Gravity modeling finds a large magma body in the deep crust below the Gulf of Naples, Italy.

We analyze a wide gravity low in the Campania Active Volcanic Area and interpret it by a large and deep source distribution of partially molten, low-density material from about 8 to 30 km depth. Given the complex spatial-temporal distribution of explosive volcanism in the area, we model the gravity data consistently with several volcanological and petrological constraints. We propose two possible models: one accounts for the coexistence, within the lower/intermediate crust, of large amounts of melts and cumulates besides country rocks. It implies a layered distribution of densities and, thus, a variation with depth of percentages of silicate liquids, cumulates and country rocks. The other reflects a fractal density distribution, based on the scaling exponent estimated from the gravity data. According to this model, the gravity low would be related to a distribution of melt pockets within solid rocks. Both density distributions account for the available volcanological and seismic constraints and can be considered as end-members of possible models compatible with gravity data. Such results agree with the general views about the roots of large areas of ignimbritic volcanism worldwide. Given the prolonged history of magmatism in the Campania area since Pliocene times, we interpret the detected low-density body as a developing batholith.

Effect of inorganic phosphate in hypoxemic chronic obstructive lung disease patients during exercise.

We have shown that normal subjects exercise more efficiently with increased plasma phosphate, presumably due to decreased hemoglobin-oxygen affinity and thus enhanced tissue O2 extraction. We subjected nine stable hypoxemic COLD patients to exercise at 0 (control), 24 (experimental) and 48 hrs (recovery) after phosphate infusion. Baseline variables were identical for each time period. Exercise responses at 0 and 48 hours were also indistinguishable. Exercise response at 24 hrs differed from those at 0 and 48 hours as follows: widening of A-V O2 content difference was more pronounced (28 +/- 6 vs 15 +/- 6 ml/L, p less than 0.03) and the increment in tissue O2 extraction was larger (14 +/- 3 vs 8 +/- 3 percent, p less than 0.03). P50 and related variables did not change during the course of the study. Thus, like normal subjects, hypoxemic patients stimulated with phosphate administration can exercise perhaps more efficiently; but, in contrast to normal subjects, this effect cannot be attributed to changes in hemoglobin-oxygen affinity. These data suggest that phosphate administration may be beneficial in hypoxemic states where adequate tissue oxygenation cannot be achieved by other more conventional methods. The mechanism of this effect remains to be elucidated.

Joint sonography in asymptomatic patients with HCV correlated hepatitis.

OBJECTIVES: Many different articular symptoms may appear in patients with HCV hepatitis, but in a relatively large number of patients no rheumatic symptoms are present. This sonographic study was undertaken to detect the possible presence of early articular changes in HCV patients without any rheumatic manifestations. METHODS: The knee, hip and shoulder were evaluated in a cohort of 29 consecutive HCV patients without any rheumatic symptoms. Results were compared with those obtained by the evaluation of 29 healthy subjects who were negative for markers of HCV and HBV infections. RESULTS: Results showed the presence of alterations in 96.5% of the patients, with significant differences in comparison to controls (p < 0.0001). Slight inflammatory changes were found in all the joints examined. The knee was involved in 79.3% of the cases, the hip in 27.6% and the shoulder in 89.6%. CONCLUSIONS: Our preliminary study shows the presence of joint changes in the majority of cases. To the best of our knowledge this is the first ultrasonographic study to focus on joint evaluation in patients with HCV hepatitis. Broader epidemiological and virological investigations, in particular for the HCV subtype and HLA genotype, will be required to elucidate the relationship between HCV infection and rheumatic symptoms.

Prevalence and clinical features of skin diseases in chronic HCV infection. A prospective study in 96 patients.

BACKGROUND: Between extra-hepatic manifestations of hepatitis C virus (HCV) infection particular interest is focused on some dermatological diseases such as: leukocytoclastic vasculitis, oral lichen planus, pruritus-urticaria, psoriasis, etc. The aim of this study was to determine the prevalence of some dermatoses in our population of patients with HCV infection and describe the more characteristics clinical pictures. METHODS: Ninety-six patients (36 men and 60 women) aged from 35 to 74 years with HCV documented by 3rd generation ELISA and RIBA tests were prospectively examined for 3 years to determine the prevalence of some skin disorders, reported as associated with HCV infection. All patients were also studied for presence and quantification of HCV-RNA by polymerase chain reaction and genotyping when possible. Eighty-one underwent a liver biopsy. Routine laboratory tests and some immunological investigations (ANA, AMA, SMA, LKM, ANCA, ICC, crioglobulins) were performed using standard procedures and indirect immunofluorescence, nephelometric, RIA methods. RESULTS: Twelve of 96 patients (12.5%) presented skin disorders in progress of chronic virus C hepatitis: 5 cases of leukocytoclastic vasculitis (LCV) by mixed cryoglobulinemia, 1 case of pruritus, 2 cases of oral lichen planus (OLP), 2 cases of alopecia areata, 1 case of urticaria, 1 case of psoriasis. CONCLUSIONS: Our findings show a calculated prevalence of clinical dermatoses in HCV infected patients around 12.5%. These findings confirm however the importance of liver examination in presence of skin diseases not related to other pathogenetic mechanisms.

Peripheral neuropathy without cryoglobulinemia in patients with hepatitis C virus infection.

BACKGROUND: An association between essential mixed cryoglobulinemia and hepatitis C virus infection has been documented by many reports. Some clinical manifestations such as purpura, arthralgia, vascular lesions and peripheral neuropathies are also connected with the presence of detectable cryoglobulins. The association between HCV infection, the presence of mixed cryoglobulinemia and peripheral neuropathy is well documented. The aim of this study was to define the possible presence of peripheral neuropathy in HCV patients without detectable cryoglobulins and the possible association with the different genotypes. METHODS: Twenty patients (11 females, 9 males) with chronic HCV hepatitis and without detectable cryoglobulins were submitted to neurological and electrophysiological studies to detect a possible peripheral neurological involvement. In all patients the HCV infection was assumed by the presence of antibodies to HCV with ELISA assay and then confirmed with recombinant immunoblot assay. HCV genotyping was obtained by INNO LIPA in 15 out of 20 patients. In 4 patients a sural nerve biopsy was possible. RESULTS: Genotype 1b was present in 80% of patients, while 1a in 13.3% and 4 in 6.6%. Thirteen patients had positive neurological anamnesis (65%), while neurological examination was positive in 40% of the cases. Electromyographic study was positive in 50% of subjects. The sural nerve biopsies agreed with axonal degeneration in amyelinated fibres. CONCLUSIONS: Our results suggest a possible peripheral neurological system involvement in patients with HCV infection without cryoglobulins.

Increased soluble P-selectin levels in hepatitis C virus-related chronic hepatitis: correlation with viral load.

BACKGROUND: Platelet functional abnormalities are commonly found in patients with chronic liver disease; however, their nature and clinical significance are still a matter of discussion. METHODS: Soluble P-selectin (sP-selectin, a marker of in vivo platelet activation) levels, lipid pattern, and clotting activity were investigated in 39 patients with histologically confirmed chronic C hepatitis. RESULTS: Serum factor VIIc (P < 0.01), total cholesterol (P < 0.005), high density lipoprotein (P < 0.001), and low density lipoprotein (P<0.05) levels were lower in patients compared with healthy subjects, whereas triglyceride and fibrinogen levels were similar in both groups. Platelet counts were lower in chronic hepatitis patients compared with controls (P < 0.0001), and approximately 20% of patients had thrombocytopenia (platelet counts < 110 x 10(3)/microL). Platelet-associated immunoglobulin G (PAIgG) was present in 30.8% of patients. Plasma sP-selectin levels were higher in hepatitis C patients compared with controls (P < 0.0001), and significant differences were observed with respect to the Scheuer score (P < 0.01). The analysis of the distribution of plasma sP-selectin showed the presence of higher levels in patients with low platelet counts compared with patients with normal platelet counts and controls (P < 0.0001); moreover, sP-selectin levels did not correlate with the presence of PAIgG. On the other hand, sP-selectin levels directly correlated with serum hepatitis C virus (HCV)-RNA (P < 0.05) and inversely correlated with platelet count, blood lipids, and factor VIIc. CONCLUSIONS: The results obtained in this study support the hypothesis that HCV infection might be directly responsible for a condition of in vivo platelet activation in patients with chronic C hepatitis.

Adrenomedullin assay and its clinical significance.

Adrenomedullin (Am) is a recently discovered peptide, first purified from pheochromocytoma specimens, with a chemical structure similar to that of CGRP and amylin. Adrenomedullin is present in numerous human body tissues and its powerful vasodilatatory activity is thought to play an essential role in cardiovascular and renal homeostasis.

CGRP and ET-1 plasma levels in normal subjects.

OBJECTIVE: Calcitonin gene-related peptide (CGRP) is a 37 amino acid peptide displaying about 50% homology with amylin which is secreted from the pancreatic islets of Langerhans. The main form, the beta-CGRP, is produced by the enteric nervous system and perivascular nerves of the vasa-vasorum. It represents one of the most powerful vasodilator yet discovered but its role is not yet completely clarified. High levels of this peptide have been shown in patients affected with thyroid medullary carcinoma, phaemocromocytoma and lung carcinoma. Recently circulating levels of CGRP have been found in normal subjects. Endothelin-1 (ET-1), a potent vasoconstrictor peptide, isolated from porcine endothelial cells, is an important regulator of the vascular tone acting in physiological antagonism with atrial natriuretic hormone (ANH). With this study we intended to investigate the presence of any correlation between CGRP and ET-1 in normal subjects. PATIENTS: For the study we considered 20 normal subjects (11 males and 9 females) aged 23 to 50. MEASURES: Plasma levels of CGRP and ET-1 were measured by radioimmunological Kit. RESULTS: A positive and significant correlation between calcitonin gene-related peptide and endothelin-1 was found. CONCLUSIONS: Our results confirms that CGRP and ET-1 have opposing actions on vessels and that they can act together in haemodinamic regulation.

Hashimoto's disease during interferon-alpha therapy in a patient with pre-treatment negative anti-thyroid autoantibodies and with the specific genetic susceptibility to the thyroid disease.

OBJECTIVES: The authors described a case of Hashimoto's disease during interferon-alpha (IFN-alpha) treatment for chronic viral C hepatitis in a patient with the specific genetic susceptibility associated with the thyroid disease. RESULTS: A 60-year-old woman with chronic active viral C hepatitis (HCV genotype = 3a) started IFN-alpha therapy in November '96. Before treatment thyroid function tests were normal and anti-thyroid (anti-thyroglobulin and anti-thyroid peroxidase) Abs were negative. During IFN therapy, serum aminotransferases fell within the normal range and viremia (serum HCV-RNA) became negative after one year. After 20 months, the patient presented clinical features of primary hypothyroidism. Anti-thyroid Abs were found positive. Hormonal, ultrasonographic, radioiodine scanning and fine needle aspiration findings were consistent with the diagnosis of Hashimoto's thyroiditis. The tissutal typing of the patient showed the presence of Human Leukocyte Antigen (HLA) DRB1*11 gene (corresponding to DR5 antigen). IFN-alpha therapy was suspended and a treatment with l-T4 started. Chronic viral infection relapsed after the suspension of the IFN-alpha therapy. CONCLUSIONS: This case report showed that the clinical appearance of Hashimoto's disease after IFN-alpha therapy for chronic C hepatitis in our patient was associated with a specific genetic predisposition (DR5) for this pathology. Further studies are necessary to evaluate whether the study of HLA antigens may be a very useful tool to detect the patients with a predisposition to develop autoimmune thyroiditis, in order to make a early diagnosis of thyroid disorders during the IFN-alpha treatment.

Evaluation of myocardial involvement in systemic lupus erythematosus by signal-averaged electrocardiography and echocardiography.

OBJECTIVE: The myocardial involvement in systemic lupus erythematosus (SLE) patients, frequently found at autopsy or at endomyocardial biopsy, is less easily detected clinically. The myocardial lesions are characterized by an increase in interstitial connective tissue and myocardial scarring. Signal-averaged electrocardiography (ECG-SA) is currently used for recording ventricular late potentials which are the expression of slowed and disorganized conduction through zones of myocardial scarring. M-mode, two-dimensional and Doppler echocardiography (ECHO) represent relatively simple methods for evaluating the left ventricular function. This study was aimed to evaluate by ECG-SA and ECHO the myocardial involvement of SLE patients without clinical and electrocardiographic evidence of cardiac disease. METHODS AND RESULTS: Twenty outpatients with SLE were studied and compared with 18 normal controls. Late potentials were recorded in 20% of SLE patients and in 5.5% of controls. A significant increase of abnormal left ventricular diastolic filling was found in the SLE patients, characterized by reduced E/A (p = 0.018), a lower deceleration rate of early diastolic flow velocity (p = 0.048) and a prolonged isovolumic relaxation time (p = 0.001). SLE patients had diastolic dysfunction of various degrees although the depolarization abnormalities detected by ECG-SA were found only in a few subjects. CONCLUSIONS: The depolarization abnormalities, revealed by ECG-SA, probably reflect a longer extent of myocardial fibrosis in SLE patients with ECHO evidence of abnormal left ventricular filling. The simultaneous occurrence of ECHO and ECG-SA alterations could be a marker of subclinical myocardial involvement.

Morphologic left ventricular patterns and prevalence of high-grade ventricular arrhythmias in the normotensive and hypertensive elderly.

In the elderly, systemic hypertension is the main risk factor for cardiovascular diseases. Left ventricular hypertrophy, the most common adaptation to chronic pressure overload, has been recognized as an independent risk factor for an increased incidence of sudden death and arrhythmic disturbances. This study compared the prevalence of serious ventricular arrhythmias in elderly individuals with uncomplicated hypertension and in normotensive age-matched controls, using left ventricular mass index (LVMI) to differentiate patterns of anatomic adaptation to systolic, diastolic, or systolic-diastolic hypertension. The study enrolled 378 consecutive untreated elderly subjects (> or = 65 years of age), without clinical evidence of heart failure; 203 were hypertensive and 175 were normotensive. Each participant underwent standard 12-lead electrocardiography, M-mode and B-mode echocardiography, and 24-hour ambulatory electrocardiographic monitoring. Serious, statistically significant arrhythmias (Lown classes > or = 3) were present in 6.8% of normal subjects versus 17.1% of individuals with systolic, 31.5% of those with diastolic, and 20.4% of participants with systolic-diastolic hypertension. Arrhythmias did not differ in terms of left ventricular morphologic patterns or LVMI or between subgroups of hypertensive patients. Our data support the hypothesis that the pathogenesis of arrhythmias is related not to the electrophysiologic derangement of hypertrophied muscle but, rather, to the effects of hypertension on the cardiac structure. Cardiac fibrosis, one of the deleterious events accompanying hypertension, may be the main substrate for ventricular arrhythmias.

Natural history of cardiac involvement in myotonic dystrophy (Steinert's disease): a 13-year follow-up study.

Myotonic dystrophy (MD) is associated with a wide spectrum of cardiac abnormalities, but only a few longitudinal studies have investigated the natural course of heart disease in MD. To assess whether neuromuscular involvement significantly predicts cardiac disorders in MD, 83 patients with various grades of disease severity were enrolled in a 13-year follow-up study (mean, 60.6 +/- 37.8 months) that included periodic physical and instrumental cardiac examinations (standard and Holter electrocardiography, echocardiography). During follow-up, muscular disease worsened clinically in 9 patients (11%) whose baseline severity grade changed accordingly; only 3 of them demonstrated parallel worsening of cardiac disturbance, however, compared with a large number of patients who showed additional cardiac abnormalities. These included further worsening of pre-existing pathologic features (19/83) and the appearance de novo of serious arrhythmias and/or conduction defects (23/83). Pacemaker implantation was necessary in 11 of 83 patients (13.2%) who had symptomatic bradyarrhythmias, bifascicular block, and P-R prolongation with a His-to-ventricle interval exceeding 55 ms, as documented by electrophysiologic study. Eight (9.6%) patients died: 2 from noncardiac and 1 from unknown causes, 1 from heart failure, and 4 from sudden death closely related to documented ventricular tachycardia. The incidence and seriousness of arrhythmic and conduction disturbances correlated with the severity of the muscular involvement. Nevertheless, cardiac and muscular disease did not show a linear progression. Cardiac involvement generally worsened more rapidly than did skeletal muscle disease.

Clinical trial of xipamide in the treatment of hypertension.

Nine patients with hypertension were given xipamide 40 mg orally as monotherapy on alternate days. An additional seventeen patients had xipamide added to an existing treatment regime of clonidine 450 micrograms per day. Xipamide alone produced a significant fall in blood pressure comparable to that obtained with clonidine alone. However, a significant further reduction was obtained when xipamide was added to the existing clonidine regime.

A clinical trial of co-trimazine (sulfadiazine + trimethoprim) in flare-ups of chronic bronchitis.

The authors treated acute flare-ups of chronic bronchitis with a combination of sulfadiazine (SDZ) and trimethoprim (TMP) (cotrimazine). They treated thirty patients for a week, with daily dosages of 900 mg SDZ and 300 mg TMP, in an open trial in comparison with ampicillin 2 g daily. The result of treatment (course and duration of the acute episode, fever, cough, dyspnoea, sputum amount and description, chest sounds, ESR, and WBC count), tested by suitable statistical methods, showed that cotrimazine had excellent therapeutic activity and was readily tolerated; over-all results compared closely with those obtained with ampicillin. In their concluding remarks the authors state that in addition to being effective in the morbid condition selected for trial, cotrimazine offers some advantages over similar combinations of TMP and other sulfonamides, both because of the intrinsic physicochemical and pharmacological properties of SDZ and because of its lower dosage in this combination.

[Reasons for diuretic therapy of cirrhotic ascites]. / Le basi razionali della terapia diuretica nell'ascite cirrotica.

The first therapeutic response to cirrhotic ascites should be a salt-free diet and bed rest. Only if this fails should anti-aldosterones, furosemide or mannitol be adopted. After an examination of the reasons for using any of these drugs, either alone or in association, it is emphasised that thiazide should never be used to treat cirrhotic ascites. Its use has been common practice for years on the basis of apparently convincing empirical evidence. Finally it is pointed out that any treatment should be approached with caution with more emphasis on the patient than on the ascites itself.

Skin diseases as extrahepatic manifestations of HCV. Review of some clinical cases.

Among extra-hepatic manifestations of hepatitis C virus (HCV) infection particular interest is focused on some dermatological diseases such as: leukocytoclastic vasculitis, oral lichen planus, pruritus-urticaria, psoriasis. Aim of this paper is to analyze these typical dermatoses in a population of patients with HCV infection and describe the characteristic clinical pictures. These clinical pictures confirm the importance of liver examination in presence of skin diseases not related to other pathogenetic mechanisms.

[Harmonic echocardiography of tissue in the diagnosis of aneurysms of the interatrial septum. Study of 550 consecutive ambulatory patients]. / Ecocardiografia in armonica tissutale nella diagnosi dell'aneurisma del setto interatriale. Studio su 550 pazienti ambulatoriali consecutivi.

BACKGROUND: It has been assessed whether echocardiographic harmonic imaging improves the detection of atrial septal aneurysm (ASA) compared with fundamental imaging. METHODS: We studied consecutively, using fundamental and harmonic imaging, 550 patients (with or without cardiopathy; 300 females and 250 males) in an outpatients' department (age 23-76 years, mean 50 years). We used a multifrequency transthoracic probe transmitting at 2 Mhz and receiving at 4 Mhz. The ASA was classified in three types according to Hanley et al. Type 1A, protruding into the right atrium without oscillation; Type 1B protruding into the right atrium with oscillation, and Type 2, protruding into the left atrium with oscillation. We compared atrial septal aneurysm definition in fundamental and harmonic mode, and assessed the interobserver agreement in the diagnosis of ASA. The echocardiographic images were recorded on magneto-optical disk and analysed by two blinded observer. With Pearson test we assessed the interobserver concordance in the ASA study; so we quantified the advantage of harmonic imaging as reduction of the inter-observer variability. RESULTS: Among 550 consecutive subjects in the echocardiographic study population, ASA was diagnosed in 8 (1.45%) and 15 (2.72%) patients using fundamental and harmonic methods respectively. A significant reduction of the inter-observer variability in the ASA diagnosis was found with harmonic imaging (harmonic imaging: r = 0.96; fundamental imaging: r = 0.70). CONCLUSIONS: The harmonic methods drastically improves echocardiographic imaging of ASA, it may be used routinely and reduces the need for more invasive technique such as transesophageal echocardiography.

Mitral prolapse. A heart anomaly in a clinical neuroendocrine context.

Mitral valve prolapse was identified as a separate nosological entity by Barlow in 1963. A characteristic of this cardiac anomaly is blood reflux into the left atrium during the systole owing to the lack of adhesion between valve flaps. The presence of symptoms linked to neuroendocrine dysfunctions or to the autonomic nervous system lead to the onset of the pathology known as mitral valve prolapse syndrome (MVPs). It is usually diagnosed by chance in asymptomatic patients during routine tests. MVPs includes complex alterations to the neurovegetative system and a high clinical incidence of neuropsychiatric symptoms, like anxiety and panic attacks. A neuroendocrine mechanism thought to underlie panic attacks was recently proposed based on a biological model. In general, the cardiovascular anomaly manifested by patients with MVPs could be defined in neuroendocrine-constitutional terms.

[Illnesses associated with high environmental temperature]. / Malattie associate ad alte temperature ambientali.

After a brief review of pathologies secondary to high environmental temperatures and of the pathophysiological mechanisms underlying different clinical patterns the authors stress the need for a more precise knowledge of the risk factors involved and detail suitable preventive measures. They also describe the situation which occurred in Rome during the 1983 heat wave during which a steep increase in mortality was observed compared to preceding years.

[Pharmacovigilance: theoretical and practical aspects]. / La farmacosorveglianza: aspetti teorici e pratici.

Pharmacovigilance is reviewed as requirement for monitoring of drug safety. The authors examine the most important theoretic pictures of postmarketing surveillance of drugs.