Bisphenol A disrupts granulosa cell function.

Because of its widespread use and potential adverse biological effects, bisphenol A (BPA) represents one of the most studied endocrine-disrupting compounds. Within the reproductive system, ovarian granulosa cells have been documented as a target of BPA action, but no consensus has been reached about functional modifications induced by BPA. On these bases, we studied the potential disrupting effects of BPA on the main granulosa cell functional activities, also taking into account a potential interference with the ovarian angiogenic process. Ovarian granulosa cells were isolated from porcine follicles and cultured in the presence or absence of BPA at different concentrations for 48h. Cell proliferation was studied by measuring adenosine triphosphate content. Progesterone (P4) and estradiol 17beta (E2) production was determined by radioimmunoassay. Vascular endothelial growth factor (VEGF) output was quantified by an enzyme-linked immunosorbent assay. Redox status was monitored by measuring superoxide anion and hydrogen peroxide, and by determining the activities of the scavenging enzymes superoxide dismutase, catalase, and peroxidase by colorimetric methods. Granulosa cell proliferation as well as redox status resulted unaffected by BPA. Concentrations of E2 were stimulated by the lower BPA concentration, whereas they were inhibited by the larger doses tested. P4 output was decreased by all BPA concentrations. To the contrary, VEGF production was stimulated. Data indicate that BPA can interfere with reproductive activity by affecting granulosa cell steroidogenesis in vitro; furthermore, BPA can exert a promoting effect on the ovarian angiogenic process by increasing VEGF output in pigs. A disruption of this finely tuned process seems particularly relevant because of the risk of uncontrolled neovascularization.

Myocardial infarction with normal coronary arteries in a patient with primary antiphospholipid syndrome--case report and literature review.

Primary antiphospholipid syndrome is associated with an increased risk of vascular thrombosis. The authors describe a young patient without any risk factor for coronary artery disease who was admitted to the hospital because of a transient cerebral ischemic attack. Standard EKG showed signs of a previous silent inferior wall myocardial infarction, confirmed by echocardiography, technetium-99 scintigraphy, and left ventricular angiography. Coronary arteries appeared normal at angiography. Blood tests showed the presence of antiphospholipid antibodies and lupus anticoagulant. Since there is evidence that these antibodies are associated with an increased risk of microvascular thrombosis, the authors conclude that this silent myocardial infarction could be caused by a cardiac microvascular disease accompanying the antiphospholipid syndrome.

Heart rate variability in Parkinson's disease patients treated with tolcapone.

Following the introduction of tolcapone, a potent, reversible Catechol-O-methyltransferase (COMT) inhibitor, it has been possible to optimise the management of Parkinson's disease (PD) patients in chronic Levodopa (L-dopa) therapy. The interaction between tolcapone and the endogenous metabolism of catecholamines points to a possible influence on autonomic cardiovascular function.Cardiovascular reflexes have been analysed in a group of seven PD patients (four males, three females; mean age 69.7years, mean disease duration 14.1years) by means of the heart rate variability (HRV) method using a continuous 24-h ECG (ECGD), before and after six months of treatment with tolcapone (in addition to L-dopa).We have observed no statistically significant differences in HRV parameters, nor any changes in the incidence of hyperkinetic and hypokinetic arrhythmias, which suggest that autonomic cardiovascular function in PD patients is not influenced by six months of treatment with tolcapone.

Technetium-99m sestamibi single-photon emission tomography detects subclinical myocardial perfusion abnormalities in patients with systemic lupus erythematosus.

In patients with systemic lupus erythematosus, involvement of the cardiovascular system is the third leading cause of death. However, although autopsy studies have demonstrated a high incidence of abnormalities in both the myocardium and coronary vessels, clinical manifestations have been reported in only a small percentage of cases. The aim of this study was to evaluate myocardial perfusion in asymptomatic lupus patients using technetium-99m sestamibi single-photon emission tomography (SPET). Twenty-eight patients without overt cardiac involvement and risk factors were studied with 99mTc-sestamibi SPET at rest and after dipyridamole infusion. Perfusion abnormalities were detected in 18 cases: six had persistent defects, three had reversible defects, seven had both persistent and reversible defects, and two showed rest defects which normalized on dipyridamole images ("reverse redistribution pattern"). Coronary angiography was performed in eight patients with positive 99mTc-sestamibi SPET, and showed normal epicardial vessels in all the cases. These results indicate that 99mTc-sestamibi SPET reveals a high prevalence (18 out of 28 patients in this study, i.e. 64%) of myocardial perfusion abnormalities in asymptomatic lupus patients, probably due to the primary immunological damage of this autoimmune disease. In conclusion, rest/dipyridamole 99mTc-sestamibi SPET can be a useful non-invasive method to identify subclinical myocardial involvement in systemic lupus erythematosus, and patients potentially at risk of later cardiac events.

Twenty-four-hour heart rate variability to assess autonomic function in Parkinson's disease.

OBJECTIVES: To evaluate the autonomic dysfunction in Parkinson's disease patients by means of a 24-h heart rate variability (HRV) method. MATERIAL AND METHODS: Thirteen patients with a diagnosis of Parkinson's disease were compared with 13 age-matched healthy persons (control group). The 13 patients had a mean age of 70.5 years, and mean disease duration of 10.9 years. The autonomic function was evaluated by HRV analysis using a continuous 24-h ECG. The parameters of SDNN (standard deviation of the normal-to-normal intervals between adjacent QRS complexes), of LF (power in low frequency) and of HF (power in high frequency) were studied during the following 3 periods: 24 h, night and day. RESULTS: The data show a statistically significant difference between groups for SDNN and LF in all the periods, while for HF parameters the difference is statistically significant only in the night period. CONCLUSION: The use of the 24-h HRV method can provide more accurate and reproducible data than other conventional cardiovascular tests.

Lupus carditis: evaluation with technetium-99m MIBI myocardial SPECT and heart rate variability.

The objective of this paper was to investigate the incidence of myocardial perfusion defects in patients with systemic lupus erythematosus (SLE) associated with dysautonomic alterations. Twenty patients without any sign or symptoms of heart disease, selected from a larger population of patients with SLE, underwent technetium-99m sestamibi (Tc-99m MIBI) single photon emission computed tomography (SPECT), at rest and after dipyridamole infusion; they also underwent heart rate variability (HRV) examination by a 24 hour ambulatory electrocardiography, analyzing in the time domain the standard deviation of the R-R intervals average (SDNN) and the percentage of R-R adjacent intervals differing from each other more than 50 msec (pNN50); in the frequency domain the low (LF) and high frequencies (HF) were analyzed. Twenty healthy volunteers served as control group for heart rate variability. At MIBI-SPECT examination, the scan was found abnormal in 15 patients and normal in five: three patients demonstrated reversible defects in the anteroseptal region, four had irreversible defects in a region (two in the anteroseptal region and two in the lateral region), two had rest defects in two different regions (lateral and inferior, lateral and anteroseptal) that improved during dipyridamole scan, and six had both reversible and irreversible defects: four in a single segment (three anteroseptal and one lateral, and two in two different regions, particularly anteroseptal and lateral, lateral and inferior). All 20 patients showed significantly lower HRV parameters in comparison with the control group, except for pNN50, which indicates decreased physiologic periodic fluctuations of the autonomic nervous system. In six patients who underwent coronary angiography, the epicardial vessels were found completely normal. In view of the high incidence of myocardial hypoperfusion in patients with HRV alterations, the authors hypothesize that autonomic dysfunction may be associated with microvascular disease or metabolic alteration. They also believe that MIBI scintigraphy is a suitable technique in detecting myocardial damage in SLE patients free of clinical manifestation.

Tobacco smoke in the development and therapy of periodontal disease: progress and questions.

In recent years, epidemiological studies have pointed to a significant correlation between cigarette smoke and poor periodontal status. Cigarette smoking is a significant risk factor for the onset and development of periodontal disease, and an association between reduced healing response subsequent to periodontal therapies and cigarette smoking has been found. The epidemiological studies reported here are also supported by the results of an in vitro study on the cytotoxicity of two of the volatile components of cigarette smoke that we ourselves conducted, in which the investigated compounds were found to damage human gingival fibroblasts. We concluded that this damage would be reflected in periodontal health and could slow down wound healing. Patients should thus be alerted by clinicians to the risks smoking poses to oral and dental health.

[Primary non-Hodgkin's lymphoma of the intestine associated with asymptomatic celiac disease in adults]. / Linfoma non-Hodgkin primitivo dell'intestino associato a malattia celiaca asintomatica dell'adulto.

Celiac disease (CD), a gluten-induced enteropathy, is characterized by typical intestinal involvement with classical clinic features in childhood and less frequent features in adult patients. Recognizing pauci- and asymptomatic patients is a critical point in the clinical management of CD because of the high mortality associated with the onset of complications. Among these, malignant diseases are the most severe, particularly squamous cell carcinoma and lymphoma, the latter accounting for 50% of all malignancies occurring in CD patients. The authors describe a 57 years old patient with CD and Enteropathy-Associated-T-Cell Lymphoma, who had no intestinal symptoms but only severe pruritus and hypereosinophilia.

[The onset of syndrome X in old age]. / Insorgenza della sindrome X in età geriatrica.

There is evidence that angina-like chest pain associated with normal coronary angiography (syndrome X) may appear in adult patients. We have reviewed the clinical documentation of all the patient aged 65 or more admitted to our hospital because of recent onset typical or atypical angina, who underwent an exercise tolerance test and coronary angiography. Exclusion criteria were ischaemic or valvular heart disease and significant arterial hypertension. The selection lead to a series of 11 patients (6 females, 5 males) aged 65-72 years (mean 69). The bicycle ergometric test was positive in 7 and negative or not diagnostic in 2 patients each. Thallium-201 scintigraphy (performed in 6 patients) revealed reversible perfusion defects in 4 and was equivocal in 2 patients. At coronary angiography 6 patients showed non obstructive lesions (range: 20-40%) and only 5 had normal findings: 2 of these patients showed gastro-intestinal disease which could be considered as possible trigger of chest pain. Thus only 3 patients fulfilled the criteria for a diagnosis of syndrome X. These were 2 females and 1 male and were followed-up for a minimum of 2 years. All were in good condition, with normal left ventricular function free of major cardiac events, although occasional chest pain was still present. We conclude that syndrome X may appear also in the elderly with the same clinical features already described in younger patients. The overall prognosis is good and symptoms are partially insensitive to standard therapy. The low incidence in the older age may be explained, in our series, also by the restricted criteria adapted to select the study population.

[The role and chronobiometric study of ambulatory arterial pressure monitoring in hypertensive patients with a recent cerebral ischemia episode]. / Ruolo e studio cronobiometrico del monitoraggio ambulatoriale della pressione arteriosa in pazienti ipertesi con recente episodio ischemico cerebrale.

Essential hypertensive patients with a history of recent TIA syndrome were investigated by ambulatory blood pressure monitoring (ABPM). The aim of this trial was to verify the presence of false normotensive patients in order to optimize the secondary prevention of hypertensive cerebrovascular damage (ischemic or hemorrhagic stroke). This study was carried out on 51 patients (26 M and 25 F, mean age = 58 +/- 14 yrs) and 225 clinically healthy control subjects (113 M and 112 F, mean age = 55 +/- 12 yrs), who underwent an ABPM. The BP time series were analyzed by chronobiometric procedures. The comparison of the individual BP within-day values to the reference limit revealed a highly significant proportion of these patients (90%) whose hypertension was not well controlled. Their BP series showed supranormal values ranging from 39% to 56% of all the readings, with a pressure excess ranging from 8.35 h to 11.34 h. The high incidence of not adequately treated patients with a history of recent TIA syndrome confirms that their hypertension should be controlled by means of the ABPM. These results suggest that the chronomodulation of the antihypertensive treatment might be the better management of BP regimen in these patients for the secondary prevention of cerebrovascular damage.

[Heart and autonomic nervous system in connective tissue disorders]. / Cuore e sistema nervoso autonomo nelle connettiviti.

UNLABELLED: Heart rate variability (HRV) is a suitable diagnostic tool in identifying patients with autonomic nervous system (ANS) disorders even in pre-clinical stage. We have enrolled in this study all patients with large variety of connective tissue disorders, given the possibility of an involvement of ANS in these diseases. The study population consisted in eighty-five patients (68 females and 17 males), 35 of whom affected by systemic lupus erythematosus, 16 by rheumatoid arthritis, 14 by Sjögren syndrome, 12 by progressive systemic sclerosis, 3 by Behçet syndrome and 5 by antiphospholipid antibodies syndrome. The mean age ranged between 33.7 of patients with lupus erythematosus and 51.8 of those with Sjögren syndrome. As control, we enrolled healthy subjects of different age, divided into two groups, to rule out the aging as potential source of considered parameters alteration. The autonomic function has been evaluated by 24 hours ambulatory monitoring, using a Zymed 1210 Scanner with Zymed 3.74-PC 1990 software. We have considered: in the time domain, the standard deviation of the RR intervals average (SDNN) and the percentage of RR adjacent intervals differing each other more than 50 msec (pNN50); in the frequency domain, the low (LF) and high (HF) frequencies, the LF/HF ratio, and the total power (RT). The HRV parameters resulted abnormal in every type of the connective tissue diseases considered: particularly SDNN, pNN50, LF, HF and RT (p < or = 0.01). IN CONCLUSION: the results of our study suggest that autonomic neuropathy may be present in any kind of connective tissue disorders even in preclinical stage.

[Arrhythmias in the aged: prevalence and correlation with symptoms]. / Le aritmie nell'anziano: prevalenza e correlazione con la sintomatologia.

Objective of our study was to evaluate the prevalence of arrhythmias as well as their correlation with the reported anamnestic symptomatology in the elderly population. With 24 hour ambulatory electrocardiography (Holter ECG) 913 patients, (440 males and 473 females, range 60-89 years, mean age 71) were consecutively studied and subdivided according to the following criteria: (1) age (3 classes: 60-69 [I], 70-79 [II], > or = 80 [III]; (2) presence/absence of "guide" symptoms (syncope/faintness, chest pain, palpitation), and (3) Holter electrocardiography results. We have demonstrated a high prevalence of arrhythmias: 72% (657), which was significantly higher in age classes II (80.5%) and III (79.1%) in comparison to class I (60.6%). A notably higher prevalence of tachyarrhythmias is documented compared to bradyarrhythmias (5:1). With a higher age the prevalence of supraventricular tachyarrhythmias increases significantly, while bradyarrhythmias do not have the same trend. We have a similar prevalence of arrhythmias between symptomatic (77.4%) and asymptomatic patients (63.6%) and no significant correlation between anamnestic symptoms and presence of arrhythmias are observed. Considering the high prevalence of arrhythmias during Holter ECG we think that the clinical importance and prognosis should be evaluated with caution.

Heart rate variability and cardiac autonomic function in systemic lupus erythematosus.

The cardiac autonomic function was evaluated in 23 patients with Systemic Lupus Erythematosus (SLE) without clinical expression of dysautonomia and in 14 healthy volunteer subjects as a control group, by analysis of Heart Rate Variability (HRV) from 24h ambulatory electrocardiography. All the patients were taking corticosteroids and 10 of them also Ciclosporin A (CsA). The following parameters of HRV were performed: Time domain: standard deviation of the RR intervals average (SDNN) and percentage of RR adjacent intervals differing from each other more than 50 msec (pNN50). Frequency domain: low frequencies (LF) and high frequencies (HF). Significant lower values were detected in SLE patients vs controls: SDNN = 69.40 vs 127.72; pNN50 = 16.44 vs 25.95; LF = 8.34 vs 34.97; HF = 3.21 vs 12.18. The incidence of autonomic dysfunction in our SLE population evaluated by considering intervals of normality is approximately 78% for SDNN; 17% for pNN50; 91% for LF and, finally, 56% for HF. The analysis of HRV may be a valuable technique in the study of the incidence of dysautonomia for these patients.

[The onset of dilated cardiomyopathy in a female HIV-seropositive patient with a history of past peripartal myocarditis]. / Insorgenza di miocardiopatia dilatativa in paziente sieropositiva per HIV con storia di pregressa miocardite peri-partum.

A case of a young woman with HIV-associated cardiomyopathy is reported. The patient had a history of peri-partum myocarditis, and underwent a blood transfusion during delivery. The very early cardiac manifestation of AIDS-related pattern in this case is underlined, since HIV cardiomyopathy usually develops in the late stage of the disease. Finally, the role of the virus in the etiology and pathogenesis of the myocarditis is discussed.

[The prevalence of arrhythmias in subjects over 80 years old. The prognostic role of anamnestic symptomatology and the therapeutic directions]. / Prevalenza dei disturbi del ritmo in soggetti di oltre 80 anni. Ruolo predittivo della sintomatologia anamnestica e orientamenti terapeutici.

24-hour Holter monitoring was performed in 129 unselected subjects older than 80 years (69 women and 60 men) in order to evaluate arrhythmia incidence and to establish significance of symptoms; 56% patients had lipothymia and/or syncope, chest pain and palpitations, 44% were asymptomatic. All patients showed high incidence of hyperkinetic and hypokinetic arrhythmias; no significant differences between symptomatic and asymptomatic patients in arrhythmia incidence were seen. Moreover, no correlation could be seen of the symptoms reported by the patient to the incidence of any particular type of arrhythmia. In conclusion, these preliminary data suggest a criticism of the opportunity of indiscriminate and long term antiarrhythmic therapy. Nevertheless, Holter monitoring is useful in detecting hypokinetic arrhythmias of asymptomatic patients in whom pacemaker implantation is essential and curative.

[Introductory notes on the origin of phrenology: the work of Vincenzo Malacarne]. / Considerazioni preliminari sull'origine della frenologia: l'opera di Vincenzo Malacarne.

The authors examine and evince the links between F.J. Gall's phrenology and Vincenzo Malacarne's studies of encephalous anatomy and mental disorders, especially in the ideas developed by the latter from 1760 to 1794. Malacarne came to believe in those years that mental disorders were organic in nature, being exhibited through alterations in the endocranium organs that could be anatomically detected and diagnosed by studying the patient's cranium. His correspondence with Bonnet enabled Malacarne to anticipate Gall in positing that the faculties of the intellect are congenital and those of the endocranium are organs consisting of individual parts each of which controls a specific intellectual activity. This in turn strengthened Malacarrne's conviction that the cranium's structure matched the development of its parts and led him to invent the cephalometer. Thus convinced of the compound nature of the endocranium's organs, Malacarne went on to develop Bonnet's thesis whereby the peculiarity of the nerve cells and their interaction were assigned a central role in intellectual activities. Yet, despite the evident fact that Malacarne attributed to the cerebellum functions proper to the brain, the points at which his and Gall's ideas overlapped were such as to make ambiguous the former's violent polemics against the latter. Many of the cricticisms he directed at Gall seemed to be dictated by Malacarne's desire to side with Napoleon's and the Catholic Church's condemnation of the former. Others showed that Malacarne wove together personal motives, especially irritation over Gall's outright rejection of his Encefalotomia and scientifically well-grounded criticism of Gall's erroneous ideas concerning the substance of the cortex and the latter's links to nerves, to name the most prominent of many such errors. Even more damaging was Malacarne's unfounded allegation that Gall had less than a thorough grasp of anatomy in that it led the Italian medical establishment to view phrenology as a popular science for many decades thereafter.