Noninvasive ventilation during persistent weaning failure: a randomized controlled trial

To assess the efficacy of noninvasive ventilation (NIV) in patients with persistent weaning failure, we conducted a prospective, randomized, controlled trial in 43 mechanically ventilated patients who had failed a weaning trial for 3 consecutive days. This trial was stopped after a planned interim analysis. Patients were randomly extubated, receiving NIV (n = 21), or remained intubated following a conventional-weaning approach consisting of daily weaning attempts (n = 22). Compared with the conventional-weaning group, the noninvasive-ventilation group had shorter periods of invasive ventilation (through tracheal intubation) (9.5 +/- 8.3 vs. 20.1 +/- 13.1 days, p = 0.003) and intensive care unit (ICU) (14.1 +/- 9.2 vs. 25.0 +/- 12.5 days, p = 0.002) and hospital stays (27.8 +/- 14.6 vs. 40.8 +/- 21.4 days, p = 0.026), less need for tracheotomy to withdraw ventilation (1, 5% vs. 13, 59%, p < 0.001), lower incidence of nosocomial pneumonia (5, 24% vs. 13, 59%, p = 0.042) and septic shock (2, 10% vs. 9, 41%, p = 0.045), and increased ICU (19, 90% vs. 13, 59%, p = 0.045) and 90-day survival (p = 0.044). The conventional-weaning approach was an independent risk factor of decreased ICU (odds ratio: 6.6; p = 0.035) and 90-day survival (odds ratio: 3.5; p = 0.018). Earlier extubation with NIV results in shorter mechanical ventilation and length of stay, less need for tracheotomy, lower incidence of complications, and improved survival in these patients.     

Diagnosis and treatment of latent tuberculosis infection in liver transplant recipients in an endemic area

BACKGROUND: Treatment of latent tuberculosis infection (LTBI) with isoniazid is recommended for transplant recipients with positive tuberculin skin test (TST). However, TST could be an imperfect identifier of LTBI in this population. In addition, the risk of isoniazid hepatotoxicity could be high in liver transplant recipients (LTR). A retrospective cohort study was performed to evaluate the diagnosis and treatment of LTBI in LTR. METHODS: Charts of all 547 patients who received primary liver transplantation at a University Hospital in Spain between 1988 and 1998 were reviewed. RESULTS: TST was performed in 373 patients (71%) before transplantation. The result was positive in 89 (24%). The median follow-up after transplantation was 49 months. None of the TST-positive patients developed tuberculosis (TB), but 5 out of 284 patients with negative TST (1.76%) had active TB (P=0.6). Twenty-three patients received isoniazid as treatment of LTBI according to the decision of the attending physician. None of these patients developed TB, but 4 of them (17%) presented isoniazid hepatotoxicity. Among patients who did not receive isoniazid, 2 out of 21 (9.52%) with radiologic previous TB developed active TB versus 0.44% (2/452) among the remaining patients (relative risk [RR], 27.8, 95% CI, 3.2-147). CONCLUSIONS: Treatment of LTBI with isoniazid can not be recommended to LTR on the basis of a positive TST because it is an imperfect identifier of patients at risk of TB. LTR with radiologic features of previous TB are at higher risk of posttransplant active TB. Isoniazid-related hepatotoxicity is more frequent among LTR than in the general population.     

Acute cellular rejection in liver transplant recipients under cyclosporine immunosuppression: predictive factors of response to antirejection therapy

BACKGROUND: Predictive factors of response to antirejection therapy in acute cellular rejection (ACR) in liver transplantation are not well established. METHODS: To investigate the possible existence of these factors, we reviewed 111 consecutive episodes of ACR fulfilling the following criteria: histologically confirmed ACR; cyclosporine-based immunosuppression; initial antirejection treatment with high-dose steroid boluses; minimum follow-up of 2 weeks after treatment; and no other graft complication interfering with evaluation of therapeutic response. ACR episodes not responding to initial steroid therapy were given additional treatment (OKT3 and/or repeated steroid boluses). We analyzed the association of the response to the antirejection treatment with different clinical, laboratory, histological, and donor-recipient compatibility variables at two times: after the initial antirejection therapy, and after all the antirejection therapy administered. RESULTS: Eighty episodes of ACR (72%) resolved after the initial therapy with high-dose steroid boluses, and another 18 (16%), initially steroid-resistant, resolved with additional antirejection treatment. Thirteen episodes (12%) were refractory to all antirejection treatment administered. Variables with independent predictive value of nonresponse to initial therapy with steroid boluses were late-onset ACR (>2 months after transplantation), high serum bilirubin and alanine aminotransferase, low blood cyclosporine concentration in the week before antirejection treatment, and severe histological endothelialitis. Late-onset ACR and high serum bilirubin were also independent predictors of refractoriness to all the treatment administered. CONCLUSIONS: Response to antirejection treatment in ACR in liver transplantation can be predicted by several clinical and laboratory data. ACR episodes with factors predictive of therapeutic unresponsiveness could benefit from more aggressive antirejection treatment.     

Instrumental activation of bid by caspase-1 in a transgenic mouse model of ALS

Transgenic expression of mutant superoxide dismutase-1 (SOD1) produces an animal model of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. We have previously shown that the mitochondrial-dependent programmed cell death (PCD) pathway, including the redistribution of Bax, the cytosolic release of cytochrome c, and the activation of caspase-9, is recruited during neurodegeneration in spinal cords of transgenic mutant SOD1 mice. Herein, we show that the pro-PCD protein Bid is highly expressed in spinal cords of both wild-type and transgenic mutant SOD1 mice. While full-length Bid is found in the spinal cord of the two groups of mice, its cleaved form is only seen in transgenic mutant SOD1 mice, as early as the beginning of symptoms. In contrast, activated caspase-8, which is known to cleave Bid, is detected only at the end-stage of the disease. We also found that the expression of a dominant negative mutant of caspase-1 attenuates Bid cleavage as well as the mitochondrial release of cytochrome c, and the ensuing activation of caspase-9 and -3 in spinal cords of transgenic mutant SOD1 mice. These findings suggest that Bid cleavage may occur in this model by a pathway other than caspase-8 and shed light onto the molecular correlates of the previously reported beneficial effect of caspase-1 inhibition in transgenic mutant SOD1 mice.     

Glial cell response: A pathogenic factor in Parkinson's disease

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The loss of these neurons is associated with a glial response composed mainly of activated microglial cells and, to a lesser extent, of reactive astrocytes. This glial response may be the source of trophic factors and can protect against reactive oxygen species and glutamate. Alternatively, this glial response can also mediate a variety of deleterious events related to the production of pro-oxidant reactive species, proinflammatory prostaglandin, and cytokines. In this review, the authors discuss the potential protective and deleterious effects of glial cells in the SNpc of PD and examine how these factors may contribute to the pathogenesis of this disease.     

Multicentre evaluation of IL Test Free PS: a fully automated assay to quantify free protein S

Deficiency of the anticoagulant vitamin K-dependent protein S (PS) is associated with increased risk of venous thrombosis. In human plasma, PS circulates in two forms: as free protein (free PS) and PS bound to C4b-binding protein (C4BP), a regulator of the complement system. Assays for free PS have higher sensitivity and specificity for protein S deficiency than assays for total protein S. We have extensively evaluated the analytical performance of a novel assay for free PS, the IL Test Free Protein S, which takes advantage of the affinity of C4BP for free PS, and compared its performance to existing methods. IL Test Free Protein S is a rapid, fully automated turbidimetric assay consisting of two reagents: a C4BP coated latex and an anti-PS monoclonal antibody coated latex. The test range, precision and linearity were adequate and the assay tolerated high concentrations of interfering substances of clinical significance. The reference range agreed with previously published studies. The analysis of 903 patient samples belonging to 20 different clinical categories with the new assay yielded free PS results that agreed well with those obtained using the assays established in the participating laboratories. The study demonstrated the IL Test Free Protein S to be rapid, reliable and easy to perform.     

Differential subcellular localization of the 5-HT3-As receptor subunit in the rat central nervous system

Following the cloning and sequencing of the A subunit of the 5-HT3 receptor, two alternatively spliced isoforms, 5-HT3-AS and 5-HT3-AL, have been identified. In order to analyse the distribution of the receptor, a polyclonal antibody has been produced against the short form which is the most abundant in the central nervous system [Doucet et al. (2000) Neuroscience 95, 881-892]. As expected from the recognition of functional 5-HT3 receptors, immunostaining by this anti-5-HT3-R-AS antibody matched the distribution of the high-affinity 5-HT3 binding sites in the rat brain and spinal cord. 5-HT3-AS-like immunoreactivity was detected at low levels in the limbic system, particularly in the amygdala and the hippocampus, and in the frontal, piriform and entorhinal cortices. High levels of immunoreactivity were found in the brainstem, mainly in the nucleus tractus solitarius and the nucleus of the spinal tract of the trigeminal nerve, and in the dorsal horn of the spinal cord. At the ultrastructural level, immunostaining was generally found associated with axons and nerve terminals (70-80%) except in the hippocampus, where labelled dendrites were more abundant (56%). This preferential localization on nerve endings is consistent with the well-documented physiological role of 5-HT3 receptors in the control of neurotransmitter release. However, the different distribution in the hippocampus raises the question of whether differential addressing mechanisms exist for preferentially targeting 5-HT3 receptors to postsynaptic dendritic sites as compared to presynaptic nerve endings, depending on the nature of the neurons bearing these receptors.     

Metameric motor paresis following abdominal herpes zoster

Motor neuropathy is an uncommon complication that may follow an outbreak of herpes zoster (HZ). About half of the reported cases have involved the cranial nerves, typically the facial nerve. The remaining cases have affected the nerves of the extremities. Interestingly, motor weakness of the thoracic segments is strikingly rare, even though this is where HZ most frequently occurs. The dermatologic literature reports only exceptions to this occurence. We report a new case of motor paresis following HZ infection in an abdominal location, where this complication can be easily misdiagnosed as abdominal herniation.