Partial cricotracheal resection for pediatric subglottic stenosis: long-term outcome in 57 patients.

OBJECTIVE: We sought to assess the long-term outcome of 57 pediatric patients who underwent partial cricotracheal resection for subglottic stenosis. METHODS: Eighty-one pediatric partial cricotracheal resections were performed in our tertiary care institution between 1978 and 2004. Fifty-seven patients had a minimal follow-up time of 1 year and were included in this study. Evaluation was based on the last laryngotracheal endoscopy, the responses to a questionnaire, and a retrospective review of the patient's data. The following parameters were analyzed: decannulation rates, breathing, voice quality, and deglutition. RESULTS: A single-stage partial cricotracheal resection was performed in 38 patients, and a double-stage procedure was performed in 19 patients. Sixteen patients underwent an extended partial cricotracheal resection (ie, partial cricotracheal resection combined with another open procedure). At a median follow-up time of 5.1 years, the decannulation rates after a single- or double-stage procedure were 97.4% and 95%, respectively. Two patients remained tracheotomy dependent. One patient had moderate exertional dyspnea, and all other patients had no exertional dyspnea. Voice quality was found to improve after surgical intervention for 1 +/- 1.34 grade dysphonia (P < .0001) according to the adapted GRBAS grading system (Grade, Roughness, Breathiness, Asthenia, and Strain). CONCLUSIONS: Partial cricotracheal resection provides good results for grades III and IV subglottic stenosis as primary or salvage operations. The procedure has no deleterious effects on laryngeal growth and function. The quality of voice significantly improves after surgical intervention but largely depends on the preoperative condition.

SOCS-1 protein prevents Janus Kinase/STAT-dependent inhibition of beta cell insulin gene transcription and secretion in response to interferon-gamma.

In the pathogenesis of type I diabetes mellitus, activated leukocytes infiltrate pancreatic islets and induce beta cell dysfunction and destruction. Interferon (IFN)-gamma, tumor necrosis factor-alpha and interleukin (IL)-1 beta play important, although not completely defined, roles in these mechanisms. Here, using the highly differentiated beta Tc-Tet insulin-secreting cell line, we showed that IFN-gamma dose- and time-dependently suppressed insulin synthesis and glucose-stimulated secretion. As described previously IFN-gamma, in combination with IL-1 beta, also induces inducible NO synthase expression and apoptosis (Dupraz, P., Cottet, S., Hamburger, F., Dolci, W., Felley-Bosco, E., and Thorens, B. (2000) J. Biol. Chem. 275, 37672--37678). To assess the role of the Janus kinase/signal transducer and activator of transcription (STAT) pathway in IFN-gamma intracellular signaling, we stably overexpressed SOCS-1 (suppressor of cytokine signaling-1) in the beta cell line. We demonstrated that SOCS-1 suppressed cytokine-induced STAT-1 phosphorylation and increased cellular accumulation. This was accompanied by a suppression of the effect of IFN-gamma on: (i) reduction in insulin promoter-luciferase reporter gene transcription, (ii) decrease in insulin mRNA and peptide content, and (iii) suppression of glucose-stimulated insulin secretion. Furthermore, SOCS-1 also suppressed the cellular effects that require the combined presence of IL-1 beta and IFN-gamma: induction of nitric oxide production and apoptosis. Together our data demonstrate that IFN-gamma is responsible for the cytokine-induced defect in insulin gene expression and secretion and that this effect can be completely blocked by constitutive inhibition of the Janus kinase/STAT pathway.

The Outlaw Pirate Heroine, An Analysis of a Durgā Figure in a 1935 Prabhat Film

(Résumé de l'ouvrage) She kills and destroys. She causes illness and disaster. The wild goddess evokes fear and terror. People worship her with blood-sacrifices and alcohol in order to appease her rage, but also in order to participate in her power for she is at once a force of destruction and a force of regeneration, of life, and of sexuality. Her creative violence reflects the ambivalent power of nature. The idea of frightening goddesses is preserved in regionally different forms throughout South Asia. The Institute for the Science of Religions, University of Berne, and the Museum of Anthropology of the University of Zurich, coordinated a symposium on wild goddesses in India and Nepal. The papers and reports on ongoing research presented at this symposium are published in this volume.

Ultrastructural, Antigenic and Physicochemical Characterization of the Mojuí dos Campos (Bunyavirus) Isolated from Bat in the Brazilian Amazon Region

The Mojuí dos Campos virus (MDCV) was isolated from the blood of an unidentified bat (Chiroptera) captured in Mojuí dos Campos, Santarém, State of Pará, Brazil, in 1975 and considerated to be antigenically different from other 102 arboviruses belonging to several antigenic groups isolated in the Amazon region or another region by complement fixation tests. The objective of this work was to develop a morphologic, an antigenic and physicochemical characterization of this virus. MDCV produces cytopathic effect in Vero cells, 24 h post-infection (p.i), and the degree of cellular destruction increases after a few hours. Negative staining electron microscopy of the supernatant of Vero cell cultures showed the presence of coated viral particles with a diameter of around 98 nm. Ultrathin sections of Vero cells, and brain and liver of newborn mice infected with MDCV showed an assembly of the viral particles into the Golgi vesicles. The synthesis kinetics of the proteins for MDCV were similar to that observed for other bunyaviruses, and viral proteins could be detected as early as 6 h p.i. Our results reinforce the original studies which had classified MDCV in the family Bunyaviridae, genus Bunyavirus as an ungrouped virus, and it may represent the prototype of a new serogroup.

Pathology of intracardiac nerves in experimental Chagas disease

Severe destruction of intrinsic cardiac nerves has been reported in experimental acute Chagas myocarditis, followed by extensive regeneration during the chronic phase of the infection. To further study this subject, the sympathetic and para-sympathetic intracardiac nerves of mice infected with a virulent Trypanosoma cruzi strain were analyzed, during acute and chronic infection, by means of histological, histochemical, morphometric and electron microscopic techniques. No evidences of destructive changes were apparent. Histochemical demonstration for acetylcholinesterase and catecholamines did not reveal differences in the amount and distribution of intracardiac nerves, in mice with acute and chronic Chagas myocarditis or in non-infected controls. Mild, probably reversible ultrastructural neural changes were occasionally present, especially during acute myocarditis. Intrinsic nerves appeared as the least involved cardiac structure during the course of experimental Chagas disease in mice.

Extra-cellular matrix changes in Schistosoma mansoni-infected Biomphalaria glabrata

Reactivity of snails against parasites exhibits a primitive focal reaction, with encapsulation, phagocytosis and destruction of parasite larvae by macrophage-like cells - the hemocytes. This reaction mimics granulomatous inflammation seen in higher animals. However, different from the latter, little is known about the participation of extra-cellular matrix in such snail defense reactions. Normal and Schistosoma mansoni-infected Biomphalaria glabrata of different strains were submitted to cytological, histological, ultrastructural and biochemical methods in order to investigate the behavior of extra-cellular tissues at the site of anti-parasite reactions. In spite of the presence of two cell-types in peripheral hemolymph, only one cell-type was present at the sites of tissue reactions. Although pre-existent collagen and elastic fibers and microfibrils sometimes appeared slightly compressed around focal reactions, no evidences of duplication, synthesis or deposition of connective-tissue extra-cellular components were observed within or around the zones of reactive cell accumulations. Thus, tissue reactions against S. mansoni in the snail B. glabrata appeared exclusively dependent on one specific population of hemocytes.

Protection of Life During Pregnancy Bill

An Act to protect human life during pregnancy; to make provision for reviews at the instigation of a pregnant woman of certain medical opinions given in respect of pregnancy; to provide for an offence of intentional destruction of unborn human life; to amend the Health Act 2007; to repeal sections 58 and 59 of the Offences Against the Person Act 1861; and to provide for matters connected therewith. Click here to download PDF 296KB

Severe anemia affects both splenectomized and non-splenectomized Plasmodium falciparum-infected Aotus infulatus monkeys

Severe anemia is the earliest and a frequently fatal complication of Plasmodium falciparum infection. Here we describe Aotus infulatus as a primate model suitable to study this malaria complication. Both non-splenectomized and splenectomized monkeys receiving different inocula of P. falciparum FVO strain presented large (> 50%) decreases in hematocrit values during infection. Non-splenectomized animals were able to control parasite growth (parasitemia did not exceed 4%), but they had to be treated because of severe anemia. Three of 4 splenectomized monkeys did not control parasitemia and were treated, but developed severe anemia after treatment when presenting a negative blood film. Destruction of parasitized red blood cells alone cannot account for the degree of anemia. Non-splenectomized monkeys repeatedly infected with homologous parasites became rapidly and progressively resistant to reinfection and to the development of severe anemia. The data presented here point to A. infulatus as a suitable model for studying the pathogenesis of severe malarial infection.

Cytotoxicity and potential antiviral evaluation of violacein produced by Chromobacterium violaceum

Natural products are an inexhaustible source of compounds with promising pharmacological activities including antiviral action. Violacein, the major pigment produced by Chromobacterium violaceum, has been shown to have antibiotic, antitumoral and anti-Trypanosoma cruzi activities. The goal of the present work was to evaluate the cytotoxicity of violacein and also its potential antiviral properties.The cytotoxicity of violacein was investigated by three methods: cell morphology evaluation by inverted light microscopy and cell viability tests using the Trypan blue dye exclusion method and the MTT assay. The cytotoxic concentration values which cause destruction in 50% of the monolayer cells (CC50) were different depending on the sensitivity of the method. CC50 values were > 2.07 ± 0.08 µM for FRhK-4 cells: > 2.23 ± 0.11 µM for Vero cells; > 2.54 ± 0.18 µM for MA104 cells; and > 2.70 ± 0.20 µM for HEp-2 cells. Violacein showed no cytopathic inhibition of the following viruses: herpes simplex virus type 1 (HSV-1) strain 29-R/acyclovir resistant, hepatitis A virus (strains HM175 and HAF-203) and adenovirus type 5 nor did it show any antiviral activity in the MTT assay. However violacein did show a weak inhibition of viral replication: 1.42 ± 0.68%, 14.48 ± 5.06% and 21.47 ± 3.74% for HSV-1 (strain KOS); 5.96 ± 2.51%, 8.75 ± 3.08% and 17.75 ± 5.19% for HSV-1 (strain ATCC/VR-733); 5.13 ± 2.38 %, 8.18 ± 1.11% and 8.51 ± 1.94% for poliovirus type 2; 8.30 ± 4.24%; 13.33 ± 4.66% and 24.27 ± 2.18% for simian rotavirus SA11, at 0.312, 0.625 and 1.250 mM, respectively, when measured by the MTT assay.

Some coccidial parasites of the lizard Amphisbaena alba (Reptilia: Amphisbaenia: Amphisbaenidae)

Five parasites are described in the lizard Amphisbaena alba (Amphisbaenidae) from the state of Pará, North Brazil. Mature oocysts of Choleoeimeria amphisbaenae n. sp., are passed already mature in the faeces. They are ellipsoidal-cylindrical, average 33.7 x 22.8 µm and are devoid of micropyle, oocyst residuum or polar body. The colourless wall is smooth and of 2 layers. The 4 dizoic sporocysts have no Stieda body and average 13 x 9.3 µm. Endogenous stages develop in the epithelial cells of the gall-bladder in the manner described for the genus and may cause extensive tissue damage. Sporulation of Isospora capanemaensis n. sp., is completed 3 days after the oocysts are voided in the faeces. They average 14.8 x 14.5 µm and have no micropyle, oocyst residuum or polar body. The 2 tetrazoic sporocysts are pear-shaped, average 8.6 x 6.6 and have an inconspicuous Stieda body. Endogenous development is in the epithelial cells of the ileum, and heavy infections cause considerable tissue destruction. Multisporocystic oocysts passed in the faeces of one A. alba possibly originated from an invertebrate host ingested by the lizard. A globidium-like cyst in the digestive tract of A. alba measured 105 x 85 µm and contained many hundreds of merozoites. A stained kidney smear of the same lizard revealed the presence of an unidentified parasite producing multinucleate cyst-like stages.

Differentiation of blue ballpoint pen by positive and negative mode LDI-MS

Usually, the differentiation of inks on questioned documents is carried out by optical methods and thin layer chromatography (TLC). Therefore, spectrometric methods were also proposed in forensic literature for the analysis of dyes. Between these techniques, laser desorption/ionization mass spectrometry (LDI-MS) has demonstrated a great versatility thanks to its sensitivity to blue ballpoint ink dyes and minimal sample destruction. Previous researches concentrated mostly on the LDI-MS positive mode and have shown that this analytical tool offers higher discrimination power than high performance TLC (HPTLC) for the differentiation of blue ballpoint inks. Although LDI-MS negative mode has already been applied in numerous forensic domains like the studies of works of art, automotive paints or rollerball pens, its potential for the discrimination of ballpoint pens was never studied before. The aim of the present paper is therefore to evaluate its potential for the discrimination of blue ballpoint inks. After optimization of the method, ink entries from 33 blue ballpoint pens were analyzed directly on paper in both positive and negative modes by LDI-MS. Several cationic and anionic ink components were identified in inks; therefore, pens were classified and compared according to their formulations. Results show that additional information provided by anionic dyes and pigments significantly increases the discrimination power of positive mode. In fact, it was demonstrated that classifications obtained by the two modes were, to some extent, complementary (i.e., inks with specific cationic dyes not necessarily contained the same anionic components).

Decreased local control following radiation therapy alone in early-stage glottic carcinoma with anterior commissure extension.

PURPOSE: To assess the patterns of failure in the treatment of early-stage squamous cell carcinoma of the glottic larynx. PATIENTS AND METHODS: Between 1983-2000, 122 consecutive patients treated for early laryngeal cancer (UICC T1N0 and T2N0) by radical radiation therapy (RT) were retrospectively studied. Male-to-female ratio was 106 : 16, and median age 62 years (35-92 years). There were 68 patients with T1a, 18 with T1b, and 36 with T2 tumors. Diagnosis was made by biopsy in 104 patients, and by laser vaporization or stripping in 18. Treatment planning consisted of three-dimensional (3-D) conformal RT in 49 (40%) patients including nine patients irradiated using arytenoid protection. A median dose of 70 Gy (60-74 Gy) was given (2 Gy/fraction) over a median period of 46 days (21-79 days). Median follow-up period was 85 months. RESULTS: The 5-year overall, cancer-specific, and disease-free survival amounted to 80%, 94%, and 70%, respectively. 5-year local control was 83%. Median time to local recurrence in 19 patients was 13 months (5-58 months). Salvage treatment consisted of surgery in 17 patients (one patient refused salvage and one was inoperable; total laryngectomy in eleven, and partial laryngectomy or cordectomy in six patients). Six patients died because of laryngeal cancer. Univariate analyses revealed that prognostic factors negatively influencing local control were anterior commissure extension, arytenoid protection, and total RT dose < 66 Gy. Among the factors analyzed, multivariate analysis (Cox model) demonstrated that anterior commissure extension, arytenoid protection, and male gender were the worst independent prognostic factors in terms of local control. CONCLUSION: For early-stage laryngeal cancer, outcome after RT is excellent. In case of anterior commissure extension, surgery or higher RT doses are warranted. Because of a high relapse risk, arytenoid protection should not be attempted.

Prefabrication of composite grafts for long-segment tracheal reconstruction.

OBJECTIVE: To investigate the prefabrication of vascularized mucosa-lined composite grafts intended to replace circumferential tracheal defects. DESIGN: Plane grafts composed of ear cartilage and full-thickness oral mucosa were revascularized by the laterothoracic fascia. The use of meshed vs nonmeshed mucosa to improve the epithelial coverage was examined. We also investigated the creation of a vascular bed over the cartilage and the subsequent application of meshed mucosa. Macroscopic aspects, viability, and degree of mucosal lining were analyzed. SUBJECTS: Twenty male New Zealand white rabbits. INTERVENTIONS: Ten animals underwent placement of auricular cartilage under the laterothoracic fascia. Intact (group 1) or meshed mucosa (group 2) was applied over the fascia and protected by a silicone sheet. After 3 weeks, prefabricated grafts were removed for comparison. In 10 other animals, a sheet of perforated cartilage was placed under the laterothoracic fascia. Two weeks later, 5 grafts (group 3) were harvested. The remaining 5 grafts were reopened for mucosal application over the cartilage and revascularized for 3 additional weeks (group 4). RESULTS: Vascularized plane grafts were obtained in all groups. Mucosal lining increased significantly with meshed mucosa (14%-68%; mean, 40%) compared with nonmeshed mucosa (3%-15%; mean, 10%) (P = .008). Induction of a vascular bed over perforated cartilage was achieved, but survival of secondary implanted mucosa was variable. CONCLUSIONS: A reliable technique to prefabricate composite grafts with cartilaginous support and mucosal lining is presented. The use of meshed mucosa significantly improves epithelial coverage.

Light receptor action is critical for maintaining plant biomass at warm ambient temperatures.

The ability to withstand environmental temperature variation is essential for plant survival. Former studies in Arabidopsis revealed that light signalling pathways had a potentially unique role in shielding plant growth and development from seasonal and daily fluctuations in temperature. In this paper we describe the molecular circuitry through which the light receptors cry1 and phyB buffer the impact of warm ambient temperatures. We show that the light signalling component HFR1 acts to minimise the potentially devastating effects of elevated temperature on plant physiology. Light is known to stabilise levels of HFR1 protein by suppressing proteasome-mediated destruction of HFR1. We demonstrate that light-dependent accumulation and activity of HFR1 are highly temperature dependent. The increased potency of HFR1 at warmer temperatures provides an important restraint on PIF4 that drives elongation growth. We show that warm ambient temperatures promote the accumulation of phosphorylated PIF4. However, repression of PIF4 activity by phyB and cry1 (via HFR1) is critical for controlling growth and maintaining physiology as temperatures rise. Loss of this light-mediated restraint has severe consequences for adult plants which have greatly reduced biomass.

Evaluation of the natural killer cytotoxicity and the levels of cytokines in rats with type I diabetes mellitus

Type I diabetes mellitus (insulin-dependent DM = IDDM) is a chronic disease characterized by specific destruction of pancreatic beta cells, resulting in an absolute lack of insulin. Immune mechanisms, genetic susceptibility, and environmental factors are all implicated in the pathogenesis of Type 1 diabetes. This study was aimed at determining the efficiency of cytokines, natural killer (NK) cells in the pathophysiology of IDDM. Therefore, we evaluated the plasma levels of cytokines by specific enzyme-linked immunosorbent assay (ELISA) and the cytotoxicity activity of NK cells by anti-candididal index in rats with type I diabetes. We found that the cytotoxicity activity of NK cells in IDDM groups significantly decreased compared to the control groups. The levels of interferon-g (IFN-g) in IDDM groups were slightly higher than in healthy controls. These results indicate that the changes of T H1 type cytokines such as IFN-g and NK cell activity can play a role in the etiology of IDDM. The data may provide new strategies for the treatment of IDDM.