Combined treatment of relapse of chronic hepatitis C with high-dose alpha2b interferon plus ribavirin for 6 or 12 months.

BACKGROUND/AIMS: Retreatment of relapses of chronic hepatitis C with a standard regimen of interferon plus ribavirin for 6 months obtains a sustained response in a minority of patients with high viraemia and genotype 1b. We aimed to assess whether increasing the interferon dose and prolonging the time of combined treatment may enhance the effectiveness, and also to evaluate the tolerability, and to identify the determinants of sustained response. METHODS: Fifty subjects with chronic hepatitis C who had relapsed after one or more courses of a-interferon monotherapy were randomised to receive alpha2b interferon (6 MU tiw) plus ribavirin (1000-1200 mg daily) for 6 or 12 months. ALT normalisation and serum HCV-RNA clearance at the end of treatment and 6 months after stopping therapy were used as markers for sustained response. RESULTS: End-of-treatment response was achieved in 48 patients (96%) and 27 (54%) had a complete sustained response. Patients treated for 12 months had a higher rate of sustained response (18/25, 72%; 95% C.I. 0.54-0.89) than those treated for 6 months (9/25, 36%; 95% C.I. 0.17-0.55, p=0.01). Twelve months of therapy was significantly more effective for patients with genotype 1b and baseline serum HCV-RNA greater than 450 000 copies/ml (p=0.005). Seven subjects (14%) discontinued treatment because of side effects. Logistic regression analysis showed 12 months of therapy, young age and low pre-treatment serum HCV-RNA to be independent predictors of sustained response. CONCLUSIONS: Relapsers with genotype 1b and high levels of HCV-RNA will benefit from a 12-month course of 6 MU tiw interferon plus ribavirin, while subjects with genotype 1b and low levels of serum HCV-RNA or with genotype other than 1b may be treated for 6 months.

[Atrial fibrillation and hyperthyroidism. The results of a retrospective study]. / Fibrillazione atriale ed ipertiroidismo. Risultati di uno studio retrospettivo.

BACKGROUND: To examine the prevalence of atrial fibrillation (AF) in cardiopathic patients with hyperthyroidism. METHODS: The data concerning the patients had been derived from registers of the Laboratory of Radioimmunoassay where cardiopathic patients' blood samples were referred from the Cardiology Unit to evaluate thyroid function, consecutively from January 1992 to December 1997. Of the 443 patients, 303 (68.4%) were classified as being euthyroid, 23 (5.2%) hypothyroid, 117 (26.4%) hyperthyroid. Thyroid function was diagnosed clinically and confirmed by serum TSH and free thyroid hormone (FT3, FT4), levels. RESULTS: Among hyperthyroid patients, the more frequent arrhythmia was AF (54.7%). After excluding from the study those hyperthyroid patients with rheumatic disease, hypertension, myocardial infarction, 37 hyperthyroid patients were selected; 18 (48.6%), (mean age 63.4 +/- 10.8 yrs), showed sinus rhythm and 19 (51.4%), (mean age 66.0 +/- 12.1 yrs), showed AF. FT3 and FT4 were higher in patients with AF than in those without AF, whereas TSH was not significantly different between the groups. Left ventricular (LV) mass index was significantly increased in hyperthyroid women with AF compared with hyperthyroid women without AF (109.80 +/- 22.33 g/m2 vs 84.50 +/- 6.20 g/m2; p < 0.005). A significant correlation was found between FT3 levels and LV mass index in the hyperthyroid women with and without AF (r = 0.77; p < 0.001). CONCLUSIONS: In this study the prevalence of AF is 51.4% in hyperthyroid patients. FT3 is higher in patients with AF than in those without AF. Finally, the correlation between FT3 and LV mass index suggests that cardiac hypertrophy is associated with thyroid hyperfunction.

Factors associated with autonomic nervous function in type 1 and type 2 diabetic subjects free of clinical manifestations of autonomic neuropathy.

Even though autonomic diabetic neuropathy is highly prevalent and a noted risk factor for cardiovascular morbidity and mortality, very little is known about factors associated with it. We carried out standard autonomic nervous system function tests by means of a computerized portable system on 55 diabetic patients (22 with type 1 diabetes, 33 with type 2 diabetes) who had no signs or symptoms of autonomic diabetic neuropathy and on 10 age- and sex-matched healthy control subjects. Test results of patients with type 1 diabetes did not differ significantly from those with type 2 diabetes. Of the clinical, metabolic, and anthropometric variables considered, only the duration of diabetes was inversely and independently correlated to deep breathing test scores (E:I ratio value of deep breathing 1.38-0.009. years of diabetes; R2 = 0.25). The duration of diabetes was inversely correlated to variations in orthostatic systolic blood pressure (r = -0.37, p < 0.01). The prevalence of diabetic retinopathy (score: 1 = no; 2 = yes) was significantly higher in the diabetic group with lower deep breathing values (1.8 +/- 0.3 vs 1.0 +/- 0.0; p < 0.01). The prevalence of ischemic electrocardiographic alterations (score: 1 = no; 2 = yes) was significantly higher in the diabetic group with a poorer orthostatic systolic blood pressure response (1.4 +/- 0.1 vs 1.2 +/- 0.1; p < 0.01). This study suggests that 1) autonomic neuropathy is correlated to disease duration; 2) type of diabetes, present level of metabolic compensation, and anthropometric characteristics do not seem correlated to this complication; 3) diabetic retinopathy and ischemic cardiopathy may be correlated to autonomic neuropathy.

[Ultrasonographic study of gallbladder kinetic activity in patients with motor-like dyspepsia]. / Lo studio ecografico dell'attività motoria della colecisti nei pazienti con dispepsia semil-motoria.

BACKGROUND AND METHODS: Forty-six subjects affected with functional dyspepsia (the coherence of illness was excluded by proper research) not classifiable, according to Drossman principles, into reflex-like or ulcer-like dyspepsia class have been studied. All the patients, asked about either the presence or the absence of any dyspeptic symptoms, with the only condition that the symptom indicated had been present at least for three months continuously, were subjected to abdominal ultrasonography and after-meal cholecystokinetic. The emptying of cholecyst has been monitored until 150 minutes after meal, at near intervals. As Control Group subjects have been used, free from dyspeptic symptomatology and superimposable by age, sex and alimentary habits to the patients of the Study Group. RESULTS: The authors observed a) that the initial cholecystic volume after 15 minutes was significantly (p<0.001) reduced in the patients with dyspeptic symptoms, compared with those of the Control Group; b) that there was not significant difference between the two groups at 30, 45, 60 minutes; c) that in the patients of the Control Group cholecyst had returned to its normal volume in 90-120 minutes while, in the Study Group it had kept its volume almost unchanged until 150 min after meal, with a highly significant difference between the two groups (p<0.001). From the clinic-symptomatologic point view, the authors have verified, besides the proper symptoms of motor-like dyspepsia, also other symptoms not indicated by other authors, and precisely ''after meal sleepiness'', ''bitter mouth'' and ''after meal cephalea'', in 41 to 63%. CONCLUSIONS: The authors suppose that in the patients with functional dyspepsia, not reflex-like or ulcer-like dyspepsia the kinetic disorder responsible for symptomatology is in any way related to a disorder of kinetic activity of cholecyst.

The impact of coexistent diabetes on the prevalence of coronary heart disease.

The increased risk of developing cardiovascular disease in diabetic population has been well documented, but the prevalent mechanism of this susceptibility is still only partly explained. We compared the impact of diabetes on ischemic heart disease in patients hospitalized in a public general hospital over a 10-year period. The prevalence of coronary heart disease (CHD) was consistently higher among diabetic population [namely, among non-insulin-dependent diabetes mellitus (NIDDM) patients] when compared with the nondiabetic population. The prevalence was similar in both genders, increasing with age, and was independent from body-mass index, history of smoking, metabolic control, or lipid pattern. Heart rate and blood pressure levels were significantly higher in NIDDM patients with CHD; similarly, there was a significant association between ischemic heart disease and atherosclerotic peripheral artery disease prevalence, and this trend was observed even in subjects with impaired glucose tolerance. These observations support the evidence that diabetes exerts a deleterious effect on general risk factors of atherosclerosis and increases susceptibility to cardiovascular disease by itself as an "independent" risk factor; on the other hand, the epidemiological evidence of an excessive occurrence of type II diabetes in individuals with pre-existing vascular disease suggests a genetically determined link between metabolic disturbances and cardiovascular disease.

[Correlation between skinfold thickness and ultrasonography in the study of subcutaneous adipose tissue in females]. / Correlazione plicometria-ecografia nello studio dell'adipe sottocutaneo in soggetti di sesso femminile.

The aim of this study was to verify if there is a 1:2 correlation between subcutaneous adipose tissue thickness measured by ultrasonography and skinfold caliper and if this correlation varies in function of the degree of obesity, subcutaneous fat thickness, and the area evaluated. Forty women (age 27.9 +/- 11.7 years, body mass index 28.75 +/- 5.40 Kg/m2, waist to hip ratio 0.77 +/- 0.06) underwent ultrasonographic measurement of subcutaneous adipose tissue and skinfold caliper measurement at nine different sites (bicipital, tricipital, subscapular, suprailiac, epigastric umbilical, hypogastric, gluteal, and femoral). Data analysis confirmed a significant correlation between measurements made by ultrasonography and skinfold plicometry at all sites when the patients were not subdivided according to body mass index or skinfold thickness. When they were subdivided on the basis of body mass index, a significant correlation was found for subjects with a body mass index < 30; when the index was > 30, the correlation was observed at only the subscapular and suprailiac sites, and to a lesser degree at the tricipital and femoral sites. Moreover, a highly significant correlation was found only at sites at which ultrasonographic thickness was not > 20 mm (p < 0.001) with an r value decreasing progressively from 0.685 (thickness < 10 mm) to 0.248 (thickness > 40 mm). Given the great variability of this correlation, we suggest that ultrasonography is preferable to plicometry for the measurement of fat.

Correlation between digestive disease and psychiatric disease: casual or causal implication?

The aim of this study was to evaluate the prevalence of psychiatric disturbances among patients affected with digestive diseases (both organic and functional) and, viceversa, the prevalence of digestive disturbances among patients with psychiatric diseases. We performed a trasversal study on: 100 patients with organic digestive diseases and 100 patients with functional digestive diseases afferent from a Gastroenterologic Ambulatory (gastroenterologic group); 50 patients afferent from a Psychiatry Service (psychiatric group) and 50 patients afferent from a General Medicine Ambulatory affected with a non gastroenterologic active problem (control group). Each patient underwent an anamnestic, laboratory and instrumental evaluation, in order to ascertain or exclude the presence of digestive symptoms and their eventual organic basis; moreover, a semistructured interview was performed aimed at identifying a psychiatric disturbance, according to DSM-IIIr criteria. Our results showed a significantly higher prevalence: 1) of psychiatric disturbances, in the gastroentorologic group versus the control group (p<0.001), especially of somatoform (p<0.05) and anxious (p<0.001) disorders; 2) of psychiatric disturbances among patients affected by functional digestive disorders versus patients affected by organic digestive disorders; 3) of gastroenterologic disorders, in the psychiatric group versus the control group (p<0.001), with a significantly higher prevalence of functional gastroenterologic syndromes in comparison the organic ones (p<0.001). The well-established bidirectional correlation between digestive functional and psychiatric disorders is a necessary but not sufficient condition to state a relationship of direct causality between the two syndromes; however we can hypothesize that the well documented neuro-hormonal alterations may cause, on clinical grounds different symptoms, that are differently interpreted by the different specialists (gastroenterologists or psychiatrists) consulted.

Circulating endothelin-1 levels in type 2 diabetic patients with ischaemic heart disease.

To investigate whether circulating endothelin-1 (Et-1) may be related to the increased incidence and severity of ischaemic heart disease in type 2 diabetes mellitus, we compared the concentrations in type 2 diabetic patients and in non-diabetic patients with coronary artery disease (CAD) angiographically documented. Plasma levels of Et-1 were determined in 34 type 2 diabetic patients with CAD (16 with stable angina, 6 with unstable angina, 12 with previous myocardial infarction) and in 19 nondiabetic patients with CAD (4 with stable angina, 5 with unstable angina, 10 with previous myocardial infarction). Fifteen diabetic patients without CAD and 9 healthy volunteers served as control subjects. In the type 2 diabetic patients, the mean Et-1 levels were 3.19 +/- 1.61 pmol/l in those with stable angina, 3.58 +/- 1.92 pmol/l in those with unstable angina, 4.24 +/- 2.53 pmol/l in those with myocardial infarction. These values were not significantly different one another, nor from the values obtained from type 2 diabetic controls (3.64 +/- 2.13 pmol/l). In the non-diabetic patients, the mean Et-1 levels were 3.92 +/- 0.73 pmol/l in those with stable angina, 4.35 +/- 1.67 pmol/l in those with unstable angina, 4.33 +/- 1.66 pmol/l in those with myocardial infarction. These values were not significantly different one another, but significantly higher than those obtained from healthy controls (2.07 +/- 0.67 pmol/l; P < 0.001). No significant differences were found in Et-1 levels between diabetic and non-diabetic patients with stable, unstable angina and previous myocardial infarction. In contrast, a statistically significant difference was found in Et-1 levels between diabetic and non-diabetic control subjects (P < 0.05). In conclusion, similar raised concentrations of Et-1 in diabetic and non-diabetic patients with stable, unstable angina and previous myocardial infarction do not support the hypothesis that higher levels of Et-1 in diabetic patients are responsible for the increased incidence of CAD in diabetes mellitus. However, the raised Et-1 levels found in diabetic patients in the absence of CAD strongly suggest that a generalised endothelial dysfunction, documented in our study by increased levels of Et-1, most probably precedes subsequent cardiovascular diseases.

[De-nol in NSAID-induced gastroduodenal lesions]. / DE-NOL nelle lesioni gastroduodenali indotte da FANS.

It is well known that prolonged use of Non Steroidal Anti-inflammatory Drugs (NSAIDs) can trigger gastroduodenal lesions and/or their complications, even in the absence of any dramatic painful and dyspeptic symptomatology. The paper reports the results of a double-blind study carried out with Colloidal Bismuth Subcitrate (CBS, DE-NOL), an antiulcer drug with cytoprotective activity, versus ranitidine (RN) with the aim of assessing its therapeutic efficacy in promoting healing of either gastric or duodenal ulcers induced by NSAIDs. It is concluded that the efficacy of DE-NOL is comparable to that of RN, although some minor differences in healing rates were observed: these being in favour of DE-NOL in the gastric ulcer patients and in favour of RN in the duodenal ulcer patients, respectively. In addition, it is stated that in patients undergoing chronic treatment with NSAIDs the use of cytoprotective drugs as a preventive treatment as well as periodic endoscopic surveillance are more useful and rational in order to combat the onset of NSAIDs-induced side-effects, given the frequent paucity of symptomatology following the occurrence of gastroduodenal lesions.

[Alizapride in upper digestive endoscopy. A double-blind study vs metoclopramide and placebo]. / L'alizapride in endoscopia digestiva superiore. Studio in doppio cieco contro metoclopramide e contro placebo.

In order to assess the antiemetic properties of alizapride in the specific context of premedication for endoscopy, a double blind test was conducted on 100 patients against both metoclopramide and a placebo. Efficacy was assessed on the basis of the following parameters: technical judgement of the endoscopist; assessment of evident signs of "discomfort" by an outside observer; comparative judgement (better, worse, same) of the patient's condition after the two endoscopies performed. In the case of the first two parameters, alizapride proved significantly more effective than the control substances. The patients themselves only expressed a significant preference for alizapride vis-à-vis the placebo. It is concluded that given its efficacy and the absence of side effects, alizapride is of value in premedication for endoscopy.

[Erosive-hemorrhagic duodenitis: natural history and management]. / Duodenite erosivo-emorragica: storia naturale e management.

A group of 32 patients with erosive-haemorrhagic duodenitis or EHD (group 5) was followed up for 36 months in order to monitor the natural history of EHD and any connections with peptic ulcers. The control group (group C) was formed of patients with similar clinical symptoms but an endoscopic picture of either a healthy duodenum or only superficial mucosal damage (non-erosive-haemorrhagic duodenitis or NEHD). The follow-up clinical, secretory and endoscopic examinations annually or whenever there were new acute attacks revealed a far higher incidence of peptic ulcer in group S than group C or in the population as a whole. The study also revealed that there is not always a link between the clinical symptoms and the severity of the endoscopic picture. It is therefore concluded that EHD patients constitute a subclass that should be kept under surveillance and given the same management as duodenal ulcer patients.

[Cytoprotective effect of rosaprostol during treatment with non-steroidal anti-inflammatory agents in arthrorheumatic pathologies]. / L'azione citoprotetiva del rosaprostol in corso di trattamento con FANS in patologie artroreumatiche.

A clinico-endoscopic study has been carried out in a group of 22 patients treated with 1 g of naproxene + 2 g of rosaprostol compared in a blind situation with another group of 19 patients treated with a similar dose of naproxene + placebo in order to evaluate the cytoprotective action of rosaprostol. Analysis of the results showed a high correlation between intake of rosaprostol and low onset of algico-dyspeptic disturbances and mucosal lesions of some gravity, although the problem of the monitoring of patients undergoing long-term treatment with NSAID remains unsolved.

Cytoprotective therapy of gastric ulcers: a controlled clinical evaluation of triletide versus carbenoxolone.

Two parallel groups, each of 10 out-patients with endoscopically confirmed benign gastric ulcer, were randomly assigned to receive either 1.5 g/day of triletide, a new tripeptide shown to increase the synthesis of gastroduodenal mucus and to antagonize thromboxane A2, or 0.3 g/day of carbenoxolone. Both drugs were given orally in 3 divided doses for 4 weeks, according to the controlled design. Endoscopy showed that a greater proportion of patients treated with triletide benefited from treatment (60%) in comparison with those who had carbenoxolone (40%), but the difference was not significant. Weekly monitoring of epigastric pain, heartburn and antacid intake showed both treatments to be effective, and triletide to be overall faster acting (p less than 0.01 for epigastric pain). Subjective complaints of possible side-reactions were not recorded with either treatment; routine physical examination, haematology and haematochemistry remained unaffected by triletide, whereas treatment with carbenoxolone was associated with a significant increase in both systolic and diastolic blood pressure and with a significant decrease (p less than 0.05) in blood potassium levels. Triletide, therefore, appeared to be an effective and well-tolerated means for the therapy of gastric ulcer, and by virtue of its significantly greater symptomatic action and greater tolerance in comparison with a standard cytoprotective treatment such as carbenoxolone, it is suggested that triletide deserves consideration in the management of peptic ulcer.