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.     

Primary malignant melanoma of the bladder

Primary malignant melanomma of bladder is extremely rare: 18 cases are reported to date. An 82 year-old man underwent trans-urethral resection of bladder for a bleeding tumor of the posterior wall. Histological diagnosis was melanoma of the bladder. There was no history of previous or regressed cutaneous malignant melanoma. Margins of the bladder lesion contained atypical melanocytes similar to those commonly seen in the periphery of primary mucous membrane lesions. Clinical studies and radiological examinations were negative for other primary site of melanoma. The patient had a bladder recurrence that was consistent with primary tumor and died of widespread disease 9 months after diagnosis.     

Synthesis of TPH-13, a new tridecapeptide from Phyllomedusa rohdei

The synthesis of TPH-13 (Glp-Glu-Lys-Pro-Tyr-Trp-Pro-Pro-Pro-Ile-Tyr-Pro-Met-OH), a tridecapeptide isolated from the skin of the South American frog Phyllomedusa rohdei, is described and alternative approaches are discussed.     

Local Activation Time Derived from Stored EGM is Associated with Failure of Antitachycardia Pacing in Patients with Implantable Defibrillator

Background : Antitachycardia pacing (ATP) is an effective treatment of ventricular tachycardia (VT). However, persistent failure of ATP in some patients is well recognized. Methods : A method of deriving the local activation time from stored intracardiac electrograms in implantable cardioverter defibrillators is described. Using a case‐control design, the local activation times were compared between patients with persistent unsuccessful ATP with comparable controls with successful ATP. Results : The local activation times during VT in patients with failed ATP were longer at 120–180 ms compared with corresponding control patients with successful ATP (60–80 ms). The local activation time expressed as a proportion of VT cycle length in patients with failed ATP compared with patients with successful ATP were 0.40 ± 0.08 versus 0.19 ± 0.08 (P = 0.012). Conclusion : A novel method of deriving local activation time is described, and delayed local activation time may explain failure of ATP in terminating VT in some patients. (PACE 2010; 549–552)     

Dehydro-dermorphins

Dehydrophenylalanine having the Z-configuration (ΔPhe) and D-Phe were incorporated in positions 3 and/or 5 into dermorphin-(1–5)-peptide amide (H-Tyr-D-Ala-Phe-Gly-Tyr-NH₂) in order to study the effect of structure or configurational changes. On GPI preparation, whereas the activity of [L-Phe⁵]-pentapeptide was fourfold higher than parent peptide and comparable to that of dermorphin, the substitution of Phe³ by its D-enantiomer was barely tolerated. The pentapeptides containing ΔPhe in positions 3 and/or 5 displayed even lower potency: particularly the unsaturation at position 3 alone or at position 3 and 5 was very detrimental to μ activity.     

Primary liver cancer in non-cirrhotic liver. Epidemiological study based on autopsies performed in Trieste, Italy and Kurume, Japan

This study, aimed at elucidating the epidemiological features of primary liver carcinoma developing in non-cirrhotic livers, was based on 25,103 autopsies performed between 1975 and 1984 in Trieste, Italy. These autopsies correspond to approximately 70% of all deaths that occurred in this area. Various factors allegedly related to carcinomas were analysed in reference to our previous study on cirrhotic livers and in comparison with 5,603 autopsies in Kurume, Japan. There were 28 cases of hepatocellular carcinoma (HCC), 16 of cholangiocellular carcinoma (CCC) not associated with cirrhosis in Trieste, and 48 HCC and 19 CCC in Kurume. On the basis of our findings, it was concluded that cirrhosis, regardless of its cause, is the main pathogenetic factor in HCC; it is responsible for a much higher frequency (14.2:1) than in non-cirrhotic livers, as well as for early occurrence of tumours (an average of 6 years earlier in cirrhotic liver) in Trieste. Patients in Trieste were older than those in Japan, and the frequency of HCC among all autopsies was much greater in the latter. By contrast, the influence of cirrhosis on cholangiocellular carcinoma (CCC) was negligible, as such association appeared purely coincidental or absent. The incidence of CCC among autopsies was greater in Japan. Our data on CCC were not sufficient to demonstrate any clear aetiopathogenetic association between this tumour and alcohol abuse and hepatitis B virus (HBV) infection, except for a possible aetiological role of gallstones. The frequency of CCC relative to HCC was greater in Trieste than in Japan; the incidence of HCC was much less in Trieste, whereas CCC was more frequent in Japan.     

Opioid peptides Synthesis and binding properties of dermorphin related heptapeptides

C-Terminal amino acid residues of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH₂) were replaced by N^α-methyl- or D-amino acids in order to examine the effect on opioid activity. In binding studies based on displacement of μ, Δ, and κ opioid receptor selective radiolabels from guinea pig brain membranes, the 13 new analogues showed, like dermorphin, a negligible affinity for the κ binding site. The introduction of N^α-methyl- or D-amino acid residues at position 5, 6, or 7 of dermorphin, when matched with C-terminal amide function modifications, generally produced analogues with reversed μ/δ specificity.     

Evaluation of the Atrial Evoked Response for Capture Detection with High-Polarization Leads

AutoCapture™ based on the evoked response can be confounded by electrode polarization. In this study, polarization was measured in human subjects who had chronic atrial leads. The aim of the study was to determine whether electrode polarization can be measured using a time integral atrial evoked-response integral (AERI) of the negative portion of the atrial paced ER evoked-response signal and to determine whether high-polarization atrial leads unsuitable for AutoCapture™ can be identified a priori. Atrial intracardiac-electrogram (IEGM) signals from 39 patients with implanted pacemakers were recorded and analyzed. The signals were recorded during conventional atrial-threshold searches. A total of 221 atrial-capture thresholds were recorded, ranging from 0.25 to 2.75 V with a mean of 0.79 V. Each evoked response was evaluated using the AERI in a 36 ms window following the 0.4 ms atrial stimulus. The polarization was estimated as a linear function of stimulus voltage using the evoked-response signal integral of captured beats identified on the IEGM. The 221 threshold-search datasets were obtained using leads with eight different electrode materials. Polarization could be measured using AERI as a function of stimulus voltage. Furthermore, this polarization measure can be used to identify high-polarization leads, which are ill suited for the atrial AutoCapture™ algorithm.