Loss of circulating CD27+ memory B cells and CCR4+ T cells occurring in association with elevated EBV loads in XLP patients surviving primary EBV infection

Detailed longitudinal studies of patients with X-linked lymphoproliferative disease (XLP) may increase our understanding of the immunologic defects that contribute to the development of lymphoma and hypogammaglobulinemia in XLP. We describe progressive changes observed in immunoglobulin concentrations, lymphocyte subsets, and Epstein-Barr virus (EBV) loads occurring in a 2-year period in a newly infected, but otherwise healthy, carrier (patient 9). We compare these findings with those observed in the patient's brother, who had hypogammaglobulinemia and XLP (patient 4). Immunoglobulin G (IgG), IgM, and IgA concentrations increased in patient 9 during acute EBV infection, but thereafter they decreased steadily to concentrations consistent with hypogammaglobulinemia, reaching a plateau 5 months after infection. In both patients, CD19+ B-lymphocyte rates remained lower than 3%, with a contraction of the B-cell memory compartment (CD27+ CD19+/CD19+) to 20% (normal range, 32%-56%). T-lymphocyte subpopulations showed a reduction in CD4+ T-cell counts and a permanent CD8+ T-cell expansion. Interestingly, CXCR3 memory TH1 cells were expanded and CCR4+ TH2 lymphocytes were reduced, suggesting that abnormal skewing of memory T-cell subsets might contribute to reduced antibody synthesis. Despite an expanded number of CD3+CD8+ lymphocytes, increased EBV loads occurred in both patients without overt clinical symptoms of mononucleosis, lymphoproliferative disease, or lymphoma.     

Utility of NT-proBNP for diagnosing heart failure in a heterogeneous population of patients with dyspnea. Spanish multicenter study

INTRODUCTION AND OBJECTIVES: Recent studies have shown that brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are useful in the diagnosis of heart failure in patients presenting with dyspnea. However, the cutoff values used with these markers vary according to patient characteristics and dyspnea severity. The aim of this study was to investigate the diagnostic accuracy of using the plasma NT-proBNP level for identifying heart failure in a heterogeneous population of patients with dyspnea. METHODS: A multicentre study involving 247 consecutive patients with recent-onset dyspnea was carried out at 12 Spanish hospitals. Patients previously diagnosed with heart failure or any other condition known to cause dyspnea were excluded. RESULTS: Of the 247 patients, 161 (65%) had heart failure. The remaining 86 (35%) presented with dyspnea of non-cardiac origin. Plasma NT-proBNP levels were higher in patients with heart failure (5600 [7988] pg/mL vs 1182 [4406] pg/mL; P=.0001), and increased as functional status deteriorated (P=.036). The area under the receiver operating characteristic curve was 0.87 (0.02) (95% CI, 0.81-0.91) for the optimum cutoff value of 1335 pg/mL. The sensitivity of this cutoff value for diagnosing heart failure was 77% (95% CI, 70%-83%), the specificity was 92% (95% CI, 84%-97%), the positive predictive value was 94%, and the negative predictive value was 68%. CONCLUSIONS: The plasma NT-proBNP concentration provides an accurate means of diagnosing heart failure. However, the negative predictive value found in this study was somewhat lower than the values found in previous studies involving more homogeneous patient populations.     

Metabolic syndrome and masticatory hypofunction: a cross-sectional study

Odontology - The objective of this paper is to clarify the rate of abdominal obesity (AO), waist-to-height ratio (WHtR), metabolic syndrome (MetS) and determine the relationship with the...     

Bond strength of orthodontic brackets using different light and self-curing cements

The purpose of the study was to evaluate the shear bond strength of stainless steel orthodontic brackets directly bonded to extracted human premolar teeth. Fifty teeth were randomly divided into five groups: (1) System One (chemically cured composite resin), (2) Light Bond (light-cured composite resin), (3) Vivaglass Cem (self-curing glass ionomer cement), (4) Fuji Ortho LC (light-cured glass ionomer cement) used after 37% orthophosphoric acid-etching of enamel (5) Fuji Ortho LC without orthophosphoric acid-etching. The brackets were placed on the buccal and lingual surfaces of each tooth, and the specimens were stored in distilled water (24 hours) at 37 degrees C and thermocycled. Teeth were mounted on acrylic block frames, and brackets were debonded using an Instron machine. Shear bond strength values at fracture (Nw) were recorded. ANOVA and Student-Newman-Keuls multiple comparison tests were performed (P < .05). Bonding failure site was recorded by stereomicroscope and analyzed by Chi-square test, selected specimens of each group were observed by scanning electron microscope. System One attained the highest bond strength. Light Bond and Fuji Ortho LC, when using an acid-etching technique, obtained bond strengths that were within the range of estimated bond strength values for successful clinical bonding. Fuji Ortho LC and Vivaglass Cem left an almost clean enamel surface after debracketing.     

Determination of corneal volume from anterior topography and topographic pachymetry: application to healthy and keratoconic eyes

Purpose: To describe a method to measure corneal volume from topography and pachymetry, and test its clinical use on a sample of healthy human subjects and a case of circumscribed posterior keratoconus. Methods: Corneal curvature (PCT 200^® corneal topography system; Optopol Technology SA, Zawiercie, Poland) and ultrasonic topographic pachometry on 25 points (Ophthasonic^® A‐Scan/Pachometer III; Teknar Inc., St Louis, MO, USA) were measured on each of 12 young healthy corneas and one cornea suffering from circumscribed posterior keratoconus. Topography and pachymetry data were used to calculate the coordinates for the corresponding points on the posterior surface of the cornea. TableCurve 3D software (Systat Software Inc., Chicago, IL, USA) was used to fit a surface to those points measured. Integration of the surface fitted to the data points, corresponding to the anterior and posterior corneal surfaces, was used to calculate the volume underneath each of them. Subtraction of volumes underneath anterior and posterior surfaces, taking into account an axial offset equal to the central corneal thickness, rendered corneal volume for the central 6 mm of the cornea. Results: Central corneal thickness ranged from 520 to 630 μm for the healthy corneas. Corneal volumes for this sample analyzed averaged 18.66 ± 1.15 mm³ (range 17.25–20.53 mm³). For the posterior keratoconic cornea, the affected area was located at about 1.5–2 mm from the corneal center on the 135° hemimeridian of the right eye, observed through topographic pachymetry. Calculated corneal volume for the central 6 mm was 16.072 mm³, noticeably lower than those found in the sample without pathology, but within the range for corneas presenting with keratoconus. Conclusions: Corneal volume is a useful parameter for characterising dystrophic corneas and can aid in the detection of rare anomalies which are hardly detected with corneal topography and/or central corneal thickness evaluation. A potentially useful measure of corneal volume can be calculated from anterior corneal topography and topographic pachymetry data. Values obtained are in good agreement with previous studies using corneal tomography techniques. The methodology has been shown to have potential for retrospective analysis of data, or where no access is available to tomographical techniques.     

Methyl p-hydroxyphenyllactate and nuclear type II binding sites in malignant cells: metabolic fate and mammary tumor growth

Previous studies in our laboratory demonstrated that methyl p-hydroxyphenyllactate (MeHPLA) is an important cell growth-regulating agent which binds to nuclear type II binding sites in normal and malignant cells. Furthermore, this compound is deficient in a variety of rat and mouse mammary tumors and human breast cancer preparations, and this deficiency correlates with the loss of regulatory control. The present studies were performed to examine the metabolic fate of [3H]MeHPLA in mouse mammary tumors. Stable analogs of this compound such as 4,4'-dihydroxy benzylidene acetophenone were also assessed for nuclear type II site binding affinity and their ability to inhibit mammary cancer cell growth and proliferation in vitro and in vivo. The results demonstrate that mouse mammary tumors contain esterase activity which hydrolyzes MeHPLA to p-hydroxyphenyllactic acid, and this was the only major metabolite detected in these tumor preparations in vitro or in vivo. 4,4'-Dihydroxy benzylidene acetophenone, an esterase-stable MeHPLA analog, was found to bind with high affinity to nuclear type II sites but not the estrogen receptor, was capable of occupying type II sites in cultured MCF-7 cells, and inhibited the proliferation of these cells in concentrations which directly correlated with type II binding site occupancy. Similarly, 4,4'-dihydroxy benzylidene acetophenone administration by silastic implant or injection resulted in a dose-dependent inhibition of the growth of transplantable mammary tumors in mice, suggesting that this stable analog mimicks MeHPLA as a cell growth-regulating agent. Taken together, these results suggest esterase hydrolysis of MeHPLA in mammary tumors may result in a deficiency in this compound which correlates with a loss of regulatory control.