Natural history of cardiac involvement in myotonic dystrophy: correlation with CTG repeats.

The authors prospectively studied the natural course of cardiac involvement and its relationship to cytosine-thymine-guanine (CTG) expansion in 50 patients with myotonic dystrophy who were submitted to periodic cardiovascular EKG and EKG-Holter monitoring during a median follow-up of 56 months. Nineteen patients (38%) developed major EKG changes. CTG length was not correlated with the frequency of EKG abnormalities, but was inversely correlated with the age at onset of EKG abnormalities (p < 0.0001). CTG length influences the timing of cardiac complications in myotonic dystrophy.

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.

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.

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.

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.

Immunoadsorption apheresis (Selesorb) in the treatment of chronic hepatitis C virus-related type 2 mixed cryoglobulinemia.

In this short-term open label clinical pilot study, conducted at one center, the immune complex dextran sulphate adsorber (Selesorb) was used to treat four female patients aged 59-69 with HCV-related cryoglobulinaemia, vasculitis and/or neuropathy. The primary trial objective was to assess the clinical efficacy of the immunoadsorber. The secondary objective of the trial was to determine the safety of the adsorber and to investigate the adsorption capacity, measured as the adsorption of cryoglobulin-related immune complexes and the resulting influence on plasma components of the immune system. The patients have been submitted to treatment with the immunoadsorber, at approximately 1-3 days intervals, completing six sessions. The follow-up was one month. In the patients treated with Selesorb, we observed a statistically significant decrease in plasma of all classes of immunoglobulins (IgA: 5-28%; IgG: 14-44%; IgM: 8-38%). In two patients with peripheral neuropathy secondary to cryoglobulinemia, the symptomatology was improved. In a third patient the neurological involvement was substantially unchanged, and the same unsuccessful outcome was observed for Sjögren syndrome is concerned. Nevertheless, the two patients with lower extremity vasculitis showed an appreciable improvement. We failed to observe significant side effects directly related to the use of this immunoadsorbent.

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.

[The effects of Levissima oligomineral water on diuresis and water exchange]. / Considerazioni sulle influenze esercitate dall'acqua oligominerale Levissima sulla diuresi e sul ricambio idrico.

Research on healthy and diseased subjects and laboratory animals have shown that Levissima oligomineral water: a) has no unpleasant or harmful subjective and/or objective side-effects even when taken at high doses for long periods. b) Encourages diuresis. Comparison with saline solution of the same osmolality showed: 1) mean increase in diuresis: 16%; 2) more rapid elimination of water; 3) significant increase in free water clearance; 4) no change in the stock of electrolytes during protracted administration. c) Influences purine exchange: 1) by increasing uric acid clearance (same comparison); 2) by reducing the hyperuricaemising effect of a rapid i.v. fructose load; 3) by opposing hyperuricaemia due to depression of mechanisms responsible for the increase of uric acid owing to enhancement of serum lactic acid after the administration of alcohol. d) Results in a characteristic change in certain coagulation parameters when compared with saline solution and tap water. It is suggested that this method be used to recognise the persistence over time of the biological activities of bottled mineral waters.

[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.

[Clinical use of echo-dipyridamole test in hypertensive subjects with suspected ischemic heart disease]. / Impiego clinico del test eco-dipiridamolo in soggetti ipertesi con sospetta cardiopatia ischemica.

The aim of this study was to assess the diagnostic capacity of the dipyridamole-echocardiography test (DET) and dipyridamole myocardial scintigraphy (DMS) for coronary artery disease in mild to moderate hypertensive subjects with chest pain. A comparison was performed with exercise stress test (EST) and stress myocardial scintigraphy (SMS) in 20 subjects. Seven patients also underwent coronary angiography. To compare test results, Mc Nemar test was employed. Our results showed a statistically significant difference between DET and EST and a good agreement, in terms of dichotomy response, between DET and SMS. Any difference was further found between SMS and DMS. In conclusion, in hypertensive subjects, DET appears to provide a useful clinical noninvasive tool for coronary artery disease diagnosis and evaluation.

Efficacy, safety and tolerability of combined low-dose simvastatin-fenofibrate treatment in primary mixed hyperlipidaemia.

OBJECTIVE: In order to assess the long-term (12 months) efficacy and safety of fenofibrate administered with simvastatin in the treatment of primary mixed hyperlipidaemia, we conducted a study that compared increasing dosages of these drugs in subgroups of men and women belonging to a clinical sample of out-patients. DESIGN: This was an open study carried out in patients with primary mixed hyperlipidaemia (lipoprotein phenotype IIb) who needed a combined therapeutic approach because of their poor response to a single-drug regimen with an HMG-CoA reductase inhibitor (simvastatin). Thus, a fibrate (fenofibrate) was added to the therapy. The study lasted 12 months. PATIENTS: Forty-five patients (mean age: 58.9 +/- 11.3 years) with primary mixed hyperlipidaemia who showed a poor response to the single-drug hypolipidaemic treatment were enrolled. Their average plasma triglyceride level was consistently above 300 mg/dL and low-density lipoprotein cholesterol (LDL-C) was over 160 mg/dL after at least 6 months of a single hypolipidaemic drug (simvastatin) regimen plus antiatherogenic dietary treatment. INTERVENTIONS: Five patients received simvastatin 10mg once daily in addition to fenofibrate 200mg; 26 patients received simvastatin 20mg once daily plus fenofibrate 200mg; 11 patients received simvastatin 20mg once daily plus fenofibrate 300mg; and three patients received simvastatin 30mg once daily plus fenofibrate 200mg. The patients were allocated to treatment groups on the basis of their relative response to the therapy. Those making up the progressively higher agent/dose groups were the individuals at higher cardiovascular risk according to the total cholesterol and non-high-density lipoprotein cholesterol (HDL-C) values. RESULTS: The double-drug regimen given for 12 months to four different groups, according to the different combined dosages of simvastatin and fenofibrate, resulted in a reduction in total cholesterol of 18% (p

[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.

[Drug-induced lung diseases]. / Pneumopatie da farmaci.

In the light of recent fresh reports of drug-induced lung lesions, the authors suggest an updated classification of these based on data found in the literature. Special attention has been reserved to the pathogenetic mechanisms underlying specific clinical pictures.

[Drugs and food]. / Farmaci ed alimenti.

The authors examine the complex relationships between drugs and foodstuffs from the various points of view of clinical pharmacology, toxicology, and nutritional science. Special attention is concentrated on the possible interference of foodstuff with drug bioavailability, changes of drug bioavailability during malnutrition, drug-induced changes of nutritional status, and incompatibility between foodstuffs and drugs.

[Main cardiotoxic drugs]. / I principali farmaci a tossicità cardiaca.

A review of the most important iatrogenic pictures is reported. Chemotherapeutic agents, antidepressants, cocaine and amphetamine, oral contraceptives and antiarrhythmic drugs are examined.

[Pericardial effusions as the initial manifestation of extracardiac tumors. A discussion of 2 cases and a review of the literature]. / I versamenti pericardici come prima manifestazione di tumori extracardiaci. Discussione su due casi e revisione della letteratura.

The authors describe two cases of cardiac tamponade that were the first manifestation of an extracardiac tumor; they stress that this type of presentation described in the literature as an extremely rare occurrence, has become more frequent in recent years as a result of both a higher prevalence in absolute terms and of a more reliable detection thanks to the availability of more sensitive and more practicable diagnostic techniques. Having briefly described the pathophysiology of pericardial effusions with special reference to those of neoplastic origin, the authors detail the most sensitive tools for a correct diagnosis.

[Nephrotoxicity of drugs]. / Nefrotossicità da farmaci.

Setting out from the high prevalence of iatrogenic toxic effects on the kidney, the authors examine the pathophysiological mechanisms underlying this toxicity, and suggest their classification. The principal pathophysiologic and clinical models of the action of various groups of drugs responsible for these effects are discussed.