Comparison of maximal midexpiratory flow rate and forced expiratory flow at 50% of vital capacity in children

BACKGROUND: The mid-portion of the maximal expiratory flow-volume (MEFV) curve is often described by values of the mean forced expired flow as lung volume decreases from 75% to 25% of vital capacity (ie, forced expiratory flow, midexpiratory phase [FEF(25-75)]). It is common practice to report also forced expired flow at 50% of vital capacity (FEF(50)). STUDY OBJECTIVE: To investigate whether FEF(50) and FEF(25-75) are highly correlated or whether the difference between them reflects a degree of airways obstruction. Also, we wanted to investigate the correlation between the two in cases of irregularly shaped MEFV curves (ie, "saw-toothing"). DESIGN: Analysis of the correlation between FEF(50) and FEF(25-75) in a single determination. We assessed the relationship between the FEF(50)/FEF(25-75) ratio and the degree of airways obstruction, as reflected by other traditional parameters such as FEV(1), FEV(1)/FVC ratio, and specific airway conductance (SGaw). PATIENTS: There were 1,350 forced expiratory maneuvers performed by children with a broad range of pulmonary abnormalities. RESULTS: FEF(50) correlated with FEF(25-75) as follows: FEF(50) (L/s) = 0.041 + 1.136*FEF(25-75)(L/s); r(2) = 0.956; standard error of the estimate = 0.013; p < 0.0001. The FEF(50)/FEF(25-75) ratio remained stable and did not correlate with FEV(1) (r = 0.12), FEV(1)/FVC ratio (r = 0.11), or SGaw (r = 0.02; difference not significant). The correlation between FEF(25-75) and FEF(50) was similar for both the smooth curve (r = 0.97) and the irregular curve (r = 0.96). CONCLUSIONS: Although not identical, FEF(25-75) and FEF(50) are highly correlated, and the ratio of the two is fairly constant. Therefore, the practice of reporting both of them is unnecessary. We suggest that it is reasonable to prefer FEF(50).     

FreeStyle Mini? Blood Glucose Results Are Accurate and Suitable for Use in Glycemic Clamp Protocols

Objective

We assessed the accuracy of the FreeStyle Mini™ (FSM) meter for use in glycemic clamp and meal protocols in comparison with the HemoCue Glucose 201 DM Analyzer (HemoCue) and the YSI 2300 STAT Glucose Oxidase Analyzer (YSI).

Methods

Seven volunteers with type 2 diabetes mellitus, 35–69 years old, underwent a frequently sampled meal test and a graded hyperglycemic test, on two separate days, with one of the volunteers undergoing each test twice. Samples for glucose measurements were obtained from arterialized venous blood. A total of 420 samples (with glucose levels ranging from 63 to 388 mg/dl) were available for comparison. On average, 10 measurements were available for every 5 mg/dl increment in glucose level in the range of 130–310 mg/dl. Blood glucose measurements were done on each sample with the FSM, HemoCue, and YSI.

Results

FreeStyle Mini blood glucose values correlated closely with the YSI readings. Of the FSM measurements, 99.0% were within the Clarke error grid zone A; 51.3%, 84.7%, and 96.2% of the FSM readings were within 5%, 10% and 15% of the YSI values, respectively. The FSM was significantly more accurate than the HemoCue (84.7% vs 76.6% of results within 10% of the YSI results; p = .0038). The mean average relative difference of the FSM (5.8%) was also significantly lower than that of the HemoCue (6.8%; p = .0013)

Conclusions

The FSM provides accurate results and constitutes a suitable alternative for bedside blood glucose measurements in experimental procedures, helping to reduce sample size, turnaround time, and cost.     

Diagnosis of iron deficiency anemia in the elderly by transferrin receptor-ferritin index

BACKGROUND: The diagnosis of iron deficiency anemia (IDA) in the elderly is difficult because of the prevalence of chronic diseases, which can cause anemia with high ferritin levels, even in the presence of iron deficiency. Therefore, we studied the sensitivity and specificity of a serum transferrin receptor assay, which is not affected by chronic diseases, in the diagnosis of IDA in elderly patients. METHODS: We performed a prospective controlled study of 49 consecutive male and female patients older than 80 years who were admitted to an acute geriatric department. Bone marrow aspirate confirmed IDA in all 49 patients. Fourteen additional patients, also older than 80 years, with anemia but without evidence of iron deficiency on results of bone marrow examination, served as a control group. All patients underwent evaluation by means of a detailed medical history and results of complete physical examination, routine blood tests, and specific tests for diagnosis and evaluation of anemia. Examination of bone marrow aspirate was performed for all patients. Levels of transferrin receptor in serum were determined by means of a specific enzyme-linked immunosorbent assay. The transferrin receptor-ferritin index (TR-F index) was defined as the ratio of serum transferrin receptor level to log ferritin level. RESULTS: Only 8 patients could be diagnosed as having IDA by means of routine blood test results (serum iron, ferritin, and transferrin saturation levels). In contrast, the TR-F index disclosed IDA in 43 of the 49 patients, thus increasing the sensitivity from 16% to 88%. CONCLUSIONS: The diagnosis of IDA in the elderly by means of routine blood tests has a very low sensitivity. The TR-F index is much more sensitive, and when results are positive, the TR-F index can eliminate the need for bone marrow examination.     

High rates of perinatal group B Streptococcus clindamycin and erythromycin resistance in an upstate New York hospital

The objective of this study was to evaluate the rates of clindamycin and erythromycin resistance among group B Streptococcus (GBS)-positive isolates cultured from pregnant women in an upstate New York community hospital. All GBS-positive perinatal rectovaginal cultures obtained from January 2010 through October 2011 were tested for resistance to erythromycin and clindamycin. Among the 688 GBS-positive cultures, clindamycin resistance was found in 38.4% and erythromycin resistance was found in 50.7%. Rates of GBS resistance to clindamycin and erythromycin are much higher than reported in earlier U.S. studies, suggesting both increasing resistance and regional variation in resistance. These findings lend strong support to the CDC and American College of Obstetricians and Gynecologists (ACOG) recommendations that clindamycin use for intrapartum antibiotic prophylaxis be restricted to penicillin-allergic women at high risk of anaphylaxis and that GBS isolates be tested for antibiotic resistance prior to the use of clindamycin in these women.     

Discriminative value of inflammatory biomarkers for suspected sepsis

Background

Circulating biomarkers can facilitate sepsis diagnosis, enabling early management and improved outcomes. Procalcitonin (PCT) has been suggested to have superior diagnostic utility compared to other biomarkers.

Study Objectives

To define the discriminative value of PCT, interleukin-6 (IL-6), and C-reactive protein (CRP) for suspected sepsis.

Methods

PCT, CRP, and IL-6 were correlated with infection likelihood, sepsis severity, and septicemia. Multivariable models were constructed for length-of-stay and discharge to a higher level of care.

Results

Of 336 enrolled subjects, 60% had definite infection, 13% possible infection, and 27% no infection. Of those with infection, 202 presented with sepsis, 28 with severe sepsis, and 17 with septic shock. Overall, 21% of subjects were septicemic. PCT, IL6, and CRP levels were higher in septicemia (median PCT 2.3 vs. 0.2 ng/mL; IL-6 178 vs. 72 pg/mL; CRP 106 vs. 62 mg/dL; p < 0.001). Biomarker concentrations increased with likelihood of infection and sepsis severity. Using receiver operating characteristic analysis, PCT best predicted septicemia (0.78 vs. IL-6 0.70 and CRP 0.67), but CRP better identified clinical infection (0.75 vs. PCT 0.71 and IL-6 0.69). A PCT cutoff of 0.5 ng/mL had 72.6% sensitivity and 69.5% specificity for bacteremia, as well as 40.7% sensitivity and 87.2% specificity for diagnosing infection. A combined clinical-biomarker model revealed that CRP was marginally associated with length of stay (p = 0.015), but no biomarker independently predicted discharge to a higher level of care.

Conclusions

In adult emergency department patients with suspected sepsis, PCT, IL-6, and CRP highly correlate with several infection parameters, but are inadequately discriminating to be used independently as diagnostic tools.     

Thrombophilic polymorphisms in Israel

Three thrombophilic polymorphisms, FV G1691A, FII G20210A and MTHFR C677T were investigated in Israeli populations by FRET, (fluorescence resonance energy transfer) real-time PCR. We observe extensive variability in the frequencies of each of the polymorphisms, as has been observed in the study of other polymorphisms in these populations. Very high allele frequencies for FV G1691A (the highest 0.087 in Turkish and Greek Jews) and FII G20210A (the highest 0.061 in Georgian Jews) in some of the Israeli populations justify a clinical investigation to assess their risk for venous thrombosis. Principal Coordinates Analysis demonstrates that the Jewish populations are interspersed among the non-Jewish populations. The resemblance of some Jewish populations to certain non-Jewish populations coincides with findings based on classical markers.     

Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission

Minor histocompatibility antigens (mHAs) are known targets of donor T cells after allogeneic hematopoietic stem cell transplantation (HSCT). In contrast, B-cell responses to mHAs have not been extensively characterized and the clinical significance of antibodies to mHAs is unknown. We tested 121 patients who underwent HSCT and 134 healthy donors for immunoglobulin G (IgG) antibodies against 5 mHAs encoded by genes on the Y chromosome (DBY, UTY, ZFY, RPS4Y, and EIF1AY). Antibodies to at least one H-Y protein developed in 52% of male patients with female donors compared with 8.7% of male patients with male donors (P < .0001), and in 41.4% of healthy females compared with 7.8% of healthy males (P < .0001). H-Y antibodies develop 4 to 12 months after transplantation and persist for long periods. The clinical significance of H-Y antibodies was characterized in 75 male patients with hematologic malignancies who received stem cells from female donors (F --> M HSCT). The presence of H-Y antibodies correlated with chronic graft-versus-host disease (GVHD) by univariate (odds ratio [OR] = 15.5; P < .0001) and multivariable logistic regression analysis (OR = 56.5; P < .0001). Antibody response to Y-chromosome encoded histocompatibility antigens (H-Y antigens) was also associated with maintenance of disease remission (P < .0001). B cells may provide a new target for immune intervention in chronic GVHD.     

Adiponectin promotes the migration of circulating angiogenic cells through p38-mediated induction of the CXCR4 receptor

Aims

Adiponectin (adipo) and exercise training (ET) contribute to the maintenance of a normal vascular tone by influencing vascular NO bioavailability and concentration and function of circulating angiogenic cells (CAC). The molecular mechanisms are only partially understood. Aim of the present study was to elucidate the effects of adipo on CAC migration and the underlying signaling pathways. Furthermore, the impact of ET on adiponectin-mediated CAC migration was investigated.

Methods and results

CACs were isolated from peripheral blood and exposed to different adipo concentrations. Adipo (5 μg/ml) enhanced the ability of CACs to migrate following an SDF-1 gradient by 345%. This was associated with a significant increase in CXCR4 expression on the surface of CACs as compared to control (10.1 ± 1.5 vs. 33.2 ± 4.5% CXCR4 positive cells, p < 0.05). Adiponectin-induced CAC migration and CXCR4-upregulation were mediated through adipo-receptor 1 (AdipoR1) and blocked by an inhibitor of PI3-kinase, p38MAP kinase and NFκb. Adipo-stimulated migration of CACs, CXCR4 expression and p38MAPK-activation is impaired in patients with coronary artery disease (CAD). ET over 4 weeks partially corrects adiponectin-stimulated CAC migration and CXCR4 expression in patients with CAD (n = 10). No change was observed in the control group (n = 10).

Conclusion

Adipo improves the migratory capacity of CACs in response to SDF1, partially through an upregulation of CXCR4. This is mediated through a pathway that involves binding of adipo to the AdipoR1 and subsequent PI3kinase/p38MAPK/ NFκb activation. In addition ET corrects the adiponectin responsiveness of CACs, and thereby might promote endogenous repair of damaged endothelium.     

Flavopiridol Induces Apoptosis in Chronic Lymphocytic Leukemia Cells Via Activation of Caspase-3 Without Evidence of bcl-2 Modulation or Dependence on Functional p53

Flavopiridol has been reported to induce apoptosis in lymphoid celllines via downregulation of bcl-2. The in vitro activity offlavopiridol against human chronic lymphocytic leukemia (CLL) cells andpotential mechanisms of action for inducing cytotoxicity were studied.The in vitro viability of mononuclear cells from CLL patients (n = 11) was reduced by 50% at 4 hours, 24 hours, and 4 days at aflavopiridol concentration of 1.15 µmol/L (95% confidence interval[CI] ±0.31), 0.18 µmol/L (95% CI±0.04), and 0.16 µmol/L (95% CI ±0.04), respectively. Loss ofviability in human CLL cells correlated with early induction ofapoptosis. Exposure of CLL cells to 0.18 µmol/L of flavopiridolresulted in both decreased expression of p53 protein and cleavage ofthe caspase-3 zymogen 32-kD protein with the appearance of its 20-kD subunit. Contrasting observations of others in tumor cell lines, flavopiridol cytotoxicity in CLL cells did not correlate with changesin bcl-2 protein expression alterations. We evaluated flavopiridol'sdependence on intact p53 by exposing splenocytes from wild-type(p53^+/+) and p53 null (p53^/) micethat demonstrated no preferential cytotoxicity as compared with amarked differential with F-ara-a and radiation. Incubation of CLL cellswith antiapoptotic cytokine interleukin-4 (IL-4) did not alter theLC₅₀ of flavopiridol, as compared with a marked elevationnoted with F-ara-a in the majority of patients tested. These datademonstrate that flavopiridol has significant in vitro activity againsthuman CLL cells through activation of caspase-3, which appears to occurindependently of bcl-2 modulation, the presence of IL-4, or p53 status.Such findings strongly support the early introduction of flavopiridolinto clinical trials for patients with B-CLL.