The surgical option in the management of acute pulmonary embolism

Abstract Objective: Massive or submassive pulmonary embolism (PE) carries a high mortality. Traditionally this condition has been treated with thrombolysis or anticoagulation and support measures. Surgical embolectomy is carried out in situations of hemodynamic instability or contraindication for thrombolysis. We present our results of surgical embolectomy in patients with massive and submassive PE. Methods: Over a three‐year period, we have carried out 20 surgical embolectomies for acute PE. The mean age was 66 years, and there were 11 males. In all cases, the diagnosis had been made by a computerized tomography (CT) pulmonary artery angiography. Nine patients (45%) arrived to the operating theater on inotropes, and two of them (10%) with ventilatory support. All patients underwent a median sternotomy, bicaval cannulation for institution of cardiopulmonary bypass (CPB), and main pulmonary arteriotomy for the removal of the thrombus. Results: The mean bypass time was 45 minutes. Two patients (12%) died after being unable to wean off CPB due to right heart failure. Among the 15 survivors, the median ventilation time in the intensive care unit was 24 hours. Twelve patients (60%) required inotropic support postoperatively for right heart failure. All but one survivor (94%) underwent an insertion of a permanent inferior vena cava filter and were anticoagulated with coumarin. The mean follow‐up is 9.8 months and is 100% complete, with a survival of 94.5%. All patients were in the World Health Organization (WHO) functional class I, with no re‐admissions for respiratory failure. Conclusion: In patients with acute massive or submassive PE, surgical embolectomy offers a valid therapeutic strategy. A right‐sided heart failure is the main complication of this condition.     

Pharmacologic treatment of fibromyalgia: Towards chemical neuromodulation

Fibromyalgia is a chronic pathology and its main symptom is pain which usually does not respond to traditional analgesia. Its clinical characteristics and the diverse neurophysiologic findings in these patients point to a central sensitization process of the nociceptive system as the central physiopathologic axis in this disease. The knowledge of the nociceptive system functioning and its behavior in this disease has led, in the past few years, to new possibilities for the therapeutic approach. In that way, drugs with a differential mechanism of action, allowing a modulation of the nociceptive system capable of producing analgesia where other medications have failed are being developed. Different drugs with the capacity increasing the activity of biologically active amines implicated in the nociceptive inhibition process and others which are destined to reduce the excitability of the system through ion channels, are being tested with some benefit in Fibromyalgia patients and may constitute a more rational neuromodulating drug profile for this disease. This article reviews the different pharmacological strategies supported by scientific evidence and points to some future research lines that fortifies the therapeutic change taking place in the treatment approach of these patients.     

The proteome of human brain after ischemic stroke

Although stroke is among the most common causes of death and chronic disability worldwide, the proteome of the ischemic human brain remains unknown. Only a few studies have investigated the ischemic brain proteome in rodent stroke models. We performed a proteomic study of the human brain after ischemic stroke using a 2-dimensional differential gel electrophoresis-based proteomic approach. In brain samples from 6 deceased stroke patients and 3 control subjects, there was an average of 1,442 ± 231 protein spots in the gels. Changes of at least 1.5-fold in the relative expression of 132 protein spots between different cerebral areas (infarct core, peri-infarct, and contralateral tissue) were identified (p < 0.05); 39 of these were successfully identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Among the identified protein spots, we validated the results of 10 proteins by Western blot and determined the cellular localization in brain parenchyma for 3 of the identified proteins: dihydropyrimidinase-related protein 2, vesicle-fusing ATPase, and Rho dissociation inhibitor 1. These results contribute to understanding the processes that follow cerebral ischemia; moreover, some of the identified proteins may be therapeutic targets or biologic markers for determining the diagnosis and prognosis of stroke.     

Neonatal rigid-akinetic syndrome and dentato-olivary dysplasia

This report describes a male infant who presented since birth with rigidity and hypokinesia. Severe developmental delay, episodic central hypoventilation, and drug-resistant epilepsy progressively added to the extrapyramidal signs in the following months and led to the patient's death at 10 months of age. Neuroradiologic and neurometabolic evaluations were negative. Normal cerebrospinal metabolites excluded a defect in dopamine metabolism, and treatment with levodopa failed to improve his motor symptoms. Neuropathologic findings demonstrated dentato-olivary dysplasia. While isolated dentato-olivary dysplasia has been described in a few cases of Ohtahara syndrome, to our knowledge, the association with infantile parkinsonism has not been previously reported.     

Tolbutamide reduces glioma cell proliferation by increasing connexin43, which promotes the up-regulation of p21 and p27 and subsequent changes in retinoblastoma phosphorylation

Our previous work has shown that tolbutamide increases gap junctional permeability in poorly coupled C6 glioma cells and that this effect is similar and additive to that found with dbcAMP, a well-known activator of gap junctional communication. Furthermore, the increase in gap junctional communication promoted by tolbutamide or dbcAMP is concurrent with the inhibition of proliferation of C6 glioma cells. In the present work, we show that tolbutamide and dbcAMP increase the synthesis of the tumor suppressor protein Cx43 and that they decrease the level of Ki-67, a protein expressed when cells are proliferating. These effects were accompanied by a reduction in the phosphorylation of pRb, mainly on Ser-795, a residue critical for the control of cell proliferation. The decrease in the phosphorylation of pRb is not likely to be mediated by a reduction in the levels of D-type cyclins, since instead of decreasing the expression of cyclins, D1 and D3 increased slightly after treatment with tolbutamide or dbcAMP. However, the Cdk inhibitors p21 and p27 were up-regulated after treatment with tolbutamide and dbcAMP, suggesting that they would be involved in the decrease in pRb phosphorylation. When Cx43 was silenced by siRNA, neither tolbutamide nor dbcAMP were able to up-regulate p21 and consequently to reduce glioma cell proliferation, as judged by Ki-67 expression. In conclusion, tolbutamide and dbcAMP inhibit C6-glioma cell proliferation by increasing Cx43, which correlates with a reduction in pRb phosphorylation due to the up-regulation of the Cdk inhibitors p21 and p27.     

Tumor necrosis factor alpha drugs in rheumatoid arthritis: systematic review and metaanalysis of efficacy and safety

Background  

To analyse available evidence on the efficacy and safety of anti-TNFα drugs (infliximab, etanercept and adalimumab) for treating rheumatoid arthritis (RA).     

Carotid angioplasty with cerebral protection and stenting: report of 164 patients (194 carotid percutaneous transluminal angioplasties)

BACKGROUND: The introduction of cerebral protection devices with systematic stent placement has changed the nature of carotid artery stenosis treatment, reducing the immediate periprocedural complications and delayed restenosis. METHODS: We treated 164 patients with 194 carotid artery stenosis procedures; 92% of them were symptomatic patients. RESULTS: The morbidity rate of our series was 1.03% and the mortality was 1.9%. CONCLUSIONS: In the future, carotid stenosis treatment should perhaps be performed as a preventative measure and not used as a cure for full-blown symptoms. This could be effective in reducing the morbidity and mortality rates of this pathology.     

Reduced fitness of HIV-1 resistant to CXCR4 antagonists

HIV-1 strains with a syncytium-inducing phenotype that use CXCR4 (X4 strains) have been associated with faster disease progression and AIDS. Antiviral agents designed to block CXCR4 may prevent the emergence of X4 HIV strains but resistant strains that maintain the X4 phenotype can be raised by sequential passage in cell cultures. We have demonstrated that a laboratory adapted strain (NL4-3) and a cloned clinical isolate (CI-1) of HIV-1 cultured in the presence of the CXCR4 antagonist, AMD3100, became resistant to the compound without a change in co-receptor use. These strains became resistant through divergence with respect to the wild-type virus. Conversely, a clinical isolate made resistant to AMD3100 switched co-receptor use from X4 to R5 through a change in diversity from the original virus population. When dual infection competition/heteroduplex tracking assays were performed, all AMD3100-resistant strains, regardless of co-receptor use showed a significantly diminished fitness compared with the wild-type virus. Single virus infections, at a similar multiplicity of infection, also indicated that the wild-type strains possess better replicative ability than their corresponding resistant strains. Thus, viral resistance development to a CXCR4 antagonist such as AMD3100 is associated with reduced viral fitness.