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Biomedical subjects

A Chamorro

Publications and source records attributed to A Chamorro.

At least 19 recordsLinked to original sources
PubMed2006

Signalling pathways mediating inflammatory responses in brain ischaemia.

Stroke causes neuronal necrosis and generates inflammation. Pro-inflammatory molecules intervene in this process by triggering glial cell activation and leucocyte infiltration to the injured tissue. Cytokines are major mediators of the inflammatory response. Pro-inflammatory and anti-inflammatory cytokines are released in the ischaemic brain. Anti-inflammatory cytokines, such as interleukin-10, promote cell survival, whereas pro-inflammatory cytokines, such as TNFalpha (tumour necrosis factor alpha), can induce cell death. However, deleterious effects of certain cytokines can turn to beneficial actions, depending on particular features such as the concentration, time point and the very intricate network of intracellular signals that become activated and interact. A key player in the intracellular response to cytokines is the JAK (Janus kinase)/STAT (signal transducer and activator of transcription) pathway that induces alterations in the pattern of gene transcription. These changes are associated either with cell death or survival depending, among other things, on the specific proteins involved. STAT1 activation is related to cell death, whereas STAT3 activation is often associated with survival. Yet, it is clear that STAT activation must be tightly controlled, and for this reason the function of JAK/STAT modulators, such as SOCS (suppressors of cytokine signalling) and PIAS (protein inhibitor of activated STAT), and phosphatases is most relevant. Besides local effects in the ischaemic brain, cytokines are released to the circulation and affect the immune system. Unbalanced pro-inflammatory and anti-inflammatory plasma cytokine concentrations favouring an 'anti-inflammatory' state can decrease the immune response. Robust evidence now supports that stroke can induce an immunodepression syndrome, increasing the risk of infection. The contribution of individual cytokines and their intracellular signalling pathways to this response needs to be further investigated.

Animals↗
PubMed2006

Interleukin 10, monocytes and increased risk of early infection in ischaemic stroke.

BACKGROUND AND PURPOSE: The pathophysiology of stroke-associated infection (SAI) is uncertain. The cytokine profile and peripheral white cell response were assessed in patients with or without SAI. METHODS: The incidence of SAI was assessed in 110 patients with ischaemic stroke allocated antibiotic prophylaxis or placebo within 24 h of clinical onset. Peripheral white cell counts, interleukin (IL)6, tumour necrosis factor (TNF)alpha and IL10 were measured in plasma. RESULTS: 17 (15%) patients developed infection and showed time-dependent increases of total white cell count, neutrophils, monocytes, lymphocytes, IL6 and IL10, whereas TNFalpha and the TNFalpha/IL10 ratio decreased. In logistic regression, IL10 (odds ratio (OR) 1.08, 95% confidence interval (CI) 1.01 to 1.16), monocyte count (OR 1.42, 95% CI 1.08 to 1.87) and National Institute for Health Stroke Survey score on admission (OR 1.17, 95% CI 1.05 to 1.31) were independent predictors of systemic infection. CONCLUSIONS: SAI is associated with stroke severity, excessive IL10-mediated response and an increased number of circulating monocytes. These results support the finding that acute ischaemic brain injury triggers a blood-borne anti-inflammatory response that decreases the antimicrobial drive of the immune system.

Aged↗
PubMed2005

The Early Systemic Prophylaxis of Infection After Stroke study: a randomized clinical trial.

BACKGROUND AND PURPOSE: Early infection after stroke is frequent but the clinical value of antibiotic prophylaxis in acute stroke has never been explored. OBJECTIVE AND METHODS: The Early Systemic Prophylaxis of Infection After Stroke (ESPIAS) is a randomized, double-blind, placebo-controlled study of antibiotic prophylaxis in patients older than 18 years with nonseptic ischemic or hemorrhagic stroke enrolled within 24 hours from clinical onset. Interventions included intravenous levofloxacin (500 mg/100 mL/d, for 3 days) or placebo (0.9% physiological serum) in addition to optimal care. A sample size of 240 patients was calculated to identify a 15% absolute risk reduction of the primary outcome measure, which was the incidence of infection at day 7 after stroke. Secondary outcome measures were neurological outcome and mortality at day 90. RESULTS: Based on a preplanned futility analysis, the study was interrupted prematurely when 136 patients had been included. Levofloxacin and placebo patients had a cumulative rate of infection of 6% and 6% (P=0.96) at day 1; 10% and 12% (P=0.83) at day 2; 12% and 15% (P=0.66) at day 3; 16% and 19% (P=0.82) at day 7; and 30% and 33% (P=0.70), at day 90. Using logistic regression, favorable outcome at day 90 was inversely associated with baseline National Institutes of Health Stroke Scale (OR, 0.72; 95% CI, 0.59 to 0.89; P=0.002) and allocation to levofloxacin (OR, 0.19; 95% CI, 0.04 to 0.87; P=0.03). CONCLUSIONS: Prophylactic administration of levofloxacin (500 mg/100 mL/day for 3 days) is not better than optimal care for the prevention of infections in patients with acute stroke.

Aged↗
PubMed2004

The -174G/C polymorphism of the interleukin 6 gene is a hallmark of lacunar stroke and not other ischemic stroke phenotypes.

BACKGROUND AND PURPOSE: The CC genotype of the -174 G/C interleukin (IL)-6 polymorphism has been associated with lacunar stroke. However, it remains unsettled whether this polymorphism is also associated with other ischemic stroke phenotypes. METHODS: The -174 G/C IL-6 polymorphism was genotyped in patients with lacunar stroke (n = 89), stroke due to large vessel disease (n = 82), cardioembolism (n = 53), stroke of undetermined cause (n = 49) and in white controls without any history of stroke (n = 105) by PCR and restriction enzyme analysis. Independent predictors of the -174 G/C IL-6 genotypes were assessed using multivariate logistic regression models adjusted for demographics, risk factors and disease state. RESULTS: The prevalence of the CC genotype was 8.5% in large vessel disease, 7.5% in embolism, 19.1% in lacunar stroke, 14.3% in stroke of undetermined cause and 8.6% in controls. The CC genotype was independently associated with lacunar stroke only (adjusted OR 3.22, 95% CI 9.09-1.12). Contrarily, there were no significant differences in genotype and allele distribution in the remainder of ischemic stroke phenotypes. Pooling of patients with nonlacunar stroke did not show any independent association with the CC genotype as compared with controls (OR 1.01, 95% CI 2.77-0.36). CONCLUSIONS: The unique association between the CC genotype of the -174 G/C IL-6 polymorphism and lacunar stroke suggests a particular susceptibility of small deep penetrators of cerebral arteries to IL-6-mediated inflammatory damage.

Aged↗
PubMed2004

Hypocomplementemia in systemic lupus erythematosus and primary antiphospholipid syndrome: prevalence and clinical significance in 667 patients.

The objective of the study was to analyse the prevalence and clinical significance of hypocomplementemia in a large series of patients diagnosed either with systemic lupus erythematosus (SLE) or with primary antiphospholipid syndrome (APS) and its association with the main clinical, hematological and immunological features of these diseases. Between 1992 and 2003, complement determinations (C3 and C4 levels, CH50 activity) were performed in 597 consecutive patients diagnosed with SLE (530 women and 67 men, mean age 32.6 years) and 70 with primary APS (57 women and 13 men, mean age 38.7) visited in our department. Complement determinations are routinely made at the first visit of patients and yearly during the follow-up. SLE and primary APS were diagnosed according to current classification criteria. Hypocomplementemia was detected in 371 (62%) of SLE patients. Compared with patients with normal complement values, those with hypocomplementemia showed a higher prevalence of female gender (P < 0.001), fever (P = 0.021), nephropathy (P < 0.001), cutaneous vasculitis (P = 0.023), positive anti-dsDNA antibodies (P = 0.012) and cryoglobulinemia (P < 0.001). In addition, patients with hypocomplementemia showed a higher prevalence of APS-related features such as hemolytic anemia (P = 0.001) and antiphospholipid antibodies (P < 0.001). Hypocomplementemia was prospectively related to accumulated hospitalization in SLE patients but not with the accumulated number of lupus flares or with the survival after follow-up of five years. In contrast, 33 (47%) patients with primary APS presented low complement values, which were associated with a higher prevalence of livedo reticularis (P = 0.022), thrombocytopenia (P = 0.004), lupus anticoagulant (P = 0.013), positive IgM-aCL (P = 0.039), positive ANA (P = 0.002) and anti-dsDNA (P = 0.046). The diagnostic value of hypocomplementemia in patients with SLE is based on the association with disease activity, immune-complex mediated manifestations (glomerulonephritis, cryoglobulinemia) and APS-related features (livedo reticularis, hemolytic anemia and aPL). Hypocomplementemia was found in nearly half of patients with primary APS, and was associated with some APS features (livedo reticularis, thrombocytopenia, aPL) but also with SLE-related immunological markers (ANA and anti-dsDNA), identifying a subset of patients with primary APS with a higher risk of evolving to SLE. These results clearly support the routine determination of complement factors in the clinical follow-up of patients with SLE and primary APS.

Adult↗
PubMed2003

Acute stroke trials: the problems of local investigators?

During stroke trials local investigators have to face many practical problems and time consuming procedures (filling in huge case report forms, performing repeat blood sample drawings for pharmacokinetic studies etc.) which, however, simply require organizational structures which is understood to be necessary to be able to conduct such kind of studies. Other, and most worrisome problems, are indeed to be solved when a sponsored research may rise potential ethical issues, or when academic research proposals clash with the interest of pharmaceutical companies or find difficulties in being funded by public institutions. It is just a greater involvement of these latter, possibly free from bureaucratic laces, which might help a balance to be struck between academic and industrial aims.

Acute Disease↗
PubMed2002

Prevalence and clinical importance of sleep apnea in the first night after cerebral infarction.

OBJECTIVE: To determine the prevalence of sleep apnea (SA) during the first night after hemispheric ischemic stroke and its influence on clinical presentation, course, and functional outcome at 6 months. METHODS: The first night after cerebral infarction onset, 50 patients underwent polysomnography (PSG) followed by oximetry during the next 24 hours. Neurologic severity and early worsening were assessed by the Scandinavian Stroke Scale and outcome by the Barthel Index. Patients were evaluated on admission, on the third day, at discharge, and at 1, 3, and 6 months. RESULTS: There were 30 males and 20 females with a mean age of 66.8 +/- 9.5 years. Latency between stroke onset and PSG was 11.6 +/- 5.3 hours. Thirty-one (62%) subjects had SA (apnea-hypopnea index [AHI] > or = 10). Of these, 23 (46%) had an AHI > or =20 and 21 (42%) an AHI > or =25. Sleep-related stroke onset occurred in 24 (48%) patients and was predicted only by an AHI > or =25 on logistic regression analysis. SA was related to early neurologic worsening and oxyhemoglobin desaturations but not to sleep history before stroke onset, infarct topography and size, neurologic severity, or functional outcome. Early neurologic worsening was found in 15 (30%) patients, and logistic regression analysis identified SA and serum glucose as its independent predictors. CONCLUSIONS: SA is frequent during the first night after cerebral infarction (62%) and is associated with early neurologic worsening but not with functional outcome at 6 months. Cerebral infarction onset during sleep is associated with the presence of moderate to severe SA (AHI > or = 25).

Aged↗
PubMed2002

[Antithrombotic treatment of fusiform aneurysms of the basilar artery].

Fusiform aneurysms are unusual, and they are most found in the vertebrobasilar system. Although the presence of such aneurysms has been related to atheromatous degeneration of the arterial wall, in many cases the cause of their formation is unknown. The clinical manifestations of fusiform aneurysms of the vertebrobasilar system are generally due to mass effect with compression of adjacent structures or to ischemic events; exceptionally they are due to subarachnoidal haemorrhage. We present the case of a patient with symptoms suggestive of brainstem ischemic damage, in which neuroimaging showed a fusiform aneurysm of the basilar artery with an intraaneurysmatic thrombus. Antiaggregation did not prevent new ischemic events, so anticoagulation therapy was initiated. The patient remained asymptomatic at 8 months of follow-up. The treatment of fusiform aneurysms is controversial; however, there are some evidences in the literature supporting that patients with ischemic events may be treated with long term anticoagulation, especially in cases of non-giant aneurysms of the vertebrobasilar system not accompanied by aneurysms in other sites.

Anticoagulants↗
PubMed2001

Effect of internal carotid artery occlusion on vertebral artery blood flow: a duplex ultrasonographic evaluation.

The aim of this study was to evaluate the effect of unilateral internal carotid artery occlusion on blood flow volume and blood flow velocities in both vertebral arteries using duplex Doppler ultrasonography in the cervical segment. Forty patients with unilateral extracranial internal carotid artery occlusion confirmed by angiography were studied, and the results were compared with those obtained in 57 age-matched patients in whom cervical duplex ultrasonography showed no abnormalities. We measured the diameter, flow velocities, and blood flow volume in both vertebral arteries, and the side-to-side differences were also calculated. Eleven patients (27.5%) with an occluded internal carotid artery had increased peak systolic velocity in the ipsilateral vertebral artery, and 6 (15%) had increased peak systolic velocity in the contralateral vertebral artery. The mean peak systolic velocity and the mean blood flow volume were statistically greater in the ipsilateral vertebral arteries than in the same-side vertebral arteries of the control group (P < .05). We also detected a mean increase of 14.29% of the net blood flow volume in the vertebral arteries compared with the control group. Patients with extracranial unilateral internal carotid artery occlusion may have a compensatory increase in both the peak systolic velocity and the blood flow volume in both vertebral arteries.

Aged↗
PubMed2000

Comparison of the acute-phase response in patients with ischemic stroke treated with high-dose heparin or aspirin.

Experimental studies have suggested that unfractionated heparin (UH) has antiinflammatory properties. It is unknown whether UH also has these properties in patients with acute ischemic stroke. Within 12-24 h of treatment onset we measured the acute-phase response as reflected by the erythrocyte sedimentation rate (ESR) and total number of leukocytes (x10(9)/l) in 706 consecutive patients with acute ischemic stroke treated with full-dose UH (n=450), or 300 mg/day aspirin (n=256). Clinical outcome (Mathew scale) at hospital discharge and the effect of factors such as treatment (UH and aspirin), and acute phase response were assessed using multivariate analyses adjusted for baseline confounders and incident complications. Separate models were created for patients with lacunar and nonlacunar stroke. Whereas there were not differences at baseline between the two treatment groups, total leukocyte counts (8. 0+/-4.1 vs. 8.6+/-3.2, P<0.01) and ESR (21.7+/-20.9 vs. 25.2+/-22.9, P<0.05) were statistically significantly lower in patients treated with UH. This effect of UH was more accentuated in patients with nonlacunar stroke. Overall, leukocytes (7.2+/-2.3 vs. 8.4+/-4.0, P<0. 01), and ESR (15.7+/-17.2 vs. 24.3+/-22.2, P=0.0001) were lower in patients with complete early recovery and this effect was restricted to patients with nonlacunar stroke. Whereas baseline impairment, symptomatic bleeding and stroke recurrence were independent negative outcome predictors, the use of UH was positively associated with early recovery in all patients. This study shows that full-dose UH reduces the acute-phase reaction that follows ischemic stroke more effectively than aspirin. The prognostic implications of such effect seem more notable in patients with nonlacunar stroke.

Acute-Phase Reaction↗
PubMed2000

Interaction between interleukin-6 and the natural anticoagulant system in acute stroke.

Inflammatory reactions mediated by cytokines are involved in the pathogenesis of acute stroke. Decrease in circulating levels of protein C (PC) and protein S (PS) induced by inflammatory cytokines has been postulated as a potential mechanism for a procoagulant tendency during acute stroke. The procoagulant state associated with impairments in natural anticoagulants may induce microvascular obstruction leading to a tissue perfusion reduction that worsens cerebral ischemia. Interleukin-6 (IL-6) regulate the synthesis of C4b-binding protein (C4BP), an acute-phase protein that also regulates PS plasma levels. We measured IL-6, C4BP, erythrocyte sedimentation rate (ESR), total and free PS and PC in 44 patients with acute ischemic stroke to determine if IL-6 decreases circulating levels of natural anticoagulants through the C4BP pathway and if these acute changes in natural anticoagulants may have clinical implications. Patients with higher levels of IL-6 had more severe neurologic deficits on admission, greater infarct size, higher levels of acute-phase reactants, and lower levels of free PS. IL-6 was significantly correlated with C4BP, ESR, and free PS levels. PC levels were also lower in the group of patients with greater IL-6, but differences were not statistically significant. No correlations were found between C4BP and natural anticoagulants. Severe neurologic deficit, greater infarct volume, atrial fibrillation, increased levels of inflammatory parameters (ESR and IL-6), and reduced levels of free PS were associated with disabling stroke at 3 months, but only neurologic severity and ESR remained as independent predictors of stroke disability on multiple regression analysis. Inflammatory reactions mediated by IL-6 during the acute phase of stroke influence the modulation of free PS. However, variations in free PS levels do not have implications for clinical outcome in stroke patients. The link between proinflammatory cytokines and free PS in the acute phase of stroke is not related to the C4BP pathway.

Blood Coagulation↗