FENTANYL THERAPY CONTROLS AUTONOMIC HYPERACTIVITY IN TETANUS

SUMMARY This report describes the use of fentanyl in severe tetanus after failure of established therapeutic modalities (heavy sedation, neuromuscular blockade and ventilation). Cardiovascular instability accompanying severe tetanus secondary to sympathetic overactivity and raised catecholamine levels is associated with a mortality of over 50%.¹ In this clinical situation, a variety of drugs with a primary or secondary action on the cardiovascular system has been used with varying success. The following case of severe generalised tetanus in the adult associated with autonomic hyperactivity, was successfully managed with large doses of intravenous fentanyl.     

Clinical experience with a new detection algorithm for differentiation of supraventricular from ventricular tachycardia in a dual-chamber defibrillator

INTRODUCTION: Inadequate therapy for supraventricular tachyarrhythmias (SVT) is a frequent problem of implantable cardioverter defibrillators (ICD). Dual-chamber ICDs have been developed to improve discrimination of SVT from ventricular tachycardia (VT). We investigated the positive predictivity, sensitivity, and specificity of a new algorithm, the SMART detection trade mark algorithm, incorporated in the Phylax AV (Biotronik) dual-chamber ICD. METHODS AND RESULTS: Two hundred nine patients (185 men, age 64 +/- 11 years) received a Phylax AV ICD with SMART detection trade mark activated. In 138 of these patients, 1,245 sustained tachycardia episodes with a detailed electrogram were stored in the device during a follow-up period of 10 +/- 6 months. Episodes were correctly classified as ventricular fibrillation (VF, n = 178) in 52 patients, VT (n = 641) in 98 patients, and SVT (n = 385) in 48 patients by the algorithm. Forty-one true SVT episodes (3.3%) were misclassified as VT: atrial fibrillation (n = 7) and flutter (n = 1), sinus tachycardia (n = 12), and other SVT (n = 21). The positive predictivity for VF/VT was 94.5% (95% CI 92.7-95.8) uncorrected and 94.5% (95% CI 92.9-95.8%) corrected with the generalized equation estimation (GEE) method. The positive predictivity for SVT was 100%. The specificity was 88.9% (95% CI 85.6-91.6%) uncorrected and 89.0% (95% CI 85.6-91.6%) corrected with the GEE method with a sensitivity of 100%. CONCLUSION: The SMART detection trade mark algorithm was safe and reliable for the detection of all ventricular tachycardias. Although its specificity was high, it should be improved with regard to SVT to avoid inappropriate ICD therapies.     

Assessment of the working capacity of patients with chronic cortico-adrenal insufficiency

A study was made of CVS function in 48 patients with Addison's disease by submaximum bicycle ergometry to specify and improve the existing criteria of assessment of a degree of gravity of disease and the working capacity of patients before and after hormonal substitution therapy. According to the results of bicycle ergometry, the working capacity of these patients was lowered, the total volume of work done, loading power, and maximum oxygen consumption were also lowered. The data obtained can be used for assessment of therapeutic efficacy and in medical labor examination to determine the working capacity of patients with hypocorticism.     

Synergistic action of calcium ionophore A23187 and phorbol ester TPA on B-chronic lymphocytic leukemia cells

The peripheral blood mononuclear cells from 16 patients with B-chronic lymphocytic leukemia (B-CLL, n = 13), B-prolymphocytic leukemia (B-PLL, n = 2) or hairy cell leukemia (n = 1) were incubated in the presence of the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) and the calcium ionophore A23187. A synergy between these inducers was found with respect to morphological changes and B cell proliferation and differentiation. A23187 used alone did not activate the cells. B-CLL cells treated with the double stimulus acquired a plasmacytoid morphology, showed significantly higher incorporation of 3H-thymidine and 3H-uridine, and produced significantly higher amounts of monoclonal immunoglobulin compared with the same cells exposed to either of the inducers alone. These results indicate that phorbol ester and calcium ionophore act synergistically on B-CLL cells to induce proliferation and differentiation. B-PLL cells responded more vigorously to the signals provided by TPA and A23187. Previous studies showed that TPA and A23187 can mimic the two physiological second messengers diacylglycerol and inositol trisphosphate in the transduction of signals leading to cell activation, proliferation, and differentiation in normal B cells. The present findings suggest that the capacity of B- CLL and B-PLL cells to differentiate in response to signals of the second messenger pathway is intact.     

Polymorphisms in p1-p6/p6* of HIV type 1 can delay protease autoprocessing and increase drug susceptibility

Maturation of infectious human immunodeficiency virus type 1 (HIV-1) particles requires proteolytic cleavage of structural polyproteins by viral protease. Inhibition of protease is a powerful tool for the treatment of HIV infection. Using a well-established phenotypic drug susceptibility assay, we found that sequences outside of the protease gene can modulate the susceptibility to protease inhibitors (PIs). Chimeric viruses carrying p1-p6/p6* sequences from patient isolates in the context of an NL4-3 molecular clone exhibited increased PI susceptibility. Furthermore, this phenotype was associated with a delay in protease autoprocessing in virions and a reduction in replication capacity. We propose that the interplay between protease and the C terminus of Gag is critical for proper protease activity and mismatches between these regions can reduce viral replication and increase drug susceptibility.