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Biomedical subjects

L Bianchi

Publications and source records attributed to L Bianchi.

At least 91 records · Page 5Linked to original sources
PubMed2000

Impact of switching from human immunodeficiency virus type 1 protease inhibitors to efavirenz in successfully treated adults with lipodystrophy.

We prospectively followed 20 consecutive patients with human immunodeficiency virus type 1 (HIV-1) with viral loads of <200 RNA copies/mL. These patients had been treated with 2 nucleoside reverse transcriptase inhibitors and > or =1 HIV-1 protease inhibitor for > or =3 months; they developed body changes consistent with lipodystrophy and requested they be switched from protease inhibitor to efavirenz. At baseline and every 3 months, we assessed the following: body mass index, waist-to-hip ratio, regional fat thickness (assessed by sonography), fasting total and high-density lipoprotein cholesterol, triglycerides, glucose, insulin, CD4(+) cells, and viral load. At baseline, hypertriglyceridemia (> or =200 mg/dL) was present in 17 (85%) patients, hypercholesterolemia (> or =200 mg/dL) in 14 (70%), and impaired fasting glucose (> or =110 mg/dL) in 8 (40%); CD4(+) T cells were 280x10(6) cells/L (range, 64-942x10(6) cells/L). HIV-1 RNA had been at <200 copies/mL for a median of 14 months (range, 3-24 months). Six months after switching to efavirenz, there was a reduction in triglyceride levels (a decrease of 31%; P=.03) and fasting insulin resistance index (a decrease of 28%; P=.03), but total and high-density lipoprotein cholesterol and glucose did not change. Waist-to-hip ratio decreased from 0.92 to 0.87 (P=.06). Subcutaneous fat thickness did not change. CD4(+) cells remained stable (363x10(6) cells/L; range, 102-741x10(6) cells/L; P=.65). Nineteen patients (95%) had HIV-1 RNA levels that remained at <200 copies/mL. Although CD4(+) response and viral suppression remained preserved after 6 months of switching from protease inhibitor to efavirenz, the benefits of this approach on the evolution of lipodystrophy were limited, and our findings do not support its routine recommendation to treat lipodystrophy.

Adipose Tissue↗
PubMed2000

Sonographic assessment of regional fat in HIV-1-infected people.

The routine clinical assessment of lipodystrophy in HIV-1-infected patients is hindered by the absence of easy and reliable methods to measure regional fat. We used sonography to measure subcutaneous fat thickness at three reference skin points (periumbilical, brachial, and malar) and intra-abdominal fat thickness in HIV-1-infected patients with and without lipodystrophy and in healthy controls. Patients without lipodystrophy had less subcutaneous fat than uninfected controls. Sonographic assessment of subcutaneous malar and brachial fat in patients with lipodystrophy was more sensitive and specific than that of intra-abdominal fat in the diagnosis of abnormal fat distribution.

Adult↗
PubMed2000

Striatal A2A adenosine receptor antagonism differentially modifies striatal glutamate outflow in vivo in young and aged rats.

The effect of the adenosine A2A receptor antagonist SCH 58261 on glutamate release was investigated in the striatum of young and old rats by microdialysis experiments. SCH 58261 (50 nM) significantly decreased the spontaneous and K+-evoked glutamate outflow in young rats. In aged rats, spontaneous glutamate outflow was significantly reduced in comparison to young rats and SCH 58261 significantly increased spontaneous and K+-evoked glutamate outflow. It is suggested that the opposite effects of the A2A antagonist on glutamate outflow in young and aged rats can be respectively attributed to blockade of striatal A2A adenosine receptors located on glutamatergic terminals and on the striatal indirect output pathway.

Adenosine↗
PubMed2000

Do glia have heart? Expression and functional role for ether-a-go-go currents in hippocampal astrocytes.

Potassium homeostasis plays an important role in the control of neuronal excitability, and diminished buffering of extracellular K results in neuronal Hyperexcitability and abnormal synchronization. Astrocytes are the cellular elements primarily involved in this process. Potassium uptake into astrocytes occurs, at least in part, through voltage-dependent channels, but the exact mechanisms involved are not fully understood. Although most glial recordings reveal expression of inward rectifier currents (K(IR)), it is not clear how spatial buffering consisting of accumulation and release of potassium may be mediated by exclusively inward potassium fluxes. We hypothesized that a combination of inward and outward rectifiers cooperate in the process of spatial buffering. Given the pharmacological properties of potassium homeostasis (sensitivity to Cs(+)), members of the ether-a-go-go (ERG) channel family widely expressed in the nervous system could underlie part of the process. We used electrophysiological recordings and pharmacological manipulations to demonstrate the expression of ERG-type currents in cultured and in situ hippocampal astrocytes. Specific ERG blockers (dofetilide and E 4031) inhibited hyperpolarization- and depolarization-activated glial currents, and ERG blockade impaired clearance of extracellular potassium with little direct effect on hippocampal neuron excitability. Immunocytochemical analysis revealed ERG protein mostly confined to astrocytes; ERG immunoreactivity was absent in presynaptic and postsynaptic elements, but pronounced in glia surrounding the synaptic cleft. Oligodendroglia did not reveal ERG immunoreactivity. Intense immunoreactivity was also found in perivascular astrocytic end feet at the blood-brain barrier. cDNA amplification showed that cortical astrocytes selectively express HERG1, but not HERG2-3 genes. This study provides insight into a possible physiological role of hippocampal ERG channels and links activation of ERG to control of potassium homeostasis.

Animals↗
PubMed2000

Endogenous nitric oxide in patients with chronic heart failure (CHF): relation to functional impairment and nitrate-containing therapies.

We assessed the levels of exhaled nitric oxide (eNO) in patients with chronic heart failure (CHF) according to the functional impairment and the use of nitrate-containing agents. Forty patients (age 55+/-9 years) were classified according to the NYHA classes I-II (n=18, group 1) and classes III-IV (n=22, group 2), and to the use of nitrate-containing drugs (Nitrate+, Nitrate-). Twenty-two healthy age-related subjects served as controls (group 3). Respiratory function, symptom-limited incremental cycloergometry and resting eNO concentration at peak (FENOp) or plateau (FENOpl) of the single-breath exhalation curve were assessed in all subjects. FENOpl was significantly lower in patients than in controls (7.8+/-2.7 and 10.6+/-2.8 ppb, respectively, P<0.005) and lower in most severe CHF patients (7.1+/-2.6 and 8.8+/-2.7 ppb in group 2 and group 1, respectively, P<0.05). A significant correlation between peak V'O(2), Watts and FENOpl (r=0.42, P<0.013 and r=0.46, P=0.008, respectively) was found. Independent of NYHA class, Nitrate+ showed higher FENOp levels than Nitrate- patients (36.9+/-15.7 vs. 28. 1+/-15.1 ppb, P<0.05). Resting eNO was lower in the most compromised CHF patients and was significantly related to exercise capacity. Nitrate-containing agents might influence the levels of eNO in these patients.

Blood Gas Analysis↗
PubMed2000

Marked genetic similarities between hepatitis B virus-positive and hepatitis C virus-positive hepatocellular carcinomas.

Hepatocellular carcinoma (HCC) is one of the most common neoplasms worldwide. Well-established risk factors include infections with two very different viruses: the DNA virus causing hepatitis B (HBV) and the RNA virus inducing hepatitis C (HCV). In order to determine whether genetic differences exist between HBV- and HCV-induced HCC, 41 HCC samples of known vival status were examined by comparative genomic hybridization (CGH). The analysis revealed frequent deletions of 1p (24%), 4q (39%), 6q (41%), 8p (44%), 9p (24%), 11q (24%), 12q (22%), and 13q (39%), as well as common gains of 1q (46%), 6p+ (20%), 8q+ (41%), 11q (27%), and 17q+ (37%). There was no significant difference in the number and type of chromosomal imbalances between 25 HCV- and 16 HBV-infected tumours. This is consistent with models suggesting that HBV and HCV cause cancer through non-specific inflammatory and regenerative processes, rather than through virus-specific interactions with defined target genes. Chromosomal imbalances were also unrelated to the grade and stage of HCC. This may suggest that most gross genomic alterations occur early during HCC development and that further progression of these tumours may be associated with other types of genetic changes, not detectable by CGH. In summary, these data show that characteristic gross genomic changes occur in HCC, but these alterations at present do not appear to have diagnostic or prognostic applications.

Adult↗
PubMed2000

Randomized controlled trial of interferon treatment for advanced hepatocellular carcinoma.

The aim of this randomized controlled trial was to assess the efficacy of interferon alfa-2b (IFN) for the treatment of advanced hepatocellular carcinoma (HCC). Fifty-eight patients with HCC who were not suitable for resection, transplantation, ethanol injection, or arterial embolization were stratified according to their Okuda stage and randomized to receive IFN (3 x 10(6), 3 times a week, for 1 year) (n = 30) or symptomatic treatment (n = 28). Both groups were identical in terms of age, sex, performance status, presence of constitutional syndrome, Child-Pugh class, Okuda stage, multinodularity, portal thrombosis, and extrahepatic spread. Adhesion to IFN treatment was adequate in 27 patients, with a mean duration of treatment of 8 +/- 3 months. However, IFN treatment was associated with side effects in 23 patients, leading to treatment discontinuation in 13 patients. Two of the 30 patients (6.6%) presented a partial response with greater than 50% size reduction and normalization of alpha-fetoprotein levels. The survival at 1 and 2 years according to intention to treat was not different between the 2 groups (58% and 38% vs. 36% and 12%, respectively, Breslow P =. 19, log rank P =.14) and the absence of difference was maintained when dividing patients according to their Okuda stage. The probability of presenting tumor progression (P =.17), or deterioration of Child-Pugh class (P =.37), performance status (P =. 07), or Okuda stage (P =.44) was not modified by IFN treatment. These results indicate that IFN is not properly tolerated in patients with cirrhosis and advanced HCC and that its administration prompts no benefit in terms of tumor progression rate and survival.

Aged↗
PubMed2000

The possible role of taurine and GABA as endogenous cryogens in the rabbit: changes in CSF levels in heat-stress.

We investigated whether heat-stress induced hyperthermia could enhance release of both endogenous taurine and GABA from nerve cells into the extracellular compartment, thus acting like endogenous cryogens. Conscious rabbits were exposed for 1 hr to 40 degrees C (heat stress) while cerebrospinal fluid (CSF) and plasma osmolality and the CSF concentrations of some cations, proteins as well as those of taurine and GABA were determined. Heat stress-induced hyperthermia was accompanied by a significant rise in CSF and plasma osmolality, CSF calcium, taurine and GABA levels. It is suggested that during heat stress taurine and GABA are released in the extracellular space of brain tissues in higher amounts, as compared to control conditions, to counteract the resulting hyperthermia, thus acting as cryogenic agents.

Animals↗
PubMed2000

Post-operative monitoring of cortical taurine in patients with subarachnoid hemorrhage: a microdialysis study.

Intracerebral MD enables the retrieval of endogenous substances from the extracellular fluid (ECF) of the brain and has been demonstrated to be a sensitive technique for early detection of subtle vasospasm-induced neurometabolic abnormalities in patients with subarachnoid hemorrhage (SAH). The aim of this study was to monitor cortical extracellular concentrations of energy metabolism markers, such as glucose and lactate, neurotransmitter amino acids, such as glutamate, aspartate, GABA and taurine to identify any neurochemical patterns of cerebral ischemia. A prospective clinical study was conducted on a group of 16 patients with non-severe SAH operated on within 72 hours after initial bleeding. Following aneurysm clipping, an MD catheter was inserted in the cortical region where vasospasm could be expected to develop, and perfused with artificial CSF at 0.3 microl/min flow rate. Dialysate was collected every 6 hours and then analyzed on High Performance Liquid Cromatography (HPLC) for glucose, lactate, pyruvate, glutamate, aspartate, GABA and taurine. Mean ECF taurine concentrations ranged from 1.4 + 0.7 to 12.3 + 7.8 micromol/l in single patients: global mean value was 5.8 + 3.8 micromol/l. In this series, the highest absolute taurine value was 25.7 micromol/l, observed in a patient who developed clinical and radiological signs of cerebral ischemia. Nine patients presented clinical disturbances related to cerebral vasospasm. In this setting, representing a mild-to-moderate hypoxic condition, MD data demonstrated that lactate is the most sensitive marker of cellular energy imbalance. Increased lactate levels positively correlated with glutamate (P<0.0001), aspartate (P<0.0001), GABA (P<0.0001) and taurine (P<0.0001) concentrations. These results suggest that also in humans increased taurine levels reflect a condition of cellular stress. This study confirms that MD is a sensitive technique to reveal subtle metabolic abnormalities possibly resulting in cell damage.

Adult↗
PubMed2000

Nasal proportional assist ventilation unloads the inspiratory muscles of stable patients with hypercapnia due to COPD.

This study was undertaken to assess the physiological effects of proportional assist ventilation (PAV), administered noninvasively through a nose mask, on ventilatory pattern, arterial blood gases, lung mechanics, and inspiratory muscle effort in stable, hypercapnic patients with chronic obstructive pulmonary disease. In 15 patients, PAV was set by adjusting volume assist (VA) and flow assist (FA) according to the "run-away" technique and the patient's comfort respectively. The level of support was fixed at 80% of the total possible assistance and averaged 13.9+/-4.1 cmH2O x L(-1) and 4.1+/-1.3 cmH2O x L(-1) x s for VA and FA, respectively. Continuous positive airway pressure (CPAP) was established at 2 cmH2O and then increased to 5 cmH2O. Physiological measurements were made during spontaneous breathing (SB), after more than 40 min of PAV, and 20 min after the rise in CPAP. On average, PAV improved ventilation (10.3+/-2.1 to 12.5+/-2.0 L x m(-1)), tidal volume (0.60+/-0.11 to 0.76+/-0.24 L), arterial oxygen tension and arterial carbon dioxide pressure (from 6.7+/-0.7 to 7.1+/-0.9 and from 7.6+/-1.0 to 7.2+/-1.2 kPa, respectively). During SB, pulmonary resistance and dynamic lung elastance averaged 15.0+/-7.6 cmH2O x L(-1) s and 15.8+/-8.0 cmH2O x L(-1), respectively. Assuming a normal chest wall elastance (5 cmH2O x L(-1)), VA and FA relieved respectively approximately 70% of the elastic and 30% of the resistive burden, with PAV set with the procedure of this study. The overall magnitude of the patients' inspiratory effort, measured by means of the oesophageal and diaphragmatic pressure time product in 10 patients was significantly reduced by PAV, on average, 328+/-122 to 226+/-118 (-31%) and 361+/-119 to 254+/-126 (-30%) cmH2O x min(-1), respectively. In 10 patients the electrical activity of the diaphragm (Edi) was also reduced by PAV to approximately 70%, on average, of the SB activity. The rise of CPAP 25 cmH2O did not cause any further significant change in the physiological variables. In all instances there was a good patient-ventilator interaction, the ventilatory breath never entering into the patient's neural expiratory time. These data show that nasal proportional assist ventilation can provide physiological benefits to the stable hypercapnic chronic obstructive pulmonary disease patients. In fact, proportional assist ventilation, which was well tolerated by all patients, unloaded the inspiratory muscles and improved arterial blood gases. Further studies can clarify whether these beneficial physiological effects of nasal proportional assist ventilation can bear profitable consequences in the overall clinical management of chronic obstructive pulmonary disease patients with chronic carbon dioxide retention.

Aged↗
PubMed2000

Clinical, virological and histopathological features: long-term follow-up in patients with chronic hepatitis C co-infected with S. mansoni.

BACKGROUND/AIMS: Infection with Schistosoma mansoni is endemic in Egypt leading to hepatic schistosomiasis and eventually portal hypertension. The prevalence of antibodies against hepatitis virus C among Egyptians is 14-51%. The aim of the present study was to investigate the influence of schistosomiasis on chronic hepatitis C with respect to the natural course of the disease, immunology, virology and histology. PATIENTS AND METHODS: One hundred and twenty-six Egyptian patients classified into three groups: group A: chronic hepatitis C (n=33); group B: chronic schistosomiasis (n=30) and group C: chronic hepatitis C and chronic schistosomiasis (n=63) were enrolled and prospectively followed for 62.7 +/- 22 months. Patients infected with other hepatic viruses and/or parasites were excluded. Detailed history, clinical examination, CD4+ and CD8+ lymphocyte counts in blood, hematological and blood chemical values, abdominal ultrasonography, upper endoscopy, HCV RNA titer by RT/PCR, genotype and histological activity index in the liver biopsy were determined. RESULTS: Thirty patients (48%) with HCV and schistosomiasis had liver cirrhosis and Child-Pugh class C vs. five (15%) in HCV patients and none in the schistosomal group. HCV RNA levels ranged between 0.07 and 13 x 10(5) copies/ml in group A, and between 1 and 25 x 10(5) copies/ml in group C. HCV genotype 4 was detected in 58 patients with co-infection (92%) and 21 patients with HCV alone (64%). Patients with coinfection showed higher grading and staging scores in their liver biopsies. Hepatocellular carcinoma was detected only in patients with coinfection. During follow-up, the mortality rate was 12%, 3% and 48% in group A, B and C, respectively. CONCLUSIONS: Patients with concomitant HCV and schistosomiasis infection were characterized by more advanced liver disease, higher HCV RNA titers, predominance of HCV genotype 4, higher histologic activity, higher incidence of cirrhosis and hepatocellular carcinoma as well as a much higher mortality rate.

Adult↗
PubMed2000

Sequential occurrence of primary sclerosing cholangitis and autoimmune hepatitis type III in a patient with ulcerative colitis: a follow up study over 14 years.

In 1983, a female patient born in 1963 presented with symptoms of ulcerative colitis and typical clinical and histological signs of primary sclerosing cholangitis (PSC). At this time only pANCA were positive while other marker antibodies for autoimmune liver disorders could not be detected. In summer 1987 the clinical picture changed and was replaced by laboratory and histological signs typical of autoimmune hepatitis (AIH). Thus, IgG levels increased considerably and cholestatic enzymes became normal. For the first time, anti-liver-pancreas antibodies (LP), a diagnostic marker for AIH type III could be detected. In the following years several relapses occurred also induced by repeated discontinuation of immunosuppressive therapy. Symptoms of colitis persisted but signs of cholestasis remained absent for the following ten years. In 1997, colitis exacerbated again and colectomy had to be performed together with liver transplantation. Surprisingly, histology of the explanted liver now showed the typical features of PSC stage III/IV while the significant criteria for AIH were now lacking. Thus, progression to cirrhosis was, probably, mainly induced by the biliary destructive and fibrotic process although biochemical and serological data were clearly indicative of an autoimmune, i.e. AIH-related manifestation.

Adult↗
PubMed2000

The antiproliferative effect of beta-carotene requires p21waf1/cip1 in normal human fibroblasts.

In normal human fibroblasts, beta-carotene induces a cell-cycle delay in the G1 phase independent of its provitamin A activity via a mechanism not yet elucidated. In this study we provide biochemical evidence showing that delayed progression through the G1 phase occurs concomitantly with: an increase in both nuclear-bound and total p21waf1/cip1 protein levels; an increase in the amount of p21waf1/cip1 associated with cdk4; the inhibition of cyclin D1-associated cdk4 kinase activity; and a reduction in the levels of hyperphosphorylated forms of retinoblastoma protein, and particularly, in phosphorylated Ser780. The role of p21waf1/cip1 in the antiproliferative effect of the carotenoid was further supported by genetic evidence that neither changes in cell-cycle progression nor in the phosphorylation status of retinoblastoma protein were observed in p21waf1/cip1-deficient human fibroblasts treated with beta-carotene. These results clearly demonstrate that p21waf1/cip1 is involved directly in the molecular pathway by which beta-carotene inhibits cell-cycle progression.

Cell Cycle↗
PubMed2000

Physiological and symptom determinants of exercise performance in patients with chronic airway obstruction.

To evaluate the physiological and symptom determinants of exercise performance (EP) as measured by a 6-min walking test (6MWD), Watt(max), and peak oxygen consumption (VO2 ml/min/kg), 105 patients with chronic airway obstruction (CAO) [50 chronic obstructive pulmonary disease (COPD): 44 men, aged 63+/-7 years, forced expiratory volume in 1 sec (FEV1) forced vital capacity (FVC)(-1)% 54+/-13; and 55 asthmatic: 23 men, aged 55+/-10 years, FEV1 FVC(-1) % 65+/-10] underwent evaluation of 6MWD, symptom limited cyclo-ergometer exercise test, spirometry, respiratory muscle function, arterial blood gases and sensation of dyspnoea [using the Borg scale, Visual Analogue Scale (VAS) and Baseline Dyspnoea Index (BDI)]. A hierarchical method of analysis identified the residual volume (RV), total lung capacity (TLC)(-1) ratio, BDI and the patient's age as the strongest and most consistent correlates of EP (r2 = 0.14-0.21). The correlation between EP and its various determinants was not influenced by diagnosis. The relationship between breathlessness and EP was different between men and women: at any given level of exercise, women were more breathless than men. In multivariate analyses that contained both RV TLC(-1) and BDI, the RV TLC(-1) ratio was the strongest correlate of EP, although the BDI remained a significant covariate. Overall, age was the major determinant of EP but inclusion of the RV TLC(-1) ratio and the BDI into the model explained a further 9-15% of the variance in EP. These three covariates together explained 26-34% of the variance between patients. We conclude that in stable CAO patients, the prediction of exercise capacity by anthropometric, demographic, clinical and physiological variables is likely to be low. Age, pulmonary hyperinflation and dyspnoea are the strongest and most consistent correlates of impaired exercise performance. Airways obstruction, measured during expiration using FEV1, does not appear to be a predictor of physiological impairment. These results underline the importance of performing exercise evaluation in CAO patients.

Aged↗
PubMed2000

Physiologic effects of early administered mask proportional assist ventilation in patients with chronic obstructive pulmonary disease and acute respiratory failure.

OBJECTIVE: To evaluate the physiologic short-term effects of noninvasive proportional assist ventilation (PAV) in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). DESIGN: Prospective, physiologic study. SETTING: Respiratory intermediate intensive care unit. PATIENTS: Seven patients with acute respiratory failure requiring noninvasive mechanical ventilation because of exacerbation of COPD. INTERVENTIONS: PAV was administered by nasal mask as first ventilatory intervention. The setting of PAV involved a procedure to adjust volume assist and flow assist to levels corresponding to patient comfort. Volume assist was also set by means of the "run-away" procedure. Continuous positive airway pressure (CPAP) amounting to 2 cm H2O was always set by the ventilator. This setting of assistance (PAV) was applied for 45 mins. Thereafter, CPAP was increased to 5 cm H2O (PAV + CPAP-5) without any change in the PAV setting and was administered for 20 mins. Oxygen was delivered through a port of the mask in the attempt to maintain a target SaO2 >90%. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases, breathing pattern, and inspiratory effort were measured during unsupported breathing and at the end of PAV, and breathing pattern and inspiratory effort were measured after 20 mins of PAV + CPAP-5. PAV determined a significant increase in tidal volume and minute ventilation (+64% and +25% on average, respectively) with unchanged breathing frequency and a significant improvement in arterial blood gases (PaO2 with the same oxygen supply, from 65 +/- 15 torr to 97 +/- 36 torr; PaCO2, from 80 +/- 11 torr to 76 +/- 13 torr; pH, from 7.30 +/- 0.02 to 7.32 +/- 0.03). The pressure-time product calculated over a period of 1 min (from 318 +/- 87 to 205 +/- 145 cm H2O x sec x min(-1)) was significantly reduced. PAV + CPAP-5 resulted in a further although not significant decrease in the pressure-time product calculated over a period of 1 min (to 183 +/- 110 cm H2O x sec x min(-1)), without additional changes in the breathing pattern. CONCLUSIONS: Noninvasive PAV is able to improve arterial blood gases while unloading inspiratory muscles in patients with acute exacerbation of COPD.

Acute Disease↗