Nitrate‐Potentiated Head‐Up Tilt Testing in Older Patients: Outcomes,Hemodynamic Responses and Prodrome Recognition

Background: To compare head‐up tilt testing (HUT) outcomes and hemodynamic responses, and the prevalence and correlates of prodromes, in elderly and younger patients with suspected vasovagal syncope (VVS). Methods: Consecutive outpatients with a history of recurrent unexplained syncope underwent HUT by being tilted to 70°; the test was potentiated by the administration of 300 μg of nitroglycerine after 20 minutes. Occurrence of VVS and hemodynamic responses during passive and nitroglycerine phases of HUT were evaluated; symptoms preceding HUT‐induced syncope were recorded, together with heart rate and arterial blood pressure values. Results: Four hundred and sixty of the 743 patients were HUT positive: 156 fainted during the unmedicated phase and 304 after nitroglycerine administration. The patients aged ≥65 years (n = 102) experienced VVS more frequently during the pharmacological stage of HUT; the overall rate of positive results was similar to that observed in the patients aged 36–64 years (n = 329) and only slightly lower than that observed in those aged ≤35 years (n = 312). In the older patients, who experienced fewer and mainly prodrome‐free spontaneous syncopal episodes, HUT increased the number of premonitory symptoms, and there were no significant age‐related differences in symptom prevalence or timing or the patients’ hemodynamic characteristics. Conclusions: The rate of VVS induced by nitroglycerine‐potentiated HUT is similar in elderly and younger patients. In the former, nitroglycerine‐potentiated HUT significantly increases the prevalence of prodromes in comparison with spontaneous episodes, which suggests that it may be useful not only for diagnosis but also for patient counseling. (PACE 2010; 33:1210–1216)     

Paraphenylenediamine, a contact allergen, induces oxidative stress and ICAM-1 expression in human keratinocytes

In an investigation of the role of keratinocytes in the pre-immunological phase of contact allergy, we have studied the effect of paraphenylenediamine (PPD) on cell proliferation, membrane lipid peroxidation and the expression of the intercellular adhesion molecule 1 (ICAM-1). Because PPD undergoes rapid autoxidation in the culture medium, the effect of PPD-modified medium on keratinocyte proliferation and ICAM-1 expression was also examined. PPD at low concentrations (up to 10 micrograms/ml) and with low exposure times (0.5 h) enhanced keratinocyte proliferation, but at high concentrations and with longer exposure times resulted in cell stasis and toxicity. These effects and the enhanced membrane lipid peroxidation that was also observed can be ascribed to the production of superoxide and hydrogen peroxide by the autoxidation of PPD in the medium. At non-cytotoxic concentrations, PPD induced ICAM-1 expression on the keratinocytes. PPD-modified medium was also cytotoxic to the keratinocytes and induced ICAM-1 expression in non-cytotoxic concentrations. It appeared that superoxide and hydrogen peroxide were not responsible for the cytotoxicity. These results are consistent with the view that oxidative stress may be an essential part of the pre-immunological phase in the induction of allergic contact dermatitis.     

Abnormal Cardiac Innervation in Patients with Idiopathic Ventricular Fibrillation

BIFFI, M., et al .: Abnormal Cardiac Innervation in Patients with Idiopathic Ventricular Fibrillation. Idiopathic ventricular fibrillation (VF) is diagnosed in up to nearly 10% of survivors of out-of-hospital cardiac arrest. The arrhythmogenic substrate is unknown. This study examined the role of cardiac innervation as a possible contributor to this arrhythmia. Eight patients with idiopathic VF were compared with eight normal subjects (controls) by [¹²³] I metaiodobenzylguanidine SPECT (MIBG), measuring peak uptake, late uptake, and clearance of the nuclear tracer. The left ventricle was divided in 13 segments in the bull's-eye target plot. Peak and late MIBG uptake was increased in the anterolateral segments (2,3,7,8) compared to the inferoposterior and septal segments, in controls and in patients. No difference was observed between controls and patients in the inferoposterior and septal segments. In contrast, a significantly higher MIBG uptake was observed in patients compared to controls in the anterolateral segments (   94 ± 4%   vs   81 ± 11%, P < 0.03   for peak uptake;   94 ± 5%   vs   79 ± 12%, P < 0.01   for late uptake). No difference was observed in MIBG clearance in any segment in either study group. Cardiac sympathetic innervation is highly heterogeneous, though predominant in anterolateral segments in normal subjects. Patients with idiopathic VF exhibit the same distribution, though have a significantly greater density of sympathetic terminals in the anterolateral segments than controls, which may promote ventricular arrhythmias. (PACE 2003; 26[Pt. II]:357–360)     

Friend or Foe? The Current Epidemiologic Evidence on Selenium and Human Cancer Risk

Scientific opinion on the relationship between selenium and the risk of cancer has undergone radical change over the years, with selenium first viewed as a possible carcinogen in the 1940s then as a possible cancer preventive agent in the 1960s–2000s. More recently, randomized controlled trials have found no effect on cancer risk but suggest possible low-dose dermatologic and endocrine toxicity, and animal studies indicate both carcinogenic and cancer-preventive effects. A growing body of evidence from human and laboratory studies indicates dramatically different biological effects of the various inorganic and organic chemical forms of selenium, which may explain apparent inconsistencies across studies. These chemical form-specific effects also have important implications for exposure and health risk assessment. Overall, available epidemiologic evidence suggests no cancer preventive effect of increased selenium intake in healthy individuals and possible increased risk of other diseases and disorders.     

Cardiac Resynchronization Therapy:

In patients with heart failure and wide QRS complex, cardiac resynchronization therapy (CRT) is associated with improvement of symptoms and cardiac function. This study examined the effects of a 3-month period of CRT on left ventricular (LV) and right ventricular (RV) ejection fraction (EF) and on LV volumes, both at rest and during exercise. A CRT system was implanted in 15 patients with severe heart failure and wide QRS. Before implant and 3 months later, all patients underwent assessment of cardiac performance with equilibrium Tc⁹⁹ radionuclide angiography with imaging in the best septal left anterior oblique view. Exercise was performed on a bicycle ergometer. At 3 months, a significant improvement in New York Heart Association functional class was observed, and radionuclide angiography showed a significant decrease in LV volumes and a significant increase in LVEF at rest, as well as a significant increase in LVEF during exercise. The remodeling processes associated with CRT did not appear to include RV function, since RVEF did not improve, and changes in RVEF did not correlate with changes in LVEF, neither at rest nor during exercise.     

DISTINCT mdm2/p53 EXPRESSION PATTERNS IN LIPOSARCOMA SUBGROUPS: IMPLICATIONS FOR DIFFERENT PATHOGENETIC MECHANISMS

Recent findings have indicated that TP53 inactivation in sarcomas may result from mutation and/or deletion of the TP53 gene or, alternatively, from binding to the MDM2 gene products. To investigate further a possible role of the two genes in sarcomas, 24 large and deep-seated lipomas and 74 liposarcomas of various subtypes were analysed for mdm2 and p53 overexpression by immunocytochemistry. Nineteen cases of the same series were also molecularly analysed for both MDM2 gene amplification and TP53 mutations, and a further ten cases for non-random chromosomal abnormalities. In the retroperitoneal well-differentiated–dedifferentiated (WD–DD) group, 15/16 WD and 8/8 DD liposarcomas displayed the mdm2+/p53+ phenotype, consistent with MDM2 gene amplification in the absence of TP53 mutations. In the non-retroperitoneal WD–DD group, 5/11 WD liposarcomas also retained the mdm2+/p53+ phenotype whereas all DD liposarcomas showed an immunophenotype and, when assessed, a genotype consistent with mutant TP53. Null mdm2 immunophenotype, coupled with evidence of a specific chromosome translocation t(12;16), was constantly observed in both the usual and the cellular subtypes of myxoid liposarcoma, three cases of which also showed TP53 alterations at the genetic or protein level. Neither mdm2 nor p53 overexpression was observed in the lipomas. The results show the existence of three main pathogenetically distinct groups of liposarcoma. The first retroperitoneal WD–DD group, which represents a novel class of tumours within a single histological category of sarcoma, where MDM2-mediated inactivation of p53 could be related to the pathogenetic mechanism. The second is the non-retroperitoneal WD–DD group, where the TP53 mutations appear to correlate with the dedifferentiation process. The third is the myxoid group, which is characterized by its own unique cytogenetic profile and never shows any involvement of TP53 or MDM2 genes. As for diagnostic significance, the absence of mdm2 and p53 reactivity in lipomas seems to represent a useful marker for differential diagnosis from lipoma-like WD liposarcomas. © 1997 by John Wiley & Sons, Ltd.