The effect of an expandable polyvinyl acetate (Merocel) pack on the healing of the nasal mucosa of sheep

BACKGROUND: There is a lack of knowledge about the healing of the nasal respiratory mucosa after endoscopic sinus surgery (ESS). Nasal packs often are placed after ESS in an attempt to improve hemostasis and reduce adhesion formation. Most nasal packs need to be removed in the postoperative period. This is uncomfortable for the patient and the affect of these packs on the healing process is unknown. METHODS: We have standardized the sheep as a suitable animal model to examine the healing of the nasal epithelium after ESS. The nasal mucosa of sheep was wounded under endoscopic guidance and either packed with expandable polyvinyl acetate-based pack (Merocel), which was removed at the 5th postoperative day, or left unpacked to serve as control. Serial biopsies of the wounded area were taken every 28 days, up to 112 days postwounding, for examination using light and scanning electron microscopy. RESULTS: There was no significant difference in the rate of reepithelialization between the packed and control sides of the sheep (p > 0.05). There was no significant difference in the total amount of surface cilia coverage between the packed and control sides at any time points (p > 0.05). There was no significant difference in the maturity of the cilia between the packed and control sides at any time points (p > 0.05). CONCLUSION: The use of Merocel packing postoperatively neither impairs nor promotes wound healing in the postoperative period.     

A novel inhaled organic nitrate that affects pulmonary vascular tone in a piglet model of hypoxia-induced pulmonary hypertension

Persistent pulmonary hypertension of the newborn is characterized by elevated pulmonary vascular resistance after birth leading to right-to-left shunting and systemic arterial hypoxemia. Inhaled nitric oxide (NO) is effective in reducing the need for extracorporeal membrane oxygenation, but it has potential toxicities, especially in an oxygen-rich environment. A number of other NO-based molecules have been given by inhalation, but their structure-function relationships have not been established. Recent studies have raised the idea that toxic and beneficial properties can be separated. We synthesized a novel organic nitrate [ethyl nitrate (ENO2)], tested it in vitro, and administered it to hypoxic piglets. ENO2 lowered pulmonary artery pressure and raised the Po2 in arterial blood but did not alter systemic vascular resistance or methemoglobin levels. In addition, we tested the effect of ENO2 in the presence of the thiol glutathione, both in vivo and in vitro, and found its action to be enhanced. Although ENO2 is less potent than inhaled NO on a dose-equivalency basis, pretreatment of hypoxic animals with glutathione, which may be depleted in injured lungs, led to a markedly enhanced effect (largely mitigating the difference in potency). These results suggest that ENO2 may hold promise as a safe alternative to NO, particularly in hypoxemic conditions characterized by thiol depletion.     

Mutations in senataxin responsible for Quebec cluster of ataxia with neuropathy

Senataxin recently was identified as the mutated gene in ataxia-oculomotor apraxia 2, which is characterized by ataxia, oculomotor apraxia, and increased alpha-fetoprotein levels. In this study, we evaluated 24 ataxic patients from 10 French-Canadian families. All cases have a homogeneous phenotype consisting of a progressive ataxia appearing between 2 and 20 (mean age, 14.8) years of age with associated dysarthria, saccadic ocular pursuit, distal amyotrophy, sensory and motor neuropathy, and increased alpha-fetoprotein levels but absence of oculomotor apraxia. Linkage disequilibrium was observed with markers in the ataxia-oculomotor apraxia 2 locus on chromosome 9q34. We have identified four mutations in senataxin in the French-Canadian population including two novel missense mutations: the 5927T-->G mutation changes the leucine encoded by codon 1976 to an arginine in the helicase domain (L1976R), and the 193G-->A mutation changes a glutamic acid encoded by codon 65 into a lysine in the N-terminal domain of the protein (E65K). The common L1976R mutation is shared by 17 of 20 (85%) carrier chromosomes. The study of this large French-Canadian cohort better defines the phenotype of this ataxia and presents two novel mutations in senataxin including the more common founder mutation in the French-Canadian population.     

Single lung transplantation--one year follow-up

Lung transplantation is now generally accepted as a modality of care for patients with end-stage lung diseases who demonstrate declining of lung function despite optimal therapy. This paper describe a case of single lung transplantation performed in patient with advanced obstructive pulmonary diseases and pulmonary fibrosis. One year follow-up with special regard to complications after operation is presented.     

Cauda equina syndrome secondary to posterior epidural migration of a lumbar disc fragment: a rare phenomenon

Most symptomatic lumbar disc herniations occur in a postero-lateral direction. Disc fragments also commonly migrate both caudally and rostrally. The extrusion of lumbar discs is usually limited by the posterior longitudinal ligament and its attachments. Migration of disc tissue around the dural sac to the posterior epidural space is a rare occurrence. There have been even fewer reports, in the published literature, of cauda equina syndrome resulting from posterior epidural migration of lumbar disc fragments. We present a case of cauda equina syndrome due to compression of the neural elements by a large fragment of sequestered lumbar disc tissue, which had migrated to the posterior epidural space.     

Vaccines and vaccine strategies against HIV

The HIV/AIDS pandemic is a global emergency and a preventive HIV vaccine is urgently needed. HIV has, however, proved a difficult pathogen to vaccinate against. This is largely because HIV has a very high mutation rate and can escape immune responses, it has a latent stage where it can rest silently integrated into host DNA, and neutralising antibodies that can neutralise diverse field strains have so far proved difficult to induce. There is however, considerable evidence now that HIV-specific CD4 and CD8 T cells can provide partial control of HIV replication and delay or prevent disease. Technologies to quantify and analyse HIV-specific T cells have advanced recently, and in particular ELISpot, intracellular cytokine staining and tetramer studies have provided clear analyses of the ability of HIV vaccines to induce T cell responses. The use of pools of overlapping HIV peptides as in vitro antigens has also provided a standardised reagent for accurate measurement of T cell responses. HIV protein vaccines have not induced broad neutralising antibodies or T cell responses and failed to protect humans in the only phase III efficacy trial yet completed. Viral vectors, such as canarypox, engineered to express HIV genes, have induced HIV-specific CD8 T cell responses in a minority of subjects in phase II trials and are proceeding to human efficacy trials. Currently, the most effective method of inducing CD8+ CTL immunity in non-human primates utilises priming with naked plasmid DNA and then boosting with recombinant viral vectors both encoding various parts of the HIV genome. Such vaccines have induced non-sterilising immunity to virulent Simian/Human immunodeficiency virus exposure in macaques and have entered phase I trials. Multiple other approaches are also being evaluated in what has become a global effort for a vaccine to prevent AIDS. Although an HIV vaccine is still a long way off, there is reason to be optimistic that a vaccine to prevent AIDS will eventually be developed.