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Biomedical subjects

G Bianchi

Publications and source records attributed to G Bianchi.

At least 19 recordsLinked to original sources

Targeting SERCA2a as an innovative approach to the therapy of congestive heart failure.

CHF prevalence is continuously increasing worldwide and maintains one of the poorest prognoses of any major disease. Abundant evidence points to derangement of Ca(2+) cycling as the primary biochemical mark of the failing myocyte. Istaroxime is a novel compound with a dual mechanism of action: inhibition of Na(+), K(+)-ATPase and stimulation of SERCA2a. The increase in cytoplasmic Ca(2+) due to Na(+), K(+)-ATPase inhibition together with greater sarcoplasmic reticulum reloading result in both increased inotropy and lusitropy. This effect is seen in normal and failing in vitro and in vivo models. Istaroxime improvement of the contraction-relaxation cycle constitutes a novel therapeutic approach to the treatment of heart failure.

Cardiotonic Agents↗

Low replication and variability of HBV pre-core in concomitant infection with hepatitis B and hepatitis C viruses.

In an attempt to define the virological profile of HBV in HCV co-infection, we analysed the viral load, the infecting genotype, and the mutational pattern of the HBV pre-core region (pre-C), which is involved in viral encapsidation and DNA replication. Eighty-six patients were studied: 32 with serological HBV/HCV-1b co-infection (group BC), 32 infected by HBV alone (group B), and 22 by HCV-1b alone (group C). Sequence analysis of the HBV pre-S and pre-C regions identified genotypes and mutational patterns. The HBV viral load was significantly lower in group BC than in group B (p < 0.001), and the distribution of HBV pre-C mutations showed a higher prevalence of wild type in concomitant infection than in the control group (p < 0.006). The predominant HBV infecting strain was genotype D in both the BC (96%) and B (87%) groups. No difference was observed in HCV viremia levels between the two groups, whereas in HBV/HCV infection, the low levels of circulating HBV were closely associated with the low degree of variability of pre-C domain (p = 0.005). In conclusion, in HBV/HCV infection, the virological pattern was characterised by the dominance of HCV associated with lower HBV replication capacity and decreased emergence of HBV pre-C variants.

DNA, Viral↗

Bone fragility in men--where are we?

INTRODUCTION: This is a summary of several aspects of the epidemiology, pathogenesis and treatment arising directly and indirectly from the proceedings of the Third International Osteoporosis in Men meeting held in Genoa in May 2005. Advances in the study of bone fragility in men have taken place, but many challenges remain. OBSERVATIONS: Although the epidemiology of hip fractures is well documented, the epidemiology of other non-vertebral fractures is less well defined even though these fractures contribute substantially to the global burden of fractures in men. The epidemiology of vertebral fragility fractures is derived mostly from cross sectional data. The comparable prevalence of vertebral fractures in men and women is likely to be misleading because of traumatic vertebral fractures that arise in young men. Prospective studies are needed to define the proportion of these fractures that are traumatic. After the age of 50 years, the incidence of vertebral fractures in men is about one third to one half of that in women. As in women, most vertebral and non-vertebral fragility fractures occur in persons without osteoporosis. Identifying these individuals is an unmet challenge. The absolute risk for fractures appears no different by sex in men and women of the same age and bone mineral density (BMD) so that the diagnostic threshold for osteoporosis in women can be used in men. Fracture risk varies around the world and is unlikely to be explained solely by variations in BMD, though there are few data comparing men and women of different races. Both the notion that men lose less bone than women from the endosteal envelope and that they gain more on the periosteal envelope during advancing age needs reassessment as recent evidence challenges these observations. Sex differences in the net gain and loss from these surfaces are likely to be site specific, and research is needed to specify this heterogeneity and the reasons for it. The independent and co-dependent effects of sex hormones and the growth hormone/insulin like growth factor 1 axis on periosteal and endosteal modeling and remodeling during growth as well as ageing are poorly defined. The anti-fracture efficacy and safety of androgens and other agents remain incompletely investigated in men. CONCLUSION: A great deal of research is needed to advance our understanding of bone fragility in men.

Aged↗

Determinants of adherence to osteoporosis treatment in clinical practice.

INTRODUCTION: Poor adherence to prescribed treatments is widespread in clinical practice and this can lead to potentially life-threatening events. This problem is apparently very common for osteoporosis treatment but the causes of discontinuation and low compliance are complex and poorly defined. METHODS: Global adherence to osteoporosis treatment was specifically addressed in a nation-wide survey carried out in 9851 postmenopausal women referred to 141 Italian centres for osteoporosis management for a follow-up assessment, at least one year after having been prescribed a treatment with one of the following drugs: calcium+/-vitamin D supplements alone (CaVitD), hormone replacement therapy (HRT), raloxifene 60 mg (RLX), intramuscular clodronate 100 mg/7-14 days (CLOD), risedronate 5 mg/day (RIS) and alendronate 10mg/daily (ALN10) or 70 mg once weekly (ALN OW). RESULTS: Overall 19.1% of the patients discontinued the prescribed drug before attending the bone mass re-evaluations, more than half of them within the first 6 months. The discontinuation rate was significantly different between the treatments. The medications most frequently interrupted within one year were CLOD (28.7%; p<0.01 versus any other treatment), while by far the least interrupted was ALN-OW (6.9%; p<0.001 versus any other treatment). The most frequent reasons for discontinuation were drug related side effects, insufficient motivation to treatment and fear of side effects. The prevalence of the reasons for discontinuation were different among treatments: safety concerns were very common for HRT, lack of motivation was the most common cause for CaVitD and CLOD, and drug related side effects for RIS, ALN and RLX. Persistence to treatment was significantly higher in patients with previous vertebral fractures, densitometric osteoporosis, on corticosteroid or anti-inflammatory treatments. A significantly increased risk of treatment interruption was found among patients on benzodiazepine or gastro-protective agents and in patients in whom a bone measurement was not readily available. The highest compliance to recommended dosing was observed with ALN OW and HRT (p<0.001 versus any other) and the lowest for CaVitD (p<0.01 versus any other). Poor treatment compliance (<50% drug taken) was significantly related to benzodiazepine and gastroprotective use, while a significantly better compliance was associated with recognized risk factors for osteoporosis: early menopause, low bone mass values values, previous vertebral fractures. The poorest adherence was observed when treatments were prescribed by General practitioners (GPs), and orthopaedic surgeons (p<0.01 versus global mean). CONCLUSIONS: The results of this large survey of Italian osteoporotic women indicates that the most important determinant of both persistence and compliance to treatment is the type of drug prescribed with a definite advantage of ALN-OW. Treatment compliance is particularly poor for CaVitD and this emphasizes the need for new ways to supplement at least vitamin D. The main reasons for discontinuation are side effects and lack of motivation while the best treatment adherence was observed in patients with severe and well documented osteoporosis.

Aged↗

Can Phyllanthus niruri affect the efficacy of extracorporeal shock wave lithotripsy for renal stones? A randomized, prospective, long-term study.

PURPOSE: Phyllanthus niruri is a plant used in Brazilian folk medicine for the treatment of urolithiasis. We assessed the efficacy of P. niruri after extracorporeal shock wave lithotripsy for renal stones. MATERIALS AND METHODS: We prospectively evaluated 150 patients with renal stones that were as large as 25 mm and composed of calcium oxalate. All patients received 1 to 3 extracorporeal shock wave lithotripsy sessions by Dornier Lithotriptor S. After treatment 78 of 150 patients (52%) underwent therapy with Uriston, a P. niruri extract (2 gm daily) for at least 3 months (group 1). Otherwise 72 of 150 patients (48%) were used as a control group (group 2). No significant difference in stone size between the 2 groups was found. Stone clearance was assessed after 30, 60, 90 and 180 days by abdominal x-ray and ultrasound scan. RESULTS: Stone-free rate (stone-free defined as the absence of any stone or residual fragments less than 3 mm) was 93.5% in group 1 and 83.3% in group 2 (p = 0.48) at the end point of the followup (180 days). For lower caliceal stones (56 patients) the stone-free rate was 93.7% in the treatment group and 70.8% in the control group (p = 0.01). Re-treatment need for group 1 was 39.7% and for group 2 it was 43.3% (p = 0.2). No side effects were recorded with extracorporeal shock wave lithotripsy or P. niruri therapy. CONCLUSIONS: Regular self-administration of P. niruri after extracorporeal shock wave lithotripsy for renal stones results in an increased stone-free rate that appears statistically significant for lower caliceal location. Its efficacy and the absolute lack of side effects make this therapy suitable to improve overall outcomes after extracorporeal shock wave lithotripsy for lower pole stones.

Adult↗

Medical therapy of urolithiasis.

Nephrolithiasis treatment has become easier and less invasive with the development of extracorporeal shockwave lithotripsy (SWL) and endourologic techniques. However, medical therapy represents a well-established and complementary approach that can improve the efficacy of SWL and endourology. During recent decades, pharmacologic intervention has become more effective in stone disease: drugs can control the pain of renal colic, interfere at various levels in lithogenesis, and contribute to the expulsion of stones. It is well known that lithogenesis is a multifactorial process influenced by environmental-nutritional factors (low urinary volume, diet rich in animal protein, etc) and metabolic alterations; i.e., hypercalciuria, hyperuricosuria, and deficiency of stone-inhibiting factors (citrate, magnesium, glycosaminoglycans [GAGs]). Specific drugs such as citrate, allopurinol, and thiazide represent highly effective treatments for the promoting factors. Furthermore, recent findings suggest an interesting role for a phytotherapeutic agent, Phillantus niruri, and its inhibitory action on calcium oxalate crystallization related to the higher incorporation of GAGs into the calculi. Another step forward in medical management of stone disease is expulsive therapy. Many studies have proven the efficacy of medical expulsive therapy with nifedipine and alpha-blockers: their specific action on ureteral smooth muscle in association with anti-edema drugs accounts for their efficacy in expelling ureteral stones. In this paper, we provide an update on the medical treatment of stone disease, focusing our attention on what is known and what is new in renal colic and litholithic and expulsive medical therapy.

Colic↗

Changes in peak systolic velocity induced by chronic therapy with phosphodiesterase type-5 inhibitor.

The aim of this study was to assess the influence of chronic therapy with phosphodiesterase type-5 inhibitor on penile haemodynamics at colour Doppler ultrasound. Thirty patients affected by erectile dysfunction (ED) of different aetiology tested with the International Index of Erectile Function (IIEF-5) were evaluated with penile colour Doppler ultrasound during basic and dynamic phases (10 microg PGE1) before and after chronic self-administration of sildenafil citrate (dosage: 100 mg as required, two to three times a week) for a period of 5-20 months (mean: 12.3). Treatment was interrupted 14-21 days before the second ultrasound evaluation. Peak systolic velocity (PSV) and end-diastolic velocity (EDV) were recorded by means of colour Doppler; cut off values were 25 and 5 cm s(-1) respectively. Data were compared by nonparametric tests. Twenty-two of the 30 patients showed normal pre-treatment PSV, while eight of 30 had an insufficient arterial flow. Mean pre-treatment EDV was 4.7 +/- 0.5. After chronic therapy with sildenafil, a global improvement of 10.5% on PSV was seen (P < 0.001), without any statistical difference between patients with normal pre-treatment peak and those with a borderline one. No statistically significant changes were found for EDV (P = 0.98). It is concluded that chronic therapy with phosphodiesterase-5 inhibitor results in a significant improvement in PSV values, probably due to a penile chronic vasoactive enhancement.

Adult↗

Superiority of alfacalcidol compared to vitamin D plus calcium in lumbar bone mineral density in postmenopausal osteoporosis.

In a randomized multicenter, double-blind, double-dummy, parallel group study a comparison of the efficacy and safety of 1 microg alfacalcidol to 880 IU vitamin D plus calcium carbonate (1 g calcium) once daily per os was performed on 148 postmenopausal osteoporotic Caucasian patients with normal vitamin D serum levels for 18 months. Bone mineral density (BMD) was measured at baseline, 12 and 18 months. Safety parameters were followed during the entire study period. Sixty-nine (90.8%) in the alfacalcidol group and 67 (93.1%) in the vitamin D group were included in the ITT analysis. Lumbar BMD in the alfacalcidol group increased by 0.017 g/cm2 (2.33%) and 0.021 g/cm2 (2.87%) from baseline (P<0.001) at 12 and 18 months, respectively, whereas in the vitamin D plus calcium group the increase was 0.005 g/cm2 (0.70%) from baseline (N.S.) at both 12 and 18 months. The higher changes from baseline in the alfacalcidol group, as compared to the changes in the vitamin D plus calcium group at both 12 and 18 months, were found to be statistically significant (P=0.018, 0.005). A small increase of mean femoral BMD was achieved in both groups (N.S.). Adverse events were similar in both groups. No significant differences were noted between the groups in serum calcium. In conclusion, alfacalcidol was found to be superior in significantly increasing lumbar BMD as compared to vitamin D plus calcium while safety characteristics were found to be similar in both treatments.

Aged↗

Laparoscopic telementored adrenalectomy: the Italian experience.

BACKGROUND: Laparoscopy is widely accepted as the gold standard for adrenalectomy. Telementoring has been developed to reduce the complications associated with surgeon inexperience. We report our preliminary experience with laparoscopic telementored adrenalectomy. METHODS: From July 2002 to May 2003, eight laparoscopic telementored adrenalectomies were performed between two separate operating sites 430 km apart. Six of these procedures were monolateral laparoscopic adrenalectomies, and one was bilateral. All cases were performed by an expert open surgeon who was skilled in laparoscopic procedure but who had no experience in laparascopic adrenalectomy RESULTS: All the procedures were successfully performed in a telementored fashion. The mean operative times, blood loss, and postoperative morbidity results were comparable to those for standard laparoscopic adrenalectomies reported in the literature. CONCLUSIONS: This preliminary experience has demonstrated the feasibility of national telementoring. It is a viable method that can potentially add to surgical education and decrease the likelihood of complications due to inexperience with new techniques.

Adolescent↗

Nonequilibrium quasiparticle relaxation in the vortex state of La2-xSrxCuO4.

We have measured the charge dynamics in the vortex state of La(2-x)Sr(x)CuO(4) by femtosecond time-resolved reflectance, which we demonstrate to be a direct probe of low-energy quasiparticle states. Application of a c-axis magnetic field induces regions surrounding vortex cores that display pseudogap charge dynamics. We determine the characteristic width approximately 130 A in optimally doped material and we show that it increases with decreasing doping. These results confirm a new experimental method of probing the microscopic properties of vortices in the cuprates.

Journal Article↗

Regional changes in the metabolite profile after long-term hypoxia-ischemia in brains of young and aged rats: a quantitative proton MRS study.

Quantitative proton magnetic resonance spectroscopy (MRS) was used to determine region-specific metabolic changes in young and aged animals subjected to a long-term hypoxic-ischemic injury. Focal ischemia, which was studied as an experimental stroke model, was induced in 3- and 24-month-old rats by unilateral common carotid artery occlusion associated with 24 h of hypoxia. Eight metabolites were quantified from extracts in three different brain regions (hippocampus, frontoparietal and occipital cortices) from both the ipsilateral and contralateral sides. Our findings showed significant differences in lactate and myo-inositol concentration values in the hippocampus of the aged rats as compared to the same area of the young adult group under normoxic conditions. After hypoxia-ischemia (HI), the most relevant changes in metabolite concentrations were found in the hippocampal region of both young and aged groups as compared to their age-matched controls. Of the three brain areas under investigation, the hippocampus proved to be particularly susceptible to the prolonged hypoxia-ischemia perturbation. The effects were more evident in the aged animals.

Age Factors↗

Balance between hypertrophic and hypoxic stimulus in caspase-3 activation during rat heart development.

During heart development, cell hyperplasia and hypertrophy are the main mechanisms by which cardiac mass grows. Both these processes along with programmed cell death lead to complete growth and function. In addition, since the establishment of cardiac function depends on the relationship between oxygen supply and demand, we investigated some of the molecular mechanisms at the basis of rat myocardial cell response to hypoxic stress at different times of neonatal life. In particular, the role played by hypertrophic and survival factors like NF-kB and IAP-1 (Inhibiting Apoptosis Protein) and by death factors ASK-1 (Apoptosis Signal Regulating Kinase), JNK/SAPK (Jun-N-Terminal-Kinase/Stress-Activated Protein Kinase) pathways in regulating caspase-3 expression and activity has been evaluated by immunohistochemical and Western blotting analyses, respectively. Level of phosphorylation of IkBalpha and IAP-1 expression were substantial in 8-day-old hypoxic hearts, suggesting the persistence of NF-kB driven hypertrophic signal along with a rescue attempt against hypoxic stress. In contrast, ASK-1 mediated JNK/SAPK activation, regulating Bcl(2) levels, allows Bax homodimerization and caspase-3 activation in the same experimental conditions. Thus, a regulation carried out by NF-kB and JNK/SAPK pathways on caspase-3 activation at day 8 of neonatal life can be suggested as the main factor for the heart 'adaptive' response to hypoxia.

Animals↗

Psychological status and depression in patients with liver cirrhosis.

BACKGROUND: Previous studies reported an impairment of both the physical and mental dimensions of quality of life in patients with cirrhosis. Very few data are available on the psychological impact of the disease and its relation to liver function. AIM: To measure the psychological status of patients with cirrhosis in relation to the severity of the liver impairment. PATIENTS AND METHODS: One hundred and fifty-six patients with cirrhosis were studied. Two questionnaires (the Beck Depression Inventory and the Psychological General Well-Being Index) were self-administered in random order. Clinical and laboratory data were collected using standardised forms. RESULTS: The global score of Psychological General Well-Being Index was severely reduced compared to Italian population norm. Among individual domains, the more severely affected was General Health, the less compromised was Positive Well-Being. A negative relation was found between Child-Pugh score (a comprehensive measure of disease severity) and global Psychological General Well-Being Index and several individual subscales. The Beck Depression Inventory scores were indicative of a depressed mood in over 50% of patients, in relation to the presence of clinical symptoms. CONCLUSIONS: Patients with cirrhosis have signs of psychological distress and depression, as assessed by Beck Depression Inventory and Psychological General Well-Being Index, in relation to the severity of liver disease. Accordingly, a non-negligible number of patients warrant treatment.

Adult↗

Osteoarticular allograft reconstruction of the distal radius after bone tumour resection.

Resection of the distal end of the radius is indicated in the treatment of locally aggressive primary benign and malignant bone tumours. The aim of this study was to evaluate the technique of osteoarticular allograft reconstruction of this bone defect. We analysed 12 patients retrospectively with a minimum follow-up of 2 years (range 26-145 months, median 52 months). Three patients had a malignant tumour and nine had a giant cell tumour. The patients ages ranged from 13 to 65 years. The mean resected length of the radius was 6.6 (range 4-14)cm. Non-union of the osteotomy line was diagnosed 6 months after surgery in one case and needed bone grafting. Distal radio-ulnar joint instability was observed in eight cases. Subchondral bone alterations and joint narrowing were present in all cases but were painful in only one patient. The mean range of motion was 51 degrees of flexion and 37 degrees of extension.

Adolescent↗