ISOTOPIC RESPONSE

Background. The occurrence of a new skin disorder exactly at the site of another one, already healed and unrelated, was first described in 1955. In 1985, Wolf et al. recognized that we are dealing with a dermatologic phenomenon and established a precise definition for this phenomenon. Fifty-eight cases corresponding to the definition of this phenomenon have been reported until now. Methods. The new phenomenon, for which the term “isotopic response” has been suggested, has been defined. Cases corresponding to the definition have been analyzed with special emphasis on the diseases involved, the time intervals, and the locations of the diseases. Eight new cases are described. Results. A total of 58 cases of isotopic response have been described. The first disease in most of the patients was herpes zoster; in three cases it was herpes simplex, in two varicella, and in one, thrombophlebitis. The second disease, which appeared exactly at the site of the first, already healed disease, was in most reported cases a carcinoma (26 cases, in particular 15 cases of breast carcinoma, 5 basal cell carcinomas (BCC), 4 squamous cell carcinomas (sec), 2 basosquamous carcinomas), or granuloma annulare (16 cases). Additional diseases were Kaposi's sarcoma (2 cases), pseudolymphoma (2 cases), sarcoid (2 cases), tinea (2 cases), tuberculoid and vasculitis granuloma (1 case), angiosarcoma, metastasis, Bowen's disease, lymphoma, leukemia cutis, and acne (1 case each). The diseases did not show any predilection for a particular location. The interval between the first and second disease was extremely variable (ranging from days to years) and showed no particular features. In the eight additional cases described in the present report, the first disease was herpes simplex (6 cases) or herpes zoster (2 cases). The second disease was viral warts (3 cases) or squamous cell carcinoma (2 cases). Additional diseases were furunculosis, contact dermatitis, and molluscum contagiosum (1 case each). Conclusions. The new term, “isotopic response,” describes the occurrence of a new skin disorder at the site of another, unrelated, and already healed skin disease. It is suggested that the term “isotopic response” be included in the lexicon (glossary) of dermatology. Introducing the new term and classifying all the cases under a single key word, will make it possible to locate and collect them easily and to search for the mechanism underlying this phenomenon.     

Transthoracic Sensor for Noninvasive Assessment of Left Ventricular Contractility: Validation in A Minipig Model of Chronic Heart Failure

Background: Invasively measured left ventricular (LV) dP/dt is the accepted standard for measuring acute and chronic directional changes in LV contractility. Recently, we developed a noninvasive force sensor based on an accelerometer positioned on the chest, which measures the vibrations generated by isovolumic myocardial contraction. The aim of this paper was to compare noninvasive (accelerometer) versus invasive (LV dP/dt) indices of myocardial contractility in a chronic minipig model of pacing‐induced heart failure (HF). Comparative assessment was performed both at rest and following dobutamine infusion. Methods: In adult male minipigs (n = 6), LV contractility was simultaneously assessed both invasively (LV dP/dt, Millar catheter) and noninvasively (accelerometer) at rest and following dobutamine (up to 7.5 mcg/kg/min), both before and after development of HF by pacing the LV at 180 beats/min for 3 weeks. Results: Invasive and noninvasive assessments were obtained in 24 conditions (12 at rest and 12 after dobutamine infusion). Sensor‐based cardiac force changes were significantly related to positive peak LV dP/dt_max changes following dobutamine infusion both in normal (r = 0.88, P < 0.001) and failing heart (r = 0.89, P < 0.001). The force‐frequency relation showed a tight correlation between invasive and noninvasive assessment (r = 0.68, P = 0.02). Conclusions: The force‐frequency relation can be assessed noninvasively by a transthoracic sensor based on an accelerometer. The method can efficiently detect the development of resting dysfunction and the contractile reserve at different HF steps, with potential for wearable HF monitoring. (PACE 2010; 795–803)     

THE FATE OF PATIENTS WITH LOCALLY ADVANCED BLADDER CANCER TREATED CONSERVATIVELY WITH NEOADJUVANT CHEMOTHERAPY, EXTENSIVE TRANSURETHRAL RESECTION AND RADIOTHERAPY: 10-YEAR EXPERIENCE

Purpose

We asses the results of bladder preservation for infiltrating cancer. The potential for neoadjuvant chemotherapy followed by extensive transurethral resection and radiotherapy was evaluated in 40 patients with T2-T4a G2-G3 bladder carcinoma.

Materials and Methods

From 1983 to 1995, 40 patients with bladder cancer underwent bladder sparing treatment, consisting of neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy. Most patients had T3G3 cancer. A deep transurethral resection biopsy was performed before and after chemotherapy, and an extensive transurethral resection was repeated at the end of radiotherapy. Of the patients 30 received cisplatin and methotrexate and 10 also received vinblastine. Total dose of radiotherapy was 60 to 65 Gy. Recurrent superficial tumors were treated transurethrally. Radical cystectomy was considered for persistent or recurrent invasive disease.

Results

Complete response occurred in 19 patients (47.5%) after chemotherapy, and in 8 patients after transurethral resection and radiotherapy (67.5%). Within 10 years 8 responding patients (30%) had local recurrences and 3 underwent cystectomy. Of the patients 14 (35%) are alive, including 13 with no evidence of disease (mean survival 65 months), 5 died of unrelated disease and 21 (52.5%) died of distant metastases (mean survival 28 months). Of the 21 patients 14 had residual tumor after radiotherapy, 3 presented with distant metastases after vesical infiltrating recurrence and 4 had distant metastases in the absence of locoregional recurrence. In 22 patients (55%) the bladder was salvaged. Patients with complete response to chemotherapy had a low risk for recurrent infiltrating tumors and metastases.

Conclusions

Complete tumor control was maintained at 5 years in more than 50% of the patients treated conservatively. Bladder salvage is feasible in select patients.     

Sympathetic and cardiovascular activity during cataplexy in narcolepsy

Autonomic nervous system activity changes have been described during cataplexy as playing a role in triggering it. To confirm these previous findings, we investigated the time course of sympathetic and cardiovascular activities during cataplexy. We made for the first time microneurographic recordings of 10 cataplectic episodes in three patients with hypocretin‐deficient narcolepsy. During microneurography, muscle sympathetic nerve activity (MSNA) was recorded simultaneously with heart rate (HR), respiratory movements, arterial finger blood pressure (BP), electroencephalography, electro‐oculogram and superficial electromyogram. Results showed no significant autonomic changes before the onset of the cataplectic episodes. Cataplexy was associated with a significant increase in MSNA and BP compared with baseline, whereas HR was markedly decreased. An irregular breathing pattern mainly characterized by apnea typically occurred during the attacks. In conclusion, our findings did not show significant changes in autonomic activity prior to cataplexy onset, ruling out a triggering role of the autonomic system. However, cataplexy was associated with co‐activation of sympathetic and parasympathetic autonomic systems, a pattern reminiscent of that reported during the vigilance reaction in animals.     

Substrate Ablation in Treatment of Atrial Fibrillation

From the time catheter ablation of atrial fibrillation (AF) was first reported, of the two dominant approaches for AF ablation, only pulmonary vein (PV) isolation has been modified, while circumferential pulmonary vein ablation (CPVA) as performed by our group in Milan has remained substantially unmodified. In fact, PV isolation as initially performed by Haissaguerre et al. has undergone rapid evolution toward substrate modification with significantly higher success rates without major complications. Modification of such technique was due to modification of the substrate. It is now evident that substrate modification is indeed crucial for curing AF particularly in patients with long-lasting or permanent AF. Indeed, to achieve good outcomes, any ablation technique should simultaneously include elimination of all triggers associated with modification of both anatomic and autonomic substrate, as we started to do many years ago by performing CPVA.