[The telemedicine as tool of management on chronic disease: the experience of ASL ROMA 3 (Italian Local Authority). Impact, outcomes and results]. / La telemedicina come strumento di presa in carico globale e per la concreta integrazione ospedale territorio: l'esperienza della ASL ROMA 3.

The increase of chronic diseases prevalence has created the need to adapt care models. Telemedicine applications play an increasingly important role in health care and provide tools that are indispensable for home health care, remote patient monitoring, disease management, and lastly are enable patients to have more control of their own well being. The paper presents an Italian Healthcare Local Authority Experience. The objective of paper was to evaluate the impact of telemedicine on patients with long-term conditions at high risk for rehospitalization or an emergency department visit, in terms of target disease control (diabetes, hypertension, heart failure, and chronic obstructive pulmonary disease). The outcomes are highly positive. They register the decrease of access to emergency care, the reduction of waiting list for the next visits and the increase of customer satisfaction.

Cone beam computed tomography for the assessment of linear scleroderma of the face.

BACKGROUND: To date, standardized methods for assessing the disease progression of linear scleroderma of the face (LSF) are lacking. OBJECTIVES: We investigated whether Cone Beam Computed Tomography (CBCT) may represent a reliable tool for assessing linear scleroderma of the face (LSF). METHODS: Ten patients with LSF and five age-matched controls underwent CBCT assessment. The transverse sections at three anatomic levels of the maxillofacial bones were analyzed. Measurements of soft tissue and total thickness of both affected and unaffected side of the face were made by a standardized methodology. Six raters evaluated CBCTs twice and blindly one from the other. The intra- and inter-rater reliability was assessed by the Intraclass Correlation Coefficient (ICC). RESULTS: CBCT was fast and well tolerated by the patients. The inter-rater concordance for the total thickness was excellent, mean ICC 0.75 for patients, 0.89 for controls. The mean ICC for soft tissue thickness was 0.49 for patients, 0.66 for controls. 58.3% of the measurements for patients and 91.2% of those for controls showed excellent ICC results (≥ 0.75). The intra-rater concordance resulted optimal (ICC 0.77-0.99). CONCLUSIONS: CBCT is a reliable technique to assess skin and bony changes of LSF.

Virtual screening strategies in drug discovery: a critical review.

Virtual screening (VS) is a powerful technique for identifying hit molecules as starting points for medicinal chemistry. The number of methods and softwares which use the ligand and target-based VS approaches is increasing at a rapid pace. What, however, are the real advantages and disadvantages of the VS technology and how applicable is it to drug discovery projects? This review provides a comprehensive appraisal of several VS approaches currently available. In the first part of this work, an overview of the recent progress and advances in both ligand-based VS (LBVS) and structure-based VS (SBVS) strategies highlighting current problems and limitations will be provided. Special emphasis will be given to in silico chemogenomics approaches which utilize annotated ligand-target as well as protein-ligand interaction databases and which could predict or reveal promiscuous binding and polypharmacology, the knowledge of which would help medicinal chemists to design more potent clinical candidates with fewer side effects. In the second part, recent case studies (all published in the last two years) will be discussed where the VS technology has been applied successfully. A critical analysis of these case studies provides a good platform in order to estimate the applicability of various VS strategies in the new lead identification and optimization.

New 2-(aryloxy)-3-phenylpropanoic acids as peroxisome proliferator-activated receptor α/γ dual agonists able to upregulate mitochondrial carnitine shuttle system gene expression.

The preparation of a series of 2-(aryloxy)-3-phenylpropanoic acids, resulting from the introduction of different substituents into the biphenyl system of the previously reported peroxisome proliferator-activated receptor α/γ (PPARα/γ) dual agonist 1, allowed the identification of new ligands with higher potency on PPARα and fine-tuned moderate PPARγ activity. For the most promising stereoisomer (S)-16, X-ray and calorimetric studies in PPARγ revealed, at high ligand concentration, the presence of two molecules simultaneously bound to the receptor. On the basis of these results and docking experiments in both receptor subtypes, a molecular explanation was provided for its different behavior as a full and partial agonist of PPARα and PPARγ, respectively. The effects of (S)-16 on mitochondrial acylcarnitine carrier and carnitine-palmitoyl-transferase 1 gene expression, two key components of the carnitine shuttle system, were also investigated, allowing the hypothesis of a more beneficial pharmacological profile of this compound compared to the less potent PPARα agonist fibrates currently used in therapy.

Synthesis, characterization and biological evaluation of ureidofibrate-like derivatives endowed with peroxisome proliferator-activated receptor activity.

A series of ureidofibrate-like derivatives was prepared and assayed for their PPAR functional activity. A calorimetric approach was used to characterize PPARγ-ligand interactions, and docking experiments and X-ray studies were performed to explain the observed potency and efficacy. R-1 and S-1 were selected to evaluate several aspects of their biological activity. In an adipogenic assay, both enantiomers increased the expression of PPARγ target genes and promoted the differentiation of 3T3-L1 fibroblasts to adipocytes. In vivo administration of these compounds to insulin resistant C57Bl/6J mice fed a high fat diet reduced visceral fat content and body weight. Examination of different metabolic parameters showed that R-1 and S-1 are insulin sensitizers. Notably, they also enhanced the expression of hepatic PPARα target genes indicating that their in vivo effects stemmed from an activation of both PPARα and γ. Finally, the capability of R-1 and S-1 to inhibit cellular proliferation in colon cancer cell lines was also evaluated.

CDC25 phosphatase inhibitors: an update.

The cell division cycle 25 (CDC25) family of proteins is a group of highly conserved dual-specificity phosphatases. They are key regulators of normal cell division and the cell response to DNA damage, and play a fundamental role in transitions between cell cycle phases during normal cell division, via the activation of CdK/cyclin complexes. Their abnormal expression, detected in a number of tumors, often correlated with a poor clinical prognosis, implies that their dysregulation is involved in malignant transformation. Thus, inhibition of these proteins represents an attractive therapeutic target in oncology, as evidenced from many patents and papers published on the subject in recent years. Hence, this review aims to provide an overview of recent developments in the field of CDC25 phosphatase inhibitor design since 2008.

STAT-3 inhibitors: state of the art and new horizons for cancer treatment.

The signal transducers and activators of transcription (STATs) include a class of cytoplasmic signaling proteins whose role in the regulation of cell growth and survival is mediated by phosphorylation of a critical tyrosine residue within the STAT protein. This occurs in response to cytokines and growth factors modulating the expression of specific target genes. In particular, phosphorylation induces STAT:STAT dimer formation between two monomers, via reciprocal phosphoTyr (pTyr)-SH2 domain interactions. To date, seven members of the STAT family, all with different roles, have been identified in mammals. After dimerization, phosphorylated STATs enter the nucleus and, working co-ordinately with other transcriptional co-activators and transcription factors, induce increased transcriptional initiation. In healthy human and animal cells, ligand-dependent activation of STATs is a transient process, lasting for several minutes to several hours. In contrast, in many cancerous cell lines and tumors, where growth factor dysregulation is frequently at the heart of cellular transformation, the STAT proteins (in particular STAT1, 3 and 5) are persistently tyrosine-phosphorylated or activated; abnormal levels of STAT3 activation have been observed in breast, ovarian, prostate, hematological and head and neck cancer cell lines. Thus, in this review, we examine the most important classes of agents designed to disrupt STAT3 signaling, with particular regard to STAT3 dimerization inhibitors, which could play a significant role in the future of cancer and adjuvant cancer therapies.

The lungs and platelet production.

Several studies have suggested that thrombopoiesis may occur in the lungs. To investigate the role of the lungs in platelet production, we measured automated platelet parameters in blood from the pulmonary artery and the radial artery (n=125) or aorta (n=26) in patients undergoing aorto-coronary bypass. No significant differences were found between pulmonary and radial arterial blood with regard to platelet count (192.132 +/- 46.250 vs. 192.004 +/- 46.294 x 10(9)/l), mean platelet volume (11.03 +/- 1.04 vs. 11.03 +/- 1.03 fl), plateletcrit (0.212 +/- 0.051 vs. 0.212 +/- 0.051 x 10(-2)), platelet distribution width (14.48 +/- 2.16 vs. 14.47 +/- 2.08 fl) and platelet-large cell ratio (0.350 +/- 0.076 vs. 0.351 +/- 0.078). Similar results were obtained in comparisons between pulmonary arterial and aortic blood. A coefficient of linear correlation of 0.98 was found between the pulmonary and radial arterial and aortic platelet counts. These findings suggest that the platelet population entering the lungs was the same as the platelet population leaving them. Our results do not therefore support the theory of pulmonary platelet production.

Respiratory changes in human red cells.

To investigate physiological respiratory changes in human red cells, we measured automated red cell parameters in samples from the pulmonary and radial arteries of 86 patients undergoing aorto-coronary bypass and from the pulmonary artery and the aorta in 23 patients. Our results showed higher mean corpuscular volume (88.53 +/- 5.06 fl vs. 88.12 +/- 4.94 fl, P < 0.000001), haematocrit (0.369 +/- 0.039 vs. 0.367 +/- 0.038, P < 0.0005), red cell distribution width (43.38 +/- 4.16 vs. 43.04 +/- 4.05 fl, P < 0.000001) and a lower mean corpuscular haemoglobin concentration (338.3 +/- 15.9 vs. 339.9 +/- 16.8 g/l, P < 0.005) in pulmonary arterial as compared to radial arterial blood. There were no differences with respect to haemoglobin concentration, red blood cell count, or mean corpuscular haemoglobin. Similar differences were observed between pulmonary arterial and aortic blood. Our results suggest cyclic respiratory modifications of red cell parameters attributable to the CO2 Jacobs-Stewart cycle.

[Weaning in cardiopulmonary bypass patients with compromised cardiac function. Comparison of enoximone and dopamine]. / Weaning dal bypass cardiopolmonare di pazienti coronaropatici a funzionalità cardiaca compromessa. Confronto tra enoximone e dopamina.

OBJECTIVE: Evaluate the effects of enoximone and dopamine in patients with impaired left ventricular function after cardiopulmonary bypass (CPB). DESIGN: Prospective study on a consecutive series of patients subdivided into two groups: enoximone (Group E) and dopamine (Group D). SETTING: Policlinico Umberto I, University La Sapienza of Rome. PATIENTS AND METHODS: Thirty patients undergoing elective myocardial revascularization. Before weaning from CPB the patients received inotropic drugs as follows: Group E: enoximone: bolus: 1 mg/kg in 10 min, and continuous infusion of 5 mcg/kg/min; Gruppo D: dopamine: continuous infusion of 5 mcg/kg/min. Hemodynamic measurements were made using a Swan-Ganz catheter inserted before the induction of anaesthesia. RESULTS: Enoximone has proved to be effective in decreasing pre-load and after-load of both right and left ventricle by a positive lusitropic effect and a reduction of systolic stress, thereby increasing the cardiac index. In group D patients maintenance of cardiac output has been demonstrated to be dependent on a chronotropic effect. As a consequence in group D the increase in rate-pressure product has reached potentially dangerous values, reflecting a marked increase in myocardial oxygen consumption. On the contrary in Group E the increase in rate-pressure product has been much more limited. Finally both drugs have proven effective, since all patients have been easily weaned from CPB. CONCLUSIONS: Enoximone is a useful and easily-handled drug to facilitate weaning from CPB of patients with preoperative impaired ventricular function.

Changes in coagulation patterns, blood loss and blood use after cardiopulmonary bypass: aprotinin vs tranexamic acid vs epsilon aminocaproic acid.

Cardiopulmonary bypass (CPB) increases risk of postoperative bleeding and need for transfusion. The aim of this study was to evaluate the effects of aprotinin, epsilon aminocaproic acid and tranexamic acid on coagulation patterns and need for banked blood transfusion. Ninety-six consecutive patients who underwent coronary artery bypass surgery were randomly assigned to 4 groups (24 patients each). The following parameters were monitored before, during and after CPB: activated lotting time, hemoglobin, prothrombin time, activated prothromboplastin time, fibrinogen, antithrombin III, xDP, Factor VIII, Thrombin-Antithrombin Complex and plasminogen. Analysis of postoperative bleeding and need for transfusion showed that the aprotinin group had significantly lower mediastinal bleeding. Transfused patients were 2, 4, 12 and 18 respectively in the aprotinin, epsilon aminocaproic acid, tranexamic acid and placebo treated group. In conclusion the use of protease inhibitors significantly reduces postoperative bleeding and transfusion. The aprotinin-treated group had the lower need for transfusion.

[Intramuscular and oral clonidine in premedication of the heart surgery patient: hemodynamic effects and interaction with high-dose fentanyl induction]. / Clonidina i.m. e per os nella premedicazione del paziente cardiochirurgico: effetti emodinamici ed interazioni con alti dosaggi induttivi di fentanyl.

OBJECTIVE: The aim of the study was to evaluate the efficacy of oral and i.m. clonidine as premedication in reducing the requirements of fentanyl for induction and to analyze its effects on the hemodynamics of patients with ischemic heart disease. SETTING: University Hospital. MATERIALS AND METHODS: The authors considered 30 patients (27 male and 3 female) undergoing CABG. Patients were premedicated 60-90 min before induction of anesthesia and were randomly distributed in three groups: Group A: oral diazepam 0.1 mg x kg -1; Group B: oral diazepam 0.1 mg x k-1 + oral clonidine 5 micrograms x kg-1; Group C: oral oral diazepam 0.1 mg kg-1 + i.m. clonidine 4 micrograms x kg-1. Induction of anesthesia was realized with fentanyl at speed of 500 mcg x min-1 until loss of consciousness was reached (no answer to three consecutive questions). MEASUREMENT: Hemodynamic data were recorded at TO(baseline), T1(induction of anesthesia), T2(3 min after intubation), T3(3 min. after skin incision). Results were analyzed by utilizing the average comparison Student "t" test and paired "t" test. A value of p < 0.05 was regarded as statistically significant. MAIN RESULTS: In groups B and C the inductive dose of fentanyl was much lower (p < 0.001) compared to control group (B = 19.23 +/- 3.57 micrograms x kg-1; C = 19.92 +/- 4.15 micrograms x kg-1; A = 28.39 +/- 6.4 micrograms x kg-1). This difference remained statistically significant (p < 0.001) also at T2 and T3 (T1: A = 42.79 +/- 3.21 mcg x kg-1; B = 29.07 +/- 6.18 micrograms x kg-1; C = 29.84 +/- 5.46 micrograms x kg-1; T2: A = 57.28 +/- 5.32 micrograms x kg-1; B = 43.22 +/- 3.87 micrograms x kg-1; C = 43.48 +/- 4.25 micrograms x kg-1). Considering the hemodynamic data, we report the heart rate in group B increased at T2 (p < 0.01), and systolic artery pressure raised in groups A (p < 0.05) and C (p < 0.01) at T2. Compared to baseline cardiac index showed a decrement at T3 in all groups of patients (p < 0.05). Systemic vascular resistance increased in all groups at T3 compared to baseline (p < 0.05). CONCLUSIONS: Clonidine proved to be useful to reduce narcotic requirements and to provide hemodynamic stability.

[Anesthesia with high dosage fentanyl in coronary patients: effects of pretreatment with droperidol and diazepam]. / Anestesia con fentanyl ad alti dosaggi nel paziente coronarico: effetti di un pretrattamento con droperidolo e diazepam.

The Authors have considered the effects of droperidol or diazepam treatments in patients undergoing high-dose fentanyl anesthesia in cardiac surgery. Twenty patients have been examined and divided in two groups: group A received droperidol (0.2 mg.kg-1) and group B diazepam (0.1 mg.kg-1) five minutes after fentanyl anesthesia induction (500 micrograms.min-1) to reach the "sleep dose". The diazepam pretreatment, as regards droperidol, reduces a dose of fentanyl necessary to obtain the conscience loss (21.5 +/- 2.5 micrograms.kg-1 vs 28 +/- 2.9 micrograms.kg-1). Hemodynamically the droperidol group is very stable, whereas the diazepam group shows certain myocardial depression and less protection at the OTI time.

Prevalence of HIV antibody among a group of paraphilic sex offenders.

Serum specimens from 77 paraphilic sex offenders in treatment at a major community-based sexual disorders clinic were examined for human immunodeficiency virus (HIV) infection. In addition to their paraphilic ("sexually deviant") activities, most patients had also had nonparaphilic sexual contacts with consenting adult partners. These patients had engaged in a variety of sexual behaviors that involved real or potential exchange of body fluids. In spite of that fact, data analysis revealed that none of the 77 paraphilic patients was seropositive for HIV infection as assessed by recombinant enzyme-linked immunosorbent assay (ELISA).

[Multiple exostoses disease (observations in 21 reported cases)]. / La malattia delle esostosi multiple (osservazioni su una rassegna di 21 casi).

With reference to 21 cases the authors describe the clinical, radiological and anatomo-pathological findings of multiple exostoses disease. The indications for the surgical treatment are discussed; they are, however, the same to the solitary osteochondroma.

[Solitary metastasis of the appendicular bones: role of orthopedic surgery]. / Metastasi solitarie dello scheletro appendicolare: ruolo della chirurgia ortopedica.

The authors report their experience in the treatment of solitary metastasis of the appendicular skeletal system with reference to a group of 59 cases treated. The importance of orthopaedic surgery, involving medical oncology, radiotherapy and physiotherapy is emphasised. The surgical methods used to obtain stable synthesis and facilitate assistance to the patients are discussed. In circumscribed lesions the use of cryotherapy with azote fluid may be useful, and in some cases skeletal reconstruction with autoplastic bone transplant is indicated.

Primary reticulosarcoma of bone (non-Hodgkin's lymphoma). A study of 12 cases.

Reticulosarcoma, nowadays usually referred to as non-Hodgkin's malignant lymphoma, is a particularly rare primary bone tumour. This study includes 12 cases observed over more than 15 years. The favourable clinical course of the tumour, and the use of complementary therapy justify a more extensive use of surgical treatment. Five cases were submitted to surgery plus complementary chemotherapy; two resections of the tibia, one of the humerus, one scapulectomy and one disarticulation of the hip. The remaining 7 cases were treated by radiation therapy. The overall prognosis of the disease is not very favourable (25% survival rate) although its slow progress gives a favourable clinical impression. Treatment may, however, influence the prognosis; much better results are obtained by radical surgery with complementary chemotherapy. In one resection of the tibial diaphysis and one radical scapulectomy there was no local recurrence or metastases at 3 and 4 years follow-up, whereas cases treated previously by less radical surgery and inadequate chemotherapy, although showing no local recurrence, did result in systemic diffusion of the disease.