Showing papers by "Marche Polytechnic University published in 2002"

Insulin Resistance in Morbid Obesity: Reversal With Intramyocellular Fat Depletion

Abstract: Obesity is a frequent cause of insulin resistance and poses a major risk for diabetes. Abnormal fat deposition within skeletal muscle has been identified as a mechanism of obesity-associated insulin resistance. We tested the hypothesis that dietary lipid deprivation may selectively deplete intramyocellular lipids, thereby reversing insulin resistance. Whole-body insulin sensitivity (by the insulin clamp technique), intramyocellular lipids (by quantitative histochemistry on quadriceps muscle biopsies), muscle insulin action (as the expression of Glut4 glucose transporters), and postprandial lipemia were measured in 20 morbidly obese patients (BMI = 49 ± 8 [mean ± SD] kg · m−2) and 7 nonobese control subjects. Patients were restudied 6 months later after biliopancreatic diversion (BPD; n = 8), an operation that induces predominant lipid malabsorption, or hypocaloric diet ( n = 9). At 6 months, BPD had caused the loss of 33 ± 10 kg through lipid malabsorption (documented by a flat postprandial triglyceride profile). Despite an attained BMI still in the obese range (39 ± 8 kg · m−2), insulin resistance (23 ± 3 μmol/min per kg of fat-free mass; P < 0.001 vs. 53 ± 13 of control subjects) was fully reversed (52 ± 11 μmol/min per kg of fat-free mass; NS versus control subjects). In parallel with this change, intramyocellular—but not perivascular or interfibrillar—lipid accumulation decreased (1.63 ± 1.06 to 0.22 ± 0.44 score units; P < 0.01; NS vs. 0.07 ± 0.19 of control subjects), Glut4 expression was restored, and circulating leptin concentrations were normalized. In the diet group, a weight loss of 14 ± 12 kg was accompanied by very modest changes in insulin sensitivity and intramyocellular lipid contents. We conclude that lipid deprivation selectively depletes intramyocellular lipid stores and induces a normal metabolic state (in terms of insulin-mediated whole-body glucose disposal, intracellular insulin signaling, and circulating leptin levels) despite a persistent excess of total body fat mass.

Clinical and serological associations of ribosomal P autoantibodies in systemic lupus erythematosus: prospective evaluation in a large cohort of Italian patients.

Abstract: Objective. To verify the association of ribosomal anti-P antibodies (anti-P), as detected by a sensitive ELISA, with serological findings and clinical manifestations, including neuropsychiatric involvement evaluated according to the American College of Rheumatology (ACR) nomenclature, in a large cohort of patients with systemic lupus erythematosus (SLE). Methods. Anti-P were evaluated in the serum of 149 consecutive Italian SLE patients by an ELISA using a multiple antigen peptide carrying four copies of a common P0, P1 and P2 epitope. A complete laboratory evaluation and clinical examination were performed in each patient. In addition, all patients underwent an accurate neuropsychiatric and neuropsychological assessment performed by trained specialists according to the 1999 ACR suggestions. Results. Serum anti-P were detected in 18 149 patients (12.1%). The anti-P prevalence was similar (11.7%) when the analysis was performed in a larger series of sera including 82 additional SLE patients, who were not included in the clinical study. The age of anti-P-positive patients at disease onset was less than 33 yr and, in comparison with the anti-P-negative patients, these patients showed more active disease activity and a higher prevalence of photosensitivity and malar and discoid rash. A strong association between IgG anticardiolipin antibodies and anti-P was also found. However, anti-P were associated with neither neuropsychiatric syndromes nor cognitive impairment. Conclusion. This study does not seem to confirm the described association of anti-P with SLE neuropsychiatric manifestations. However, it supports the anti-P association with different skin manifestations as well as the presence of anticardiolipin in a subset of patients with SLE characterized by early disease onset.

Carotid artery intima-media thickness and lacunar versus nonlacunar infarcts.

Abstract: Background and Purpose— Increases in the thickness of the intima and media of the carotid artery have been associated with an increased risk of myocardial infarction and stroke in subjects without a history of cardiovascular disease. Lacunar infarcts, one of the most common subtype of ischemic stroke, show unique pathological and clinicoradiological characteristics. The present study examines the relationship between vascular risk factors, including carotid artery intima-media thickness (IMT), and lacunar versus nonlacunar infarcts. Methods— We collected data from patients with acute ischemic stroke admitted to hospital. Patients and 129 control subjects underwent B-mode ultrasonographic measurements of IMT of the common carotid artery. We examined the association of lacunar and nonlacunar infarcts with age, sex, and potential vascular risk factors. Results— Of 292 adult patients with an acute first-ever ischemic stroke, 96 were considered lacunar and 196 were considered nonlacunar strokes. We did not fin...

Incidence of Adipose Tissue Alterations in First-Line Antiretroviral Therapy: The LipoICoNa Study

Abstract: Background Adipose tissue alterations (ATAs) are a frequent untoward effect of antiretroviral therapy, the causes of which remain incompletely explained. Objectives To assess the incidence of ATAs and to identify the associated risk factors in patients infected with human immunodeficiency virus type 1 starting their first-line antiretroviral treatment. Methods In a multicenter investigation designed to study issues related to the treatment of patients starting antiretroviral therapy, physicians were requested to assess the presence of ATAs at enrollment and every 6 months thereafter. The ATAs were considered altogether and grouped as fat loss (lipoatrophy), adipose tissue accumulation (lipohypertrophy), and combined forms. Results A total of 655 patients were followed up for a median of 86 weeks; 128 patients (19.6%) were diagnosed as having at least 1 morphologic alteration during the study. Female gender and positivity for hepatitis C virus were independently linked to an increased risk of developing morphologic alterations. Age was another independent correlate of risk of developing ATAs. To have been infected through drug injection was a correlate of reduced risk of ATAs. Stavudine exposure was predictive at borderline statistical significance of lipoatrophy (but not of the other forms), and indinavir exposure was associated with a significantly higher risk of developing combined forms. Patients who started therapy with 2 nucleoside reverse transcriptase inhibitors and subsequently added a protease inhibitor during the follow-up had a significantly higher risk of having ATAs compared with patients who continued taking 2 nucleoside reverse transcriptase inhibitors up to the end of follow-up. Conclusions Different types of ATAs might derive from distinct pathways and multifactorial causes. Adipose tissue alterations are a frequent and relatively early finding during first-line antiretroviral therapy.

Effects of complete androgen blockade for 12 and 24 weeks on the pathological stage and resection margin status of prostate cancer.

Abstract: Aims: To compare the pathological stage and surgical margin status in patients undergoing either immediate radical prostatectomy or 12 and 24 weeks of neoadjuvant hormonal treatment (NHT) in a prospective, randomised study. Methods: Whole mount sections of 393 radical prostatectomy specimens were evaluated: 128 patients had immediate surgery, 143 were treated for 12 weeks and 122 for 24 weeks with complete androgen blockade. Results: Histopathology revealed organ confined tumours in 40.4% of patients with clinical stage B disease in the immediate surgery group, whereas 12 and 24 weeks of NHT increased the number of organ confined tumours to 54.6% and 64.8%, respectively. Among patients with clinical stage C tumours, pathological staging found organ confined disease in 10.4%, 31.4%, and 61.2% in the immediate surgery, 12 weeks of NHT, and 24 weeks of NHT groups, respectively. Preoperative NHT caused a significant decrease in positive margins both in patients with clinical stage B and C disease. The extent of margin involvement was not influenced by preoperative treatment. Conclusions: Neoadjuvant androgenic suppression is effective in reducing both the pathological stage and the positive margin rate in patients with stage B and C prostatic cancer undergoing radical surgery. Some beneficial effects are evident in those patients treated for 24 weeks, and it is reasonable to assume that the optimal duration of NHT is longer than three months.

An evaluation of the strategy of maintenance of sinus rhythm by antiarrhythmic drug therapy after ablation and pacing therapy in patients with paroxysmal atrial fibrillation

Abstract: Aims Permanent atrial fibrillation develops in many patients after ablation and pacing therapy. We compared a strategy that initially allowed patients to remain in atrial fibrillation with a strategy that initially attempted to restore and maintain sinus rhythm. Methods and Results In this multicentre randomized controlled trial, 68 patients affected by severely symptomatic paroxysmal atrial fibrillation were assigned, after successful atrioventricular junction ablation and pacing treatment, to antiarrhythmic drug therapy with amiodarone, propafenone, flecainide or sotalol and were compared with 69 patients assigned, after successful AV junction ablation and pacing treatment, to no antiarrhythmic drug therapy. The patients were followed-up for 12 to 24 months (mean 16±4). The drug arm patients had a 57% reduction in the risk of developing permanent atrial fibrillation (21% vs 37%, P =0·02). Evaluation after 12 months revealed similar quality of life scores and echocardiographic parameters in the two groups, but the drug arm patients had more episodes of heart failure and hospitalizations ( P =0·05). The outcome was similar between the 40 patients who developed permanent atrial fibrillation and the 97 who did not. Conclusion Conventional antiarrhythmic therapy reduces the risk of development of permanent atrial fibrillation after ablation and pacing therapy. The present data do not support the concept that the development of permanent atrial fibrillation is related to an adverse outcome when a perfect control of heart rate is obtained by ablation and pacing. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved

PPARγ expression in normal human placenta, hydatidiform mole and choriocarcinoma

Abstract: Peroxisome proliferator-activated receptor (PPAR) γ belongs to a subclass of nuclear hormone receptors that execute their transcriptional functions as heterodimers with the retinoid X receptors (RXR). PPARγ plays a pivotal role in cellular differentiation. This study investigated PPARγ protein expression in normal human placentas, hydatidiform moles and choriocarcinoma, using immunohistochemical and Western blot analyses. In first trimester normal placenta, PPARγ was mainly localized in the nuclei of the villous cytotrophoblastic cells, whereas at term it was mainly localized in the nuclei of the syncytiotrophoblast. Extravillous cytotrophoblast of cell islands and cell columns also showed nuclear PPARγ immunostaining. A striking result was the altered expression patterns of PPARγ in pathological tissues; PPARγ showed a reduced immunostaining in the trophoblastic diseases. In hydatidiform moles, PPARγ was mainly localized in the nuclei of the trophoblastic collections of the pathological villi and in the extravillous trophoblastic cells, whereas in the choriocarcinoma, only a few trophoblastic cells showed weak PPARγ nuclear immunostaining. These findings suggest an involvement of PPARγ in trophoblast differentiation during normal placental development. The down-regulation of PPARγ expression in the gestational trophoblastic diseases analysed in this study provides a new insight into the progression of these pathologies.

Observational Multicentric Trial Performed with Doxazosin: Evaluation of Sexual Effects on Patients with Diagnosed Benign Prostatic Hyperplasia

Abstract: Introduction: The aim of our study is to verify the effects of doxazosin on sexual function in patients with benign prostatic hyperplasia (BPH). Materials and Methods:

Transcontinental communication and quantitative digital histopathology via the Internet; with special reference to prostate neoplasia.

Abstract: Objective : To describe practical experiences in the sharing of very large digital data bases of histopathological imagery via the Internet, by investigators working in Europe, North America, and South America. Materials : Experiences derived from medium power (sampling density 2.4 pixels/μm) and high power (6 pixels/μm) imagery of prostatic tissues, skin shave biopsies, breast lesions, endometrial sections, and colonic lesions. Most of the data included in this paper were from prostate. In particular, 1168 histological images of normal prostate, high grade prostatic intraepithelial neoplasia (PIN), and prostate cancer (PCa) were recorded, archived in an image format developed at the Optical Sciences Center (OSC), University of Arizona, and transmitted to Ancona, Italy, as JPEG (joint photographic experts group) files. Images were downloaded for review using the Internet application FTP (file transfer protocol). The images were then sent from Ancona to other laboratories for additional histopathological review and quantitative analyses. They were viewed using Adobe Photoshop, Paint Shop Pro, and Imaging for Windows. For karyometric analysis full resolution imagery was used, whereas histometric analyses were carried out on JPEG imagery also. Results : The three applications of the telecommunication system were remote histopathological assessment, remote data acquisition, and selection of material. Typical data volumes for each project ranged from 120 megabytes to one gigabyte, and transmission times were usually less than one hour. There were only negligible transmission errors, and no problem in efficient communication, although real time communication was an exception, because of the time zone differences. As far as the remote histopathological assessment of the prostate was concerned, agreement between the pathologist9s electronic diagnosis and the diagnostic label applied to the images by the recording scientist was present in 96.6% of instances. When these images were forwarded to two pathologists, the level of concordance with the reviewing pathologist who originally downloaded the files from Tucson was as high as 97.2% and 98.0%. Initial results of studies made by researchers belonging to our group but located in others laboratories showed the feasibility of making quantitative analysis on the same images. Conclusions : These experiences show that diagnostic teleconsultation and quantitative image analyses via the Internet are not only feasible, but practical, and allow a close collaboration between researchers widely separated by geographical distance and analytical resources.

Smooth blood pressure control obtained with extended-release felodipine in elderly patients with hypertension: evaluation by 24-hour ambulatory blood pressure monitoring.

Abstract: To assess, by smoothness index (SI), distribution of the antihypertensive effect of extended-release (ER) felodipine over 24 hours in elderly patients with hypertension. After a 4-week washout phase, 35 elderly patients (mean age 69 ± 4 years) with mild-to-moderate hypertension received 2 weeks’ treatment with ER felodipine 5mg once daily. The dosage of ER felodipine was doubled to 10 mg/day and given for a further 2 weeks in non-responders (sitting clinic blood pressure > 140/90mm Hg). The study had an open-label design with no placebo control. After each period, clinic and ambulatory blood pressures were measured. Trough-to-peak (T/P) ratio was computed by dividing the blood pressure (BP) change at trough (22 to 24 hours after drug intake) by the change at peak (2 adjacent hours with a maximal BP reduction between the second and eighth hour after drug intake). SI was calculated as the ratio between the average of the 24, hourly, treatment-induced BP changes and its standard deviation. After the initial 2-week treatment period, clinic and 24-hour ambulatory BP values were higher in non-responders (145 ± 11/87 ± 8 and 135 ± 17/80 ± 6mm Hg, respectively) than in responders (133 ± 6/81 ± 3 and 130 ± 9/77 ± 7mm Hg). In non-responders, clinic and 24-hour BP values were lowered after a further 2 weeks of treatment with ER felodipine 10 mg/day (128 ± 11/78 ± 6 and 128 ± 12/75 ± 5mm Hg). SI was high in responders (0.8 ± 0.8/0.7 ± 0.7 for systolic/diastolic BP) and low in non-responders (0.5 ± 0.6/0.3 ± 0.6) during the first 2-week treatment period. It increased in non-responders after an additional 2 weeks of treatment with ER felodipine 10 mg/day (1.0 ± 0.8/0.7 ± 0.6). Median T/P ratios were 0.73 and 0.61 (systolic BP and diastolic BP) in responders and 0.41 and 0.61 in non-responders after 2 weeks of treatment. At variance with SI, T/P ratios did not increase in non-responders after doubling the dosage of ER felodipine (0.34 and 0.18). ER felodipine did not increase 24-hour heart rate. A total of nine adverse events were recorded in six patients (17%), but no patients withdrew from the study. ER felodipine 5 to 10 mg/day smoothly and safely reduces 24-hour ambulatory BP in elderly patients with hypertension.

Chromosomal studies on ten species of notothenioid fishes (Notothenioidei: Bathydraconidae, Channichthyidae, Nototheniidae).

Abstract: The results of a cytogenetic study conducted with banding and in situ hybridization techniques using ribosomal and telomeric probes on various species belonging to three families (Bathydraconidae, Channichthyidae and Nototheniidae) of the perciform suborder, Notothenioidei, are reported. The heterochromatin distribution and composition, nucleolar organiser and localisation of telomeric sequences seem to indicate that both in karyologically conservative families such as channichthyids and in families exhibiting greater karyological variability, certain DNA fractions like ribosomal genes and centromeric and telomeric DNAs are prone to some variability. This could play an important role in favouring or hampering chromosome rearrangements.

Therapeutic efficacy of intraperitoneal polymyxin B and polymyxin-like peptides alone or combined with levofloxacin in rat models of septic shock

Abstract: The efficacy of two polymyxin-like peptides, KFFKFFKFF and IKFLKFLKFL, alone and combined with levofloxacin, was investigated in a rat model of septic shock. Rats were given an ip injection of 2 x 10(10) cfu of Escherichia coli and randomized to receive ip isotonic sodium chloride solution, 7 mg/kg levofloxacin, 1 mg/kg polymyxin B and 1 mg/kg of each polymyxin-like peptides alone or combined with 7 mg/kg levofloxacin. Polymyxins achieved a significant reduction in plasma endotoxin and tumour necrosis factor alpha (TNF-alpha) concentration. Levofloxacin significantly reduced the bacterial growth and TNF-alpha concentration. The combinations of polymyxin-like peptides and levofloxacin demonstrated the highest efficacy.

A Centralized Monetary Union for Mercosur: Lessons from EMU

Abstract: The paper starts with the assumption that the Mercosur countries have decided to pursue monetary integration. These countries have essentially two options: a decentralized monetary union (MU) whereby each member country either pegs to the U.S. dollar or dollarizes outright; or a centralized MU with its own currency, its own central bank, and the adoption of common minimum financial standards. A centralized MU is preferable to a decentralized one, although it is more complex and involves significant institution building. On the other hand, a centralized monetary union enjoys the flexibility of counteracting union-wide shocks and gives member countries a say in the conduct of the common monetary policy; neither feature is present in a dollarized economy. A centralized monetary union cannot be built overnight: it took 30 years for EMU to become a reality. We stress a rather long transition approach during which member countries give independence to their national central banks and pursue inflation targeting, while adjusting to idiosyncratic shocks. The final phase would be consummated when economic and financial integration would have made shocks sufficiently symmetric in the region and inflation rates would have converged.

Anestesia epidurale vs generale

Abstract: Background. Aim of this study is to determine if and how the anaesthesia technique can significantly influence the outcome in patients after major orthopaedic surgery in terms of: patrimony of red blood cells (blood loss and erythropoiesis), incidence of intra and postoperative complications, postoperative pain control and hospital stay. Methods. 210 patients, ASA physical status I-III, undergoing elective primary total hip replacement were randomly allocated in three groups of 70 patients to receive either epidural anaesthesia (Group EA), general anaesthesia (GA), or epidural anaesthesia integrated with mild general anaesthesia (IA). Results. Data show a significant difference between the amount of pain measured by VRS immediately after surgery: prevalently absent in groups IA (84.3%) and EA (85.7%) and prevalently severe and moderate in group AG (34.3%). The measurement of the basic circulating erythrocyte mass in the first, third and fifth postoperative day, calculated by the Mercuriali formula, which considers blood loss, autologous and homologous transfusions and erythropoiesis, showed that general anaesthesia leads to a significant delay in the resumption of haemopoiesis. This result was attenuated by its combination with epidural anaesthesia. Conclusions. On the basis of the literature and the results of our study, epidural anaesthesia seems to be the most appropriate technique for patients scheduled for total hip replacement: due to its simpler analgesic cover, its tendency to be associated with a lower incidence of complications in the first 24 hours after surgery. The incidence of relevant hypotension is minor compared to integrated anaesthesia. General anaesthesia produced a significant decrease in postoperative erythropoiesis.

Natriuretic peptides and essential arterial hypertension

Abstract: Natriuretic peptide system plays a well-defined role in the regulation of blood pressure and fluid volume. Although the effects of natriuretic peptides (atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide) are mediated by specific biologic receptors, their plasma level is influenced by clearance receptors. It has been demonstrated that in hypertensive subjects plasma levels of natriuretic peptides are impaired; furthermore peptide receptor polymorphisms have been shown to be significantly associated with hypertension and cardiac hypertrophy. Studying normotensive subjects at high genetic risk of developing hypertension on the basis of family history makes it possible to investigate the role of natriuretic peptide system in the genesis of hypertension. It has been shown that plasma atrial and ventricular natriuretic peptide levels are significantly reduced in normotensive subjects with a family history of hypertension. Our study is the first one showing association among positive family history of essential hypertension and natriuretic peptide receptor polymorphisms. We identified a novel insertion/deletion polymorphism at position 15,129 in the 3'-untranslated region (3'-UTR) of NPRA receptor mRNA. The NPRA gene deletion variant is associated with hypertensive family history and higher systolic blood pressure. The "deletion 15129" variant might participate in the functional impairment of natriuretic peptide system defining an increased genetic susceptibility to hypertension.

[Vertical ridge augmentation using a microplate in conjunction with a Gore-Tex membrane. A case report].

Abstract: Oral implantology is considered an acceptable treatment modality to replace missing teeth when a recipient site with a sufficient horizontal and vertical bone volume exists. Guided bone regeneration is based on the principle of selective exclusion of non osteogenic cells from the bony defect by a barrier membrane. Several supporting systems of the barrier membrane have been successfully used to treat non space-mantaining de-fects. A 35-year-old female affected by a partial edentulism in the molar area of the right mandible showed 8 mm of bone height of the residual ridge above the alveolar canal. A vertical ridge augmentation was performed using a Gore-Tex membrane in conjunction with a microplate and an irradiated freeze-dried cortico-cancellous allograft. Six months after the surgical procedure a 11.5 mm by 5 mm threaded implant was placed into the regenerated bone. After three months of healing, the implant was uncovered and considered integrated. Before the implant placement, a biopsy of the regenerated bone was arried out by a triphine. The histological examination of the bony core showed the attainment of biological goals of guided bone regeneration. The surgical technique followes in this case report has been effective in regenerating a vertical bone volume sufficient for implant treatment.

Morpho-Structural Investigations of Biomaterials for Biocidal Activity

Abstract: A new wound dressing made of gelatin and Ag, was evaluated for the management of tissue reconstitution in rats. The gelatin–based dressing, with metabolic stimulation properties that favored the recovery of the skin was made of stiff sheets to supply the repairingtissue with mechanical support. The gelatin sheets enhanced the development of collagen fibers and subsequently cell proliferation at the level of stromal and vascular elements. A protocol based on the utilization of natural biomaterials in the presence of low concentrations of a biocidal was proposed which could control microbiocidal activities principally in burned and debilitated patients.