Time and Frequency Repolarization Domains in Elderly Candidates to Transcatheter Aortic Valve Replacement.

Background and aim: Aortic valve stenosis (AVS) is a well-known risk factor for sudden cardiac death. Therefore, some non-invasive, electrocardiographic markers are capable to stratify the risk of sudden death at rest and during light mental challenge [mini-mental state examination (MMSE) administration]. Method: We compared short period RR, QT and Te intervals variability in 42 candidates to and 12 age-matched hypertensive control patients at rest and during mental challenge. Results: At rest, AVS patients showed a higher QT standard deviation (sd), QT low frequency power (LF), QT High Frequency (HF), Tpeak-Tend intervals sd (Te sd) and Te HF than the control group. During mental challenge AVS group showed a decrease of RR mean and RR HF, expressed in normalized units (NU), and an increase of RR total power (TP), RR LF, RR LF NU, RR LF, HF ratio (LF/HF). During this same mental test, QT sd, QT LF, QT HF, Te sd, Te LF, Te HF, QT variability index (VI), TeVI, QT normalized variance (VN) were higher in AVS patients than the control group. During mental challenge Te LF (r:0.825, p<0.05) was significantly associated to: serum albumin (ß:-0.473, p<0.001), MMSE (ß:-0.267, p:0.038), diastolic blood pressure (ß:-0.443, p:0.03) and cardiac index (ß:-0.303, p:0.029). Conclusion: AVS patients showed temporal dispersion of ventricular repolarization phase, useful maker to individuate high risk patients. MMSE administration induced a sympathetic sinus activation and vagal deactivation in AVS subjects. Frailty and mental function influenced Te HF and Te LF.

Short-Period Temporal Dispersion Repolarization Markers in Elderly Patients with Decompensated Heart Failure.

Objectives: Aging and chronic heart failure (CHF) are responsible for the temporal inhomogeneity of electrocardiogram (ECG) repolarization phase. In the past, short period repolarization-dispersion parameters were used as makers of mortality risk in different heart diseases, yet. Aim of this work was to evaluate risk of mortality or worsening condition in CHF elderly subjects by mean of these repo-larization variables. Method: An observational, prospective cohort study was performed, collecting 5 minutes ECG recordings to assess the mean and standard deviation (SD) of the following variables: QT end (QTe), QT peak (QTp) and T peak to T end (Te) in 117 decompensated CHF (age range: from 49 to 103 years). 30-day mortality and high levels of NT-pro BNP (<75 percentile) were considered markers of decompensated CHF. Results: A total of 27 patients (23%) died during the 30-day follow-up (overall mortality rate 23%). Te mean (odd ratio (OR): 1.04, 95% confidence limit (Cl 7u): 1.02-1.09, p<0.01), NT-pro BNP (OR: 1.00, 95% cl: 1.00-1.00, p<0.01) and LVMI (OR : 0.98, 95% cl: 0.96-0.10, p<0.05) were associated to risk of mortality at the multivariable logistic analysis. On the contrary, the same statistical analysis selected TeSD (OR: 1.36, 95% cl: 1.16-1.59, p<0.001) and LVEF (OR: 0.91, 95% cl: 0.87-0.95, p<0.001) as marker of decompensated CHF. Conclusion: In decompensated CHF elderly subjects, Te mean seem be associated to mortality and TeSD could be considered a risk factor for CHF worsening and complications. These evidences could provide useful tools for telemonitoring CHF elderly patients, amelio-rating treatments and outcomes.

Changes in left ventricular repolarization after short-term testosterone replacement therapy in hypogonadal males.

BACKGROUND AND AIM: Evidences suggest that androgen deficiency is associated with sudden cardiac death (SCD). Our purpose was to analyse some electrocardiographic (ECG) markers of repolarization phase in hypogonadal patients either at baseline or after testosterone replacement therapy (TRT). PATIENTS AND METHODS: Baseline and after 6 months of testosterone replacement therapy, 14 hypogonadal patients and 10 age-matched controls underwent a short-term ECG recordings at rest and immediately after a maximal exercise test. The following ECG parameters have been collected: QTe (the interval between the q wave the end of T wave), QTp (the interval between the q wave and the peak of T wave), and Te (the interval between the peak and the end of T wave). RESULTS: At baseline, in the hypogonadal patients, corrected QTe and QTp values were longer at rest than in the controls at rest (p < 0.05), whereas, during the recovery phase, only the QTp remained significantly longer (p < 0.05). After TRT, hypogonadal patients showed an improvement only in Te (p < 0.05). Conversely, any difference between hypogonadal patients and control subjects was found with respect to the markers of temporal dispersion of repolarization phases, except for a worse QTp → Te coherence (p = 0.001) obtained during the recovery phase. CONCLUSIONS: In conclusion, at rest, hypogonadal patients suffer from a stable increase in the myocardial repolarization phase without an increase in its temporal dispersion and, hence, the SCD risk seems to be low.

[Syncope: physiopathology, diagnosis and therapy]. / La Sincope: Fisiopatologia, Diagnosi e Terapia

Nowadays, syncope still generates complicated challenges for clinicians for the alarm it arises in patients and, at the same time, for the multiple causes it has determined by. In almost one third of cases, syncope is neuromediated, in young subjects in vasovagal, whereas in elderly is often determinated by carotid sinus hypersensitivity. These two kinds of syncope have two completely different diagnostic approach. In some cases pace-maker implantation will be suggested to avoid new syncope episodes. In a 20% of cases, the underlying cause is arrhythmic, most of all bradiarrhythmia which is treated with pace-maker implantation. In a little number of cases, syncope is caused by ventricular arrhythmias, that require the implantation of a defibrillator device. In this review, we analyze in detail every cause of syncope with its diagnostic and therapeutic approach.

Exercise tolerance in systemic sclerosis patients without pulmonary impairment: correlation with clinical variables.

OBJECTIVES: In systemic sclerosis (SSc) patients pulmonary vasculopathy (PV) is present in the early stage of disease and impairs dilation of affected pulmonary blood vessels, impeding pulmonary blood flow during exercise. Abnormal gas exchange findings were early investigated by cardiopulmonary exercise test (CPET). METHODS: A total of 34 female and 6 male [median age 49 (20-63) years] SSc patients with normal chest imaging and pulmonary function tests were enrolled. Twenty healthy controls age and sex matched [16 female and 4 male; median age 51 (35-73) years] were also recruited. All subjects underwent a full clinical examination, including a nailfold video capillaros copy (NVC). An incremental symptom-limited CPET was performed with estimation of minute ventilation (VE), workload (WR), peak oxygen uptake (pVO22), and ventilatory efficiency (VE/VCO2 slope). RESULTS: A reduced exercise tolerance (pVO2<80% of predicted) was documented in 18 out of 40 subjects (45%). Six out of 18 patients with a reduced exercise tolerance showed indirect signs of ventilation perfusion mismatch (VE/ VCO2 slope >34). Patients with digital ulcers (DUs) history showed VE/VCO2slope values significantly higher [31.4 (18-39.6)] than in patients without DUs history [26.9 (22-29.4)] (p<0.0001). VE/VCO2slope values also significantly differed between the three capillaroscopic groups: early [26.3 (18-29.4)], active [28 (26.8-39.6)], and late [32.9 (22.4-39)] (p<0.0001). A positive correlation was found between the VE/ VCO2slope and both Disease Activity Index (p<0.0001, r=0.59) and Disease Severity Scale (p<0.0001, r=0.73). CONCLUSIONS: In SSc patients without evidence of pulmonary and cardiac involvement, CPET might be useful in disclosing an early PV.

Surfactant protein B and RAGE increases in the plasma during cardiopulmonary bypass: a pilot study.

Surfactant derived protein B (SPB) and plasma receptor for advanced glycation end products (RAGE) have been proposed as markers of lung injury. The former is produced specifically by pneumocytes while RAGE production is present in several body tissues. Cardiopulmonary bypass (CPB) generates a transient lung injury. We measured SPB and RAGE in plasma before surgery and after CPB, as well as 24 h and 48 h later. We analysed plasma samples from 20 subjects scheduled for elective coronary artery bypass grafting. We performed a quantitative analysis of plasma levels of RAGE and SPB mature form (8 kDa) by ELISA and a semi-quantitative analysis of SPB immature form (~ 40 kDa) by Western blotting. Surgery procedures were uneventful. After CPB RAGE median (75th-25th interquartile difference) increased from 633 (539) pg·mL⁻¹ to 1,362 (557) pg·mL⁻¹ (p < 0.01), while mature SPB increased from 5,587 (3,089) ng·mL⁻¹ to 20,307 (19,873) ng·mL⁻¹ (p < 0.01). RAGE and mature SPB returned to normal values within 48 h. This behaviour was confirmed when RAGE and SPB were normalised for protein content. Parallel changes were observed for immature SPB. Plasma RAGE and SPBs are sensitive and rapid markers of lung distress.

Is Cupressus sempervirens native in Italy? An answer from genetic and palaeobotanical data.

This study represents the first large-scale analysis using nuclear molecular markers to assess genetic diversity and structure of Cupressus sempervirens L.. Genetic and fossil data were combined to infer the possible role of human activity and evolutionary history in shaping the diversity of cypress populations. We analysed 30 populations with six polymorphic nuclear microsatellite markers. Dramatic reductions in heterozygosity and allelic richness were observed from east to west across the species range. Structure analysis assigned individuals to two main groups separating central Mediterranean and eastern populations. The two main groups could be further divided into five subgroups which showed the following geographical distributions: Turkey with the Greek islands Rhodes and Samos, Greece (Crete), Southern Italy, Northern Italy, Tunisia with Central Italy. This pattern of genetic structure is also supported by SAMOVA and Barrier analyses. Palaeobotanical data indicated that Cupressus was present in Italy in the Pliocene, Pleistocene and Holocene. Furthermore, our molecular survey showed that Italian cypress populations experienced bottlenecks that resulted in reduced genetic diversity and allelic richness and greater genetic differentiation. Recent colonization or introduction may also have influenced levels of diversity detected in the Italian populations, as most individuals found in this range today have multilocus genotypes that are also present in the eastern range of the species. The data reveal a new interpretation of the history of cypress distribution characterized by ancient eastern populations (Turkey and Greek islands) and a mosaic of recently introduced trees and remnants of ancient, depauperate populations in the central Mediterranean range.

Increased QT variability in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

BACKGROUND AND PURPOSE: Although sudden death (SD) accounts for numerous cases of premature mortality in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the risk factors responsible for this dramatic event remain unclear. We sought possible differences in the QT variability index (QTVI) -- a well-known index of temporal dispersion in myocardial repolarization strongly associated with the risk of SD -- between a group of patients with CADASIL and healthy controls. METHODS: A total of 13 patients with CADASIL and 13 healthy volunteers underwent a 5-min electrocardiogram recording to calculate the QTVI. All the patients also underwent a clinical assessment, including functional status by Rankin score, and a magnetic resonance imaging (MRI) brain scan for quantitative analysis of T2-weighted (T2-W) and T1-weighted (T1-W) lesion volume (LV). RESULTS: Short-term QT-interval analysis showed significantly higher QTVI (P = 0.029) in patients than in controls. In patients, notwithstanding the limitations of the small sample size, QTVI also well correlated with T1-W LV (r = 0.747, P = 0.003) and T2-W LV (r = 0.731, P = 0.005). CONCLUSION: Because patients with CADASIL have increased temporal cardiac repolarization variability as assessed by QTVI, this mechanism could underlie these patients' risk of SD. Whether this easily assessed, non-invasive marker could be used to stratify the risk of malignant ventricular arrhythmias in patients with CADASIL and, possibly, to guide their therapeutic management warrants confirmation from larger prospective studies.

The distribution of Quercus suber chloroplast haplotypes matches the palaeogeographical history of the western Mediterranean.

Combining molecular analyses with geological and palaeontological data may reveal timing and modes for the divergence of lineages within species. The Mediterranean Basin is particularly appropriate for this kind of multidisciplinary studies, because of its complex geological history and biological diversity. Here, we investigated chloroplast DNA of Quercus suber populations in order to detect possible relationships between their geographical distribution and the palaeogeographical history of the western Mediterranean domain. We analysed 110 cork oak populations, covering the whole distribution range of the species, by 14 chloroplast microsatellite markers, among which eight displayed variation among populations. We identified five haplotypes whose distribution is clearly geographically structured. Results demonstrated that cork oak populations have undergone a genetic drift geographically consistent with the Oligocene and Miocene break-up events of the European-Iberian continental margin and suggested that they have persisted in a number of separate microplates, currently found in Tunisia, Sardinia, Corsica, and Provence, without detectable chloroplast DNA modifications for a time span of over 15 million years. A similar distribution pattern of mitochondrial DNA of Pinus pinaster supports the hypothesis of such long-term persistence, in spite of Quaternary climate oscillations and of isolation due to insularity, and suggests that part of the modern geographical structure of Mediterranean populations may be traced back to the Tertiary history of taxa.

Recombinant interferon alpha-2b in the treatment of diffuse malignant pleural mesothelioma.

Fourteen patients with diffuse malignant pleural mesothelioma (DMPM) were enrolled in a Phase II study to assess activity and toxicity of the systemic administration of recombinant (r)-alpha-interferon (IFN)-2b. The IFN schedule was: 3 x 10(6) IU i.m. days 1-4, 6 x 10(6) IU days 5-8, 10 x 10(6) IU days 9-12; then IFN was administered at 10 x 10(6) IU 3 days/week. If grades II-III toxicity occurred, IFN dose was reduced and drug continued at the previous dose level. All patients were evaluated by CT scan. Only one patient was not evaluable for response and toxicity because of inadequate follow-up. Of 13 evaluable patients, we observed 1 objective response, 6 stable disease, and 6 failures (3 progressive disease and 3 early interruptions due to subjective toxicity). The median time to progression was 19 weeks, and the median overall survival was 62 weeks. Toxicity was mild: of 13 patients evaluable for toxicity we observed fever (9 patients), flu-like syndrome (3 patients), fatigue (4 patients), anorexia (2 patients), myelosuppression (3 patients), and muscle pain (1 patient). The results of this study indicate only marginal activity of r-alpha-IFN in the treatment of DMPM.

[Morphine in the inferior cerebellar cisterna for oncologic pain in the ORL area]. / Morfina in cisterna cerebellare inferiore per le algie oncologiche della sfera ORL.

The study aimed to assess whether the infusion of microdoses of morphine in the cisterna magna, close to the sensitive nuclei of the cranial nerves (V-VII-IX-X) involved in painful syndromes of the head and neck, is able to control severe oncological pain in this region which does not respond to traditional pain killing treatment or neurolesive practices. Cisternal catheters were inserted in eight patients with cancer of the head and neck. The intensity of pain was assessed using VAS and the quality of analgesia obtained using cisternal morphine was judged to be: excellent, good, inadequate or null. Treatment lasted a mean of 121 days. Good or excellent analgesia was achieved in 7 patients using a mean daily dose of 1.5 mg morphine during the initial stage and 4.8 mg during the final stage; in one patient with a large component of "deafferent pain", good pain relief was obtained by associating cisternal morphine with chlorimipramin per os. The side-effects observed were almost always short-term and easily resolved. Morphine treatment was begun in the hospital and in all cases continued at home. This efficacious pain killing method should be given adequate attention in the global strategies used to treat oncological pain in the head and neck region.

Head and neck cancer and ageing: a retrospective study in 438 patients.

To evaluate whether age over 70 years represents a prognostic factor in head and neck cancer, we reviewed all cases observed between 1981 and 1984. Four hundred and thirty-eight (438) patients were considered in relation to three age groups (less than or equal to 59, 60-69, and greater than or equal to 70 years, defined as non-elderly, mid-elderly and elderly respectively). The main parameters analyzed included histological diagnosis (no difference emerged among the three age groups); anatomical site (hypopharyngeal carcinoma was most frequent in non-elderly patients); TNM stage (an higher incidence of early stages was seen in the elderly); performance status (better in the non-elderly); previous illnesses (life-style related diseases were more frequent in the non-elderly); contraindications to surgery (more frequent in the elderly); surgical treatment ('en bloc' resections were more often employed in the non-elderly); post-operative complications and local control (no difference between the three groups); multiple primary malignancies (head and neck, oesophagus and lung were more frequent in non-elderly patients) and survival (no difference). Although age affects several features of head and neck cancer patients, it does not appear from the present study to be an independent prognostic factor for local control and survival. With regard to survival, stage appeared to be the most important prognostic factor.

Combined radiotherapy and chemotherapy versus radiotherapy alone in locally advanced epidermoid bronchogenic carcinoma. A randomized study.

Between June 1980 and December 1983, 111 patients with inoperable epidermoid bronchogenic carcinoma (limited disease) were entered into a randomized trial comparing radiotherapy alone versus radiotherapy and combination chemotherapy with cyclophosphamide, Adriamycin (doxorubicin), methotrexate, and procarbazine. Thirty-five of 62 (56.4%) patients treated with 4500 rad in 15 fractions in 3 weeks and 19 of 49 (38.8%) patients treated with the same radiation treatment and chemotherapy had an objective response. The difference in response rate was not significant (P = 0.900). Median time to progression was 5.9 and 7.02 months, respectively, for the radiation treatment and the combined treatment. Median survival was 11.74 and 10.03 months, respectively, without statistically significant differences between the two groups of patients. The toxicity was acceptable and no treatment-related death occurred in either treatment schedule. In this study no significant superiority of combined radiotherapy and chemotherapy treatment over radiation therapy alone was evidenced. Whether different chemotherapy regimens may prove more effective in this context should be clarified by further studies.

Medical treatment of metastatic renal cell carcinoma.

Thirty five patients with metastatic RCC were observed over a 57 months period in our Division of Radiotherapy and Medical Oncology, and 30 are evaluable for this analysis. MPA was selected as primary treatment agent in 23 patients, VLB singly, in combination with MPA or in combination with CCNU was used in 1.4 and 2 patients. With MPA the TR rate was 3/23 (1 CR and 2 PR). Duration of response for the patient with CR was 6 months whereas for the patients with PR was 21 and 14 months respectively. 4 additional patients showed NC. With VLB-MPA the TR rate was 1/+ (1 PR). Duration of PR was 3 months. The median duration of survival for the 11 patients with CR, PR and NC was 14 months whereas for the 19 patients with NR was 7 months (p < 0.01). TES and TAM showed no or minimal activity as second treatment agents.

[Method for the characterization of peripheral lymphocytes in humans and their significance]. / Metodica per la caratterizzazione dei linfociti periferici nell'uomo e loro significato.

The Authors describe a technique for the identification of the lymphocytic subpopulations of peripheral human blood. It is pointed out the importance of using iron powder, AET, 20 hours incubation. The percentages of cells forming E rosets in patients suffering of acute lymphatic leukaemias and in normal subjects is valued.

Clinical and immunological evaluation of 5 cases of mycosis fungoides in advanced stages.

Five patients with mycosis fungoides, hospitalized in the Division of Radiotherapy and Medical Oncology of the Ospedale Civile, Pordenone, from January 1975 to December 1978, were studied and treated as non-Hodgkin lymphomas. All patients had evidence of disseminated disease: 3 with bone marrow infiltration, 1 with splenic involvement and 1 with lymph node involvement. Three patients were treated with CVP, resulting in 2 complete remissions that lasted 18 months and 1 PR greater than 50% maintained for 7 months. One patient was treated with ABVD with a PR greater than 50% maintained for 10 months. The last patient was treated with prednisone and then with CV, but expired from pulmonary embolism after 1 cycle. Lymphocyte function, using E and EAC rosette and PHA, was evaluated before therapy in all patients: in the 2 patients who obtained a CR, an improvement in T-lymphocyte function was noted after therapy. The chromosome pattern of peripheral blood lymphocytes was altered before therapy in only one patient. Even if the follow-up period is still relatively brief, the duration of the 2 complete remissions must be stressed. In addition, a strict correlation between T-lymphocyte function and response to therapy was revealed in our study.