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Biomedical subjects

M Bernardi

Publications and source records attributed to M Bernardi.

At least 19 recordsLinked to original sources

Anthropometric characteristics of healthy Italian nonagenarians and centenarians.

Available anthropometric reference values for elderly people do not include specific norms for over-90-year-old subjects despite their increasing number. In the present study, weight, height and a number of anthropometric variables related to body muscle and fat mass were collected from fifty-seven nonagenarian and forty-one centenarian healthy, non-institutionalized subjects living in an Italian area. Recumbent anthropometry was used to avoid errors associated with impaired mobility. Nonagenarians and centenarian men were taller and heavier than women of corresponding age and had a greater amount of muscle and trunk fat, whereas women showed a marked peripheral adipose distribution. Anthropometric values of both age-groups were generally lower than published norms for 70-89-year-old American and European elderly people. However, differences were less marked when comparing Italian nonagenarians and centenarians with French and British people aged 85 years and over than when comparing Italian subjects with American octogenarians and younger European elderly people. Taken together these findings suggest a dramatic loss of muscle and fat mass in over-90-year-old subjects with respect to younger elderly people. However, changes between successive generations and geographical influences cannot be excluded. The need for local and age-specific norms in nutritional assessment of over-90-year-old people is emphasized. It is also suggested that current anthropometric indices may not be reliable when evaluating the oldest elderly subjects.

Aged

Clinical and pathologic features of hepatocellular carcinoma in young and older Italian patients.

BACKGROUND: It is not known whether putative etiologic factors and clinical and pathological features of hepatocellular carcinoma (HCC) differ between young adult and older white patients. METHODS: We examined the characteristics of 498 consecutive patients with HCC age < 50 years (Group 1: 54 patients) and age > or = 50 (Group 2: 444 patients), an age beyond which the tumor occurrence rate briskly increases. RESULTS: Demographic characteristics, alcohol and coffee intake, and cigarette smoking did not differ between the two groups. Group 1 had a greater prevalence of the hepatitis B surface antigen (HBsAg) carriers (P = 0.006), while the prevalence of either past hepatitis B virus infection (P = 0.008) or antivirus C antibodies (P = 0.016) was higher in Group 2. The lack of both hepatitis B and C virus serologic markers was more common in Group 1 (P = 0.018). In these patients, HCC was less frequently superimposed on cirrhosis (P = 0.002) and was more advanced at the time of diagnosis. In fact, despite a better histologic differentiation grade (P = 0.019), monofocal (solitary and massive) tumors were larger (P = 0.012), small lesions (< or = 5 cm) less frequent (P = 0.028), and either diffuse (P < 0.001) or massive (P = 0.011) types more common. An elevation of serum alpha-fetoprotein was less frequent in group 1 (P = 0.016), but this difference disappeared when the "diagnostic" cut-off of 400 ng/mL was considered. Albeit the prevalence of presenting symptoms did not significantly differ between the two groups, the clinical stage was more advanced in young patients (P = 0.004). The 9-year cumulative rate of survival was similar in the 2 groups. CONCLUSIONS: An early exposure to the virus and/or an accelerated hepatocarcinogenesis in HBsAg carriers can be inferred. Moreover, in the period of life at low risk for hepatoma: (1) the impact of nonalcoholic chemical carcinogenesis seems to be greater; (2) the tumor occurrence is less dependent on cirrhosis development; (3) although histologically better differentiated, the neoplasm is more advanced at the time of diagnosis; and (4) the long term survival is similar to that of the patients age 50 years or older.

Adolescent

Blockade of the polyamine site of NMDA receptors produces antinociception and enhances the effect of morphine, in mice.

The possible effect of ifenprodil--a potent antagonist at the polyamine site of the NMDA receptor complex--on nociceptive threshold and morphine analgesia was investigated in mice. In the hot plate test, the intraperitoneal (i.p.) injection of ifenprodil significantly prolonged the reaction time of mice at the dose of 30 mg/kg, and increased the analgesic effect of morphine. In the phenylquinone writhing test, ifenprodil reduced the number of abdominal constrictions of mice starting from the dose of 2.5 mg/kg i.p., and increased the effect of morphine. The effect of ifenprodil on pain threshold was prevented by naloxone. Moreover, ifenprodil antagonized the pain threshold-reducing effect of alpha-melanocyte-stimulating hormone (0.05 microgram/mouse, intracerebroventricularly). These data show that blockade of the polyamine site of the NMDA receptor complex produces analgesia and increases the analgesic effect of morphine.

Analgesia

A randomized controlled trial of thymosin-alpha1 versus interferon alfa treatment in patients with hepatitis B e antigen antibody--and hepatitis B virus DNA--positive chronic hepatitis B.

It has recently been shown that thymosin-alpha1(T-alpha1), a synthetic polypeptide of thymic origin, is able to promote disease remission and inhibition of hepatitis B virus (HBV) replication in patients affected by hepatitis B e antigen (HBeAg)-positive chronic active hepatitis. We evaluated the efficacy and safety of T-alpha1 treatment in patients with hepatitis B e antibody (anti-HBe) and HBV-DNA-positive chronic hepatitis. Thirty-three patients were randomly assigned to receive either T-alpha1 900 microg/m2 body surface area twice weekly (17 patients) or 5 MU of interferon alfa (IFN-alpha) three times weekly (16 patients) for 6 months. At baseline, both groups were comparable concerning age, sex, liver histology, and alanine transaminase (ALT) levels. At the end of treatment, complete response (defined as ALT normalization and HBV-DNA loss) occurred in 5 of 17 (29.4%) in the T-alpha1 group and in 7 of 16 (43.8%) in the IFN-alpha group (P = not significant). After a follow-up period of 6 months, a complete response was observed in 7 of 17 (41.2%) in the T-alpha1 group and in 4 of 16 (25%) in the IFN-alpha group (P = n.s.). Compared with the results observed in a group of 15 patients never treated with IFN-alpha and followed for 12 months, the rate of complete response was significantly higher in the IFN-alpha group at the end of therapy (1 of 15 vs. 7 of 16, respectively; P < .05) and in the T-alpha1 group at the end of follow-up (1 of 15 vs. 7 of 17, respectively; P < .05). Unlike IFN-alpha, T-alpha1 was well tolerated by all patients. The only side effect, reported by some, was local discomfort at injection sites. The results of this trial suggest that T-alpha1 is able to reduce HBV replication in patients affected by anti-HBe-positive chronic hepatitis. Furthermore, compared with IFN-alpha, T-alpha1 is better tolerated and seems to induce a gradual and more sustained ALT normalization and HBV-DNA loss. In conclusion, T-alpha1 appears to be a safe and effective alternative treatment for anti-HBe-positive chronic hepatitis. The benefit of this agent in producing long-term inhibition of HBV replication must be confirmed by future trials.

Adult

Motor unit recruitment strategy changes with skill acquisition.

The modifications of motor unit recruitment strategy due to skill acquisition was determined in the elbow flexor-extensor muscles of normal human subjects. The median frequency of the power density spectra of the electromyograms recorded from the biceps and triceps muscles during a 3-s linear increase in flexion force in the range of 0-100% maximal voluntary contraction (MVC) was calculated for each subject, every 2 weeks over a total 6-week period during which subjects practiced linear flexion force increase three times a week. Electromyograms were recorded with two pairs of electrodes of different size and electrode spacing. It was shown that skill acquisition due to the 360 practice trials over the 6-week period caused an increase in the initial motor unit recruitment phase of the agonist's force generation cycle from about 0-65% MVC to about 0-85% MVC. The increase in the recruitment range was gradual and statistically significant for the measurements made every 2 weeks. The recruitment range of the antagonist triceps demonstrated a minor, but statistically insignificant, decrease over the same training period. There was a minor, but statistically insignificant, advantage of using small electrodes and inter-electrode spacing. It was concluded that skill acquisition, due to repeated functional use of a muscle in the same contraction mode, results in a slower, prolonged recruitment of motor units in the initial segment of the force generation cycle, thereby allowing a more precise and accurate control of the increments of force increase. Such conclusions reinforce the concept advocating the plasticity of motor unit control according to the functional demands imposed on the muscle. The results have significant implications in the design of various athletic, occupational and rehabilitation training modalities for optimal performance of various movement functions.

Adult

Effect of ethanol on adenosine triphosphate, cytosolic free calcium, and cell injury in rat hepatocytes. Time course and effect of nutritional status.

The events implicated in the early phases of acute ethanol-induced hepatocyte injury and their relation with the nutritional status of the liver are not clearly defined. We aimed to determine the effect of ethanol on ATP and cytosolic free Ca2+ in hepatocytes isolated from fed or fasted rats. Cell injury was assessed by LDH release and trypan blue uptake, ATP by [31P]NMR spectroscopy, and cytosolic free Ca2+ with aequorin. In control conditions, cells from fasted animals had a lower ATP level (-52%) and a higher cytosolic free Ca2+ (+101%) than did those isolated from fed animals. Ethanol caused a dose-dependent cell injury in both groups. At all ethanol doses, greater, damage occurred when using hepatocytes isolated from fasted rats. In both groups, a dose-dependent decrease in ATP content and a rise in cytosolic free Ca2+ were seen. The magnitude of these changes were significantly greater in the fasted group. In conclusion, these data showed that fasting affects the energy status and cytosolic free calcium level in hepatocytes; ethanol causes a dose-dependent cell injury that occurs in association with a fall in ATP and a rise in cytosolic free Ca2+ levels. The nutritional status of an animals is an important determinant of the severity of ethanol-induced damage to liver cells.

Adenosine Triphosphate

Influence of pattern of clinical presentation and of gluten-free diet on bone mass and metabolism in adult coeliac disease.

Since no information is available on bone derangements in subclinical coeliac disease (CD), we evaluated bone mineral density (BMD, expressed as z score) at lumbar spine, by X-ray dual-photon absorptiometry, and serum indices of bone metabolism and remodeling in 14 subclinical or silent patients, 10 classical patients, and 15 healthy volunteers all on a gluten-containing diet. In the subclinical group, BMD at lumbar spine was significantly higher than in the classical group (-1.3 +/- 0.8, 73% vs. -2.6 +/- 0.6, 88%, respectively; p < 0.001), but significantly lower than in volunteers (+0.4 +/- 1.1, 104%; p < 0.001). Similar changes were observed in serum calcium, whereas, as regards parathyroid hormone, no significant difference was found between subclinical and classical patients. 25-vitamin D was significantly lower, and 1,25-vitamin D was significantly higher in subclinical and classical patients than in healthy volunteers. Indices of bone remodeling were higher in the subclinical and classical groups than in the volunteers, but lower in the subclinical than in classical patients. Eight subclinical and 8 classical patients were reexamined after a period of gluten-free diet (GFD), and in both groups BMD had significantly improved. Our results show that osteopenia is a frequent feature also in subclinical CD, although the extent of bone and mineral metabolism derangements is lower than in classical CD. GFD is able to normalize BMD in subclinical and to significantly improve it in classical patients.

Absorptiometry, Photon

Plasma endothelin-1 and -3 in cirrhosis: relationship with systemic hemodynamics, renal function and neurohumoral systems.

BACKGROUND/AIMS: The postural change from upright to supine is a physiological maneuvre which increases central blood volume. This model was used to investigate the effects of changes in effective volemia on plasma endothelin-1 and -3 concentrations in cirrhosis. METHODS: Plasma endothelin concentrations, measured by radio-immunoassay, were determined in 20 patients with cirrhosis, 10 of whom has ascites, and nine healthy control subjects, in the upright posture and 30, 60 and 120 min after the assumption of the supine position. RESULTS: In the upright posture, endothelin-1 was 8.9 +/- 0.4 pg/ml and endothelin-3 3.7 +/- 0.6 (mean +/- SEM) pg/ml in control subjects. Endothelin-1 was increased only in patients with ascites (12.7 +/- 1.4 pg/ml, p < 0.05; patients without ascites: 9.7 +/- 0.7 pg/ml), while endothelin-3 was elevated in both patients with and without ascites (8.0 +/- 1.5 pg/ml, p < 0.01; 5.9 +/- 0.5 pg/ml, p = 0.01, respectively). In the supine position, no significant changes in endothelin-1 or -3 occurred either in patients with ascites or in controls throughout the observation period, while a reduction in endothelin-3 was found in compensated patients after 30 and 60 min. In patients, we found negative correlations between endothelin-3, but not endothelin-1, and mean arterial pressure, both in upright (r = -0.59; p < 0.01) and supine (r = -0.56; p = 0.01) positions, atrial natriuretic factor (r = 0.50; p < 0.05) and plasma renin activity (r = 0.67; p = 0.001) in the supine position alone. In patients with ascites, endothelin-1 was inversely correlated with both glomerular filtration rate (upright: r = -0.62; p = 0.06; supine: r = -0.71, p < 0.05) and renal sodium excretion (upright: r = -0.82; p < 0.01; supine: r = -0.88; p < 0.001). CONCLUSIONS: Plasma endothelin-1 and -3 were increased in cirrhosis with ascites, while, in pre-ascitic cirrhosis, only endothelin-3 was increased in the upright posture. Although increased endothelin-3 was associated with features suggesting a reduced effective volemia, it is likely that other mechanisms than hypovolemia were mainly responsible for high plasma endothelin levels. Increased endothelin production may play a role in circulatory and renal function abnormalities of advanced cirrhosis.

Adult

Prognostic value of the galactose test in predicting survival of patients with cirrhosis evaluated for liver transplantation. A prospective multicenter Italian study. AISF Group for the Study of Liver Transplantation. Associazione Italiana per lo Studio del Fegato.

AIMS/METHODS: The present study aimed to examine whether the galactose elimination capacity can be used to predict the survival of patients with advanced liver disease. We studied 194 patients with cirrhosis, belonging to Child class B and C, for 2 years each. RESULTS: The overall probability of survival was 79% at 6 months, 72% at 1 year and 62% at 2 years. Variables significantly associated with the duration of survival, as assessed by univariate analysis, were the Child-Pugh score, presence of ascites, size of esophageal varices, prothrombin time, albumin, bilirubin, urea, creatinine, glucose and galactose elimination capacity. By a multivariable analysis, only Pugh score (p = 0.005), creatinine (p < 0.001), varices (p = 0.001) and galactose elimination capacity (p < 0.001) were independent predictors of mortality. The galactose elimination capacity was even more sensitive when the end-point was limited to deaths due to liver failure and hepatorenal syndrome. A new score obtained by summing the Pugh score with a score derived from galactose elimination capacity was quite simple and accurate for predicting survival. CONCLUSIONS: The quantitative measurement of liver function as the galactose elimination capacity could be of use to identify patients with cirrhosis and probable short survival who might benefit most from urgent transplantation.

Adolescent

An open multicentric study evaluating 4-hydroxybutyric acid sodium salt in the medium-term treatment of 179 alcohol dependent subjects. GHB Study Group.

We report the results of an "open' multicentre study evaluating the use, tolerability and therapeutic efficacy of the sodium salt of 4-hydroxybutyric acid (GHB) for the medium-term treatment of withdrawal symptoms in 179 patients with alcohol dependence followed up as outpatients. The follow-up of patients was 6 and 12 months after drug discontinuation. Following a daily oral administration of 50 mg/kg for approximately 6 months, no serious systemic or single-organ consequences leading to drug discontinuation were reported, and tolerability was fair in all patients. Eleven subjects (10.1%) showed craving for the drug and voluntarily increased their doses (6-7 times the recommended levels). GHB led to complete abstinence during drug administration in 78.0% of the patients. A significant reduction of compulsive desire ("craving') was observed in parallel, as deduced from evaluation of a specific questionnaire, the Alcohol Craving Scale. At follow-up examination, 43 of the treated subjects remained abstinent at 6 months, and 30 subjects were abstinent for 1 year after drug discontinuation.

Adolescent

A double-blind, placebo-controlled, pilot trial of thymosin alpha 1 for the treatment of chronic hepatitis C.

A randomized, double-blind, placebo-controlled trial was performed to evaluate the efficacy and safety of thymosin alpha 1 (alpha 1) in treating chronic hepatitis C. Nineteen Italian patients with chronic active hepatitis C, proven by biopsy were randomly assigned to receive a six month course of thymosin alpha 1 (900 micrograms/m2 of body surface area twice weekly) or a placebo. All had HCV-RNA in their serum (by PCR), with serum ALT levels more than double the upper limit of the normal range for at least six months before enrollment. After treatment, patients were followed for an additional six months. All patients completed the trial. One patient treated with thymosin alpha 1, but no patient in the placebo group, normalized serum ALT levels by the end of the treatment. This patient, however, relapsed at the sixth month of the follow up. Overall, there were no significant changes in mean serum ALT levels in either group during the treatment or follow-up period. No patient cleared HCV-RNA. No side effects were reported except for local discomfort at the injection sites, reported by some patients treated with thymosin alpha 1. In conclusion, this regimen of thymosin alpha 1 is not effective in the treatment of chronic hepatitis C.

Adult

Incidence of hepatitis C virus infection in Italian patients with idiopathic pulmonary fibrosis.

BACKGROUND: A viral cause of idiopathic pulmonary fibrosis (IPF) was recently suggested by a Japanese study in which a high prevalence of anti-hepatitis C virus (HCV) antibodies was detected. A subsequent British study failed to confirm these results. METHODS: Antibodies to HCV were evaluated in 60 patients with IPF, 130 patients with non-interstitial lung disease, and in 4614 blood donors. HCV-RNA and HCV genotypes were evaluated in the anti-HCV positive patients with IPF. Anti-HCV antibodies were evaluated by ELISA and confirmed by recombinant immunoblotting assay (RIBA). HCV-RNA and genotypes were detected by reverse transcriptase polymerase chain reaction (PCR). RESULTS: Eight patients with IPF had anti-HCV antibodies detected by ELISA (13.3%). In the blood donor control group the prevalence of HCV antibodies was lower (0.3%). In patients with non-interstitial lung disease HCV antibody prevalence was 6.1%. In all eight patients with IPF found to be anti-HCV positive by ELISA, HCV antibodies were also detected by RIBA. Furthermore, all were HCV-RNA positive by PCR assay. HCV genotypes were identified in four of these eight patients. In all four genotype II was present and in two it was associated with genotype III and/or genotype IV. In the remaining four cases the genotype was not identified. CONCLUSION: Italian patients with IPF show an increased prevalence (approximately 13%) of HCV infection and viral replication, but the prevalence of anti-HCV antibodies does not differ from other lung diseases.

Adult

The relationship of dehydroepiandrosterone sulfate (DHEAS) to endocrine-metabolic parameters and functional status in the oldest-old. Results from an Italian study on healthy free-living over-ninety-year-olds.

Dehydroepiandrosterone sulfate (DHEAS), the major circulating adrenal hormone, has been suggested to have a role in many aging related diseases and perhaps in aging itself. Its precise biologic effects are still unknown, and data on healthy people over 90 yr of age are not available. We measured serum DHEAS levels in 75 healthy subjects aged 90-106 yr of both sexes and searched for correlations between DHEAS and several endocrine-metabolic parameters (serum thyroid hormones, GH-insulin-like-growth factor I (GH-IGF-I) axis, serum lipid profile, anthropometric indices of body composition) of the same subjects. The resulting data, normalized by logarithmic transformation (geometric mean at age 90-99, 551 ng/mL in men, 364 ng/mL in women; at age > 100 yr, 404 ng/mL in men, 521 ng/mL in women) resulted five-fold lower than DHEAS levels measured in a young control group (geometric mean at < 40 yr of age, 3110 ng/mL in men, 2824 ng/mL in women). In women over ninety yr, DHEAS was positively correlated with serum free triodothyronine (FT3) levels (r = 0.34, P = 0.05) and inversely with triglycerides (r = -0.45, P = 0.05). In men over 90 yr, DHEAS had positive correlations with body mass index (r = 0.41, P < 0.03) and waist-to-hip ratio (r = 0.47, P < 0.01) taken as indices of body's energy reserves (fat). To determine whether low serum DHEAS levels predict poor functional status in the very old, the Activity Daily Living (ADL) test was administered in all over-ninety subjects. Men with the highest functioning levels had the highest DHEAS levels (P < 0.03). Our data suggest that DHEAS levels may influence and/or be influenced by several endocrine and metabolic features of oldest-old people, depending on the sexual steroid milieu. DHEAS seems also to have a strong interrelation with functional activities. A favorable role for DHEAS in successful aging is proposed.

Activities of Daily Living

[Virus titre and histological inflammation activity in chronic hepatitis C].

We determine the correlation between viremia in serum specimens, transaminase activity (ALT and AST) and histological grading in 37 patients with chronic hepatitis C. In addition we compared two PCR methods for hepatitis C virus (HCV)-RNA in serum specimens. For the histological grading we used a modified Knodell score. For detection and quantification we measured the viremia (HCV-RNA titer) with a standardized "nested primer" PCR (end-point dilution method) and the commercially available Amplicor HCV Monitor. The mean HCV-RNA and AST level was significantly higher in patients with a histologically active inflammation. In the individual patient we could not conclude from the titer of HCV-RNA on the histologic grading because of the wide range of the results. We did not find a significant difference in ALT in patients having varying histological gradings. HCV-RNA titer and transaminases (ALT and AST) did not correlate significantly. The HCV-RNA titer was significantly marked in older patients (above 40 years) and patients having sporadic hepatitis than in younger patients and patients with chronic hepatitis after drug abuse. The "nested primer" PCR (end-point dilution method) was more sensitive for detection of HCV-RNA in serum specimens than Amplicor HCV Monitor. The lack of HCV-RNA with Amplicor HCV Monitor in 12 of 37 patients (32%) did not rule out viremia. We conclude that in patients with a chronic hepatitis C marked viremia points to a histologically active inflammation. In the individual patient we could not conclude from the titer of HCV-RNA on the histological grading. Because of the lower sensitivity of Amplicor HCV Monitor it is necessary to confirm negative results with a "nested primer" PCR.

Adult