The predictive value of ABCB1, ABCG2, CYP3A4/5 and CYP2D6 polymorphisms for risperidone and aripiprazole plasma concentrations and the occurrence of adverse drug reactions.

We investigated in ninety Caucasian pediatric patients the impact of the main polymorphisms occurring in CYP3A, CYP2D6, ABCB1 and ABCG2 genes on second-generation antipsychotics plasma concentrations, and their association with the occurrence of adverse drug reactions. Patients with the CA/AA ABCG2 genotype had a statistically significant lower risperidone plasma concentration/dose ratio (Ct/ds) (P-value: 0.007) and an higher estimated marginal probability of developing metabolism and nutrition disorders as compared to the ABCG2 c.421 non-CA/AA genotypes (P-value: 0.008). Multivariate analysis revealed that the ABCG2 c.421 CA/AA genotype was found associated to a higher hazard (P-value: 0.004) of developing adverse drug reactions classified as metabolism and nutrition disorders. The ABCB1 2677TT/3435TT genotype had a statistically significant lower aripiprazole Ct/ds if compared with patients with others ABCB1 genotypes (P-value: 0.026). Information obtained on ABCB1 and ABCG2 gene variants may result useful to tailor treatments with these drugs in Caucasian pediatric patients.

Vitamin D and autoimmunity: what happens in autoimmune polyendocrine syndromes?

PURPOSE: To evaluate the Vitamin D status of patients with a single autoimmune disease and of patients with several autoimmune diseases. METHODS: We enrolled 35 patients with isolated type 1 diabetes mellitus (T1DM), 60 with autoimmune polyendocrine syndromes (APS) including T1DM and 72 control subjects. Among patients with APS, 10 were classified as type 2 (Addison's disease + T1DM), whereas the other 50 as type 3 (autoimmune thyroid disease + T1DM + other autoimmune diseases). Vitamin D (25-OHD) levels were assessed by a chemiluminescent immunoassay in all patients and controls on samples drawn in the morning of the same months. RESULTS: Both groups of APS and T1DM patients showed 25-OHD levels significantly lower than healthy controls (p < 0.001 for both vs controls), without any significant difference between the two groups (p = 0.80). The highest prevalence of vitamin D deficiency (values <20 ng/ml) was observed in APS type 3 subgroup (8 out of 50 patients, 16%). CONCLUSIONS: Patients with APS present reduced vitamin D circulating levels, but the vitamin D status is not different between patients with single or multiple autoimmune diseases. The kind of autoimmune disease, rather than the association of several autoimmune diseases, may influence negatively the levels of vitamin D. Further prospective studies are needed to clarify if impaired vitamin D level is a causal factor in the pathogenesis of autoimmune diseases or a consequence of them.

Effect of metabolic syndrome and its components on prostate cancer risk: meta-analysis.

BACKGROUND: Literature data examining the role of metabolic syndrome and its components in prostate cancer risk are limited and contradictory. AIM: We did a meta-analysis of studies that evaluated the association between metabolic syndrome, its components, and risk of prostate cancer. SUBJECTS AND METHODS: We conducted an electronic search for articles published through September 2012 without restrictions. Every included study was to report risk estimates with 95% confidence intervals for the association between metabolic syndrome and prostate cancer. RESULTS: The final number of papers included in the meta-analysis was 14, all published in English, with 4728 prostate cancer cases. Metabolic syndrome was associated with a 12% increase in prostate cancer risk (p=0.231), that was lower in cohort studies (7 studies, RR=1.04, p=0.791) than other studies (RR=1.23, p=0.125). The association was significant in the 8 European studies (RR=1.30, p=0.034), but not in the 4 U.S. or 2 Asiatic studies. The risk estimates of prostate cancer for higher values of body mass index, dysglycemia or dyslipidemia (high triglycerides, low HDL-cholesterol) were not significant; on the contrary, hypertension and waist circumference >102 cm were associated with a significant 15% (p=0.035) and 56% (p=0.007) greater risk of prostate cancer, respectively. CONCLUSIONS: Metabolic syndrome is weakly and non significantly associated with prostate cancer risk, but associations vary with geography. Among single components of the syndrome, hypertension and higher waist circumference are significantly associated with increased risk of prostate cancer.

Adiponectin elevation by telmisartan ameliorates ischaemic myocardium in Zucker diabetic fatty rats with metabolic syndrome.

AIM: This study investigated whether telmisartan, a selective angiotensin type 1 (AT1) receptor antagonist and gamma peroxisome proliferator-activated receptor (PPAR-γ) partial agonist, reduces myocardial ischaemia/reperfusion (I/R) injury in an experimental model of metabolic syndrome. METHODS: Zucker Diabetic Fatty (ZDF) rats were treated for 3 weeks with telmisartan at doses of 2, 7 and 12 mg/kg/day. After treatment, rats were subjected to a 25-min occlusion of the left descending coronary artery followed by 2-h reperfusion (I/R). RESULTS: Telmisartan reduced the extension of the infarct size in a dose-dependent fashion and decreased the levels of plasma troponin I, a specific marker of myocardial damage. Telmisartan also caused a dose-dependent increase in adiponectin both in plasma and cardiac tissue of infarcted ZDF rats. These levels were minimally increased (p < 0.05 vs. vehicle) by telmisartan 7 mg/kg/day and reached the maximum values with the highest dose of 12 mg/kg/day (p < 0.01 vs. vehicle). In contrast, within the infarcted tissue telmisartan decreased the expression of markers of inflammation such as the transcription factor NF-κB, the toll-like receptors TLR2 and TLR4 as well as TNF-α cytokine. Nitrosative stress was maximal in vehicle-treated infarcted hearts as evidenced by increased expression of iNOS, which was almost abolished after treatement with telmisartan. CONCLUSIONS: Treatment of ZDF rats for 3 weeks with telmisartan, a dual angiotensin II receptor antagonist and partial PPAR-γ receptor agonist, resulted in a significant reduction of myocardial damage induced by I/R and was associated with increased adiponectin and a decrease in inflammatory markers.

Well-differentiated liposarcoma of the tongue. A case report.

Liposarcoma of the oral cavity is very rare. The difficulty in clinical and histopatologic differentiation of these oral lipomatous lesions have been recognized by several authors. The aim of this article is to present a case report of a well-differentiated lipoma-like liposarcoma of the tongue, in a 36-year-old woman, and to review the existing literature.

Blood-borne cells involved in arterial repair upon experimental incision injury.

We had previously shown that microscopically detectable infiltration of dendritic cells and expression of Hsp47 in tissue lysates occur during repair upon experimental arterial injury. We have further analysed here the cell types involved in the repair process by histology, electron microscopy and immunofluorescence. Rat carotid arteries were subjected to brief crushing and full thickness incision and were analysed up to 21 d thereafter. Adhesion and activation of platelets occurred 3 h after surgery. A neointima had formed 7 d after surgery, where immature cells entered from the lumen and gave rise to cells rich in organelles of the secretory pathway and endowed with bundles of phalloidin-binding microfilaments. Alpha smooth muscle-positive, secretory and contractile smooth muscle cells were found in the neointima 14 and 21 d after injury. Seven to 21 d after surgery, endothelial cells appeared immature and the newly formed tissue contained MHC-II positive, CD43 positive dendritic cells which clustered with lymphocytes, a few macrophages containing apoptotic remnants and cells labelled for Hsp47. Thin elastic fibrils appeared in the neointima 21 d after injury. The results suggest that the response to acute arterial incision injury is mediated by blood borne cells which differentiate along multiple pathways; the process evolves without reaching stabilization within the observed time lapse; the secretion of extracellular matrix is marked by the expression of Hsp47; and the constant presence of dendritic cells clustered with lymphocytes makes these cells candidate to a pivotal role in the tissue response to injury.

Antibiotic prophylaxis in surgery: an observational prospective study conducted in a large teaching hospital in Naples.

This was a 9-month observational prospective study conducted in two steps to evaluate surgical prophylaxis procedures used by surgeons in several departments of the Second University of Naples (SUN). In step 1 (4 months), we collected and analyzed data on surgical interventions and antibiotic prophylaxis. Surgeons were informed of the analysis outcome and were given an antibiotic prophylaxis protocol based on international guidelines. In step 2 (5 months), we collected data on surgical interventions and antibiotic prophylaxis, and compared them with step 1 data. The analysis of 354 forms (step 1) showed that third-generation cephalosporins were the preferred prophylactic antibiotics. The analysis of 369 forms (step 2) showed that ceftriaxone and ampicillin were the most frequently used antibiotics. Surgeons did not comply with guidelines for antibiotic prophylaxis as regards type of antibiotic and treatment duration but implementation of antibiotic prophylaxis protocols resulted in more appropriate and better timing of antibiotic prophylaxis.

The effect of laminin and its peptide SIKVAV on a human salivary gland myoepithelioma cell line.

We have demonstrated that the basement membrane regulates the myoepithelioma. We are now studying the effect of laminin, a basement membrane protein, in the morphology of a cell line (M1) derived from human salivary gland plasmacytoid myoepithelioma. These cells were grown inside a three-dimensional preparation of laminin-1. Phenotype differences were assessed by light and transmission electron microscopy. In addition, we analysed the effect of a molecular domain of laminin-1, the peptide SIKVAV, on M1 cells. This peptide was chosen because it is effective in cell proliferation and differentiation. M1 cells grown inside laminin-1 were mostly plasmacytoid-like, while cells treated by SIKVAV showed light and electron microscopic features of typical plasmacytoid cells. This peptide also modulated smooth-muscle actin expression in M1 cells. We demonstrated that laminin-1 and its derived peptide SIKVAV morphoregulates myoepithelioma cells in culture.

Modification of patients' endogenous bacterial flora during hospitalization in a large teaching hospital in Naples.

The increasing attention addressed to methicillin-resistant staphylococci, vancomycin-resistant enterococci (VRE) and Extended Spectrum beta-Lactamases (ESbetaL)-producing enterobacteria is due to their etiologic role especially in nosocomial infections. In March 2001 we started an 8-month microbiological prospective surveillance of patients in the General Surgery, Orthopedic and Obstetric & Gynecology wards of the Azienda Universitaria Policlinico, 2nd University of Naples, Italy, to monitor the possible changes in endogenous flora during patients' hospital stay and the possible emergence of bacterial resistance. Data concerning antibiotic surgical prophylaxis (antimicrobial agent and duration) and length of hospitalization (pre- and post-surgery) were also collected. All patients underwent a microbiological screening by culturing nasal, pharyngeal and rectal swabs performed at admission and during hospitalization. Overall, 526 nasal swabs, 506 pharyngeal swabs and 482 rectal swabs were performed. Methicillin-resistant staphylococci were isolated from nasal swabs at admission in 2.1% of patients and in 7.5% of patients during hospitalization (day-14). VRE and ESbetaL-producing strains were isolated from rectal swabs in 1.9 and 4.7% of patients, respectively, with no change during hospital stay. Nasal and pharyngeal flora significantly changed after 7-14 days of hospitalization, Gram-negative microorganisms being isolated more frequently following hospitalization. The authors conclude that excessive hospital stay duration, along with the inappropriate duration of surgical antibiotic prophylaxis could be important causes of bacterial flora modification.

Antibiotic use in an Italian university hospital.

The aim of this retrospective observational study was to investigate: a) expenditure for antibiotics with respect to the total pharmacy drug budget and to costs of other medical devices; b) the most frequently used antimicrobial classes and molecules; c) the clinical units that most frequently use antimicrobial therapy; d) the preferred route of administration; e) consumption patterns of antibiotics over two periods (January-September 1999 and January-September 2000). The consumption of a single antimicrobial agent was expressed as daily defined doses (DDD) per 100 bed days. In 1999 drugs accounted for 56% of the total costs but decreased to 46% in 2000. Antibiotics accounted for 15% of the pharmacy's overall acquisition costs in 1999 and dropped to 13% in 2000. In both 1999 and 2000, penicillins were used most, followed by cephalosporins and aminoglycosides. In 1999, the most frequently used antibiotic was amoxicillin (4.02 DDD per 100 bed days) followed by ceftazidime, ampicillin, ceftriaxone, and co-amoxiclav. In 2000 ceftriaxone was the most commonly used antibiotic (4.35 DDD per 100 bed days) followed by co-amoxiclav, amoxicillin, ceftazidime. The general surgery, medical therapy and infectious diseases units accounted for the majority of penicillin consumption, while cephalosporins were most widely used in general surgery, orthopedics and neurosurgery units. Parenteral administration was the most widely used route in both years.

Membrane distillation of human plasma ultrafiltrate and its theoretical applications to haemodialysis techniques.

Membrane Distillation (MD) is a technique that allows the extraction of water from aqueous solutions. The basic principle is that vapour, but not liquid water, can pass through hydrophobic micro-porous membranes, along a temperature gradient, with consequent separation of water from solutes. In this study we evaluated the possibility to utilise MD to extract water from Plasma Ultrafiltrate (PU) of patients with Chronic Renal Failure (CRF). The experiments were carried out in vitro by a hydro-phobic polypropylene hollow-fibre distillation module; PU was obtained by a CRF patient utilising a high permeability polisulphone membrane. The results show that water can be extracted by MD from PU of CRF subjects at a constant rate and that none of the substances analysed in PU was able to pass through the polypropilene membrane. In the future MD could integrate extra-corporeal blood purification techniques allowing the re-utilisation of plasmatic water thus ameliorating the treatment of uraemia.

[Necrotic lesions of the oral cavity in chronic leukemia. Treatment with CO2 laser]. / Le lesioni necrotiche del cavo orale nelle leucemie croniche. Il trattamento con laser CO2.

The main characteristics of oral necrotic lesions in leukemia and the treatment and consequence of these pathologies are described. These lesions are classified as noma-like lesions, necrotic gangrenous ulcers of the oral cavity mucosa appearing in severe organic diseases. A new therapeutical approach in the treatment of oral necrotic lesions in chronic leukemia by the use of CO2 laser is tried and a case with the results obtained is presented.

Gross hematuria of uncommon origin: the nutcracker syndrome.

Left renal vein hypertension, also called "nutcracker phenomenon" or "nutcracker syndrome," is a rare vascular abnormality responsible for gross hematuria. The phenomenon is attributable to the idiopathic decrease in the angle between the aorta and the superior mesenteric artery with consequent compression of the left renal vein. The entrapment of the left renal vein is not easily detectable by ordinary diagnostic procedures. We report two cases of gross hematuria (persistent in one patient and recurrent in the other) caused by "nutcracker phenomenon." In both cases, no remarkable findings were obtained from medical history, urinary red blood cells morphology, repeated urinalysis, pyelography, cystoscopy, or ureteroscopy. Left renal vein dilation in one case was found with a computed tomography (CT) scan performed on the venous tree of left kidney. The diagnosis of "nutcracker phenomenon" was confirmed by renal venography with measurement of pressure gradient between left renal vein and inferior vena cava in both cases. In one case, the diagnosis was complicated by the presence of Mycobacterium tuberculosis in urine. The "nutcracker phenomenon" is probably more common than thought. Early diagnosis is important to avoid unnecessary diagnostic procedures and complications such as the thrombosis of the left renal vein. Many procedures are available to correct the compression of the left renal vein entrapped between the aorta and the superior mesenteric artery: Gortex graft vein interposition, nephropexy, stenting, and kidney autotransplantation. After surgery, gross hematuria ceases in almost all patients.

Short-term effects of low protein-normal sodium diet on renal function in chronic renal failure.

To investigate the short-term renal effects of protein restriction and unchanged salt intake in chronic renal failure (CRF), patients with moderate CRF (creatinine clearance 41 +/- 5 ml/min) and healthy controls (CON) ate a normal protein diet (NPD) for four weeks, and thereafter a low protein diet (LPD, 0.4 g/kg body wt/day) for three weeks. The two diets were isocaloric and with a salt intake of 10 to 13 g/day. No differences in body weight, serum proteins and plasma sodium were recorded throughout the study. During LPD, inulin and PAH clearances in CON demonstrated a progressive 25% decline of basal GFR and RPF; on the contrary, in CRF, basal renal function did not change in presence of a significant reduction of proteinuria. In CON patients after protein restriction, fractional free-water generation (CH2O/CIn) and fractional urinary excretion of sodium (FENa) measured under maximal water diuresis increased progressively, both being doubled at the end of LPD, while in CRF, CH2O/CIn did not change and FENa values remained unmodified and much higher (above 4%) than in CON after both diets. The renal response to an acute oral protein load (OPL) and i.v. low-doses of dopamine (D) was measured at the end of each period; in the two groups, GFR and RPF significantly increased following OPL + D after both diets. In CRF, however, the vasodilatory response was blunted overall being reduced after both LPD and NPD, and, unlike CON, it did not increase after LPD.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cardiovascular emergencies in dental surgery]. / Emergenze cardiovascolari in chirurgia odontostomatologica.

More often to day odontologist must face emergency situations especially of cardiovascular kind. The article reviews the principal clinical aspects: syncope, cardiac arrest, arrhythmias, acute hypertension, acute myocardial infarction. The authors besides describe cardiopulmonary-resuscitation (CPR) techniques. The article ends with some recommendations to prevent cardiovascular emergency and to incite medical and paramedical staff to learn perfectly CPR techniques.

[Use of diadynamic currents for analgesia in dentistry. Preliminary note]. / Uso delle correnti diadinamiche a scopo antalgico in chirurgia odontostomatologica: nota preliminare.

In this article the authors have taken in to account the use of diadynamic currents with antalgic aim in odontostomatologic surgery. Based on clinical results in a number of cases, which cannot be analysed statistically due to insufficient number of patients to provide reliable data, the authors conclude that the results obtained justify further research in this field.