Upright Tilt Test: Correlation Between Results and Patient Clinical Features

The aim of our study was to analyze how the clinical history and the main clinical characteristics of patients suffering from loss of consciousness may influence the results of the upright tilt test. A series of 745 patients (333 males, 412 females; mean age 44 ± 18 years) with recurrent episodes of syncope or presyncope underwent complete clinical and noninvasive laboratory examination, including vagal maneuvers and upright tilt test (60° for 45 min). Cardiological and neurological findings were normal in every case. Upright tilt test was positive in 462 patients (62%). Patients with presyncope showed a lower positivity compared to patients with syncope (70.2% vs 42.9%, P < 0.001). Younger patients (< 25 years) displayed highest upright tilt test positivity (68.5%), while familial occurrence of syncope or presyncope, results of vagal maneuvers, and different gender did not correlate with the results of the test. The time interval between the last syncopal episode and the day of upright tilt test negatively influenced the proportion of positive tests (> 30 days = 45.1 % vs < 30 days = 77.2%; P < 0.001). Patients with more than three syncopal episodes in the 2 months preceding the test showed a higher upright tilt test positivity (83.9% vs 64.5%, P < 0.001). In conclusion, upright tilt test seems to be more sensitive in young patients with syncopal episodes during symptomatic periods. These findings suggest both an individual and temporal variability in autonomic nervous system activity, the implication of which are relevant to the indications for testing as well as the analysis of results.     

Contribution of cross-sectional echocardiography to the diagnosis of right ventricular dysplasia at the asymptomatic stage

The diagnostic accuracy of conventional exercise electrocardiographywas compared with exercise algorithms specifically aimed atapplication in females, with R wave and heart rate adjustedST-segment changes, and with discriminant analysis. A symptom-limitedbicycle exercise test was performed by 189 females without previousinfarction with a normal electrocardiogram (ECG) at rest. Franklead ECG was computer processed. ST-segment amplitudes in leadX were superior to measurements in lead Y, but their sensitivityamounted only to 50% at a specificity of 90%. Correction forR wave amplitude marginally increased sensitivity. It was confirmedthat leads with inferiorly directed vectors such as standardleads II, III, a VF or Frank lead Y should not be used for diagnosticpurposes in females. Exercise-induced increases in R-wave amplitudeof at least 01 mV occurred in only 8% of females with coronarydisease. Previously described discriminant function using attainedheart rate, ST-segment depression and a sex-dependent ST segmentcorrection factor yielded a sensitivity of 60% at a specificityof 90%. Sensitivities of heart rate adjusted ST-segment changesand of a previously proposed discriminant function were greaterthan 70% at a specificity of 90%. It is concluded that the diagnosticyield of exercise testing in females can be improved by useof more sophisticated electrocardio-graphic and exercise variables.     

Fenbufen Pretreatment Potentiates the Anticonvulsant Activity of CPPene and NBQX in DBA/2 Mice

Abstract— The anticonvulsant activity of 3-((±)-2-carboxypiperazin-4-yl)-***l-propenyl-***l-phosphonic acid (CPPene) and 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxoline (NBQX), two excitatory amino acid antagonists, was studied against audiogenic seizures in DBA/2 mice, following intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration. Maximal anticonvulsant protection was observed 15–30 min following NBQX and 45–180 min after CPPene. Coadministration with fenbufen (20mgkg-¹, i.p.), a non-steroidal anti-inflammatory agent, enhanced and prolonged the anticonvulsant actions of CPPene and NBQX and also potentiated and prolonged the impairment of rotarod performance. The enhancement of the anticonvulsant activity and the prolonged impairment of rotarod performance suggests that fenbufen may have some pharmacokinetic interactions with CPPene and NBQX and that fenbufen is able to increase the brain levels of these excitatory amino acid antagonists. In particular, fenbufen was able to exert a major degree of potentiation of effects of NBQX rather than those of CPPene, suggesting that the chemical structures of these excitatory amino acid antagonists are responsible for the different degree of interactions between CPPene or NBQX and fenbufen. NBQX appears to have a notable similarity with quinolones whilst CPPene does not. Additionally fenbufen may displace CPPene and NBQX from plasma binding sites or inhibit the renal excretion. The present data are also consistent with previous studies showing pharmacokinetic interactions between fenbufen and quinolones.     

Mechanistic implications of cyanide binding to carboxypeptidase B

The putative metal coordinating ligand cyanide was used to study the effects of modifications of the metal coordination sphere on the spectral properties and catalytic activity of cobalt and zinc carboxypeptidases. The absorption spectra of Co²⁺-carboxypeptidase B in the presence of cyanide pointed to a direct interaction of the ligands with the metal. Gel-filtration experiments showed that the binding of one mole of ligand per mole of enzyme metal ion resulted in maximal spectral effects. Binding of cyanide to the metal ion as measured by absorption spectroscopy was inhibited by acetyl- L-arginine, a peptide pseudosubstrate, and by acetyl-D-arginine, a competitive peptide inhibitor. Addition of acetyl arginine to the enzyme-cyanide complex caused displacement of the ligand, as evidenced by the spectral parameters. Cyanide inhibited peptide hydrolysis in a partially noncompetitive manner, i.e. it did not prevent binding of the substrate to the enzyme but the enzyme-substrate-cyanide complex was hydrolyzed at a slower rate than the enzyme-substrate complex. The dissociation constant evaluated from kinetic studies for the binding of cyanide to Co²⁺-carboxy-peptidase B was in good agreement with that obtained from spectral measurements. Hydrolysis of the ester analog of the basic peptide substrate was not affected by cyanide. Based on these data a model is proposed in which the peptide carbonyl group displaces the water molecule from the metal coordination sphere during catalysis without increasing the coordination number.     

Long-Term Follow-Up of Patients with Single Lead VDD Stimulation

The purpose of this study was to assess the long-term results of a single lead VDD pacing system (Phymos MPS) in 85 patients (48 males, 37 females, mean age 74 ± 9 years). The system, which incorporates two atrial floating electrodes (Phymos 830-S). was implanted for second- or third-degree Mobitz II AV block. The percentage of AV synchronized pacing, the presence of fusion beats due to short AV delay, and the occurrence of supraventricuiar arrhythmias was evaluated by Holter monitoring at 6-month intervals. Over a mean period of follow-up of 44 months (range 2–56), over 90% of AV synchronized pacing events were noted in 74 patients (87%). The presence of persistent fusion beats was detected in 12 patients (14%). In ten patients the pacemaker was reprogrammed to VVI mode for supraventricuiar arrhythmias (7 patients, 8.2%) or unsatisfactory atrial sensing (3 patients, 3.5%). One pacemaker was removed for pocket infection and two for battery depletion. These observations support the use of VDD single lead pacing to combine a physiological mode of stimulation with simple implantation techniques.