo-beta-(1,3)-glucans were chemically modified in order to introduce a structural variation specifically on the reducing end of the oligomers. The impact of well defined structural modulations was further studied on cancer cells and murin models to evaluate their cytotoxicity and immunostimulating potential.

Fine-needle aspiration for nucleic acid-ased molecular analyses in breast cancer.

BACKGROUND: With the widespread development of genomic analysis, an accurate and quick method for obtaining high-quality nucleic acids is needed. The objective of the current study was to evaluate the quality and potential use of material obtained from fine-needle aspiration cytology (FNAC). METHODS: Ultrasound- or palpation-guided FNAC was performed in 124 consecutive patients who had nodular breast lesions. The authors evaluated the amount of messenger RNA (mRNA) obtained, its quality through the RNA Integrity (RIN) score, and the factors that influenced both. For malignant lesions, the authors attempted to correlate estrogen receptor 1 (ESR1) and HER-2 (c-erb-B2) mRNA expression measured by real-time quantitative polymerase chain reaction with estrogen receptor and HER-2 detection obtained by immunohistochemistry (IHC) and/or fluorescent in situ hybridization (FISH) on the surgical specimen. RESULTS: The amount of mRNA obtained was >1 microg in 89.5% of 124 samples (43 benign lesions and 81 adenocarcinomas). Overall, 59.3% of samples yielded >1 microg RNA with a RIN score >6. The most significant predictors of quality and quantity of mRNA were the cytopathologist who sampled the tumors and a diagnosis of cancer versus benign lesion. The median ESR1 expression level, which was expressed as the polymerase chain reaction cycle threshold (CT) level minus the average 18S value (dct), was 17.7 dct in patients with estrogen receptor-negative tumors and 11.1 dct in patients with estrogen receptor-positive tumors. The median HER-2 expression level was 15.1 dct in patients with HER-2-negative tumors and 10.7 dct in patients with HER-2-positive tumors. mRNA expression was concordant with the IHC/FISH evaluation in 90.3% of patients for estrogen receptor status and in 98.5% of patients for HER-2 status. CONCLUSIONS: In 70% of cases, FNAC of breast lesions in well trained hands allowed the extraction of mRNA suitable for gene expression analysis.

Results after conservative treatment of serous borderline tumors of the ovary with a micropapillary pattern.

OBJECTIVE: The aim of this study was to assess the outcomes of patients treated conservatively for a serous borderline ovarian tumor with micropapillary patterns (SBOT-MP). METHODS: Retrospective study collecting cases of conservative treatment of SBOT-MP. There are 15 patients treated with conservative management for a stage I (n = 8) or III (n = 7) SBOT-MP. Eight patients underwent a unilateral salpingo-oophorectomy with a contralateral cystectomy, three a unilateral salpingo-oophorectomy, two a cystectomy, and two a bilateral cystectomy. Four patients had stromal microinvasion associated with MP at histological examination of the ovarian tumor. Noninvasive implants were observed in eight patients and invasive implants in one. Three patients had residual disease <1 cm on the peritoneum. One patient received adjuvant chemotherapy. RESULTS: After a median interval of 63 months (range, 18-120 months), 11 recurrences were observed: six of them exclusively on the ovary, three exclusively on the peritoneum (invasive peritoneal disease in one), and two on the ovary and peritoneum. One of the last two patients succumbed to the recurrence (under the form of invasive adenocarcinoma). The other patients were actually disease free. Five patients achieved eight spontaneous pregnancies. CONCLUSION: This study demonstrates that spontaneous pregnancies can be achieved after conservative treatment of SBOT-MP. Nevertheless, as 2/3 of patients had bilateral ovarian involvement at the time of initial management, the recurrence rate is high. However, making definitive conclusions about the safety of conservative surgery is limited by the small sample size. So, further studies are warranted to evaluate conservative management of advanced-stage disease.

Aminocarbonyl group containing Hoveyda-Grubbs-type complexes: synthesis and activity in olefin metathesis transformations.

Three novel "boomerang" precatalysts bearing different aminocarbonyl functions are reported. Comparative kinetic studies show that this functional group allows for a control of the catalytic activity in metathesis transformations. The scope of the more active catalyst is investigated and shows a good tolerance to various substrates in ring-closing metathesis, enyne metathesis, and cross metathesis. ICP-MS analyses illustrate the good affinity of this catalyst for silica gel, as levels of Ru contamination lower than 6 ppm are detected in the final products.

Synthesis of archaeal bipolar lipid analogues: a way to versatile drug/gene delivery systems.

A synthetic route for the preparation of symmetrical and unsymmetrical archaeal tetraether-like analogues has been described. The syntheses are based upon the elaboration of hemimacrocyclic tetraether lipid cores from versatile building blocks followed by simultaneous or sequential introduction of polar head groups. Functionalizations of the tetraether lipids with neutral lactose or phosphatidylcholine polar heads and cationic glycine betaine moieties were envisaged both to increase membrane stability and to exhibit interactions with charged nucleic acids. Additionally, mannose and lactose triantennary clusters designed as multivalent ligands for selective interaction with lectin-type receptors were also efficiently synthesized for active cell/tissue targeting.

Granular cell tumor of the breast.

We report a case of a 43-yr-old woman with a granular cell tumor of the breast. She presented with a palpable mass of the left breast of 2-yr duration. On physical examination, a firm, painless, well-defined mass located at the union of the upper quadrants was observed and a palpable homolateral axillary lymph node. The tumor was dense with ill-defined borders at mammography and hypoechoic, hypovascular, and poorly limited at ultrasonography. Fine needle aspiration cytology of the lesion was performed. Cytologic examination revealed the presence of highly cellular material, composed of both large cohesive groups and single cells often admixed with connective tissue. These cells had ill-defined abundant granular cytoplasm and bland regular small nuclei. Nucleoli were inconspicuous. Neither mitoses nor necrosis were noted. The cytological diagnosis of granular cell tumor of the breast was confirmed by histological examination of the surgical specimen following a breast lumpectomy.

Highly recoverable pyridinium-tagged Hoveyda-Grubbs pre-catalyst for olefin metathesis. Design of the boomerang ligand toward the optimal compromise between activity and reusability.

Whereas the boomerang ligand of Hoveyda-Grubbs pre-catalysts can be modified by attachment of a pyridinium tag to its benzylidene moiety, a precise adjustment of the length of the spacer allows the optimum balance to be reached between the activity of the catalyst and its recoverability, exceeding 98% after 6 catalytic runs in the best case.

Detection of impaired growth of the corpus callosum in premature infants.

OBJECTIVE: There is an urgent need for a bedside method to assess the effectiveness of neonatal therapies designed to improve cerebral development in very low birth-weight infants. The aim of this study was to assess the impact of preterm birth on the serial growth of the corpus callosum and how soon it could be detected after birth with cranial ultrasound. METHODS: We recruited 61 very low birth-weight infants admitted to a single regional level III NICU from 1998 to 2000. Study infants had 2 cranial sonograms > or = 7 days apart in the first 2 weeks of life and further sonograms at 6 weeks and at term equivalent. At each time point, the length of the corpus callosum and cerebellar vermis was measured on midline sagittal images, with growth rates calculated in millimeters per day. We compared growth of corpus callosum and cerebellar vermis in individuals, between birth age groups, and with corrected gestational age. We used antenatal growth rate of the corpus callosum of 0.2 to 0.27 mm/day as a reference. Relationships between corpus callosum growth rates and neurodevelopmental outcome at 2 years of age (corrected) were also examined. RESULTS: Growth of the corpus callosum was normal in most infants during the first 2 weeks of life but slowed after this (0.21 mm/day from 0-2 weeks vs 0.11 mm/day for weeks 2-6). Slowing of corpus callosum growth below expected reference range was consistently detectable by age 6 weeks for 96% of infants born between 23 and 33 weeks' gestation. Although some improvement in growth rate was observed for 15% of infants after 6 weeks, this was confined to infants born after 28 weeks. Vermis length correlated strongly with corpus callosum length. By 2 years of age, serious motor delay and cerebral palsy were associated with poorer growth of the length of the corpus callosum between 2 and 6 weeks after birth. CONCLUSIONS: The effect of preterm birth on growth of the corpus callosum is detectable by 6 weeks after delivery in preterm infants born at gestations of 23 to 33 weeks. Reduced growth of the corpus callosum in weeks 2 to 6, places these infants at elevated risks of later psychomotor delay and cerebral palsy.

Growth rate of corpus callosum in very premature infants.

BACKGROUND AND PURPOSE: It is desirable to develop a bedside method for assessing cerebral development in the very premature infant to monitor the effectiveness of interventions aimed at improving cerebral development. Our aim was to describe the growth trajectory of the corpus callosum (CC) on cranial sonography in very premature infants. METHODS: We recruited 100 very-low-birth-weight infants admitted to a single regional level III neonatal intensive care unit from November 1998 to November 2000. Cranial sonography images of the CC were obtained for 64 (32 boys) infants (mean gestational age, 28 weeks; range, 23-33 weeks) in the first week of life and at term equivalency. The growth rate of the CC was compared in the 64 study infants to the expected growth rate of 0.20-0.27 mm/day from antenatal data and correlated with clinical outcome at 2 years of age by using Mental Development Index (MDI) and Psychomotor Development Index (PDI). RESULTS: The average growth rate of the CC was half of that expected from antenatal data. Mean growth rates were similar for all gestational ages (mean, 0.11 mm/day; range, 0.05-0.29; P = .4). The CC at term equivalency was longer for those in MDI class 2 (mean, 44.3 mm) compared with MDI class 3 (mean 40.2 mm; P = .003) as well as for PDI class 2 versus 3 (P = .017). CONCLUSION: Measurement of the length of the CC at cranial sonography is reproducible. Those with poorer neurodevelopmental outcomes have a shorter CC at term equivalency. The CC grows at a much lower rate postnatally than in utero among very premature infants.

Preparation of synthetic glycoconjugates as potential vaccines against Shigella flexneri serotype 2a disease.

The synthesis of three neoglycopeptides incorporating carbohydrate haptens, differing in length, covalently linked to a non natural universal T helper peptide is disclosed. They were synthesized according to a blockwise strategy based on the condensation of appropriate di-, tri-, and tetrasaccharide trichloroacetimidate donors onto an azidoethyl 2-acetamido-2-deoxybeta-D-glucopyranoside acceptor. Use of thiol-maleimide coupling chemistry allowed site-selective efficient conjugation.

Factors predicting long-term efficacy of Hylan GF-20 viscosupplementation in knee osteoarthritis.

OBJECTIVES: To describe the long-term effects of Hylan GF-20 viscosupplementation in patients with knee osteoarthritis and to identify factors predicting efficacy. METHODS: One hundred and fifty-five patients (80 women and 75 men; mean age, 69 years) with symptomatic knee osteoarthritis each received three intraarticular Hylan GF-20 injections. Effectiveness, safety, and satisfaction were evaluated 7-14 months later based on a physician's examination and a five-item questionnaire. Radiological data (distribution and degree of joint space loss), size of the effusion (none, moderate, large), injection route (anterior, medial to the patella, or lateral to the patellar), and side effects were recorded. Factors predicting effectiveness were looked for by univariate analysis followed by multivariable analysis with adjustments on age, body mass index, gender, and time from treatment to questionnaire administration. RESULTS: Satisfaction was good in 78% and 58.9% of the patients according to the physician examination and questionnaire, respectively. Safety was considered excellent or good in 96.2% of the patients. Factors significantly (P < 0.05) associated with a good outcome were a moderate effusion, injection lateral to the patella, joint space loss in a single compartment, and radiological meniscal calcinosis. CONCLUSION: The factors predictive of a good response to Hylan GF-20 in this study need to be confirmed, and their impact quantitated, in prospective studies.