Circulating Secretory Phospholipase A2 Activity following Snakebites and Its Relationship with Envenomation Status and Progression of Local Swelling.

We studied whether circulating secretory phospholipase A2 (sPLA2) activity reliably distinguished patients with snakebite envenomation from those with nonvenomous/dry snakebites, and whether patients with progressive local swelling had persistence of circulating sPLA2 activity despite antivenom treatment. We prospectively enrolled adults presenting to the emergency with a history of snakebite in the past 24 hours. We estimated circulating sPLA2 activity at baseline before antivenom administration and after 48 hours in those with envenomation. We enrolled 52 patients with snakebites (mean age 39.3 ± 12.6 years; 35 [67%] men), and 16 patients with infective cellulitis as controls. Thirty patients had local ± systemic envenomation; 15 were classified as dry/nonvenomous bites; and envenomation status was unclear in seven patients. Baseline sPLA2 activity was significantly higher in snakebite patients than that in those with infective cellulitis (4.64 [3.38-5.91] versus 3.38 [1.69-4.01] nmol/minute/mL; P = 0.005). Among patients with snakebites, sPLA2 activity in the highest quartile was significantly associated with envenomation (12 of 27 versus two of 22; P = 0.010). However, median sPLA2 activity did not differ significantly between patients with envenomation and the rest. Baseline sPLA2 activity was significantly associated with the maximum extent of limb swelling (P = 0.031 for trend). In envenomed patients, circulating sPLA2 activity significantly decreased after 48 hours compared with the baseline (5.49 [3.38-8.86] versus 3.38 [2.53-4.64]; P = 0.003) including those with progressive swelling. Although circulating sPLA2 activity was elevated following snakebites, its sensitivity to diagnose envenomation appears to be limited. Administration of more antivenom after systemic manifestations had reversed might not benefit patients with progressive local swelling.

Cerebrospinal fluid matrix metalloproteinase 9 levels, blood-brain barrier permeability, and treatment outcome in tuberculous meningitis.

OBJECTIVES: Tuberculous meningitis is characterized by elevated levels of matrix metalloproteinase 9 (MMP9) in the cerebrospinal fluid (CSF). However, it is unclear whether elevated MMP9 levels are associated with poor treatment outcome. We tested the hypothesis that pretreatment MMP9 levels in the CSF would be higher in tuberculous meningitis patients experiencing a poor treatment outcome. METHODS: We prospectively assessed the treatment outcome in a consecutive sample of human immunodeficiency virus-negative patients with tuberculous meningitis. We defined good outcome as survival without severe neurological disability (modified Rankin scale scores 0-2). We estimated levels of MMP9 and its tissue inhibitor (TIMP1) on pretreatment CSF samples. We used albumin index to assess blood-brain barrier permeability. RESULTS: We studied 40 patients (23 males [58%]) with tuberculous meningitis. Sixteen patients (40%) had stage 3 disease. On follow-up, 18 (45%) patients had a poor treatment outcome-15 patients died and 3 had severe neurological disability. Pretreatment MMP9 levels were not associated with treatment outcome (median [interquartile range], 254 [115-389] vs. 192 [60-383] ng/mL in good vs. poor outcome groups; P = 0.693). MMP9 levels did not correlate with the albumin index (Spearman's rho = 0.142; P = 0.381). However, MMP9 levels significantly correlated with CSF glucose levels (rho = -0.419; P = 0.007) and admission Glasgow coma scale score (rho = 0.324; P = 0.032). Likewise, TIMP1 levels also did not differ by treatment outcome (1239 [889-1511] vs. 1522 [934-1949] ng/mL; P = 0.201). MMP9/TIMP1 ratio that reflects net proteolytic activity was also not different between the two groups (0.191 [0.107-0.250] vs. 0.163 [0.067-0.34]; P = 0.625). CONCLUSION: Our findings do not support the hypothesis that pretreatment levels of MMP9 would be higher in tuberculous meningitis patients experiencing a poor treatment outcome. Further, MMP9 levels in the CSF did not correlate with blood-brain barrier permeability in patients with tuberculous meningitis.

SERUM LEVELS OF COPPER AND IRON IN DENGUE FEVER.

The role of trace elements in dengue virulence is not yet known. The present study assessed the serum levels of two micronutrients, copper and iron, in cases of dengue fever. The study involved 96 patients of whom 48 had either severe or non-severe forms of dengue (with and without warning signs), and the remaining 48 were patients with other febrile illnesses (OFI), used as controls. Serum levels of copper and iron were evaluated at admission and by the time of defervescence using commercially available kits. At admission, no difference in the level of serum copper was observed between cases and controls. In the group of dengue cases, the copper level was found to be significantly decreased in severe and non-severe cases with warning signs, compared to non-severe cases without warning signs. In contrast, by the time of defervescence the copper level was found to be increased in all dengue cases compared to OFI controls, but no difference was observed among dengue cases. Unlike OFI controls, dengue cases showed an increasing pattern of copper levels from admission until defervescence. On the other hand, no such significant differences were observed in the serum level of iron in the clinical groups, except for a decreased iron level found in severe cases, compared to non-severe dengue without warning signs. The results show that copper is associated with dengue severity and this finding emphasizes the need to investigate the involvement of trace elements in disease severity so as to improve the prognosis of dengue.

Serum levels of copper and iron in dengue fever / Níveis séricos de cobre e ferro na dengue

SUMMARYThe role of trace elements in dengue virulence is not yet known. The present study assessed the serum levels of two micronutrients, copper and iron, in cases of dengue fever. The study involved 96 patients of whom 48 had either severe or non-severe forms of dengue (with and without warning signs), and the remaining 48 were patients with other febrile illnesses (OFI), used as controls. Serum levels of copper and iron were evaluated at admission and by the time of defervescence using commercially available kits. At admission, no difference in the level of serum copper was observed between cases and controls. In the group of dengue cases, the copper level was found to be significantly decreased in severe and non-severe cases with warning signs, compared to non-severe cases without warning signs. In contrast, by the time of defervescence the copper level was found to be increased in all dengue cases compared to OFI controls, but no difference was observed among dengue cases. Unlike OFI controls, dengue cases showed an increasing pattern of copper levels from admission until defervescence. On the other hand, no such significant differences were observed in the serum level of iron in the clinical groups, except for a decreased iron level found in severe cases, compared to non-severe dengue without warning signs. The results show that copper is associated with dengue severity and this finding emphasizes the need to investigate the involvement of trace elements in disease severity so as to improve the prognosis of dengue.

RESUMOO papel dos elementos-traço na virulência da dengue não é ainda conhecido. O presente estudo avaliou os níveis séricos de dois micronutrientes, cobre e ferro, em casos de dengue. O estudo envolveu 96 pacientes dos quais 48 apresentavam dengue grave ou não grave (com ou sem sinais de alerta), e outros 48 pacientes com outras doenças febris (OFI) representaram os controles. Níveis séricos de cobre e ferro foram avaliados na admissão e no momento da defervescência usando kits comerciais disponíveis. À admissão, nenhuma diferença nos níveis séricos de cobre foi observada entre casos e controles. No grupo com dengue, os níveis de cobre se encontravam significativamente reduzidos nos casos graves e não graves com sinais de alerta, em comparação aos casos não graves sem sinais de alerta. Contrariamente, no momento da defervescência os níveis de cobre se encontravam aumentados em todos os casos de dengue em relação aos controles com outras doenças febris (OFI), no entanto, nenhuma diferença foi observada entre os casos de dengue. Diferentemente dos pacientes com outras doenças febris, os casos de dengue mostraram um padrão de elevação dos níveis de cobre do dia da admissão até a defervescência. Por outro lado, estas diferenças não foram observadas em relação aos níveis de ferro entre os dois grupos, com exceção de níveis de ferro reduzidos encontrados nos casos graves, em comparação aos não graves com sinais de alerta. Os resultados mostram que o cobre está associado à gravidade da dengue e esta observação enfatiza a necessidade de investigação do envolvimento de elementostraço na gravidade da doença para melhorar o prognóstico da dengue.

Diagnostic significance of total creatine kinase and its isoform in tubal ectopic pregnancy.

AIM: Tubal ectopic pregnancy (tEP) must be diagnosed as early as possible because it is one of the leading causes of pregnancy-related death in the first trimester. The aim of this study was to evaluate the diagnostic value of serum total creatine kinase (CK) and its isoforms in diagnosis of tEP. METHODS: The study included 32 tEP cases, and gestational age-matched intrauterine (IU) abortion and normal pregnancy cases (n = 31 each). Serum total CK and CK-MB fraction were measured by the principle of spectrophotometry and CK-MM fraction was calculated from the above parameters. Serum ß-hCG was measured using chemiluminescent immunoassay. All study parameters were measured at the time of presentation. RESULTS: Serum ß-hCG levels were significantly low in patients with both tEP and IU abortion than normal pregnancy. Women with tEP had higher concentrations of total CK, CK-MM and lower concentrations of CK-MB% compared to both gestational age-matched IU pregnancy controls and IU abortion. Receiver-operator characteristic analysis revealed that the optimal cut-off for total CK, CK-MM and CPK-MB% as predictors of ruptured EP were 147 IU/L, 135 IU/L and 10%, respectively, with the former two having higher specificity, and latter high sensitivity. CONCLUSION: Estimation of CK and its CK isoenzyme fractions can aid in quick and accurate diagnosis of tEP.

Incidence and etiology of acute kidney injury in southern India.

OBJECTIVES: To determine the incidence, etiology, short term outcome and predictors of mortality in hospitalized children aged 1 mo to 13 y with Acute Kidney Injury (AKI). METHODS: This prospective observational study was conducted in the pediatric wards and the pediatric intensive care unit (PICU) of a tertiary hospital in southern India, to study the clinico-etiological profile of AKI (defined according to the Acute Kidney Injury Network criteria). From June 2010 through March 2011, 2376 children were included in the study. RESULTS: The incidence of AKI was 5.2 % in the pediatric wards and 25.1 % in the PICU. AKI occurred in association with infections (55.4 %), acute glomerulonephritis (16.9 %), cardiac disease (4.8 %), envenomations (4.2 %) and hemolytic uremic syndrome (3.6 %). Pneumonia constituted 26.1 % of the infections. Tropical febrile illnesses (dengue, scrub typhus, enteric fever, cholera, tuberculosis, malaria and leptospirosis) constituted 15.6 % of children with AKI. Dialysis was required in 14.5 % of patients; mortality was 17.5 %. A significant proportion of children (17.5 % of survivors) had partial renal recovery at discharge. On multivariate logistic regression, dysnatremia and meningoencephalitis were independent predictors of mortality in AKI. CONCLUSIONS: The incidence of AKI is high in the patient population, including the non-critically ill children. AKI continues to be associated with adverse outcomes. Presence of dysnatremia and meningoencephalitis are poor predictors of outcome in AKI.