Correlation between clinical presentation and delayed-enhancement MRI pattern in myocarditis.

PURPOSE: The exact incidence of myocarditis is unknown, as the diagnosis is frequently delayed or missed. Clinical presentation and disease course are extremely variable, as there may be acute onset with acute coronary syndrome, or cardiogenic shock, or progressive heart failure or arrhythmias. The purpose of this study was to identify prognostic factors on magnetic resonance imaging (MRI) performed in patients with bioptically proven myocarditis at presentation and after 6 months. MATERIALS AND METHODS: Fifty-six consecutive patients with different presentations of myocarditis (20 with acute coronary syndrome, 20 with heart failure, 16 with arrhythmias) were enrolled. All patients underwent B-mode echocardiography (echo) and tissue Doppler imaging, coronarography, ventriculography, endomyocardial biopsy and contrast-enhanced MRI examination, as well as clinical and echo follow-up at 6 months. RESULTS: At 6-month follow-up, patients were divided in two groups according to values of end-systolic volume and ejection fraction: patients with negative remodelling and those with positive remodelling. Late enhancement was found to be an independent predictor of negative remodelling. CONCLUSIONS: Contrast-enhanced MRI is useful both in the diagnosis and as a prognostic indicator in the clinical suspicion of myocarditis.

Regulatory T Cells in Severe Persistent Asthma in the Era of Monoclonal Antibodies Target Therapies.

Asthma is an immunoinflammatory disease characterized by bronchial hyper-reactivity to different external stimuli. New monoclonal target treatments have been developed, but few studies have investigated the role of regulatory T cells in severe asthma and the modulatory effect of biological therapy on regulatory T cell functions. Their dysfunction may contribute to the development and exacerbation of asthma. Here we review the recent literature on the potential immunological role of regulatory T cells in the pathogenesis of severe asthma. The analysis of the role of regulatory T cells was performed in terms of functions and their possible interactions with mechanisms of action of the novel treatment for severe asthma. In an era of biological therapies for severe asthma, little data is available on the potential effects of what could be a new therapy: monoclonal antibody targeting of regulatory T cell numbers and functions.

NK and NKT-like cells in granulomatous and fibrotic lung diseases.

ABTRACT: Background The pathogenetic and regulatory roles of natural killer (NK) and natural killer T-like cells in interstitial lung diseases (ILDs), fibrotic and granulomatous of unknown etiology are unclear. Objectives Here we investigated NK and NKT-like cells in peripheral blood (PB) and Bronchoalveolar lavage (BAL) from patients with ILDs. Method 190 patients (94 male mean age 61 ± 14.3 years) and 8 controls undergoing bronchoscopy for ILD diagnostic work-up were enrolled consecutively; 115 patients sarcoidosis, 24 chronic fibrotic hypersensitivity pneumonitis and 43 patients other ILDs [32 idiopathic pulmonary fibrosis (IPF) and 11 non-specific interstitial pneumonia (NSIP)]. PB and BAL were processed by flow cytometry using monoclonal antibodies to differentiate NK and NKT-like cells. Results NK% in BAL was significantly different among ILDs (p = 0.02). Lower NK% was observed in BAL from sarcoidosis than other ILDs (p < 0.05). Similar findings were observed for NKT-like, whereas no differences were found for PB NK%. Difference of NK% was observed between BAL and PB in all groups (p < 0.001). Sarcoidosis patients reported the best area under the curve for NKT-like (AUC = 0.678, p = 0.0015) and NK cells (AUC = 0.61, p = 0.001). In the IPF-NSIP subgroup, NK% cell was inversely correlated with FVC% (r = - 0.34, p = 0.03) and DLCO% (r = - 0.47, p = 0.0044). Conclusions NK and NKT-like were expressed differently in BAL from patients with different ILD and were significantly depleted in sarcoidosis respect to other ILDs. This suggests that these cells may play a protective role in the pathogenesis of sarcoidosis.

Exhaled carbon monoxide in sarcoidosis.

BACKGROUND: Exhaled Carbon monoxide has been proposed as a non-invasive marker in several inflammatory diseases of the lung, but no data are available in patients with sarcoidosis. METHODS: We evaluated the levels of exhaled CO in 78 nonsmoker patients with sarcoidosis and we compared the results with 25 healthy non smoker controls, of 25 patients with a variety of interstitial lung diseases, and 77 smokers. RESULTS: Mean value of exhaled CO in sarcoidosis was 3.3 (2.9-3.8) ppm (GM with 95% CI in parenthesis), resulting significantly higher than both normal controls, 1.4 (1.2-1.7) ppm (p<0.001), and clinical controls, 2.1 (1.7-2.7) ppm (p<0.02). All these levels, however, were markedly lower than those observed in smokers, 14.6 (12.7-16.9) ppm. No correlation was found with radiological stage, steroid therapy, respiratory function, or serum ACE activity. Using an upper normal value of 4 ppm, an increased level of exhaled CO was found in 50% of patients with sarcoidosis, in 24% of clinical controls, and in 97% of smokers. CONCLUSIONS: Our data indicate that significant release of endogenous CO occurs in sarcoidosis. It is unlikely that the measurement of exhaled CO could be of diagnostic usefulness, due to its low specificity and to the possible influence by occasional or passive smoke.

Immunosuppressive treatment of chronic non-viral myocarditis.

Inflammatory cardiomyopathy defined as myocarditis associated with cardiac dysfunction, represents a main cause of heart failure. Despite the improvement of diagnostic techniques, a specific standardized treatment of myocarditis is not yet available. The immunohistochemical detection of myocardial HLA up-regulation has been demonstrated useful in the identification of a sub-group of autoimmune inflammatory dilated cardiomyopathy (DCM) in part susceptible to immunosuppression. Recently, in a retrospective study, we defined the virologic and immunologic profile of responders and non-responders to immunosuppressive therapy of active lymphocytic myocarditis and chronic heart failure in patients who had failed to benefit from conventional supportive treatment. Non-responders were characterized by high prevalence (85%) of viral genomes in the myocardium and no detectable cardiac autoantibodies in the serum. Conversely, 90% of responders were positive for autoantibodies, while only 3 (15%) of them presented viral particles at PCR analysis on frozen endomyocardial tissue. With regard to the type of virus involved in non-responders, enterovirus, adenovirus, or their combination was associated with the worst clinical outcome. Hepatitis C virus (HCV) was the only viral agent of our series associated with detectable cardiac autoantibodies, suggesting a relevant immunomediated mechanism of damage by HCV and explaining the relief of myocardial inflammation after immunosuppressive treatment. The assessment of virologic and immunologic features of patients with biopsy-proven inflammatory cardiomyopathy may allow us to identify a specific treatment leading to recovery of cardiac function.

Inflammatory left ventricular microaneurysms as a cause of apparently idiopathic ventricular tachyarrhythmias.

BACKGROUND: We sought to investigate the arrhythmogenic role, incidence, treatment, and prognosis of inflammatory left ventricular (LV) microaneurysms in patients with apparently idiopathic ventricular tachyarrhythmias. Methods and Results-- We studied 156 consecutive patients (71 men, 85 women; mean age, 44.1+/-11.8 years) with severe ventricular arrhythmias and normal 2D echo cardiac parameters by coronary and ventricular angiography, biventricular endomyocardial biopsy, and electrophysiological study. Polymerase chain reaction was used to detect genomic sequences of enterovirus, adenovirus, Epstein Barr virus, cytomegalovirus, herpes simplex viruses, influenza A and B viruses, and hepatitis C virus in frozen endomyocardial samples. Of these patients, 15 (9.6%) showed angiographic evidence of single or multiple LV microaneurysms. All 15 patients had recurrent episodes of ventricular tachycardia with right bundle-branch block morphology, and the arrhythmias originated within or close to the aneurysms in those patients (n=6) undergoing ventricular mapping. A lymphocytic myocarditis was observed in LV biopsies of all patients and in the right ventricles of 3 patients. Polymerase chain reaction analysis was performed in 12 and viral genomes were found in 5 (42%): hepatitis C virus in 2, enterovirus in 2, and influenza virus A in 1. The patients were treated with antiarrhythmics, and cardiac function was preserved for the next 47+/-39.5 months of follow-up. No major clinical event was registered, and arrhythmias were successfully treated by antiarrhythmics. CONCLUSIONS: Inflammatory LV microaneurysms, often of viral origin, are a consistent cause of apparently idiopathic ventricular arrhythmias. Their prognosis so far has been benign, and aggressive therapeutic strategies have been unnecessary.

Efficacy and tolerability of nimesulide in asthmatic patients intolerant to aspirin.

Inflammation of the airways accompanied by eosinophil infiltration appears to play a fundamental role in the pathogenesis of bronchial asthma. Therefore, anti-inflammatory agents (at present corticosteroids, cromoglycate and nedocromil) are the first-line treatment for this condition. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin (acetylsalicylic acid) and indomethacin, however, have never been used in this setting, mainly for fear of adverse effects (e.g. severe obstructive reactions); these can occur, in a consistent number of patients as a consequence (according to the most widely accepted theory) of inhibition of prostaglandin synthesis. In a double-blind crossover placebo-controlled study involving 20 aspirin-sensitive patients with asthma, we found that oral nimesulide 100mg was well tolerated both clinically and functionally (no significant changes in forced expiratory volume in 1 second and specific airway resistance after drug intake). In a more recent study, we observed a mild obstructive reaction (easily controlled with inhaled bronchodilators) after oral administration of nimesulide 400mg to 3 patients who had previously tolerated a 100mg dose. On the basis of clinical experience, nimesulide (unlike most other NSAIDs) in the recommended doses appears to be well tolerated in aspirin-sensitive asthmatic patients. Furthermore, this distinctive anti-inflammatory agent might provide a novel approach to the treatment of bronchial asthma.

Idiopathic myocardial vasculitis presenting as restrictive cardiomyopathy.

A previously unreported case of small-vessel myocardial vasculitis presenting as restrictive cardiomyopathy and congestive heart failure is described. The hemodynamic study, showing severely increased and equalized diastolic pressures in atrial and ventricular chambers, and cardiac MRI, showing normal pericardium and ventricular endomyocardial biopsy, not including myocardial vascular component, were insufficient to make a diagnosis. This made a thoracotomy and surgical cardiac biopsy necessary. Steroids and cyclophosphamide, introduced after histologic evidence of necrotizing vasculitis, unassociated with a systemic disease, became available and improved the clinical profile and the diastolic dysfunction at two-dimensional echocardiographic Doppler analysis.

Prognostic significance of left ventricular aneurysms with normal global function caused by myocarditis.

OBJECTIVES: To evaluate the prognosis of left ventricular (LV) aneurysms with normal global function caused by myocarditis. BACKGROUND: LV aneurysms may result from idiopathic or viral myocarditis. The prognosis of inflammatory LV aneurysms when associated with a normal cardiac function is unknown. METHODS: Among 353 patients with a histologic diagnosis of myocarditis, 12 (3.3%) had single or multiple localized LV aneurysms (length, 10.6 +/- 3.1 mm; width, 7.4 +/- 4.2 mm) with normal cardiac function. Presenting symptoms were ventricular tachycardia (VT) in nine patients and unexplained chest pain in three. All patients underwent laboratory tests and noninvasive and invasive cardiac examinations, including biventricular endomyocardial biopsy. RESULTS: In all patients, LV endomyocardial biopsy specimen showed a lymphocytic myocarditis with focal intense myocytolysis or damage of intramural vessels, whereas right ventricular biopsy was diagnostic for myocarditis only in three. Serologic study suggested a viral infection in 3 patients and an immunologic disorder in 2, although it was negative in 7. Treatment included antiarrhythmics in 9 patients with VT, ss-blockers in 1 with chest pain, and immunosuppression (prednisone and azathioprine for 5 months) in 4 with active myocarditis (2 with chest pain and 2 with VT). At intermediate-term follow-up (mean, 53 months; range, 12 to 120 months), LV function was persistently normal in all patients, with an LV aneurysm occlusion being observed in two patients. All patients were asymptomatic, with no VT recurrence or major clinical events. None required implantable electrical devices or a surgical intervention. CONCLUSIONS: LV aneurysms with normal global function caused by myocarditis are an uncommon benign entity in which major therapeutic regimens are usually unnecessary.

Giant cell myocarditis responding to immunosuppressive therapy.

An unusual case of giant cell myocarditis presenting with cardiogenic shock that dramatically responded to conventional dose of steroids and azathioprine is reported. Cardiac recovery was rapid, complete (left ventricular ejection fraction rose to 55% from 10%), and was accompanied by the disappearance of the inflammatory infiltrates including giant cells in the control endomyocardial biopsy. Maintenance of the recovery at 16 months of follow-up on a low dose of azathioprine suggests that giant cell myocarditis might be a heterogeneous disease having either a negative untreatable trend necessitating cardiac transplantation, or a curable substrate responding to immunosuppressive drugs.

Protective effect of inhaled piretanide on the bronchial obstructive response to ultrasonically nebulized H2O. A dose-response study.

Inhaled furosemide prevents the obstructive response to several bronchoconstrictor stimuli in asthma. To verify whether this protective effect is also shared by other loop diuretics, we investigated the effect of inhaled piretanide on the bronchial obstructive response to ultrasonically nebulized distilled water (UNW) in ten patients with moderate, stable asthma. In a randomized, single-blind dose-response study, each subject performed an UNW test immediately after nebulization of different doses of piretanide between 12 and 48 mg or placebo. The effect of a single 40-mg dose of inhaled furosemide was also investigated in six subjects. Piretanide caused a significant, dose-dependent increase in UNW PD20 with respect to placebo, corresponding to 0.6 +/- 0.2 doubling doses (mean +/- SE) after 12 mg, 1.3 +/- 0.2 after 24 mg, and 2.0 +/- 0.2 after 48 mg, and had a remarkable diuretic effect; 40 mg of furosemide increased UNW PD20 by 2.3 +/- 0.3 doubling doses (p < 0.01), but showed only a modest diuretic activity. These data indicate that inhaled piretanide is as effective as furosemide in preventing UNW-induced asthma, and this effect is unrelated to their diuretic potency.

Coronary angiodysplasia of epicardial and intramural vessels.

A case of coronary angiodysplasia combining large aneurysms of epicardial arteries with diffuse malformation of intramural vessels is reported. Clinical presentation may mimic a vascularized cardiac tumor. Although leaking of the aneurysms in the pericardial space may occur, this entity seems to have a benign prognosis not requiring surgical repair.

Enlargement of synaptic size as a compensative reaction in aging and dementia.

A quantitative investigation has been carried out on synaptic contact zones of dentate gyrus supragranular layer and cerebellar glomeruli in autoptic samples from adult, old and demented patients. During physiological aging and senile dementia, the synaptic average area was significantly increased as compared to adult values in both the CNS areas investigated. Conversely, the number of contacts and their total surface contact area per unit volume of tissue were decreased. Current literature reports that, in animal models, enlarged synapses undergo perforations and splitting to modify synaptic connectivity. As against these assumptions, the increased synaptic size observed in our study appears to represent a compensative reaction of old and demented CNS to counteract the reduction in number and in total contact area of the synaptic junctions.

Domperidone in defective and insufficient lactation.

The clinical use of anti-dopaminergic drugs to stimulate plasma PRL levels, to induce lactogenesis and maintain an adequate lactation has been widely suggested, taking into consideration the main inhibitory role of hypothalamic dopamine on PRL secretion. We therefore studied the effects of domperidone (DOM), a direct anti-dopaminergic drug with a low tendency to be secreted in the milk and which does not cross the blood-brain barrier, on inducing lactogenesis in 8 puerperal women with a history of defective lactogenesis (group A) and inducing galactopoiesis in 9 puerperal women who showed 2 weeks after delivery an insufficient lactation (group B). A placebo treatment was performed in 7 and 8 puerperal women with the same characteristics of group A and B, respectively. PRL plasma levels were assayed in basal conditions and after suckling from the 2nd to the 5th day of puerperium in group A and through a 10-day treatment in group B. In both groups domperidone-treated subjects always showed baseline PRL levels and daily milk yield significantly higher than those of the placebo group (P less than 0.01). The lack of any side-effects and the positive results suggest a high usefulness of such a drug in inducing and/or maintaining successful breast feeding, which is at present considered so important for a healthy development of infants.

Neurobiology of the aging brain: morphological alterations at synaptic regions.

Computer-assisted morphometric studies have been carried out on nerve cell terminal regions in rats of different ages. The numerical density (Nv), the average area (S) and the surface density (Sv) of ethanol phosphotungstic acid stained (E-PTA) synaptic junctions were evaluated in cerebellar glomeruli and dentate gyrus supragranular layers. The volume density (Vv), the average volume (V) and the numerical density (Nvm) of synaptic mitochondria were measured in the cerebellar glomeruli of young (3 months), adult (11 months) and old (28 months) animals. We found that during aging Nv and Sv undergo a significant decrease, whereas S is significantly increased. The mitochondrial Vv is unchanged in all the age groups analysed, whereas in old rats V is increased and Nvm decreased, respectively. We interpret our results as supporting that the old CNS retains part of its remodelling activity and is capable of adaptive morphological response at synaptic terminal regions.

[Influence of posture in respiratory function examination in obese subjects. II. In the patient with ventilation disorders]. / L'influenza della postura nell'esplorazione funzionale respiratoria del soggetto obeso. Nota II.--Nel paziente affetto da disventilazione.

On earlier occasions healthy subjects, and normal weight cold patients and obese subjects not suffering from hypoventilation were subjected to respiratory function tests in different postures using the plethysmographic and helium dilution methods. This protocol was then applied to a series of obese patients with the functional characteristics of alveolar hypoventilation identified in preliminary functional tests. The study revealed: a) significant differences between plethysmographic and helium dilution findings; b) not significant volumetric differences produces by different postures (standing or squatting) especially as far as Total Lung Capacity and the main lung volume parameters are concerned. These results confirm the findings of others (Sharp et al., 1986) that diaphragmatic adjustment to changes in posture is inadequate in the obese with bronchial obstruction in whom absence of the fibre-length compensation phrenophrenic reflex and by the muscle flattening cause by the alveolar hyperinsufflation. On the basis of these data and others already published an index of "diaphragmatic passivity" based on the ratio between TLC in squatting and TLC in standing x 100 is proposed as an indicator of the lung volume available for use. This simple system would indicate the functional condition of the diaphragm and provide information for the functional assessment of patients proposed for rehabilitation treatment during follow-up.

[Tachycardia-induced tachycardia: definitive treatment with radiofrequency ablation. Presentation of three cases]. / Taquicardia que induce taquicardia: tratamiento definitivo con ablación con radiofrecuencia. Presentación de tres casos.

Tachycardia-induced tachycardia is the phenomenon in which one tachycardia degenerates into another. Few data are available in patients suffering from AV nodal reentrant tachycardia an atrial fibrillation. For related to AV nodal reentrant triggered by tachycardia; there is a possible effective treatment by eliminating the slow nodal pathway, with radiofrequency ablation, as shown by other authors. In this study we present data on three patients with repeated episodes of documented atrial fibrillation and at least one episode of AV nodal reentrant tachycardia or regular palpitations. Radiofrequency ablation of the slow AV nodal pathway was successfully performed in both, and at a follow up of 6, 9 and 10 months, respectively, no new episode of AV nodal reentrant tachycardia or atrial fibrillation was documented.

[A clinical screening can predict coronary artery disease in women]. / Un cribado clínico puede pronosticar la enfermedad arterial coronaria en la mujer.

INTRODUCTION AND OBJECTIVE: Cardiovascular disease is the leading cause of death in women. Approximately one of every two women will die of some cardiovascular event, such as myocardial infarction. Thereby, the significance of discarding or confirming coronary artery disease in women presenting with chest pain. The objective of this trial was to demonstrate that on the bases of the Douglas and Ginsburg's clinic screening, it is possible to predict the existence of coronary artery disease in the angiography. MATERIAL AND METHODS: For this research only women with angina pectoris were included. These were 189 patients (cineangiographies) whose clinical determinants and angiographic findings were related. RESULTS: Taking in to account the estimated likelihood, there was a low-risk group A with 29 patients, a moderate-risk group B with 55 patients and a high-risk group C with 105 patients. There was no significant coronary artery disease in the first group, there was a significant coronary artery disease in 13 patients in the second group and 72 patients in the third group. Group A had 0%, 72%, 0% and 47%, group B 15.2%, 59.6%, 23.6% and 46.3%, and group C had 84.7%, 68.3%, 68.5% and 84.5%, of sensibility, specificity, positive and negative predictive value, respectively. CONCLUSION: The usage of the Douglas and Ginsburg's clinic Screening is very effective at the time of deciding whether to perform a coronary angiograpy or not, and it has very good correlation between the probability degree and the presence of coronary artery disease in the coronary angiography.

[Occupational asthma caused by inhalation of cuttlefish bone dust]. / Asma professionale da inalazione di polvere di osso di seppia.

This report describes a new case of occupational asthma in a goldsmith. A 25-year-old female suffered attacks of urticaria and asthma at each exposure to the dust of cuttle-fish bone used to polish gold jewellery. A specific occupational bronchial provocation challenge showed a dual asthmatic response with a maximum fall in FEV1 of 26% of the baseline value after 6 hours. A prick-test with crude cuttle-fish bone dust in glycerin 10% also gave a positive response.

Exhaled nitric oxide in interstitial lung diseases.

Nitric oxide (NO) is a biomarker of nitrosative stress, which is involved in the pathogenesis of idiopathic interstitial pneumonias (IIP). This study evaluates exhaled NO levels in IIP patients and relates alveolar concentrations of NO (CalvNO) to pulmonary function test (PFT) and 6-minute walking test (6MWT) parameters. We measured fractional exhaled nitric oxide (FeNO), CalvNO and maximum conducting airway wall flux (J'awNO) in 30 healthy subjects and 30 patients with IIP (22 idiopathic pulmonary fibrosis and 8 idiopathic non-specific interstitial pneumonias). IIP patients had higher FeNO at flow rates of 50-100-150 ml/s and higher CalvNO levels than healthy controls (p<0.0001). CalvNO was significantly correlated with 6-minute walking distance (p<0.0001), recovery time (p<0.0005), TLC (p<0.001), FVC (p=0.01) and TLCO (p<0.01). IIP patients showed abnormal nitric oxide production, probably due to lung fibrosis and oxidative-mediated lung injury. CalvNO was correlated with PFT and 6MWT parameters and is proposed as a potential biomarker of lung fibrosis and exercise tolerance.