Polyclonal expansion of CD3(+)/CD4(+)/CD56(+) large granular lymphocytes and autoimmunity associated with dysregulation of Fas/FasL apoptotic pathway.

Evidence is accumulating regarding CD95/CD95 ligand (Fas/FasL) pathway dysregulation in clonal diseases of the lymphohaemopoietic lineages. According to these observations, it has been proposed that this defect may represent one of the mechanisms of tumour progression. In large granular lymphocyte (LGL) leukaemia, dysregulated apoptosis may represent a key event in the development of malignancy and autoimmunity. This case report describes dysregulation of the Fas/FasL pathway in a chronic polyclonal expansion of CD3(+) LGLs associated with numerous serological immune abnormalities.

[Relationship among VIP plasma levels, esophageal dysfunction, and microcirculation in systemic sclerosis]. / Rapporti fra livelli plasmatici di VIP, disfunzione esofagea e del microcircolo in corso di sclerosi sistemica.

BACKGROUND: Recent studies suggest that esophageal dysmotility occurring in systemic sclerosis might be caused by neurotransmitter levels decrease. The aim of the present study is to value VIP plasma levels, and to relate them with the pressure of the inferior esophageal sphincter (IES) and the capillaroscopy score in a group of patients affected by Systemic Sclerosis (SSc). METHODS: Eleven subjects affected by SSc (eight male and three female, age from 30 to 72 years old) have been studied through esophageal manometry, capillaroscopy and VIP plasma levels evaluation. Fifteen healthy volunteers, as control group, have been enlisted. RESULTS: Our results show a decrease of VIP plasma levels in patients with SSc compared with control group. The difference between two groups has statistical significance (p < 0.01). Capillaroscopy has shown remarkable microcirculatory impairment and the esophageal manometry proved a decreased IES pressure. The scores of capillaroscopy, VIP plasma levels and pressures of IES have been compared and it has been observed that there is a relationship between VIP plasma level and pressure of IES. CONCLUSIONS: VIP plasma levels decrease enhances the role of the autonomic disorder in SSc and may contribute to produce the alteration of vascular tone as well as the gastroenteric musculature dysfunction.

The chaotic component of human heart rate variability shows a circadian periodicity as documented by the correlation dimension of the time-qualified sinusal R-R intervals.

OBJECTIVE: This study investigates the hypothesis that the nonlinear component of human heart rate (HR) variability might show a periodic structure over the 24-h span. Such a postulate could explain how the chaotic component might coexist with the deterministic periodic variability of instantaneous HR in beat per minute. MATERIALS AND METHODS: The sinusal R-R intervals (sRRi) of the Holter EKG of 10 clinically healthy subjects (5 M, 5 F, 23-30 years) were analyzed per each hour of the day-night span according to two methods for the nonlinear chaotic variability, i.e., the correlation dimension method, and the linear periodic variability, i.e., periodic regression analysis. RESULTS: The hourly-qualified correlation integrals were found to show a significant circadian rhythm, with an acrophase located during the night in coincidence with the longest duration of the sRRi and the lowest rate of cardiac pulse. CONCLUSIONS: The rhythmic structure of the chaotic component of the human HR variability let us to think that a deterministic periodic chaos of fractal type regulates the nonlinear cardiac dynamics. Such a periodic structure allows the chaos to be compatible with the deterministic linear periodicity of circadian type which characterizes the within-day variability of human HR.

[The heart rate variability indices and the circadian rhythm of the hourly heart rate: 2 prognostic indicators of mortality and malignant ventricular arrhythmias in patients with a myocardial infarct]. / Indici di variabilità della frequenza cardiaca e ritmo circadiano della frequenza cardiaca oraria: due indicatori prognostici di mortalità e di aritmie ventricolari maligne nei pazienti con infarto miocardico.

The aim of this study was to investigate the circadian variability of heart rate in acute myocardial infarction (AMI) in identifying patients at high risk for malignant ventricular arrhythmias (MVA) and sudden death within 1 year of the acute event. The investigation was carried out in 43 patients, who underwent 24-hour Holter monitoring within 3 months of AMI. Besides the time domain indexes of heart rate variability (SDNN, SDNN index, pNN50, rMSSD), the circadian rhythm of hourly total beats (HTB) and hourly qualified beats (HQB) has been analyzed by the Cosinor method. The AMI patients with MVA and those with MVA who died within 1 year the acute event showed SDNN, SDNN index and pNN50 values lower than subjects without MVA and survived patients with MVA, respectively; the individuals with AMI at high risk for MVA and for sudden death had an SDNN value < 105 ms and 50 ms, respectively. The circadian rhythm of HTB and HQB was statistically validated only in the group without MVA; patients without the circadian rhythm of HTB and HQB showed a higher mortality rate within 1 year of AMI, and the majority was in the group with MVA. The contemporary evidence of an SDNN value < 105 ms and the lack of HTB and HQB circadian rhythm increased sensitivity for identifying patients with MVA to 75%. On the other hand, the contemporary evidence of an SDNN value < 50 ms and the lack of HTB and HQB circadian rhythm increased sensitivity for identifying patients who died within 1 year of AMI to 100%. In conclusion, the assayed methods seem to be both useful and complementary in identifying patients at high risk for MVA and sudden death within 1 year of AMI.