[B] serum procalcitonin level may discriminate bacterial and viral meningitis in children

Acute childhood meningitis is a life threatening condition often leaving the survivors with neurological impairments. Latex agglutination test is negative in early meningitis cases and is unreliable in the detection of St. pneumoniae, Staphylococci, H. influenzae and Enteric bacilli. Antibiotic treatment should not be deferred until awaiting the result of CSF cultures, nor aggressive antimicrobials should be given unnecessarily in cases of viral meningitis. Procalcitonin [PCT] is a potentially sensititve and rapid marker for invasive bacterial infections but remains low in viral infections. We aimed to assess the reliability of serum PCT in differentiating bacterial from viral meningitis in children. We measured serum PCT and C-reactive protein [CRP] levels and cerebrospinal fluid [CSF] total protein [TP], and absolute neutrophil count [ANC] in fifty children admitted for meningitis. Bacterial cultures of CSF were positive in 17 children [group of bacterial meningitis] and 33 patients were diagnosed as acute viral meningitis. Serum PCT levels were measured by immunoluminometric assay: "BRAHMS Diagnostica, Berlin". CRP levels were determined by rate nephelometry. PCT and CRP levels and CSF ANC and TP were significantly higher [P< 0.001] in the group of bacterial meningitis than the group of viral meningitis. Assay of serum CRP and CSF proteins and cells showed a zone of overlapping values between the two groups. Receiver operating characteristic [ROC] curves were plotted for serum PCT and CRP levels to determine the optimal cut off points that maximized the sum of the sensitivity and specificity of each test. A serum PCT level of 2microg/l was retained as the diagnostic threshold since at this value both the sensitivity and negative predictive value [NPV] were 100%. Area under the receiver operating characteristic curve [AUROCC] was 1.0 for PCT which was significantly higher than that for CRP [0.93; P< 0.05]. These data suggest that serum PCT at the cut off value 2microg/l might be discriminant of bacterial and viral meningitis in children

Analysis of novel troponin T cut off values that improve early risk stratification of patients with suspected myocardial ischemia

TroponinT [TnT] is accepted as a sensitive and specific marker of myocyte necrosis. A consensus recommendation developed by a joint committee of the European Society of Cardiology/American College of Cardiology [JESC/ ACC] that a TnT level above the 99[th] percentile of a reference control population [i.e., TnT >0.01 micro g/1] at a coefficient of variation [cv] of /= 0.1 micro g/1], which the manufacturer continues to recommend, as minor elevations of troponin are associated with increased cardiovascular risk in selected patients with acute coronary syndromes [ACSs]. Therefore, the accepted cut off level of TnT as a sensitive evidence of ischemic cardiac damage is currently under debate. This level is likely to be between 0.03 and 0.1 micro g/1. We evaluated TnT as a risk stratification tool in 235 unselected patients presenting with symptoms of myocardial ischemia [MIS]. We compared a 99[th] percentile MI cut off limit for TnT [at 0.06 micro g/1] determined by constructing a receiver operator curve [ROC] for the patient cohort, in whom ST segment elevation ACS was excluded, to the standard MI cut off value of 0.1 micro g/1 in assessing cardiovascular risk. We also assessed the prognostic significance of detectable TnT values below this 99[th] percentile MI cut off, but above the upper reference limit of healthy controls [i.e., TnT >0.01-<0.03 micro g/1] and of CKMB/total CK ratio [MB%]. TnT was estimated by An electrochemiluminescence immunoassay, CK was assayed by a trichromatic rate technique, and CKMB was measured by mass immunoassay. The diagnosis of ACS was more frequent in groups with higher TnT concentrations: 3.3% with normal TnT [TnT<0.03 micro g/1], 16.7% [p<0.01] with TnT values between 0.03 micro g/1 and the 99[th] percentile MI cut off, 70.6% [p<0.001] with detectable TnT between the 99[th] percentile MI cut off and the standard MI cut off [0.06 and 0.099 micro g/1], and 81.6% [p<0.001] with TnT values >/= 0. 1 micro g/1. The 30 day cardiovascular event rate, likewise, increased progressively with increasing TnT values: 0.8% with normal TnT. 3.3% with detectable TnT below the 99[th] percentile MI limit, 11.8% [p<0.01] with TnT concentrations between 0.06 and 0.099 micro g/1, and 13.2% [p <0.01] with TnT detectable above the standard MI cut off value [>/= 0. 1 micro g/1]. In conclusion: using a MI cut off value for TnT from a reference cohort with suspected MIS including patients with non-ST segment elevation ACS [NSTE-ACS] improves risk stratification but further studies are required to ascertain the exact cut off

Effects of metformin on serum insulin levels and ovarian steroidogenesis in nonobese women with polycystic ovary syndrome

Evidence indicates that nonobese women with polycystic ovary syndrome [PCOS] are insulin resistant and hyperinsulinemic. This work was conducted to study the hypothesis that hyperinsulinemia stimulates the steroidogenic enzyme P450c17 alpha activity in these patients, with consequent increase in serum androgen levels. We assessed the activity of the cytochrome P450c17 alpha by measuring the response of 17 alpha-hydroxypro- gesterone [17-PROG] to a GnRH agonist [leuprolide] in 30 normal-weight women with PCOS. Fasting and the 2h serum glucose and insulin, and serum levels of sex hormone binding globulin [SHBG], testosterone [TSN], free testosterone [F-TSN], dehydroepiandrosterone sulphate [DHEAS] estradiol [E[2]], progesterone [PGN], 17-PROG, LH, and FSH were measured before and after oral administration of either metformin 500 mg tab [in 18 patients] or a placebo [in 12 patients] t.d.s. for 8 weeks. We also estimated fasting and the 2h serum glucose and insulin, serum SHBG, and sex hormones in 12 normal controls before and after metformin administration. Serum glucose was measured by a hexokinase method and serum insulin was assayed by a double antibody technique. 17-PROG and DHEAS concentrations were determined by radioimmunoassay after chromatographic purification. F-TSN and SHBG were measured by a competitive protein binding assay. An electrochemiluminescence immunoassay intended for use on Roche Elecsys 1010/2010 analyzers was used for determination of, TSN, E[2], PGN, LH and FSH. The metformin and placebo groups of PCOS women did not differ in both the fasting and the 2h serum glucose values whether before or after treatment. However, these values in the control group showed a significant decrease [p<0.001] as compared to the metformin group. Metformin administration was associated with significant [p<0.01] decrease both in the fasting and the 2h serum insulin values in the metformin group and the control women but not in the placebo group. Serum SHBG was significantly increased on metformin therapy in PCOS women [p<0.001] but not in the placebo group nor in the controls. The metformin group showed a significant posttreatment decrease in serum TSN, F-TSN, E[2] and DHEAS and a significant increase in Serum PGN both before and after leuprolide administration [p<0.001]. There was a nonsignificant change in serum sex steroids, on treatment, in the placebo group. In the metformin group, the mean basal and peak levels of 17-PROG decreased significantly [p<0.001] after treatment. As for serum LH, the metformin group showed a significant decrease in the mean basal levels [p < 0.05], the early [p < 0.05] and late serum responses [p < 0.001] to leuprolide after metformin treatment. These values for LH and 17-PROG did not change [on treatment] in the placebo group. These findings suggest that Hyperinsulinemia stimulates ovarian cytochrome P450c17 alpha activity in nonobese women with PCOS. They also indicate that decreasing serum insulin with metformin reduces cytochrome P450c 17 alpha activity and ameliorates the hyperandrogenism of these women. Improvement of the endocrine profile of PCOS on metformin therapy was also discussed