Sonography detection of small intra-abdominal fat variations.

The aim of this study was to check the reliability of sonography in measuring small variations in quantities of subcutaneous and intra-abdominal fat. Twenty-six obese women (BMI 39 +/- 6) underwent a 15 day very low calorie diet. The study included, both before and after very low calorie diet, computed tomography measurements of total (AT), visceral (VAT) and subcutaneous (SAT) adipose tissue areas, visceral/subcutaneous area ratio (V/S), waist/hip circumference ratio measurements (W/H), and ultrasound measurements of abdominal subcutaneous skin-muscle thickness, intra-abdominal muscle-aorta thickness and intra-abdominal/subcutaneous thickness ratio. Weight reduction was from 101 +/- 17 to 95 +/- 16 kg (P less than 0.001). W/H dropped from 0.83 +/- 0.06 to 0.82 +/- 0.07 (n.s.). VAT dropped from 158 +/- 72 to 134 +/- 61 cm2 (P less than 0.005), SAT from 572 +/- 151 to 566 +/- 164 cm2 (n.s.) and V/S from 0.29 +/- 0.15 to 0.25 +/- 0.11 (P less than 0.01). Abdominal subcutaneous fat thickness decreased from 36 +/- 8 to 35 +/- 10 mm (n.s.), intra-abdominal thickness from 39 +/- 25 to 20 +/- 20 mm (P less than 0.001) and intra-abdominal/subcutaneous from 1.1 +/- 0.7 to 0.8 +/- 0.6 (P less than 0.005). VAT measurement accurately identified small intra-abdominal fat variations. W/H could not evaluate visceral fat loss, because of simultaneous decreases in waist and hip circumferences. Ultrasound was able to measure small reductions in intra-abdominal fat.     

Long-lasting modulation of synaptic input to Purkinje neurons by Bergmann glia stimulation in rat brain slices

Information processing in the nervous system is achieved primarily at chemical synapses between neurons. Recent evidence suggests that glia-neuron interactions contribute in multiple ways to the synaptic process. In the present study we used the frequency of spontaneous postsynaptic currents (sPSC) in Purkinje neurons in acute cerebellar brain slices from juvenile rats (13-19 days old) as a measure of synaptic activity. Following 50 depolarizing pulses to an adjacent Bergmann glial cell (50 mV; duration 0.5 s; 1 Hz) the sPSC frequency of the Purkinje neuron was reduced to 65 ± 7 % of control values within 10 min after glial stimulation and remained depressed for at least 40 min. Depolarizing pulses to 0 mV had a comparable effect (70 ± 5 % of control). The frequency of miniature PSCs, as recorded in 300 n m TTX, was not modulated after glial stimulation. Blockade of ionotropic glutamate receptors (iGluRs) with kynurenic acid (1 m m ) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5 μ m ) suppressed the reduction of neuronal activity induced by glial depolarization, whereas the glial modulation of synaptic activity was not inhibited by a block of N -methyl- d -aspartate iGluRs, metabotropic glutamate receptors, cannabinoid receptors or GABA_B receptors. Fluorometric measurements of the intraglial Ca²⁺ concentration revealed no glial Ca²⁺ transients during the depolarization series, and glial cell stimulation reduced the neuronal sPSC frequency even after loading the glial cell with 20 m m of the Ca²⁺ chelator BAPTA. Our results indicate a glia-induced long-lasting depression of neuronal communication mediated by iGluRs.     

Analog validation of German-language symptom validity tests and the influence of coaching.

Although symptom validity testing is an integral part of the repertory of neuropsychologists in a number of countries, this is not yet true for Germany. The German adaptations of two effort tests, the Medical Symptom Validity Test (MSVT) by Green and the Amsterdam Short-Term Memory Test (ASTM) by Schmand et al., were investigated with a German-language sample. An analog study was performed with 18 healthy experimental malingerers and 18 controls with a mean age of 25.4 years. The scenario contained detailed information about mild post-traumatic cognitive impairment, as well as an explicit warning against symptom exaggeration. In addition to MSVT and ASTM, the Trail Making Test (TMT), the Complex Figure Test (CFT), and Digit Span were performed. Half of the sample were also given Rey's 15-Item-Test (FIT). Both groups were significantly different in all effort and performance measures, with the exception of the ratio TMT-B:TMT-A. With MSVT and ASTM, correct classification of group membership was between 97 and 100%. For the ratio TMT-B:TMT-A, there was a considerable overlap in the test scores for the two groups and the sensitivity of the FIT was too low. Although the ASTM and the MSVT were identified by a number of subjects as possible effort measures, both tests obtained very good results within this analog design.     

Recombinant soluble tumor necrosis factor receptor proteins protect mice from lipopolysaccharide-induced lethality.

The in vivo efficacy of human recombinant soluble tumor necrosis factor (TNF) receptor protein to prevent and to treat lipopolysaccharide (LPS)-induced lethal toxicity in D-galactosamine-treated mice was investigated. Chimeric proteins of the receptor extracellular domains fused to the hinge region of human IgG3 were expressed in myeloma cells (rsTNFR-h gamma 3). The fusion proteins had a disulfide-bonded dimeric structure. Upon intravenous injection, their serum concentration decreased relatively slowly after an initial phase of rapid elimination. D-galactosamine-sensitized mice were fully protected from the toxic effects of LPS, if the animal were pretreated with rsTNFR-h gamma 3 at 20 micrograms/animal. Partial protection was seen at significantly lower doses and when rsTNFR-h gamma 3 was given up to 3 h after LPS.     

Neuropsychological studies in children with elevated tooth-lead concentrations

Summary In contrast to blood-lead (PbB), tooth-lead concentrations (PbT) provide retrospective information about longterm, cumulative childhood lead-intake. From a basic sample of 458 school age children from the city of Duisburg (FRG), whose lead-concentrations in shed incisor teeth had been measured ( =4.6 ppm; range: 1.4–12.7 ppm), two extreme-groups of 26 children each (mean age: 8.5 years) with low ( =2.4 ppm) and elevated ( =9.2 ppm) PbT were selected. After pair-matching both groups for age, sex, and father's occupational status, these children were tested under double-blind precautions for intellectual performance (German WISC), for perceptual-motor integration (Göttinger Formreproduktionstest = GFT, Diagnostikum für Cerebralschädigung = DCS, Benton-Test), and for gross motor-coordination (Körper-Koordinationstest für Kinder = KTK). Significant (P<0.05) inferiority of the lead-children was found in two tests of perceptual-motor integration (increased GFT-errors; lower success rate for DCS). In addition a near significant (P<0.1) reduction of 5–7 IQ-points was determined in these children. Although this pilot study has provided some evidence for an association between childhood lead-exposure and neuropsychological impairment, this association cannot yet be considered proven, because the observed effects were discrete and statistically confirmed only in part, and because there was a slight prevalence of perinatal risk factors in the lead group. Further research to clarify the issue is necessary.Based on an MD-thesis (Hrdina 1978), as well as on papers presented at Arbeitstagung der Deutschen Gesellschaft für Hygiene und Mikrobiologie, October 2–3, 1978 in Mainz, and at the symposium on Toxic effects of Environmental Lead, May 10, 1979 in London (Hrdina and Winneke 1978; Winneke 1979)     

Can cardiorespiratory polygraphy replace portable polysomnography in the assessment of sleep-disordered breathing in heart failure patients?

Purpose

Portable polysomnography (PSG) and cardiorespiratory polygraphy are increasingly being used in the assessment of sleep-disordered breathing (SDB) in heart failure patients. Scoring of SDB from cardiorespiratory polygraphy recordings is based only on respiratory signals, while electroencephalographic, electrooculographic and electromyographic channels are taken into account when using PSG recordings. The aim of this study was to assess the agreement between these two scoring methods.

Methods

An overnight sleep study was performed in 67 heart failure patients using a standard portable polysomnograph. Each recording was scored twice, once using all acquired signals (PSG mode) and, after a median of 64 days, using only respiratory signals (cardiorespiratory mode). Agreement was assessed by Bland–Altman analysis and Cohen’s kappa.

Results

We found that (1) more respiratory events were detected using cardiorespiratory analysis [median (25th percentile, 75th percentile), 75 (39, 200) events] compared to analysis of portable PSG [69 (29, 173) events, p?<?0.0001], the extra events being, for the vast majority, central in origin; (2) the apnea/hypopnea index (AHI) estimated by cardiorespiratory polygraphy [11.9 (5.7, 30.8)/h] showed a negligible negative bias relative to portable PSG [15.1 (5.7, 33.6)/h; bias, ?0.8 (?2.9, 0.4)/h, p?=?0.0002]; (3) limits of agreement between the two systems (?6.2/h, 1.7/h) were much smaller than those previously observed between two nights using the same scoring modality; and (4) the kappa coefficient using categorised AHI was 0.89 (95 % confidence interval (CI) 0.82, 0.96).

Conclusions

We found a high degree of agreement between the AHIs obtained from the two scoring methods, thus suggesting that cardiorespiratory polygraphy may be used as an alternative to portable PSG in the assessment of SDB in heart failure patients.

     

Identification of two types of tumor necrosis factor receptors on human cell lines by monoclonal antibodies.

The pleiotropic cyto/lymphokine tumor necrosis factor (TNF) exerts its functions by binding to specific cell-surface receptors. We have prepared two sets of monoclonal antibodies (mAbs) against TNF-binding proteins from the HL-60 (htr-mAb series) and U-937 (utr-mAb series) cell lines. The htr antibodies inhibit the binding of 125I-labeled TNF-alpha to HL-60 cells only partially, whereas they block the TNF-alpha binding to several adenocarcinoma cell lines (HEp-2, HeLa, and MCF7) almost completely. In contrast, the utr antibodies have no effect on TNF-alpha binding to the adenocarcinoma cell lines but partially inhibit TNF-alpha binding to HL-60 and U-937 cells. However, htr-9 and utr-1 antibodies in combination fully inhibit the TNF-alpha binding to HL-60 and U-937 cells. The binding of TNF-beta to HEp-2 and U-937 cells is also inhibited by htr and utr antibodies. Neither htr nor utr mAb has an effect on the TNF-sensitive murine cell lines L929 and WEHI 164. Flow cytometry studies show that mAbs htr-9 and utr-1 detect two distinct TNF-binding sites on human cell lines. Immunologic blot and immunoprecipitation analyses indicate that mAbs htr-9 and utr-1 recognize proteins of approximately 55 kDa and 75 kDa, respectively. These data provide evidence for the existence of two distinct TNF receptor molecules that contribute to varying extent to the TNF binding by different human cells.     

Tobramycin inhalation powder for P. aeruginosa infection in cystic fibrosis: The EVOLVE trial

Tobramycin inhalation solution is used to treat chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients. We evaluated the efficacy and safety of a novel, light‐porous particle, dry‐powder formulation of tobramycin, which was developed to improve delivery efficiency to the airways and substantially reduce the delivery time. In this randomized, double‐blind study, patients with CF (age 6–21 years) received tobramycin inhalation powder (112 mg tobramycin) twice daily (n = 46) or placebo (n = 49) via the T‐326 Inhaler for one cycle, followed by two open‐label cycles (all patients). Cycles were 28 days on, 28 days off treatment. The primary endpoint was change in forced expiratory volume in 1 sec (FEV₁) % predicted from baseline to Day 28 of Cycle 1. The study was terminated early based on positive results in the interim analysis. Tobramycin inhalation powder significantly improved FEV₁ % predicted versus placebo at Day 28 (difference 13.3, 95% CI: 5.31–21.28; P = 0.0016). Similar changes in FEV₁ were seen in patients switching from placebo to tobramycin inhalation powder in Cycle 2; improvements were maintained over time. Tobramycin inhalation powder also reduced sputum P. aeruginosa density, respiratory‐related hospitalization and antipseudomonal antibiotic use versus placebo. The most common adverse event was cough; the frequency of cough was higher in patients receiving placebo (26.5%) versus tobramycin inhalation powder (13.0%) in Cycle 1. Tobramycin inhalation powder was not associated with ototoxicity or nephrotoxicity. Administration time was between 4 and 6 min. In conclusion, tobramycin inhalation powder was effective and well tolerated in CF patients, and may offer an important treatment option to decrease the treatment burden of CF pseudomonas lung infections. Pediatr Pulmonol. 2011; 46:230–238. © 2011 Wiley‐Liss, Inc.     

Soluble TNF receptors in amniotic fluid and in urine from pregnant women.

Secretion of soluble cytokine receptors has been suggested as a mechanism for regulation of cytokine activity in vivo. The present investigation was performed to study whether secretion of soluble TNF (tumor necrosis factor) receptors (TNFRs) might be associated with pregnancy. There are two known molecular species of the TNFR, the 55-kDa TNFR and the 75-kDa TNFR. The 75-kDa, as well as the 55-kDa TNFR, was detected in urine from pregnant women, whereas only the 75-kDa TNFR was detected in urine from the non-pregnant group. The concentration of TNFRs in urine increased towards term and was reduced in association with spontaneous delivery. The soluble forms of both TNFRs were also detected in amniotic fluid. Collectively, the data suggest that secretion of soluble TNFRs during pregnancy might be a defence mechanism for the protection of the fetus against TNF action.