Primary Prevention of Sudden Cardiac Death: Can We Afford the Cost of Cardioverter-Defibrillators? Data from the Search-MI Registry-Italian Sub-study

Background: Large randomized trials show that in appropriately selected patients with left ventricular dysfunction, implantable cardioverter-defibrillators (ICDs) can improve overall survival at 2–5 years. Since direct implementation of the criteria used in the MADIT II and SCD-HeFT will lead to a marked rise in ICD implants, there is a growing fear that increased use of ICDs may cause a dramatic burden to health care systems. The ICD has traditionally been seen as an expensive form of treatment, which is difficult to accept at the first look. This is mainly due to the nonlinear character of the ICD investment, characterized by high initial expenditure, followed by a deferred pay-off in terms of clinical benefits. Cost-effectiveness analysis may help provide a different perspective on the problem of ICD cost, as may estimation of the daily cost of ICD treatment, assuming a time horizon of 5–7 years—a particularly interesting subject for further registry studies.
Methods and Results: Based on real expenditure data from 2002 to 2005, as recorded in the Search-MI Registry-Italian Sub-study of patients implanted on MADIT II indications, we estimated the daily costs associated with the device and leads. Over a 5–7 year time horizon, the average daily cost was estimated to be €4.60–€6.70. Translation of these figures into U.S. market conditions suggests a daily cost of around $7.90–$11.40.
Conclusions: These findings appear useful to help evaluate the affordability of ICD in comparison with other therapeutic options in a context of limited available economic resources.     

Excretory/secretory antigen of Toxocara canis: recognition profiles of polyclonal and larvicidal monoclonal antibodies

Summary Five monoclonal antibodies against the excretory/secretory (E/S) antigen of Toxocara canis were obtained and characterized. Immunoprecipitating activity was demonstrated in an in-vitro micropre-cipitating assay using live T. canis larvae. Their capacity to kill larvae was also shown in an in-vitro assay. Two zones of reactivity were observed in 7.5 and 12.5% SDS-PAGE (177-77 kD, 43-15 kD) of immunoprecipitates of human and mouse positive polyclonal anlisera. The murine monoclonal antibodies showed a common pattern of reactivity with the proteins in the 177-77 kD range.     

Effect of divalent cations on structure-function relationships of the antitumor protein α-sarcin

α-Sarcin binds one Zn(II) cation per protein molecule, with a K_d value of 0.9 mM, determined by equilibrium dialysis experiments. Ca(II), Mg(II), and Mn(II) do not bind to α-sarcin. Cd(II) and Co(II) also behave as Zn(II). The binding produces local modifications on the protein conformation affecting the microenvironment of tryptophan residues. The three cations modify the fluorescence emission of the protein. The near-u. v. circular dichroism spectrum of the protein is also altered. The binding of Zn(II) and related cations does not modify the secondary structure of the protein. The ribonucleolytic activity of a-sarcin is inhibited upon Zn(II) binding, but no alteration of the ability of the protein to aggregate phospholipid vesicles has been observed.     

Relation Between Cycle Length, Volume, and Pressure in Type I Atrial Flutter

Assuming that type I atrial flutter is a macroreentrant circuit, its cycle length should vary with the atrial dimensions. In order to test this hypothesis, flutter cycle length was measured while inducing atrial volume and pressure changes by postural and pharmacological means in seven patients undergoing a therapeutic programmed stimulation for type 1 atrial flutter conversion. Right atrial volume was estimated from B-mode echocardiography data. Basal values were compared with those obtained during inspiration, expiration, Valsalva maneuver, negative tilt (head down), and positive tilt (head up) with 0.8–1.6 mg p.o. nitroglycerin. The right atrial size increased slightly from 17.8 to 18.3 cm² (P = 0.04) during the pressure load induced by negative tilt (+ 3 mmHg), with a corresponding lengthening of the flutter cycle length from 228 to 233 msec (P = 0.02). Similarly, pressure unloading of -2 mmHg by positive tilting and nitrates was accompanied by a decrease in right atrial size to 16.6 cm² (P = 0.04), with a corresponding decrease in cycle length from 228 to 219 msec (P = 0.03). Respiratory maneuver yielded similar results with an inspiratory cycle lengthening, expiratory shortening, and further shortening during Valsalva maneuver. These experiments demonstrate a direct relation between cycle length and atrial volume in human type I atrial flutter. They underline the importance of the right heart preload and atrial size for the electrophysiological characteristics of type I atrial flutter. Beside its fundamental interest, this finding is important for the understanding of the mechanism of maintenance and therapeutic responses of this common arrhythmia.     

Heart rate variability and apnea during sleep in Down's syndrome

Autonomic system dysfunction has been reported to occur frequently in patients with Down's syndrome (DS) and is constituted mainly by an imbalance between the sympathetic and vagal systems. The analysis of heart rate variability (HRV) during sleep is a quantitative reliable method for studying such a mechanism, but it has not yet been extensively and adequately applied in DS. In this study, HRV during sleep was evaluated in seven DS patients and in six normal controls, by also controlling for the presence of sleep apnea or arousal. The main results were an increased sympathetic function (low-frequency component of HRV) and a decreased vagal activity (high-frequency component of HRV) in DS with respect to normal controls, during apnea-free periods. Moreover, the presence of apnea, in DS, induced a further significant increase in low-frequency and very low-frequency components of HRV during sleep Stage 2. This study provides additional evidence of a brainstem dysfunctioning in DS, responsible for the abnormal imbalance between the sympathetic and vagal systems and confirms the brainstem involvement already suggested in the literature in order to explain brainstem-auditory evoked potential abnormalities and central sleep apnea in these patients.     

Attentional modulation of the cardiac defense response in humans

How cardiac components of the defense reaction are modulated by attentional factors related to sensory intake versus sensory rejection was examined. Forty-eight men participated in a test of the heart rate response to three presentations of an intense auditory stimulus while performing one of three attentional tasks during the 80 s following stimulus onset: (a) internal (rejection) task, (b) external (intake) task, and (c) no task. Results showed a potentiation of the defense response only under the external attention condition. We concluded that defensive reactions, far from provoking the rejection of the aversive stimulus, require allocation of attention to processing that stimulus in detail.     

Airway eosinophilia and expression of interleukin-5 protein in asthma and in exacerbations of chronic bronchitis

Background An increased nutnber of eosinophils in the bronchial mucosa has been demonstrated both in asthma and in exacerbations of chronic bronchitis. Oiyective To investigate whether the airway eosinophilia present in asthma and in chronic bronchitis during exacerbations is associated with interleukin (IL)-5 protein expression in the bronchial mucosa. Methods We obtained bronchial biopsies in 18 subjects with asthma (four intrinsic, seven extrinsic and seven occupational) and in II subjects with chronic bronchitis examined during an exacerbation. The findings were compared wilh those of bronchial biopsies from 10 subjects with chronic bronchitis examined under baseline conditions and from seven normal subjects, taken as controls. By immunohistochemistry, we assessed the expression of IL-5 protein and the number of eosinophils (EG2), mast cells ftryptase), and T-lymphocytes (CD3) in the submucosa. Results As compared with controls, the number of eosinophils was increased to a similar degree in both asthma (P < 0.001) and in exacerbations of ehronic bronchitis (P < 0.001). whereas the number of I L-5 immunopositive cells was increased significantly only in asthma (P < 0.01). No diflerences were observed in the number of tnast cells and T-lymphocytes between the four groups of subjects examined. Conciusions This study shows that the degree of airway eosinophilia is similar in asthma and in exacerbations of ehronic bronchitis, but only in asthma is it associated with an increased expression of I L-5 protein in the bronchial tnucosa.     

Protein A Reactivity of Lymphocytes from Some Patients with Chronic Lymphocytic Leukaemia Mediated by an Interaction with the F(ab')2 Region of Surface Immunoglobulin

Peripheral blood lymphocytes (PBL) from 15 of 38 patients with chronic lymphocytic leukaemia (CLL) were capable of forming rosettes with human erythrocytes coated with staphylococcal protein A (SpA-HRBC). PEL from seven patients also showed a marked proliferafive response after stimulation with Staphylocccus aureus bacteria strain Cowan I (Cowan Staph). The SpA-rosetling of CLL cells was inhibited by incubation with F(ab')₂ fragments of anli-immimoglobuiin (Ig) antibodies. In addition, incubation with these fragments inhibited the proliferative response of leukacmie B cells to Cowan Staph. The Cowan-Siaph-induced proliferation of CLL cells was also impaired by the addition of normal human IgG and human IgG F(ab')₂ fragments to the cultures, whereas non-immune rabbit IgG was not inhibitory, The inhibitory activity of human IgG F(ab')₂ fragments was retained hy a SpA-Sepharose column, and it was found in the material recovered from the same column by acid elution. These data indicate thai an interaction between SpA and a structure located in the F(ab')₂ region of surface Ig of different classes is responsible for either SpA-binding or the Cowan-Staph-induced proliferate response of PBL from some patients with CLL.