Randomized comparative trial of three antivenoms in the treatment of envenoming by lance-headed vipers (Bothrops jararaca) in Sao Paulo, Brazil

In São Paulo City, Brazil, 121 patients with moderatelysevere envenoming by Bothrops snakes (principally B. jararaca)were randomized for treatment with Brazilian polyspecific Bothropsantivenoms: Instituto Butantan (39 patients), Instituto VitalBrazil (41), Fundação Ezequiel Dias (FUNED) (41).The initial dose was four ampoules (40 ml) in 89 patients withless severe envenoming and eight ampoules (80 ml) in 32 patientswith more severe envenoming. A second dose of four ampouleswas required in 20 patients. Patients receiving the three antivenoms were comparable in allrespects before treatment There were no deaths. The majorityshowed rapid clinical improvement, resolution of local envenoming,cessation of bleeding and restoration of blood coagulability.No differences in the efficacy of the three antivenoms wererevealed by clinical or laboratory observations, including measuresof haematological, haemostatic and biochemical ab normalities.Twelve patients developed abscesses (Butantan 1, Vital Brazil6, FUNED 5) and seven developed local necrosis (3,1,3). Of 88patients followed up 20–30 days after the bite 33 (37.5%)still had symptoms or signs of local envenoming, especiallyswelling. Early (anaphylactic) reactions were unexpectedly frequent afterall three antivenoms but were significantly more frequent withButantan (87%) than with Vital Brazil (37%) or FUNED (56%) antivenoms(p < 0.001). A possible explanation was the higher totalprotein content and percentage immunoglobulin of Butantan antivenom. The doses of antivenom recommended in Brazil and used in thisstudy may be unnecessarily high, resulting in an unacceptablyhigh incidence of reactions. Results of the study should prompta critical re-evaluation of antivenom production techniquesand dosage recommendations in Brazil.     

Long-Term Survival in Patients Treated with Cardiac Resynchronization Therapy: A 3-Year Follow-Up Study from the InSync/InSync ICD Italian Registry

Background: Studies reporting the long-term survival of patients treated with cardiac resynchronization therapy (CRT) outside the realm of randomized controlled trials are still lacking. The aim of this study was to quantify the survival of patients treated with CRT in clinical practice and to investigate the long-term effects of CRT on clinical status and echocardiographic parameters.
Methods: The study population consisted of 317 consecutive patients with implanted CRT devices from eight Italian University/Teaching Hospitals. The patients were enrolled in a national observational registry and had a minimum follow-up of 2 years. A visit was performed in surviving patients and mortality data were obtained by hospital file review or direct telephone contact.
Results: During the study period, 83 (26%) patients died. The rate of all-cause mortality was significantly higher in ischemic than nonischemic patients (14% vs 8%, P = 0.002). Multivariate analysis showed that ischemic etiology (HR 1.72, CI 1.06–2.79; P = 0.028) and New York Heart Association (NYHA) class IV (HR 2.87, CI 1.24–6.64; P = 0.014) were the strongest predictors of all-cause mortality. The effects of CRT persisted at long-term follow-up (for at least 2 years) in terms of NYHA class improvement, increase of left ventricular ejection fraction, decrease of QRS duration (all P = 0.0001), and reduction of left ventricular end-diastolic and end-systolic diameters (P = 0.024 and P = 0.011, respectively).
Conclusions: During long-term (3 years) follow-up after CRT, total mortality rate was 10%/year. The outcome of ischemic patients was worse mainly due to a higher rate of death from progressive heart failure. Ischemic etiology along with NYHA class IV was identified as predictors of death. Benefits of CRT in terms of clinical function and echocardiographic parameters persisted at the time of long-term follow-up.     

Pre- and Postjunctional Effects of Diadenosine Polyphosphates in the Guinea-pig Vas Deferens

The pre- and postjunctional activities of a number of diadenosine polyphosphates were examined in the guinea-pig isolated vas deferens at the level of the membrane-potential, using a modified sucrose-gap technique. P¹,P³-Di(adenosine 5′)triphosphate (Ap₃A), P¹,P⁴-di(adenosine 5′)tetraphosphate (Ap₄A) and P¹,P⁵-di(adenosine 5′)pentaphosphate (Ap₅ A) all caused concentration-dependent depolarization of the smooth muscle membrane. The potency order was: Ap₅A > Ap₄A. Ap₃A. P¹, P²-Di(adenosine 5′)pyrophosphate (Ap₂A) did not evoke depolarization even at the highest concentration tested (1 mM). All the dinucleotides caused a reduction in the amplitude of evoked excitatory junction potentials (e.j.ps). The potency order was: Ap₅A = Ap₄A > Ap₃A > Ap₂A. The depolarizations evoked by the dinucleotides were markedly reduced by the selective P_2X-purinoceptor antagonist, pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS, 10 μM), as was the amplitude of the fully facilitated e.j.p. The inhibition of the e.j.p. evoked by Ap₃A and Ap₂A was reduced by the P₁-purinoceptor antagonist, 8-p-sulphophenyltheophylline (8-pSPT, 50 μM), but that evoked by Ap₅A and Ap₄A was not. Thus, Ap₃A, Ap₄A and Ap₅ A evoke depolarization of the guinea-pig vas deferens via P_2X-purinoceptors, and additionally Ap₂A and Ap₃A exert a prejunctional effect via P₁-purinoceptors. The prejunctional activity of Ap₄A and Ap₅A is mediated via an undefined purinoceptor, which is neither P₁ nor P_2X.