Unusual case of difficult double-lumen endotracheal tube removal

A reusable Robertshaw red rubber double-lumen endotracheal tube (DLT) was placed to facilitate lung isolation for thoracoscopy in a 49-year-old atopic patient. In spite of its smooth insertion, it was then not possible to remove the DLT. Direct laryngoscopy showed severe laryngeal edema. After 48 hours of medical treatment with steroids, the trachea was extubated. The laryngeal edema could have been the result of physical and chemical irritation by the reusable rubber DLT itself, or from the substances formed during repeated cleaning and sterilization of the DLT. Atopic patients who are prone to developing latex allergy are also more liable to develop severe reactions to chemical, mechanical, and physical irritation from reusable red rubber DLTs or from the chemical solution used for its cleaning and sterilization.     

Orofacial dyskinesia associated with tiemonium

Tiemonium, an anti-spasmodic drug, can have adverse effects related to its anti-muscarinic effect. Dyskinesia is described with other anti-cholinergic drugs, but there are no reports of dyskinesia associated with tiemonium. We report a reversible orofacial dyskinesia following tiemonium intake (contained in Viscéralgine forte) in a woman with positive rechallenge. She presented these symptoms two times after two separate injections with an interval of 2 months. The case was reported to the Tunisian Centre of Pharmacovigilance.     

Not all "quality-adjusted life years" are equal

BACKGROUND: There is evidence that utility elicitation methods used in the calculation of quality-adjusted life years (QALYs) yield different results. It is not clear how these differences impact economic evaluations. METHODS: Using a mathematical model incorporating data on efficacy, costs, and utility values, we simulated the experiences of 100,000 hypothetical rheumatoid arthritis patients over 10 years (50,000 exposed to infliximab plus methotrexate [MTX] and 50,000 exposed to MTX alone). QALYs, were derived from the Health Utilities Index 2 and 3 (HUI2 and HUI3), the Short Form 6-D (SF-6D), and the Euroqol 5-D (EQ-5D). Incremental cost-utility ratios were determined using each instrument to calculate QALYs and the results were compared using cost-effectiveness acceptability curves. RESULTS: Using the different utility measurement methods, the mean difference in QALYs between the infliximab plus MTX and MTX groups ranged from a high of 1.95 QALYs (95% CI=1.93-1.97) using the HUI3 to 0.89 QALYs (95% CI=0.88-0.91) using the SF-6D. Adopting the commonly cited value of society's willingness to pay for a QALY of $50,000, 91% of the simulations favored the cost utility of infliximab plus MTX when using the HUI3 to calculate QALYs. However, when using the EQ-5D, HUI2, or the SF-6D utility values to calculate QALYS, the proportion of simulations that favored the cost utility of infliximab were 63%, 45%, and 12%, respectively. CONCLUSION: Depending on the method for determining utility values used in the calculation of QALYs, very different incremental cost-utility ratios are generated.     

Prognostic value of the immunohistochemical expression of: Ki67, p53, PCNA and Bcl2 in the superficial tumors of the bladder

AIM: To study a serie of superficial tumors of the bladder and to assess the prognostic significance of p53, Ki67, PCNA and bcl2 in these tumors. METHODS: We studied 59 bladder tumors: 43 pTa and 16 pT1. All Patients had cystoscopy 3 months after the resection and tumors that did not recur had a minimum follow up of 5 years. RESULTS: Age more than 65 years (p = 0,001), multifocality (p=0,022) and tumoral size > or = 3 cm (p = 0,022) were correlated with the recurrence. The expression of p53 was correlated with the recurrence in the year following the tumoral resection (p = 0,035). That of of Ki67 was correlated with the histological grade (p = 0,03) and stage (p=0,002). CONCLUSION: Our results suggest to practise regular endoscopic controls during the first year following the resection of the primitive tumor if it expresses p53. The immunohistochemical expression of Ki67 being correlated with the grade, this marker could help to better classify the tumors of intermediate grade.     

Inhibition of rat brain glutamate receptors by philanthotoxin

The actions of philanthotoxin (PhTX) were studied on the function of glutamate receptors expressed in Xenopus oocytes injected with rat brain mRNA and on binding of radioligands to rat brain glutamate receptors. PhTX reversibly inhibited the oocyte responses to quisqualate, N-methyl-D-aspartate (NMDA) and kainate in a dose-dependent manner. The NMDA receptor was the most sensitive to PhTX action (10-fold more than the kainate receptor) and the least sensitive was the smooth current component of the quisqualate response. Recovery from PhTX block differed among the three amino acids. NMDA responses recovered completely within a few minutes whereas responses to kainate and quisqualate recovered more slowly. PhTX had no effect on equilibrium binding of [3H]glutamate to rat brain cortical membranes studied in buffer treated to eliminate microorganisms. Based on the drug specificity of this [3H]glutamate binding, it is suggested to be mostly to the NMDA receptor. Low concentrations of PhTX (1-10 microM) potentiated binding of [3H] MK-801, a specific noncompetitive inhibitor of the NMDA receptor. However, higher PhTX concentrations inhibited this binding with an IC50 of 20 microM, similar to its inhibition of the oocyte-expressed NMDA receptor. Inhibition of [3H]MK-801 binding by PhTX was noncompetitive. It is suggested that PhTX, like the more potent MK-801, binds to an allosteric site on the NMDA receptor and inhibits its function but its binding site is not identical with the MK-801 binding site.     

In vivo activities of farnesyl pyrophosphate synthase inhibitors against Leishmania donovani and Toxoplasma gondii

The in vivo activities of three bisphosphonates were determined against Leishmania donovani and Toxoplasma gondii. Alendronate was essentially inactive against both parasites. Pamidronate was active against L. donovani by intravenous administration. Risedronate had a 50% effective dosage of five 2.6-mg/kg of body weight intraperitoneal doses against L. donovani-infected mice but was less effective against T. gondii-infected mice.     

Multifunctional cytomegalovirus (CMV)-specific CD8+ T cells are not restricted by telomere-related senescence in young or old adults

Antigen-specific multifunctional T cells that secrete interferon-γ, interleukin-2 and tumour necrosis factor-α simultaneously after activation are important for the control of many infections. It is unclear if these CD8⁺ T cells are at an early or late stage of differentiation and whether telomere erosion restricts their replicative capacity. We developed a multi-parameter flow cytometric method for investigating the relationship between differentiation (CD45RA and CD27 surface phenotype), function (cytokine production) and replicative capacity (telomere length) in individual cytomegalovirus (CMV) antigen-specific CD8⁺ T cells. This involves surface and intracellular cell staining coupled to fluorescence in situ hybridization to detect telomeres (flow-FISH). The end-stage/senescent CD8⁺ CD45RA⁺ CD27⁻ T-cell subset increases significantly during ageing and this is exaggerated in CMV immune-responsive subjects. However, these end-stage cells do not have the shortest telomeres, implicating additional non-telomere-related mechanisms in inducing their senescence. The telomere lengths in total and CMV (NLV)-specific CD8⁺ T cells in all four subsets defined by CD45RA and CD27 expression were significantly shorter in old compared with young individuals in both a Caucasian and an Asian cohort. Following stimulation by anti-CD3 or NLV peptide, similar proportions of triple-cytokine-producing cells are found in CD8⁺ T cells at all stages of differentiation in both age groups. Furthermore, these multi-functional cells had intermediate telomere lengths compared with cells producing only one or two cytokines after activation. Therefore, global and CMV (NLV)-specific CD8⁺ T cells that secrete interferon-γ, interleukin-2 and tumour necrosis factor-α are at an intermediate stage of differentiation and are not restricted by excessive telomere erosion.