Synthesis of conjugates between luteinizing hormone releasing hormone (LH-RH) and N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP) models of totally synthetic vaccines

Two glycopeptides associating the aminoacid sequence of LH-RH with MDP were prepared, using a Lys residue as a linker. These conjugates, Nα MDP N^e (LH-RH)-Lys and Nα MDP N^e (LH-RH)-Lys-NH₂ obtained by condensation of fragments were synthesized by liquid as well as solid phase methods. Both compounds were able to induce anti LH-RH antibodies and immunological castration. They retained the immuno-adjuvant activity of MDP. Such antigen-adjuvant constructs, devoid of carrier and obtained by chemically defined and reproducible synthetic methods could offer suitable tools for structure-activity relationship studies aiming at defining synthetic vaccines.     

Interaction of Soman with {beta}-Cyclodextrin

Interaction of Soman with ß-CycIodextrin. DESIRE,B., AND SAINT-ANDRE, S. (1986). Fun-dam. Appl. Toxicol. 7, 646-657.Of the following neurotoxic agents, pinacolyl methylphospho-nofluoridate(soman), isopropyl methylphosphonofluoridate (sarin) and ethylN, N-dimethyl-phosphoramidocyanidate (tabun), only soman wasinactivated appreciably at pH 7.40 by ß-cyclodextrin.The interaction of soman, a mixture of four stereoisomers designatedas C(+)P(–), C(–)P(–), C(+)P(+), and C(–)P(+),with cyclodextrins was revealed by methods based on (i) theirreversible inhibition of acetylcholinesterase (AChE) thatis phosphonylated chiefly by P(–)-isomers of racemic somanand (ii) continuous titration of fluoride ions released by somanusing a fluoride-specific electrode. Soman and ß-cyclodextrinform a 1:1 complex. At pH 7.40 and 25°C the dissociationconstant Kd of this complex and the rate constant k2 of cleavageof soman by ß-cyclodextrin are (0.53 ± 0.05)mM and (5.9 ± 0.6) x 10² min¹, respectively. The rateconstant k₂^max for the cleavage of soman by monoionized ß-cyclodextrinhas a value of 2.8 x 103 min¹ and the second order rate constantk₂^max/K_d 5.3 x 106 M^–1 min^–1. Consequently, somanis hydrolyzed about 2500 times faster by the monoanion of ß-cyclodextrin,than by the hydroxide ion. The cleavage of P(–)-somanby ß-cyclodextrin as estimated by AChE inhibitionproceeds apparently at the same rate for the C(–)P(–)-and C(+)P(–)-isomers. However, the release of fluorideions indicated a stereospecific rate of reaction, the P(-Hsomersreacting faster than the P(+)-isomers. At pH 7.40, the inactivationrate of soman by ß-cyclodextrin was as fast in humanplasma in vitro as in Tris buffer. This interaction betweensoman and ß-cyclodextrin, and other data from theliterature, suggests that the introduction of catalytic or noncatalyticgroups on ß-cyclodextrin might possibly make it abetter catalyst for soman inactivation through improvement inthe catalytic or in the binding process.     

Performance of Implantable Cardiac Rhythm Management Devices

Our data represent use, follow-up, and management decisions from seven independently functioning centers and most importantly, actuarial survival of ICRMDs that have been implanted for sufficient time period to allow assessment of time versus failure. General patterns of possible target durations for adequate performance for present or future generations of similar clinical devices may be suggested by the data that we have presented. However, it would be inappropriate to conclude from these data that any presently implanted ICRMD would have a particular functional reliability. These data, furthermore, only summarized device hardware performance and cannot and must not be used to determine either short-term or long-term individual patient status, management, or outcome.     

Influence of Sympathetic Heart Rate Modulation on RT Interval Rate Adaptation in Conscious Dogs

PLADYS, P., et al. : Influence of Sympathetic Heart Rate Modulation on R Interval Rate Adaptation In Conscious Dogs . The objective was to test if changes in autonomic tone still influenced the RT-RR relationship when full RT adaptation is completed, when heart rate is controlled, and when beat-to-beat variability is abolished by atrial pacing. Eight dogs (8–11 kg) were chronically instrumented with atrial pacing electrodes. Digital ECG (1,000 Hz, 12 bits) were recorded from healthy conscious dogs during spontaneous sinus rhythm and during atrial pacing. The protocol was repeated before and after atenolol (2 mg/kg), prazosin (0.5 mg/kg), or atenolol + prazosin. A vocal incitation was used as sympathetic stimulation. Beat-to-beat quantitative analysis of the RT interval (from QRS apex to end of T wave) was correlated with the preceding RR by linear regression. In spontaneous rhythm, atenolol increased RR (P < 0.001), RT (P < 0.001), and short-term heart rate variability (P < 0.01) and decreased RT-RR slopes (P < 0.001). Prazosin did not significantly modify any parameter. Sympathetic stimulation decreased RR (P < 0.001), RT (P < 0.05), and short-term heart rate variability (P < 0.01) and increased RT-RR slopes (P < 0.001). In atrial pacing, the RTRR slopes were steeper during pacing than during spontaneous rhythm but were not modified by pharmacological manipulation of the autonomic nervous system. During sinus rhythm the RT-RR relationship is increased by sympathetic stimulation and decreased by β–blockade. When heart rate modulation and the effects of the time delay in RT rate adaptation are abolished by atrial pacing, the influence of autonomic tone on RT rate adaptation disappears.     

Cost Considerations in the Provision of Magnetic Resonance Imaging Services

Data from the Australian MRI Assessment Program, which involved five public hospitals, are presented covering the second year of operation at each MRI unit when stable conditions of service provision had become established. The data relate to two 15T super conductive units, one 1.OT super conductive unit and two 0.3T resistive magnetic resonance imaging units. A review of the cost data suggests the need for the operation of expensive facilities for extended periods with careful patient selection in order to reduce the average cost per scan and to maximise the clinical benefit to patients. There were variations in the conditions of use of the equipment between the differing centres and there will be a need for a consensus on optimum levels of matters such as operating times and staffing levels. As the results from the MRI Assessment Program were obtained in a teaching hospital environment with a particular referral pattern, the benefits of the technology in other situations will need further consideration.     

Permanent Cardiac Pacing After Open Heart Surgery: Congenital Heart Disease

A retrospective review of 6,004 patients who underwent open repair of congenital heart defects revealed that 132 patients (2.2%) required permanent cardiac pacing postoperatively. The indications for pacing were early atrioventricular (AV) block in 55%, late onset AV block in 31%, and sick sinus syndrome in 14%. A ventricular septal defect (VSD) was the most common congenital anomaly present alone or in association with other lesions in 67% of the patients. Atrial surgery accounted for 21% of the patients requiring pacing. Ten-year patient survival was found to be 66% (+/- 6%). Thirty-five percent of the deaths were sudden and unexpected, presumably due to an arrhythmia. Reoperation for pacing system failure has occurred too frequently (12% per year). The most common causes for reoperation were battery failure (44%) and exit block (25%).