Acute Hemodynamic Improvement by Pacing in Patients with Severe Congestive Heart Failure

Since the first report on dual chamber pacing for congestive heart failure (CHF) in 1991, a number of investigators have explored the topic with conflicting results. These conflicts may arise from an incomplete understanding of the mechanisms by which pacing improves cardiac function. Potential mechanisms include: (1) increase in filling time: (2) decrease in mitral regurgitation: (3) optimization of left heart mechanical atrioventricular delay (left heart MAVD); and (4) normalization of ventricular activation. One or more of these mechanisms may be operative in an individual patient, implying that patients may require individuol optimization. Acute pacing studies were conducted on nine CHF patients, NYHA Class II-III to Class IV. Measurements of conduction times in sinus rhythm revealed: (1) normal interatrial conduction times (59 ± 5 ms) in all patients, with wide variations in interventricular conduction times (range, ?15–105 ms); and (2) a wide range of left heart MAVD (range, 97–388 ms). While pacing the right, left, or both ventricles, measurement of high fidelity aortic pressure and mitral and aortic velocities revealed the following: (1) 6 of 9 patients increased mean pulse pressure over sinus value during RV orLV pacing at an optimal A V delay: (2) the maximum aortic pulse pressure was achieved when the atrium was not paced: an 8% increase over sinus pulse pressure with paced RV versus a 5% decrease for paced atrium and RV at optimum AV delay (paired Student's t-test, P = 0.01), and a 0% increase over sinus with paced LV versus 7% decrease for paced atrium and LV at optimum AV delay, P < 0.05: (3) significant dependence on pacing site was noted, with 4 patients doing best with RV pacing. 3 patients achieving a maximum with LV pacing, and 2 patients showing no preference; and (4) 2 of 4 patients with restrictive filling patterns were converted to nonrestrictive patterns with optimum pacing. Patient hemodynamics appear to benefit acutely from individually optimized pacing. Increases in filling time, optimization of left heart MAVD, and normalization of intraventricular activation are the most significant mechanisms. Atrial pacing is inferior to atrial sensed modes if the patient has a functional sinus node.     

Rhythm Discrimination by Rate Branch and QRS Morphology in Dual Chamber Implantable Cardioverter Defibrillators

BORIANI, G., et al. : Rhythm Discrimination by Rate Branch and QRS Morphology in Dual Chamber Implantable Cardioverter Defibrillators. Morphology Discrimination is a discriminator based on QRS morphology analysis that has been recently implemented in dual chamber implantable cardioverter defibrillators (ICDs). Detected events are initially classified according to median atrial and ventricular rates (Rate Branch). Then, a series of discriminators (Morphology Discrimination, Stability, Sudden Onset) analyze the rhythm according to specific criteria and the number of discriminators required for VT diagnosis (i.e., requiring "any" or "all" of the specific discriminators to indicate VT). The discriminating accuracy of the algorithm was evaluated in 645 detections recorded during the follow-up of 25 patients. The overall specificity for 397 supraventricular arrhythmias was 73.5% (292/397) with the tachycardia diagnosis criteria set to "any" and 90.9% (361/397) with the tachycardia diagnosis criteria set to "all." Sensitivity for VT was 100% and 98.7% (231/234) with the tachycardia diagnosis criteria set to "any" and "all," respectively. With the tachycardia diagnosis criteria set to "any," specificity for atrial fibrillation was 88.6%, for atrial flutter 40.3%, for atrial tachycardia 0%, and for sinus tachycardia 97.0%. With the tachycardia diagnosis criteria set to "all," specificity for atrial fibrillation was 92.40%, for atrial flutter 93.5%, for atrial tachycardia 54.7%, and for sinus tachycardia 99.0%. The contribution of Morphology Discrimination was crucial to improve the specificity of the Rate Branch algorithm. The implementation of Morphology Discrimination in a dual chamber ICD with Rate Branch rhythm classification allows the attainment of high specificity and high sensitivity for ventricular tachyarrhythmias. (PACE 2003; 26[Pt. II]:466–470)     

Influence of the paraoxonase‐1 Q192R genetic variant on clopidogrel responsiveness and recurrent cardiovascular events: a systematic review and meta‐analysis

Summary. Background: A poor biological response to clopidogrel is associated with an increased risk of major cardiovascular ischemic events (MACE). Paraoxonase 1 (PON1) enzyme activity is modulated by the PON1‐Q192R variant (rs662) and was recently suggested to be strongly involved in clopidogrel bioactivation, but the influence of the PON1‐Q192R variant on the risk of MACE in clopidogrel‐treated patients is controversial. Objectives: To determine whether the PON1‐Q192R variant influences clopidogrel biological responsiveness and the risk of MACE in patients treated with clopidogrel. Methods: Systematic review and meta‐analysis of studies of the association between the PON1‐Q192R polymorphism and the biological response to clopidogrel and/or the risk of MACE during clopidogrel administration. Results: Seventeen studies were included. In the 12 studies of the biological response to clopidogrel (n = 5302 patients), there was no significant difference between 192QQ and 192QR + 192RR subjects, whatever the laboratory method used (global mean standardized difference = 0.10 [?0.06; 0.25], P = 0.22). Eleven studies assessed the risk of MACE, four using a case–control design (n = 2739 patients) and seven a prospective design (n = 5353 patients). Overall, MACE occurred in 19% of patients in case–control studies and in 6% of patients in prospective cohort studies, with no significant difference between 192QQ and 192QR + 192RR patients (OR = 1.28 [0.97; 1.68], P = 0.08). Similar results were obtained when study design was taken into account. Heterogeneity was mainly driven by one publication. Conclusions: This meta‐analysis suggests that the PON1‐Q192R polymorphism has no major impact on the risk of MACE and does not alter the biological response to clopidogrel in clopidogrel‐treated patients.     

Complement Activation is Associated with the Presence of Specific Human Immunodeficiency Virus (HIV)-Anti-HIV Immune Complexes in Patients with Acquired Immunodeficiency Syndrome-Related Complex or Lymphoadenopathy Syndrome

The complement system was examined in a group of eight patients (six with lymphoadenopathy syndrome (LAS); two with acquired immunodeficiency syndrome (AIDS)-related complex (ARC], who were found to be human immunodeficiency virus (HIV)-positive, for the presence of specific HIV-anti-HIV complexes. A significant impairment of the classical and/or alternative pathway was found associated with the presence of cleavage fragments of C3 and/or B and a significant reduction in the complement factors studied. Ultracentrifugation fractions of serum samples obtained from one of the patients were assessed for the detection of specific HIV-anti-HIV (GP41-anti-GP41) complexes and were incubated with normal human serum to determine their complement activation capacity. A clear complement activation was found with the fraction in which a clear peak of HIV-anti-HIV (GP41-anti-GP41) immune complexes was present. The results demonstrate that specific immune complexes and complement activation are sometimes concomitantly present in patients with AIDS-related disease and that specific immune complexes may be one of the causal factors of the pathogenesis of complement activation in these patients. Possible consequences for the severe immune regulation with relevance to the dramatic failure in treating the virus effectively are discussed.     

Chronic Gastric Torsion in Infancy: A Revisited Diagnosis

Twenty out of 108 infants with vomiting, who underwent an upper gastrointestinal X-ray study during a period of 2 years, showed a peculiar shape and position of the stomach already described as chronic gastric torsion. We examined clinical, radiologic and laboratory findings of these 20 infants. Our results showed that chronic gastric torsion is frequently associated with gastroesophageal reflux and has a wide spectrum of symptoms, complications and nutritional abnormalities.     

Synthesis and conformational studies of peptides encompassing the carboxy-terminal helix of thermolysin

The 21-residue fragment Tyr-Gly-Ser-Thr-Ser-Gln-Glu-Val-Ala-Ser-Val-Lys-Gln-Ala-Phe-Asp-Ala-Val-Gly-Val-Lys, corresponding to sequence 296–316 of thermolysin and thus encompassing the COOH-termi-nal helical segment 301–312 of the native protein, was synthesized by solid-phase methods and purified to homogeneity by reverse-phase high performance liquid chromatography. The peptide 296–316 was then cleaved with trypsin at Lys³⁰⁷ and Staphylococcus aureus V8 protease at Glu³⁰², producing the additional fragments 296–307, 308–316, 296–302, and 303–316. All these peptides, when dissolved in aqueous solution at neutral pH, are essentially structureless, as determined by circular dichroism (CD) measurements in the far-ultraviolet region. On the other hand, fragment 296–316, as well as some of its proteolytic fragments, acquires significant helical conformation when dissolved in aqueous trifluoroethanol or ethanol. In general, the peptides mostly encompassing the helical segment 301–312 in the native thermolysin show helical conformation in aqueous alcohol. In particular, quantitative analysis of CD data indicated that fragment 296–316 attains in 90% aqueous trifluoroethanol the same percentage (～58%) of helical secondary structure of the corresponding chain segment in native thermolysin. These results indicate that peptide 296–316 and its subfragments are unable to fold into a stable native-like structure in aqueous solution, in agreement with predicted location and stabilities of isolated subdomains of the COOH-terminal domain of thermolysin based on buried surface area calculations of the molecule     

Crystal structure,conformation, and potential energy calculations the chemotactic peptide N- formyl-l-Met-l-Leu-l-Phe-OMe

The tripeptide N-formyl-L-Met-l -Leu-l -Phe-OMe (FMLP-OMe) crystallizes in the orthorhombic system, space group P 2₁2_l2₁, with the following unit-cell parameters: a = 21.727, b = 21.836, c = 5.133Å, Z = 4. The structure has been solved and refined to a final R of 0.068 for 1838 independent reflexions with I > 2σ(I). The peptide backbone is folded at the Leu residue (φ_L=?67.7,Ψ_L=?49.1°) without intramolecular hydrogen bonds. Considering each peptide plane, the Leu side-chain is oriented on the same side of that of the Phe residue and on the opposite side of that of the Met residue, respectively. The crystal conformation differs from all the other conformations proposed for FMLP-OMe and the anionic form of N-formyl-l -Met-l -Leu-l -Phe-OH (FMLP) in solution accounts for the amphiphilic character of the peptide, giving rise, through intermolecular hydrogen bonds, to a stacking of molecules which could be maintained in the aggregation states experimentally observed in solvents of low polarity. Intramolecular potential energy calculations have ben carried out in order to compare the energies of the various backbone conformers.     

Plasma Levels of Testosterone, LH and FSH after Prostatic Adenomectomy

Plasma-Werte für Testosteron, LH und FSH nach operativer Entfernung einer benignen Prostatahyperplasie
Bei 19 Männern im Alter von 60–80 Jahren mit einer benignen Prostatahyperplasie wurden vor und nach der operativen Entfernung die RIA-Werte im Plasma für Testosteron, LH und FSH bestimmt. Es wird festgestellt, daß der Testosteronwert am 5. postoperativen Tag signifikant niedriger lag als vor derselben; 1 Jahr nach der Operation lag dieser Wert dann signifikant höher.
Der LH-Wert war 1 Jahr nach der Operation signifikant niedriger, während für FSH keinerlei Veränderung festzustellen war. Aus diesen Ergebnissen wird die Schlußfolgerung gezogen, daß die hyperplastischen Knoten der Prostata in hohem Grade Testosteron brauchen.