Cultured rat and purified human Pneumocystis carinii stimulate intra- but not extracellular free radical production in human neutrophils

The production of free radicals in human neutrophils was studied in both Pneumocystis carinii derived from cultures of L2 rat lung epithelial-like cells and Pneumocystis carinii purified from human lung. Using the cytochrome C technique, which selectively measured extracellular superoxide generation, hardly any free radical production was observed after stimulation with cultured rat-derived P. carinii. A chemiluminescence technique, which separately measured intra- and extracellular free radical production, was subsequently employed to differentiate the free radical generation. It was established that 1) P. carinii stimulated intra- but not extracellular free radical production in human neutrophils, 2) opsonized cultured rat-derived P. carinii stimulated human neutrophils to a strong intracellular response of superoxide production, and 3) opsonized P. carinii, purified from human lung also stimulated human neutrophils to produce intracellular free radicals.     

Increased tendency towards gingival bleeding caused by joint effect of alpha-tocopherol supplementation and acetylsalicylic acid

Alpha-tocopherol (vitamin E) may play a role in the treatment of arterial thromboembolic disease, possibly by inhibiting platelet aggregation. Thus far, no clinical evidence exists for this effect. The objective of this study was to assess the effect of alpha-tocopherol supplementation on gingival bleeding either in combination with acetylsalicylic acid (ASA) or without it. This study was an end-point examination of a random sample of male smokers who had participated in a controlled clinical trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) for 5-7 years. The study included 409 men aged 55-74 years of whom 191 received alpha-tocopherol supplementation (50 mg/day); 56 used ASA, 30 received both and 132 received neither. Gingival bleeding was examined by probing with a WHO probe and reported as a percentage of bleeding sites adjusted by the logistic regression model. Gingival bleeding was more common in those who received alpha-tocopherol compared with nonreceivers among subjects with a high prevalence of dental plaque (P < 0.05). ASA alone increased bleeding only slightly. The highest risk of gingival bleeding was among those who took both alpha-tocopherol and ASA (33.4% of probed sites bleeding vs 25.8% among subjects taking neither alpha-tocopherol nor ASA, P < 0.001). In the ATBC Study, more deaths from haemorrhagic stroke and fewer from ischaemic heart disease were observed among those participants who received alpha-tocopherol compared with those who did not. Based on the results of the present study and the ATBC Study, we conclude that alpha-tocopherol supplementation may increase the risk of clinically important bleedings, particularly when combined with ASA.     

Selective excitatory amino acid uptake in glutamatergic nerve terminals and in glia in the rat striatum: quantitative electron microscopic immunocytochemistry of exogenous (D)-aspartate and endogenous glutamate and GABA

To characterize glutamate/aspartate uptake activity in various cellular and subcellular elements in the striatum, rat striatal slices were exposed to 10 and 50 mu M exogenous (D)-aspartate. After fixation with glutaraldehyde/formaldehyde the distribution of (D)-aspartate was analysed by postembedding immunocytochemistry and the ultrastructural distribution was compared with the distributions of endogenous glutamate and GABA. Light microscopically, (D)-aspartate-like immunoreactivity was localized in conspicuous dots along very weakly labelled dendritic profiles and neuron cell bodies. At the electron microscope level gold particles signalling (D)-aspartate occurred at highest density in nerve terminals making asymmetrical contacts with postsynaptic spines (i.e. resembling synapses of cortical afferents). Astrocytic processes also contained gold particles, but at a lower density than nerve endings. In contrast, dendritic spines were only weakly (D)-aspartate-positive. The difference in labelling at 10 and 50 mu M (D)-aspartate was consistent with 'high-affinity' uptake. Neighbouring sections processed with other antibodies showed that the D-aspartate labelling. Occurred in nerve terminals strongly immunoreactive for glutamate, rather than in terminals very weakly glutamate-immunopositive or in nerve endings immunoreactive for GABA. Glutamate labelling of perfusion-fixed striatum confirmed that terminals forming asymmetrical synaptic contacts with spines were enriched with gold particles, suggesting that these terminals use glutamate as a transmitter. This study demonstrates that high-affinity uptake sites for excitatory amino acids in the striatum are most strongly expressed on presumed glutamatergic nerve terminals and on astrocytes.     

On the future of the speciality of Obstetrics and Gynecology. A Dutch view

Between 4 and 15 ng/ml serum prostate-specific antigen (PSA) has a low specificity for prostate cancer (PCa). One accepted method to enhance this specificity is transrectal ultrasonography (TRUS)-measured PSA-density (PSA-D). We compared this method with a new alternative, transition zone PSA (PSA-TZ). We measured total and transition zone prostatic volumes by TRUS and calculated PSA-D and PSA-TZ in 59 patients with suspicion of PCa and PSA between 4 and 15 ng/ml. All patients then had sextant biopsies of the prostate, 30 were positive for PCa and 29 showed benign tissue. With a cut-off value of 0.35, PSA-TZ had a positive predicted value of 77% for PCa, whereas PSA-D, with a cut-off value of 0.12, had a positive predicted value of 55%. Our data suggest PSA-TZ to be more reliable for avoiding unnecessary biopsies in patients with PCa suspicion and serum PSA below 15 ng/ml. PSA-TZ, calculated by TRUS, enhances the specificity of PSA for needle biopsy diagnosis of PCa.     

Gate etch induced diode leakage prevention with 7-nm CVD stackedgate dielectric

Using a CVD stacked oxide, containing a thermally grown layer and a deposited CVD film, as the gate dielectric for MOS devices provides significant advantages over a single thermally grown oxide, due to mismatch of weak spots in the two layers, reduced substrate consumption and stress compensation between component layers. This paper discusses how a 7-nm stacked gate oxide reduced process-induced diode leakage by ~10², an advantage not reported previously. Micropore misalignment in the two component layers of the stacked gate oxide preventing the reactive etchant ions from reaching the substrate could explain the enhanced “etch stop” provided by the stacked oxide     

The detection of recurrent sarcoidosis by FDG-PET in a lung transplant recipient

PURPOSE: While advanced cardiac life support (ACLS) training is widely available, it is not mandatory for all anaesthetists. We hypothesised that adherence to ACLS guidelines during resuscitation of ventricular fibrillation (VFib) as assessed in a simulator environment would be poor by anaesthetists not trained in ACLS compared with those who had received training. METHODS: With approval by the ethics review board, 89 subjects participated in the study. The simulation system consisted of a computer controlled mannequin with lifelike qualities set in a mock operating room. Each subject was given a test scenario that contained several standard anaesthetic problems. A VFib cardiac arrest occurred after approximately one hour into the simulation. A perfect score (score = A) defined complete compliance with the ACLS guidelines, whereas minor deviations (score = B) included changes in energy levels, drug doses or treatment order. The failure to discontinue the anaesthetic, defibrillate or administer epinephrine were considered major deviations (score = C). RESULTS: Eight subjects followed the ACLS guidelines (9%, score = A), while 27 subjects showed minor (30%, score = B) and 54 subjects major deviations (61%, score = C). Sixty-two of the 89 participants (70%) had taken the ACLS course and achieved higher scores than did anaesthetists without such training (P < 0.05). Forty-two participants (47%) did not discontinue the anaesthetic, 10 (11%) never gave epinephrine and 5 (6%) never used the defibrillator. CONCLUSION: Adherence to ACLS guidelines was poor. A greater proportion of subjects without previous ACLS training had deviations from protocol than did subjects who had received training. We need to consider ways to ensure that anaesthetists obtain and retain resuscitation skills according to ACLS guidelines.     

Differential localization of delta glutamate receptors in the rat cerebellum: coexpression with AMPA receptors in parallel fiber-spine synapses and absence from climbing fiber-spine synapses

The delta 2 glutamate receptors are prominently expressed in Purkinje cells and are thought to play a key role in the induction of cerebellar long-term depression. The synaptic and subsynaptic localization of delta receptors in rat cerebellar cortex was investigated with sensitive and high-resolution immunogold procedures. After postembedding incubation with an antibody raised to a C-terminal peptide of delta 2, high gold particle densities occurred in all parallel fiber synapses with Purkinje cell dendritic spines, whereas other synapses were consistently devoid of labeling. Among the types of immunonegative synapse were climbing fiber synapses with spines and parallel fiber synapses with dendritic stems of interneurons. At the parallel fiber-spine synapse, gold particles signaling delta receptors were restricted to the postsynaptic specialization. By the use of double labeling with two different gold particle sizes, it was shown that delta and AMPA GluR2/3 receptors were colocalized along the entire extent of the postsynaptic specialization without forming separate domains. The distribution of gold particles representing delta receptors was consistent with a cytoplasmic localization of the C terminus and an absence of a significant presynaptic pool of receptor molecules. The present data suggest that the delta 2 receptors are targeted selectively to a subset of Purkinje cell spines and that they are coexpressed with ionotropic receptors in the postsynaptic specialization. This arrangement could allow for a direct interaction between the two classes of receptor.     

A centroid-based PWM switching technique for full-bridge inverterapplications

A novel centroid-based pulse-width-modulation (PWM) switching strategy is proposed which is suitable for full-bridge inverter applications. This method is evaluated, and its performance is compared with existing PWM switching strategies. The performance evaluation and comparison are based on the total harmonic distortion (THD) and number of pulses per cycle of the inverter output waveform. The objective of the new switching strategy is to minimize both the THD and low-order harmonics. Simulation results show that this technique yields a significant improvement in performance. In addition, a hybrid switching sequence is developed for the proposed scheme, which can lead to further reduction in switching losses