Prevention of anterior cruciate ligament injuries in soccer

Proprioceptive training has been shown to reduce the incidence of ankle sprains in different sports. It can also improve rehabilitation after anterior cruciate ligament (ACL) injuries whether treated operatively or nonoperatively. Since ACL injuries lead to long absence from sports and are one of the main causes of permanent sports disability, it is essential to try to prevent them. In a prospective controlled study of 600 soccer players in 40 semiprofessional or amateur teams, we studied the possible preventive effect of a gradually increasing proprioceptive training on four different types of wobble-boards during three soccer seasons. Three hundred players were instructed to train 20 min per day with 5 different phases of increasing difficulty. The first phase consisted of balance training without any balance board; phase 2 of training on a rectangular balance board; phase 3 of training on a round board; phase 4 of training on a combined round and rectangular board; phase 5 of training on a so-called BABS board. A control group of 300 players from other, comparable teams trained normally and received no special balance training. Both groups were observed for three whole soccer seasons, and possible ACL lesions were diagnosed by clinical examination, KT-1000 measurements, magnetic resonance imaging or computed tomography, and arthroscopy. We found an incidence of 1.15 ACL injuries per team per year in the control group and 0.15 injuries per team per year in the proprioceptively trained group (P<0.001). Proprioceptive training can thus significantly reduce the incidence of ACL injuries in soccer players.     

Simultaneous recording of pattern electroretinogram (PERG) and visual evoked potential (VEP) in multiple sclerosis

We studied 18 multiple sclerosis (MS) patients affected by retrobulbar neuritis (RBN). The patients were subdivided into two groups. Group 1: 14 patients with RBN. Group 2: 4 patients with optic atrophy. An ophthalmological examination (visual acuity, fundus oculi, visual field) was carried out in all the patients. A simultaneous visual evoked potential (VEP) and pattern electroretinogram (PERG) recording at two spatial frequencies (45' and 15') was performed. All the data obtained in Group 1 were compared (Student T-Test) with those of a control group of normal subjects matched for age and sex. Group 1. VEP: a comparison of the data in MS patients affected by RBN with the control group revealed a statistically significant P100 latency delay with both spatial frequencies (P less than 0.001). PERG: no "b" wave latency change at 45' and 15' spatial frequencies were seen. A "b" wave amplitude reduction was observed; this reduction reached significant values at 45' (P less than 0.001). Group 2. In optic atrophies the PERG was absent in 4 eyes at 45' and in 5 eyes at 15'.     

Pharmacodynamic evaluation of the epidermal growth factor receptor inhibitor OSI-774 in human epidermis of cancer patients.

BACKGROUND: OSI-774 is an inhibitor of the epidermal growth factor receptor tyrosine kinase (EGFR-TK) currently in clinical development. In preclinical models, the antitumor activity of OSI-774 was directly related to its ability to inhibit the EGFR-TK. On the basis of these data, we hypothesized that inhibition of the EGFR-TK will be required for this agent to be effective in the clinic. This study evaluated the pharmacodynamic effects of OSI-774 in normal skin tissues collected from patients treated with the agent in a Phase I study. METHODS: Patients with advanced cancer who were treated in a Phase I study of OSI-774 underwent a biopsy of normal skin epidermis at baseline and after the last dose of drug in the first course of treatment. The expression and activation of the EGFR, downstream signaling extracytoplasmatic-regulated kinase (Erk), and cell cycle regulator p27 were determined in paraffin-embedded skin tissues using an immunohistochemical method (IHC). The IHC data were analyzed using both a semiquantitative scoring system and an automatic absorbance quantitative IHC method. The number of cells with nuclear staining of p27 per 500 cells was determined. Plasma samples were collected to quantitate OSI-774 plasma concentrations. RESULTS: A total of 56 skin specimens was collected from 28 patients treated with OSI-774 at doses ranging from 25 to 200 mg/day. There was a significant decrease in phospho-EGFR (Tyr 1173) expression as determined semiquantitatively with OSI-774 treatment [2.75 +/- 0.51 (mean +/- SD) pretreatment versus 2.36 +/- 0.76 after treatment, pair comparison P = 0.01]. The quantitative ratio [(phopho-EGFR/EGFR) x 100] of phospho-EGFR (Tyr1173) decreased from 64.16 +/- 36.58 pretreatment to 48.87 +/- 35.37 post-treatment (pair comparison, P = 0.02). No significant differences were observed in phospho-Erk (Thr202/Tyr204) expression. The mean number of cells with nuclear staining for p27 increased from 185 +/- 101 (mean +/- SD) pretreatment to 253 +/- 111 post-treatment (pair comparison P = 0.02). A total of 12 (42.8%), 7 (25%), and 14 (50%) patients had >25% variation in the ratio of phospho-EGFR (Tyr1173), phospho-Erk (Thr202/Tyr204), and p27 expression, respectively. Only changes in p27 expression were related to the administered dose of OSI-774. CONCLUSIONS: OSI-774 exerted pharmacodynamic effects in skin tissues of 30-50% of patients treated with the agent. Up-regulation of p27, which is a downstream effect of EGFR inhibition, was dose related. Although there was a significant decrement in phospho-EGFR (Tyr1173), it was not related to the administered dose of OSI-774. On the basis of these findings and the relatively simple and reliable method to measure p27 expression, this biomarker appears to be the most promising and is being evaluated in Phase II studies as a predictor of clinical outcome.     

Activity of nonpeptide tachykinin antagonists on neurokinin a induced contractions in dog urinary bladder

PURPOSE: There is abundant evidence indicating that tachykinin (TK) containing sensory nerves (C-fibers) play an important role in neural regulation of reflex micturition in mammals. Desensitization of urinary bladder C-fibers with resiniferatoxin ameliorates bladder hyperreflexia and incontinence and supports a similar role for C-fibers in man. TK-induced contraction of isolated human urinary bladder smooth muscle appears to be exclusively neurokinin NK2-receptor mediated. Dog urinary bladder contractility to a series of TK-receptor agonists also suggests a predominance of NK2-receptor activation by tachykinins and indicates the dog may provide a useful model for the development of pharmacotherapy for bladder hyperreflexia. MATERIALS AND METHODS: We evaluated the activity of the nonpeptide NK-receptor selective antagonists SR 48968 (NK2), SB 223412 (NK3) and CP 99994 (NK1) against neurokinin A (NKA)-induced contractions in isolated dog urinary bladder strips to determine the NK-receptor type which mediates contractile responses to NKA. The dual NK1 and NK2 antagonist MDL 103392 was also tested in this preparation. RESULTS: NKA-induced contractions (pD2 = 8.0) were dose dependently blocked by SR 48968 (pA2 = 8.2 +/- 0.2) while CP 99994 (1.0 microM) and SB 223412 (1.0 microM) were inactive. MDL 103392 was a weak functional antagonist (pKb = 6.1 +/- 0.1) of NKA. CONCLUSIONS: Relative activities of SR 48968, CP 99994 and SB 223412 confirm that the NK2-receptor is the mediator of NKA-induced contractions of dog urinary bladder smooth muscle.     

Combined treatment with haloperidol and trazodone in patients with tic disorders

The combination of haloperidol and trazodone was evaluated in an open-label trial in 10 patients with chronic tic and Tourette's syndrome. We found a mean reduction of symptoms of 58.9% on the Yale Global Tic Severity Scale, with a statistically significant difference (p < 0.001) between the baseline and endpoint treatment conditions. This approach significantly reduces clinical symptoms, with the advantage of a lower dose of haloperidol than usual, with no side effects reported by the patients.     

Hepatitis B Virus-Associated Hepatocellular Carcinoma

Hepatitis B virus (HBV) is DNA-based virus, member of the Hepadnaviridae family, which can cause liver disease and increased risk of hepatocellular carcinoma (HCC) in infected individuals, replicating within the hepatocytes and interacting with several cellular proteins. Chronic hepatitis B can progressively lead to liver cirrhosis, which is an independent risk factor for HCC. Complications as liver decompensation or HCC impact the survival of HBV patients and concurrent HDV infection worsens the disease. The available data provide evidence that HBV infection is associated with the risk of developing HCC with or without an underlying liver cirrhosis, due to various direct and indirect mechanisms promoting hepatocarcinogenesis. The molecular profile of HBV-HCC is extensively and continuously under study, and it is the result of altered molecular pathways, which modify the microenvironment and lead to DNA damage. HBV produces the protein HBx, which has a central role in the oncogenetic process. Furthermore, the molecular profile of HBV-HCC was recently discerned from that of HDV-HCC, despite the obligatory dependence of HDV on HBV. Proper management of the underlying HBV-related liver disease is fundamental, including HCC surveillance, viral suppression, and application of adequate predictive models. When HBV-HCC occurs, liver function and HCC characteristics guide the physician among treatment strategies but always considering the viral etiology in the treatment choice.     

Historically Accurate Reconstruction of the Materials and Conservation Technologies Used on the Facades of the Artistic Buildings in Lecce (Apulia,Italy)

The protection of the stone surfaces of the buildings of the city of Lecce (Apulia, Italy) represents an ancient practice, which has always allowed the conservation of the historical-artistic heritage of the city, which nowadays is an international touristic and cultural destination. The identification of ancient recipes, materials and methodologies for the protection of historical buildings plays an important role in establishing correct protocols in order to ensure the durability of stone surfaces over time. This work presents a historically accurate reconstruction of the materials and conservation technologies used on the facades of the artistic buildings in Lecce. Several historical buildings, both civil and religious, have been selected in order to investigate the treatments applied on their facades and to know the traditions spread in the past in the field of building conservation in the Salento territory. Thanks to non-invasive or micro-destructive techniques (optical microscopy, ATR-FTIR spectroscopy, pyrolysis–gas chromatography–mass spectrometry), the characteristic molecular markers of the materials and the products of degradation have been identified, deepening the knowledge of the mechanisms of deterioration and interaction between the stone material, the surface finish and the surrounding environment. The paper is a valuable tool for the knowledge of ancient traditions and the planning of proper restoration works.     

Down syndrome biochemical markers and screening for preeclampsia at first and second trimester: correlation with the week of onset and the severity

OBJECTIVES: To estimate the combined screening performance of first and early second trimester prenatal serum markers for Down syndrome, in screening for the development of preeclampsia, and analyze the correlation among marker levels, week of onset, and severity of the disease. METHODS: A retrospective cohort study was carried out on 32 women with preeclampsia and 3044 controls. Serum samples from these pregnancies were assayed for pregnancy-associated plasma protein-A (PAPP-A), alpha-fetoprotein (AFP), unconjugated estriol (uE3), human chorionic gonadotrophin (hCG), and inhibin-A. A likelihood ratio and the odds of being affected given a positive result (OAPR) of various combinations of markers were calculated and receiver operating characteristic (ROC) curves analysis was performed. RESULTS: In the pregnancies that subsequently developed preeclampsia, first trimester PAPP-A concentration was significantly lower and concentrations of early second trimester inhibin-A and hCG significantly elevated. Levels of early second trimester uE3 and AFP were not significantly altered. We also found that inhibin-A correlates with both onset of the disease and the severity. CONCLUSION: Down syndrome biochemical markers levels are altered in those patients who subsequently developed preeclampsia and may be a useful screening test for preeclampsia. Inhibin-A is the most predictive marker and correlates with the severity of subsequent preeclampsia and inversely with the week of occurrence of preeclampsia.