Clinical reactivation during lamivudine treatment correlates with mutations in the precore/core promoter and polymerase regions of hepatitis B virus in patients with anti-hepatitis B e-positive chronic hepatitis.

BACKGROUND: Drug-resistant mutants may emerge in patients with chronic hepatitis B receiving lamivudine therapy. AIM: To evaluate whether different viral mutational patterns may be associated with clinical reactivation during lamivudine treatment in patients with chronic B hepatitis. METHODS: Eight anti-hepatitis B e-positive patients with (group A) and 14 patients without clinical exacerbation (five anti-hepatitis B e-positive, group B1; nine hepatitis B e antigen-positive, group B2) during lamivudine treatment were investigated. RESULTS: 'Polymerase region': M204V/I variants were found in all group A patients, but in none of group B1 (P=0.0007) and in four of nine of group B2 (44%; P=0.02) patients. The L180M substitution was detected in four of eight (50%) of group A and in none of groups B1 and B2. 'Core promoter': the double basic core promoter (A1762T/G1764A) variant was detected in seven of eight (87%) of group A and in one of five (20%; P=0.03) of group B1 and one of nine (11%; P=0.002) of group B2 patients. 'Precore': the G1896A stop codon mutation was present in seven of eight (87%) of group A and in zero of five (P=0.004) of group B1 and one of nine (11%; P=0.002) of group B2. CONCLUSIONS: Different mutational patterns were observed in the lamivudine-treated patients with and without exacerbation. There was an association of the basic core promoter and stop codon mutations with lamivudine resistance in patients with disease exacerbation.

Homocysteine-induced inhibition of nitric oxide production in platelets: a study on healthy and diabetic subjects.

AIMS/HYPOTHESIS: The molecular mechanisms involved in the platelet activation observed in hyperhomocysteinemia are not known. We aimed to discover if homocysteine concentrations are associated with abnormal platelet nitric oxide production in healthy and diabetic subjects. METHODS: The study cohort included 28 patients with Type I (insulin-dependent) diabetes mellitus, 30 patients with Type II (non-insulin-dependent) diabetes mellitus, and 34 healthy subjects. Homocysteine plasma concentrations were measured by high-performance liquid chromatography. Platelet nitric oxide production was measured using a nitric oxide meter before and after a 3-h incubation with 100 micromol/l homocysteine. Stimulation experiments were done in vitro by the addition of alpha-thrombin (0.2 U/ml). RESULTS: Basal platelet nitric oxide production was lower in diabetic patients than in healthy subjects. Nitric oxide release was reduced by in vitro homocysteine incubation, being lower in platelets from diabetic patients than in platelets from control subjects. Thrombin increased nitric oxide synthesis in platelets from healthy subjects both in the presence and absence of homocysteine. In diabetic subjects thrombin increased nitric oxide release in the absence of homocysteine. But in the presence of homocysteine the response was reduced. An inverse relation was found between plasma homocysteine levels and basal platelet nitric oxide release in diabetic and healthy subjects. CONCLUSION/INTERPRETATION: Homocysteine could exert its atherogenic action in healthy and diabetic subjects partly by inhibiting platelet nitric oxide production with the subsequent increased platelet activation and aggregation.

Vitamin E intake reduces plasminogen activator inhibitor type 1 in T2DM patients.

Previous studies hypothesised that vitamin E could protect against coronary heart disease and vascular complications in diabetes, but no studies have been performed regarding its eventual effects on fibrinolysis. Nevertheless, in Type 2 diabetes mellitus (T2DM) a profound reduction in the fibrinolytic activity has been demonstrated to be involved in vascular complications, probably due to plasminogen activator inhibitor type 1 (PAI-1) overproduction. On this basis we aimed to verify whether an antioxidant treatment with vitamin E is able to lower PAI-1 plasma levels in T2DM. Thirteen T2DM patients (9 males and 4 females; mean age+/-SD, 64.4+/-3.3 yr) were selected through strict admission criteria. These patients were treated with vitamin E (500 IU/die) for 10 weeks. Glyco-lipometabolic, oxidative and haemocoagulative parameters were evaluated at baseline and after 5, 10, 30 and 60 weeks. Vitamin E levels at different times were [median (interquartile range)] 6.1 (5.3-7.7), 8.5 (7.3-9.9), 9.7 (8.9-12.9), 5.6 (4.4-6.8), 5.7 (4.5-7.1) microg/ml, respectively. Significant differences were found for PAI-1 antigen (p=0.006), PAI-1 activity (p=0.028), apolipoprotein B (p=0.015) and antioxidant defence, evaluated as ferric reducing ability of plasma (FRAP) values (p=0.005). Particularly, decrements were detected for PAI-1 antigen between baseline and the 10th week (p<0.05), followed by an increase back to basal at the 30th week. Similar behaviour was found for PAI-1 activity. Regarding the antioxidant defence, FRAP values increased until the 30th week (p<0.05) with a decrease at the 60th week. These results demonstrate that vitamin E is able to lower PAI-1 levels in diabetic patients but this effect does not seem related to improvements of glycometabolic data or to the increase in FRAP values, suggesting that PAI-1 overproduction can be decreased by other effects of vitamin E on endothelial cells.

Physical activity and biochemical markers of bone turnover in elderly patients.

To assess the role of physical therapy in improving the remodelling processes of bone turnover, biochemical markers of bone formation and resorption (osteocalcin, parathormone, bone-specific alcaline phosphatase, somatotropic hormone, C-terminal propeptide type I procollagen, somatomedin, insulin-like growth factor bound protein, C-terminal telopeptide type I collagen) have been investigated in elderly patients before and after a cycle of physical therapy. Patients of both sexes, immobilized on hospital admission day because of fractures or neurologic diseases, underwent physiotherapy for one month. Following physical treatment we found significant increases of osteocalcin, bone-specific alcaline phosphatase and somatomedin in the female group, while no significant difference was detected in males. Our data support that the mechanical stimulus significantly improves the recovery of osteoblastic activity in women, while in men the increases in bone remodelling markers are not significant. Differences in life-style between male and female patients are proposed as determinants in the bone remodelling response to physical therapy.

Morphological alterations and increased resistance to hemolysis in t-butyl hydroperoxide incubated RBC from elderly subjects.

The response of human red blood cells (RBC) to oxidative stress has been studied with the aim to evaluate any difference in the behavior of cells from young and old subjects. Thus, RBC from 5 young (27 +/- 2 years) and 5 old (80 +/- 5 years) individuals have been treated with the organic peroxide t-butyl hydroperoxide (TBHP). The two groups behaved differently: after 4 hrs of incubation in 0.5 mM TBHP, RBC from young donors showed a higher level of hemolysis; instead, RBC from old individuals showed abnormal morphologies, being absent in unstressed RBC, with constriction and budding, which could be identified as poikilocytosis. The same abnormal forms are found in patients with spectrin mutation, leading us to hypothesize that TBHP causes damage to the cytoskeletal spectrin. This suggests that poikilocytosis might be an early stage of red blood cell hemolysis because their presence is associated to a lower level of hemolysis.

[Congenital isolated complete atrioventricular block: long-term experience with 38 patients]. / Blocco atrioventricolare completo congenito isolato: esperienza a lungo termine in 38 pazienti.

BACKGROUND: The management of patients with isolated congenital complete heart block is controversial, and indications for cardiac pacing are not clearly defined. In the present study we report our long-term experience in the management of patients with this disease. METHODS: Thirty-eight consecutive patients aged 2 days to 28 years (mean age 10 years) were studied and followed up for 130 +/- 57 months (range 18 to 274). They underwent an extensive evaluation including history, physical examination, electrocardiography and echocardiography; thirty-seven patients had Holter monitoring and exercise test. Electrophysiologic study was performed in 24 patients. RESULTS: Twenty-two patients were asymptomatic, sixteen had symptoms as syncope or presyncope (7 patients), marked exercise intolerance (1 patient), presyncope and marked exercise intolerance (1 patient), heart failure (1 patient), mild dyspnea on exertion (6 patients). Electrocardiograms showed a narrow QRS in all patients. Holter monitoring showed a marked bradycardia (awake heart rate < or = 55 beats/min in infants, < or = 40 beats/min in children and adults) in 15 patients and junctional pauses of > 3 seconds in 9 of them. The exercise test showed a markedly reduced exercise tolerance in 2 patients and exercise-induced complex ventricular arrhythmias in 3 patients. Echocardiography showed a structurally normal heart and a normal left ventricular function in all patients. The electrophysiologic study always showed a suprahisian site of block. Twenty patients (53%) underwent cardiac pacing at a median age of 14 +/- 10 years and were followed up for 110 +/- 59 months (range 18 to 253) after pacing; prophylactic pacing was performed in 10 patients. Indications for cardiac pacing were: syncope or presyncope (7 patients), presyncope and marked exercise intolerance (1 patient), neonatal heart failure (1 patient), marked exercise intolerance (1 patient), neonatal marked bradycardia (2 patients), marked bradycardia with junctional pauses of > 3 seconds and/or complex ventricular arrhythmias (7 patients), complex ventricular arrhythmias (1 patient). No death occurred during the follow-up. In 9 of 20 patients who had cardiac pacing, indication for this procedure appeared during the follow-up (development of symptoms, marked bradycardia and/or complex ventricular arrhythmias). Complications of pacing were infrequent (9 complications in 7 patients) and mainly occurred in the first years of our experience. At present 12 patients have an atrioventricular sequential pacing and 8 have a rate-responsive ventricular one. All patients who had pacing showed an improvement of exercise tolerance; 11 of them underwent exercise test after pacing which showed a significant increase in exercise duration (from 11.1 +/- 1.9 to 15.3 +/- 1.1 min, p < 0.01). In the 3 patients with complex ventricular arrhythmias we observed their suppression after atrioventricular sequential pacing. At present 35 patients are asymptomatic and 3 have mild dyspnea on exertion. CONCLUSIONS: Our results confirm that patients with isolated congenital complete heart block often have symptoms and/or signs of electric instability without symptoms. Cardiac pacing relieves symptoms and improves working capacity. Although in this study we are not able to draw conclusions on the therapeutic value of prophylactic pacing, our favourable follow-up results suggest that this therapeutic approach may prevent complications.

Relationships between obesity and ischaemic heart disease in type II diabetic subjects homozygous for the apoprotein E3 allele.

The purpose of the present study was to evaluate the influence of obesity on ischaemic heart disease frequency in a well-documented type II diabetic population. To eliminate one of the possible sources of variability for plasma lipid concentrations, only subjects showing the apoprotein E phenotype, indicative of homozygosity for the epsilon 3 allele (i.e. an E3/E3 genotype), have been recruited. A larger prevalence of ischaemic heart disease was noticed among obese patients as compared to non-obese or merely overweight subjects according to a higher frequency of hypertension and to higher triglyceride concentrations. These results corroborate the hypothesis of a common pathogenesis of the major cardiovascular risk factors.

[Idiopathic scoliosis in a student population]. / Studio della scoliosi idiopatica in una collettività scolare.

The etiology of idiopathic thoracic scoliosis is a relevant problem in the fields of scholastic medicine and orthopaedics. This disease affects a population of pre-adolescent between ten and fifteen years of age. This study is based on our observations within a population of junior high school students in a suburban town of central Italy. Our data are based on clinical examinations, and the analysis of biophysical and environmental factors evidentiate the genetic and hereditary factors that are of prime importance in the pathogenesis of thoracic idiopathic scoliosis. It's our goal, to inform the scholastic doctor, the orthopaedist, the pediatrician and the internist on the main clinical and evolutionary aspects of thoracic idiopathic scoliosis and other related vertebral pathology. We therefore believe, that a good diagnosis should be based on a thorough genetic and clinical examination; not to mention an examination of vertebral bone morphology in order to exclude other forms of thoracic scoliosis.

[Postoperative constrictive pericarditis]. / La pericardite costrittiva post-chirurgica.

Seven cases of postoperative constrictive pericarditis (PCP) were discovered in a retrospective study of patients given heart surgery in a hospital receiving patients from all over Italy in 1970-85. Five of those patients had received surgery for chronic rheumatic heart disease, 2 for congenital heart defects. Four had received a second heart operation before the pericardial condition was recognised. All were females and all presented systemic venous hypertension (one of them only after acute doses of physiological solution) with thickening of the pericardial layers revealed by sonography. In six cases the electrocardiographic ventricular complexes were normal or increased in amplitude and the heart/chest ratio was greater than 0.55. Pericardial knock was masked by natural or artificial atrioventricular valve opening noises in 6 cases. In one case only there were pericardial calcifications or signs of an earlier postpericardiotomy syndrome. The haemodynamic investigation revealed signs of ventricular diastolic constriction in 6 patients. Three patients died from complications of cardiac cirrhosis: 2 of them had previously received partial pericardiectomy. Another two, given the same operation, preserved a reasonable functional capacity 5 and 10 years after the pericardiectomy. One patient in NYHA functional class III has so far refused haemodynamic assessment (and surgical treatment) of the pericardial disease. Finally, the last patient complains only of attacks of heart palpitation caused by atrial flutter and controlled by antiarrhythmic treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

[Aortic coarctation surgically treated in the 1st year of life. Results in 36 cases]. / La coartazione aortica operata nel primo anno di vita. Risultati in 36 casi.

Thirty-six infants under one year of age underwent surgical repair of coarctation of the aorta between 1968 and 1983 in our institution. Coarctation was isolated or associated to a patent ductus arteriosus in sixteen cases, while in twenty it was associated with significant intracardiac disease. Twenty-nine patients were operated on in the first three months of life and in twenty a severe heart failure was present before the operation. Nine patients (25%) died while in the hospital: all of them were less than three months of age and all but one were affected by major intracardiac anomalies and severe heart failure. Surgical repair was by subclavian flap aortoplasty in twenty-nine cases, resection with end-to-end anastomosis in three, patch aortoplasty in three and Blalock-Park anastomosis in one. Operative mortality was unaffected by the surgical technique. The surviving children were followed-up for 30 +/- 7 months; one late death occurred suddenly, two months after the repair of a ventricular septal defect. An arm/leg pressure gradient, indicative of recoarctation, was detected in five cases: only one had been repaired by the subclavian flap technique, while the others were the only survivors of the end-to-end anastomosis and patch aortoplasty group. Subclavian flap aortoplasty is suggested as the operation of choice for coarctation of the aorta in the first year of life.