Intra-articular clodronate in patients with knee osteoarthritis non-responder to intra-articular hyaluronic acid - a case report series of 9 patients with 8-month follow-up.

Background: Osteoarthritis (OA) is a common disease in the elderly people, inducing pain and functional limitations. Clodronate (CLO) a first generation non-nitrogen containing bisphosphonate has been purposed as a treatment of OA, being effective on pain, inflammation, bone marrow oedema, osteophytosis and cartilage regeneration. Intra-muscular routes of CLO showed efficacy in the treatment of Knee OA (KOA) and erosive OA of the hand. In KOA intraarticular CLO at low doses (0.5-2 mg) showed efficacy as well as hyaluronic acid (HA), being able to improve the effectiveness if associated to HA. Methods: Nine Consecutive patients (4 female, 5 male, mean age 78,22) with KOA at 2nd or 3rd degree following Kellgren-Lawrance scale, non responder to HA and unintended to surgery. They were treated with intraarticular CLO at the weekly dose of 20 mg, plus lidocaine 1% in 5 cc of saline solution for a route of 5 weekly infil-trations, followed by a second route of 5 intraarticular infiltrations 3 months after the first course. Visual analog score (VAS) pain and Tegner-Lysholm Score (TLS) were used to assess changes following CLO treatment. Results: Baseline pain was 6,77/10, reduced to 1,09 at day 150 (after second course) and to 2,3/10 at day 240. TLS at baseline was 56,7/100, improved to 96,7 at day 150 and to 84,1 at day 240. At day 240 only 2 out of 9 patients had a negative judgement of the treatment and decided to stop it, while 7 were satisfied and available to a further course. There was no increase of consumption of anti-inflammatory or analgesic drugs. A short time lasting pain after the injections was registered in all patients. Conclusions: In a small cohort of patients affected by KOA, non responders to intraarticular HA a higher dose of intraarticular CLO in KOA showed good compliance, amelioration of pain and functionality.

Age, Sex, Hypertension and HDL-C Alter Serum BACE1 Activity in Cognitively Normal Subjects: Implications for Alzheimer's Disease.

BACKGROUND: Increasing evidence indicates that ß-secretase 1 (BACE1) activity and concentration in blood are candidate biomarkers for Alzheimer's disease (AD). Investigating potential demographic, biological, and clinical determinants of BACE1 in the blood matrix is the critical step to validate and qualify BACE1 bio-indicators for different contexts-of-use (CoU), such as risk assessment, early detection, diagnosis, prognosis, management of AD, and outcome of amyloid pathway targeted drugs. OBJECTIVES: To evaluate the influence of age, sex, HDL-cholesterol and comorbidities (cardiovascular diseases, hypertension, diabetes) on circulating BACE-1 activity. DESIGN: prospective analysis of serum samples, clinical, biological, and demographic variables. SETTING: Three cohorts: 1) Memory Clinic of the Department of Internal Medicine, S. Anna University Hospital, Ferrara (Italy); 2) outpatients attending the Menopause and Osteoporosis Centre (MOC) of the University of Ferrara (Ferrara, Italy); 3) Prevention Center of the University of Ferrara. PARTICIPANTS: 504 cognitively healthy individuals (median age: 62 years, interquartile range: 51-73) and 175 patients with AD (78 years, 74-82). MEASUREMENTS: serum BACE1 (sBACE1), age, sex, HDL-cholesterol, major comorbidities. RESULTS: Age was the strongest independent predictor of sBACE1 variance (ß=0.425, p<0.0001), followed by sex (ß=0.180, p<0.0001), high density lipoprotein-cholesterol (HDL-C) (ß=-0.168, p<0.0001) and hypertension (ß=0.111, p<0.05) (overall model, R2: 0.232). The probability of having elevated sBACE1 activity increased after 70 years of age, with women being more susceptible to higher sBACE1 activity than men. CONCLUSIONS: We provide evidence about potential clinical and biological determinants of sBACE1 activity with a strong association among biomarker, female sex, and older age.

The surveillance of occupational diseases in Italy: the MALPROF system.

BACKGROUND: Occupational diseases data can guide efforts to improve worker's health and safety. AIMS: To describe MALPROF, the Italian system for surveillance of work-related diseases collected by the subregional Department of Prevention. METHODS: The MALPROF system started in 1999 with contributions from Lombardy and Tuscany and spread in the following years to collect contributions from 14 out of the 20 Italian regions. MALPROF data were explored to follow-up work-related diseases and to detect emerging occupational health risks by calculating proportional reporting ratio (PRR), as in pharmacosurveillance. It classified work-related diseases according to economic sector and job activity in which the exposure occurred. Occupational physicians of the Italian National Health Service evaluate the possible causal relationship with occupational exposures and store the data in a centralized database. RESULTS: From 1999 to 2012, the MALPROF system collected about 112000 cases of workers' diseases. In 2010, more than 13000 cases of occupational diseases were reported. The most frequently reported diseases were hearing loss (n = 4378, 32%), spine disorders (n = 2394, 17%) and carpal tunnel syndrome (n = 1560, 11%). The PRR calculated for cervical disc herniation, a disease whose occupational origin has to be studied, in 1999-2010 was 2.47 [95% confidence interval (CI) 1.76-3.47] for drivers and 36.64 (95% CI 22.03-60.93) for air transport workers. CONCLUSIONS: MALPROF is a sensitive system for identifying possible associations between occupational risks and diseases, it can contribute to the development of preventive measures, to evaluate the effectiveness of preventive interventions and to stimulate research on new occupational risks and diseases.

A case of postvaricella cerebral angiopathy with a good outcome in a child.

Cerebral vasculopathy is a serious but uncommon complication of varicella-zoster-virus (VZV) infection. Diagnosis is based on a recent history of VZV infection, signs and symptoms of transient ischemic attack or stroke, and vascular anomalies on neuroimaging. We report a case of postvaricella cerebral angiopathy in a 5-year-old child, who was admitted after three episodes of transient right hemiplegia, each one lasting a few minutes. He had contracted chicken pox, the month prior to admission. Brain magnetic resonance imaging showed hyperintense signals in the left lenticular and caudate nuclei, which can be considered to be a result of vasculopathy.

4-mer hyaluronan oligosaccharides stimulate inflammation response in synovial fibroblasts in part via TAK-1 and in part via p38-MAPK.

4-mer hyaluronan (HA) oligosaccharides stimulate pro-inflammatory effects in different cell types by interacting with both the toll-like receptor-4 (TLR-4) and -2 (TLR-2). This interaction induces the activation of the transforming growth factor activated kinase-1 (TAK-1) that activates the nuclear factor kappaB (NF-kB) either directly and/or through the activation of p38-mitogen-activated protein kinase (p38-MAPK). This in turn induces the transcription of proinflammatory mediators that prime inflammation. Our aim was to investigate the involvement of TAK-1 and p38-MAPK in 4-mer HA oligosaccharide-induced inflammatory response in mouse synovial fibroblasts obtained from normal DBA/J1 mice (NSF) and from mice subjected to collagen-induced arthritis (CIA). Treatment of NSF and rheumatoid arthritis synovial fibroblasts (RASF) with 4-mer HA showed a marked up-regulation of TLR-4, TLR-2, TAK-1 and p38-MAPK mRNA expression and of the related proteins, as well as NF-kB activation. High levels were also detected of TNF-α, IL- 1ß, MMP-13 and iNOS. Treatment of NSF and RASF, previously stimulated with 4-mer HA oligosaccharides, with TAK- 1 and/or p38-MAPK specific inhibitors significantly reduced all the parameters, although the inhibitory effect of p38- MAPK was less effective than that of TAK-1. The addition of CD44 antibody to both NSF and RASF showed that CD44 was not involved in 4-mer HA-induced inflammation.

Bladder papilloma in a 9-year-old girl: a case report.

Transitional cell carcinoma of the bladder is a rare entity in childhood. We report on a 9-year-old girl with transitional cell carcinoma of the bladder who presented with gross hematuria. Ultrasonography revealed a papillary lesion in the bladder, and the diagnosis was confirmed by cistoscopy. Complete transurethral resection of the lesion was performed and follow-up with urine cytology, vesical ultrasound and transurethral cystoscopy at 4 years showed no evidence of recurrence.

Randomized, double-blind comparison of effects of abiciximab bolus only vs. on-label regimen on ex vivo inhibition of platelet aggregation in responders to clopidogrel undergoing coronary stenting.

BACKGROUND: On top of aspirin, an abciximab bolus-only regimen results in a 30% drop in platelet inhibition at 6 h as compared with the on-label regimen. The concomitant administration of high loading dose clopidogrel, by bridging with abciximab bolus, may sustain suppression of platelet activity over time. OBJECTIVES: To investigate the non-inferiority of abciximab bolus-only and concomitant high loading dose clopidogrel vs. abciximab bolus + infusion with respect to the inhibition of platelet aggregation (IPA) as determined by light transmission aggregometry. PATIENTS/METHODS: Seventy-three patients with non-ST segment elevation acute coronary syndromes underwent double-blind randomization to abciximab bolus followed by a 12-h placebo infusion and concomitant 600-mg clopidogrel vs. abciximab bolus + a 12-h infusion and 300 mg of clopidogrel. IPA was determined by light transmission aggregometry throughout 24 h. Clopidogrel poor responsiveness was defined as ≥ 50% 5 µmol L⁻¹ ADP-induced maximum platelet aggregation. RESULTS: In clopidogrel responders (n = 68), IPA after 20 µmol L⁻¹ ADP at 4 h was 89% ± 13% in the bolus-only arm vs. 92% ± 14% in the bolus + infusion arm (P = 0.011 for non-inferiority). IPA after 5 or 20 µmol L⁻¹ ADP and 5 or 15 µmol L⁻¹ TRAP and the proportion of patients showing ≥ 80% IPA did not differ at any time point, irrespective of clopidogrel responsiveness status. Thirty-day outcomes were similar, whereas hemoglobin (0.91 ± 0.8 vs. 0.5 ± 0.7 g dL⁻¹ ; P = 0.01) and platelet count mean drop (41.7 ± 57 vs. 18.6 ± 34 109 L⁻¹; P = 0.042) were significantly reduced in the bolus-only arm. CONCLUSIONS: Withholding abciximab post-bolus infusion in patients receiving high loading dose clopidogrel does not impair platelet inhibition throughout 24 h, and has the potential to improve the safety profile of the drug at reduced costs.

[Thoracic epidural analgesia vs patient-controlled analgesia with intravenous fentanyl in children treated for pectus excavatum with the Nuss procedure]. / Analgesia epidural torácica frente a analgesia con fentanilo controlada por el paciente en niños operados de pectus excavatum con la técnica de Nuss.

BACKGROUND AND OBJECTIVE: Thoracic epidural analgesia and patient-controlled analgesia (PCA) with intravenous fentanyl have both been shown to be effective in pediatric patients treated surgically for pectus excavatum using the Nuss procedure. We compare the efficacy and safety of these techniques. METHODS: Retrospective study of pediatric cases in which the Nuss procedure was used to treat pectus excavatum between October 1997 and February 2009. Weight, age, sex, and Haller index were analyzed. Pain was assessed every 8 hours on a visual analog scale of 0 to 10 or on a scale based on observation of distress (LLANTO scale). Daily use of analgesics was also recorded. The incidence of catheter-related complications or adverse events of treatment such as nausea, vomiting, and respiratory depression were also noted. RESULTS: We identified 31 patients in 2 groups: the epidural group (n=22) and the PCA group (n=9). Demographic characteristics, the incidences of complications or adverse events, and mean (SD) pain scores (epidural group, 1.8 [3.8]; PCA group, 2.1 [3.4]; P = .775) were statistically similar in the 2 groups. However, analgesic requirements and the duration of analgesic use in days differed significantly, at 2.9 (1.1) days in the epidural group and 5.9 (1.4) days in the PCA group (P =.001). CONCLUSIONS: The efficacy and safety of thoracic epidural analgesia is similar to that of PCA with intravenous fentanyl, although the use of epidural analgesia is associated with a markedly shorter duration of requirement for postoperative analgesia.

Gene-gene and gene - clinical factors interaction in acute myocardial infarction: a new detailed risk chart.

AIMS: The complex pathogenesis of acute myocardial infarction (AMI) implicates phenotypic and genetic heterogeneity. In this pilot case-control study single nucleotide polymorphism (SNP) in several inflammatory genes, such as interleukin (IL)-1beta, IL-6, IL-10, alpha-1-antichymotrypsin (ACT), tumor necrosis factor alpha (TNF)-alpha and interferon gamma (IFN)-gamma genes along with SNPs of genes regulating vascular functions (vascular endothelial growth factor; VEGF) and cholesterol synthesis (hydroxy-methyl-glutaryl CoA reductase; HMGCR) were investigated. METHODS: Patients were genotyped with RT-PCR technique and data were analyzed with a new mathematical algorithm named Auto Contractive Map. RESULTS: The Auto Contractive Map (AutoCM), was applied in AMI patients with the aim to detect and evaluate the relationships among genetic factors, clinical variables and classical risk factors. Genes were selected because their strong regulatory effect on inflammation and SNP in these gene were located in the promoter region. In the connectivity map generated by AutoCM a group of variables was directly linked with the AMI status; these were: gender (male), early age at onset (50-65 years), HMGCR gene (CC wild type genotype), IL-1betaCT, IL-6 GG and VEGF CC genotypes. This direct link suggested a possible pathogenetic association with AMI. Other genetic, clinical and phenotypic variables were associated to the disease under a statistically defined hierarchy showed in the new connectivity map generated by AutoCM. CONCLUSION: These analyses suggested that genotypes of few inflammatory genes, a SNP in HMGCR gene, middle age, gender, low HDL and diabetes were very informative variables to predict the risk of AMI.

[Setting up a national information system for prevention]. / La costruzione di un sistema informativo nazionale per la prevenzione.

BACKGROUND: The recent law (D.lgs n. 81/2008) redesigned all the Italian regulations regarding safety and health at work. It redesigned rules that up to now were contained in laws that were introduce over a period of over nearly sixty years, with due review and extension. METHODS AND RESULTS: Article 8 of the law is dedicated specifically to a national information system for the prevention at the workplace (called SINP), created "with the aim of supplying useful data in order to guide, programme, to plan, and assess the effectiveness of actions taken for the prevention of injuries and occupational diseases... and to provide guidance in matters of inspection". It is important to emphasize that the course followed to define the SINP is due to the joint efforts that INAIL, ISPESL, the Regions and the independent Provinces started in 2002, by agreeing to a protocol, with the common aim of creating an integrated information system for prevention in the workplace. CONCLUSIONS: At present data are available on a national scale and they are useful in order to acquire more detailed knowledge of the area in question (on enterprises, accidents, occupational diseases) and in order to define intervention priorities, to plan and program activities and verify the results.

[The contribution of the Italian scientific community to efficacy studies in Occupational Health (1990-2006)]. / L'apporto della comunità scientifica Italiana alle prove di efficacia in medicina del lavoro.

INTRODUCTION: Evidence-based prevention (EBP) is gaining growing interest among the international scientific community in the field of Occupational Health. In order to ascertain the commitment that has been made in Italy to participation in EBPR, we conducted a systematic review of scientific publications on efficacy evaluations in Italy. METHODS: We hand-searched journals and interrogated the PubMed database to identify reports of studies evaluating interventions designed to improve workers' health in Italy between 1990 and 2006. The selected articles were classified by institutional category (of the first author), intervention methodology, study design, type of risk factor, and occupational sector. RESULTS: We found 23 eligible publications in the Italian language and 9 in English. The most frequent study-design was pre-/post-intervention evaluation; 3 studies were randomized trials. The interventions were aimed mainly at controlling the effects of chemical hazards and noise; health-care settings were the most frequent. We found only 2 studies (1 in English) evaluating the efficacy of interventions targeting injury prevention. DISCUSSION: The systematic approach of EBP can be applied to most occupational health interventions. These results may contribute to the debate on methodology and outcomes in the scientific community.

[Ovarian hyperstimulation syndrome]. / Síndrome de hiperestimulación ovárica.

Experience with ovulation induction treatment and understanding of the physiopathology of ovarian hyperstimulation syndrome (OHS), the risk factors and the clinical characteristics are of key importance for preventing and managing OHS. Light manifestations ofOHS are fairly common, occurring in up to a third of the cycles with superovulation induced by exogenous gonadotropins. A worsening of the symptoms of OHS can still normally be managed in out-patient form, but frequent monitoring and evaluation are essential. Serious disease resulting from OHS is much less common, but can involve risk to life. Hospitalisation might be necessary in some cases.

Glansectomy with split-thickness skin graft for the treatment of penile carcinoma.

Using our prospectively derived database, we identified 17 patients with squamous-cell carcinoma involving the glans penis, who were treated using organ-sparing surgery between March 2003 and January 2008. Of them, two were treated with partial glansectomy with primary glans closure, and 15 underwent total glans amputation and reconstruction of a new glans using a split-thickness skin graft (STSG). These 15 patients represent the subject of our study (mean age 51 years, range 42 to 59 years). Overall, two patients had early partial loss of the graft and of them, one required surgical regrafting. Two late complications occurred, consisting of one meatal stenosis and one postoperative phimosis. At a mean follow-up of 36 months, functional results were extremely satisfactory. All patients maintained their erectile function with good vaginal penetration starting from 3 months after surgery, with a range between 2 and 6 months. Orgasm and ejaculation were preserved in all patients, although reduced glans sensitivity was reported by all patients. No local recurrences were reported.

Effect of cytokines on hyaluronan synthase activity and response to oxidative stress by fibroblasts.

Cytokines such as tumour necrosis factor-alpha (TNFalpha), interferon-gamma (IFNgamma), and transforming growth factor-beta (TGF1beta) modulate hyaluronan synthase (HAS) gene expression and protein activity. The aim of this research is to evaluate the response of HAS gene expression and the related protein synthesis in fibroblasts after treatment with TNFalpha, IFNgamma and TGF1beta and to assess the potential protective effect of increased hyaluronan (HA) synthesis during oxidative stress. In this study, gene expression, protein synthesis, hyaluronan content, cell death, lactate dehydrogenase (LDH) activity, membrane lipid peroxidation and endogenous antioxidant depletion are determined for HAS1, HAS2 and HAS3. Messenger RNA (mRNA) expression and protein formation of the three HAS genes is modulated using different cytokines and various doses and correlated with increased HA synthesis. Protection of fibroblasts from injury induced by exposure to reactive oxygen species was significantly increased by TGF1beta and was associated with increased gene expression and protein formation of HAS1 and HAS2 enzymes synthesising high-molecular-weight HA. It is proposed that specific HAS enzyme activity and HA molecular weight specificity is involved in the protective mechanism.