Understanding capture detection.

Automatic capture detection systems are currently available in several cardiac pacing devices. All current systems use low-polarization electrodes and no beat to beat detection system is available for all types of electrodes. In addition the success ratio for currently available systems is not always 100%. Failure to detect capture reliably is often related to the behaviour of the electrode-tissue interface under different circumstances. Pacemaker electrodes can be considered electrochemical cells with complicated characteristics depending on time, temperature and electrical charge. This electrochemical cell is disturbed when a charge is transferred across the electrode-tissue interface during pacing. Several measures can be taken in order to minimise this disturbance or pace polarization artefact (PPA) including the use of high active surface area electrodes and application of tri-phasic pacing pulses. Another factor influencing detection of evoked potentials is the input circuit of the pacemaker affecting the PPA and the evoked response. Positive PPAs can be falsely interpreted as evoked potentials due to the undershoot of the second order filters applied in modern cardiac pacemakers. This paper explains the behaviour of the interface between the electrode and the cardiac tissue in combination with the pacemaker output circuits and input amplifiers under different circumstances.     

Selective homing of phenotypically lytic cells within nasopharyngeal carcinoma biopsies: numerous CD8- and CD16-positive cells in the tumor.

We present a comparative analysis of cell-mediated immunity between circulating lymphocytes and tumor-infiltrating lymphocytes (TIL) from patients with nasopharyngeal carcinoma (NPC). Phenotypic analysis using a panel of monoclonal antibodies (MAbs) to define lymphocytic subsets has revealed a selective homing of phenotypically lytic cells such as CD8- and CD16-positive cells, but a low percentage of macrophages when compared to PBL of NPC patients. Also, PBL and TIL contain an equivalent percentage of activated T-lymphocytes expressing HLA-DR molecules and IL-2 receptors. Functionally, TIL exhibit an abolished NK-cell activity and concomitant decrease of proliferative response to phytohemagglutinin (PHA) and concanavalin A (ConA) stimulation when compared with PBL.     

Tumor necrosis factor-alpha in whole blood cultures of preeclamptic patients and healthy pregnant and nonpregnant women.

OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) is recognized as a likely mediator of the excessive endothelial activation and injury that is a key pathogenetic mechanism of preeclampsia. We used whole blood cell cultures from 12 patients with severe preeclampsia and from 12 healthy pregnant and nonpregnant women to determine the release of TNF-alpha by unstimulated leukocytes as a measure of their state of activation, and their response to stimulation with lipopolysaccharide (LPS) as an indicator of their state of priming. METHODS: Blood was cultivated without and with LPS, and TNF-alpha release was measured after six and 24 hours of cultivation by enzyme-linked immunoassays. Differential leukocyte counts were performed, and TNF-alpha values calculated per 10(5) monocytes. RESULTS: In unstimulated whole blood cultures, TNF-alpha release after six hours of cultivation was similar in all three groups; but after 24 hours, TNF-alpha concentrations in culture supernatants from preeclamptic patients were significantly higher than were values obtained in blood from normotensive pregnant women. In LPS-stimulated blood cultures with a maximum of TNF-alpha release at six hours cultivation time, TNF-alpha concentrations were significantly lower in preeclamptic women than they were in both control groups. We showed in an additional experiment that a strong LPS challenge following preactivation with high doses of LPS resulted in reduced release of TNF-alpha compared with release of TNF-alpha following preactivation with low doses of LPS. CONCLUSIONS: The observed high capacity for spontaneous TNF-alpha release by leukocytes in preeclampsia indicates activation of TNF-alpha producing leukocytes by the disease process. Preactivation and exhaustion of leukocytes by leakage of TNF-alpha could lead to the reduced response to TNF-alpha inducer LPS as observed in blood cultures from preeclamptic patients.     

A novel cubic phase of medium chain lipid origin for the delivery of poorly water soluble drugs.

The existence of a novel cubic liquid crystalline phase is described within the pseudo-ternary system comprising lauric acid, monolaurin, and simulated endogenous intestinal fluid (SEIF). This phase behaviour has been characterized using cross-polarizing light microscopy (CPLM), and the structure of the cubic phase identified by small angle X-ray scattering (SAXS). The presence of the cubic phase was found to be temperature sensitive within the 20-37 degrees C range making it putative material for in situ gelation purposes. The cubic phase was shown to have a high capacity to solubilise a model poorly water-soluble drug, cinnarizine, and initial in vitro release data highlight the potential of this phase to provide sustained release. Absorption of cinnarizine from the cubic phase was studied in an unconscious rat model via duodenal administration and blood sampling via the carotid artery. The rate of absorption was significantly reduced when compared to a simple suspension formulation, a likely combination of retarded erosion of the cubic phase together with hindered drug release from the cubic matrix. The results of this study suggest that this cubic phase may potentially be of benefit in the delivery of poorly water-soluble compounds due to its high loading capacity and potential for sustained release. The ability to manipulate this system using temperature may warrant further interest in delivery applications via other routes of administration.     

Densitometer type and impact on risk assessment for osteoporosis.

Studies have shown a high correlation between measurements of bone mineral density (BMD) obtained on differentdual-energy X-ray absorptiometry machines. Challenger osteodensitometers (Diagnostic Medical System [DMS],Montpellier, France) are becoming widely used but little is known about their clinical performance. The aim of this study was to compare BMD measurements and the resulting patient classification based on T-scores obtained on a DMS Challenger device to those obtained on Hologic 4500A (Bedford, MA) device. Fifty-three volunteers were studied.The BMD of the spine and of the hip were simultaneously measured on both densitometers. BMD values obtained on the Challenger were significantly higher than those obtained with the Hologic QDR4500 (p<0.001). The correlations coefficients between the Hologic QDR4500 and the DMS Challenger measured BMDs were r=0.70 at the femoral neck, r=0.70 at the trochanter, and r=0.83 at the spine (p<0.001). Among the 35 postmenopausal women, there was discordance in the WHO T-score-based classification in 28 subjects (80%) at the spine, 18 subjects (52%) at the femoral neck, and 14 subjects (42%) at the trochanter. The intermachine agreement was low: The kappa score was -0.10 at the spine, 0.2 at the femoral neck, and 0.3 at the trochanter. In conclusion, this study cautions against the use of non established densitometers that leads to underdiagnosis of patients and, subsequently, to inappropriate treatment strategies.     

L’électroencéphalogramme n’est pas un examen légitime pour la confirmation du diagnostic de mort cérébrale

PURPOSE: In France, legislation mandates that the clinical diagnosis of brain death be confirmed by one paraclinical test before organ donation is allowed. That test may be either the electroencephalogram (EEG) or cerebral angiography. We report a case in which the clinical diagnosis of brain death was first confirmed by two EEGs performed according to the French guidelines, but ruled out by cerebral angiography. Considering that the EEG is no longer recommended to establish the diagnosis of brain death, we discuss the relevance of maintaining the EEG for brain death diagnosis in France. CLINICAL FINDINGS: A 58 yr-old man was admitted to the intensive care unit because of coma secondary to a massive subarachnoid hemorrhage with herniation below the falx shown by computed tomography. Clinical criteria of brain death were rapidly present. Two EEGs first confirmed the diagnosis but a four-vessel cerebral angiography was finally performed because the patient moved spontaneously. This cerebral angiography showed flow in the right internal carotid artery. A computed tomography performed the next day definitely confirmed the absence of brain death and organ donation did not occur. CONCLUSIONS: This case demonstrates the limitations of the EEG for this indication and suggests that angiography should be preferred. French legislation is probably maladjusted and would benefit by incorporating guidelines of other countries like Canada. International harmonization of criteria for brain death diagnosis would also be welcome.