Indagine sulle alterazioni morfologiche eritrocitarie nel cane: artefatti o realta?

La valutazione microscopica dello striscio ematico resta una componente essenziale dell’esame emocromocitometrico nonostante la presenza di sofisticati analizzatori ematologici. Infatti, consente la validazione dei dati generati dai contaglobuli e fornisce, ad un osservatore esperto, molte informazioni utili dal punto di vista clinico. Lo scopo di questo lavoro è stata la valutazione nel cane della poichilocitosi in genere e l’indagine su un’alterazione eritrocitaria insolita (denominata “a quadrifoglio” o “a croce di Pisa”, finora mai descritta). Questi rilievi sono stati studiati retrospettivamente con la consultazione delle schede cliniche e degli esami di laboratorio. Sono stati considerati i risultati di 3958 campioni di sangue di cane analizzati presso il Laboratorio di Biochimica ed Ematologia Clinica Veterinaria del Dipartimento di Clinica Veterinaria nel periodo compreso fra Maggio 2009-Ottobre 2010. La poichilocitosi è stata osservata nel circa 34% degli strisci ematici canini. La formazione eritrocitaria “a quadrifoglio” è stata osservata su 139 cani. Questa alterazione è stata osservata anche in alcuni gatti, cavalli ed in un cinghiale. Solo nei campioni di cane che presentavano la formazione “a quadrifoglio” sono stati approfonditi e valutati i dati segnaletici, i parametri eritrocitari e i risultati di diverse analisi di laboratorio e quindi confrontati con una popolazione di controllo mediante appropriate indagini statistiche. La conferma dell’effettiva presenza dell’alterazione “a quadrifoglio” sugli strisci ematici e un’idea più precisa della disposizione spaziale degli eritrociti coinvolti è stata possibile grazie allo studio al microscopio elettronico a scansione. L’analisi statistica sui dati riguardanti l’alterazione “a quadrifoglio”, non ha evidenziato correlazioni significative, eccetto che per l’età dei soggetti interessati (più anziani), il valore dei leucociti totali (leucopenia) e dei neutrofili (neutropenia) (p<0,0001). Sulla base dei risultati ottenuti non è stato possibile identificare con certezza l’origine ed il significato dell’alterazione “a quadrifoglio”, nonostante sia stata confermata la sua effettiva presenza sugli strisci ematici. Al riguardo sono state formulate alcune ipotesi, tra cui cause artefattuali o patologie infiammatorie che modificano la carica elettrica eritrocitaria. Saranno necessari ulteriori studi per indagare con maggior precisione questo tipo di alterazione

Influence of infill panels on the seismic behaviour of a r/c frame designed according to modern buildings codes

It has been broadly shown that presence of infill panels as closing elements of R/C frame buildings has a significant influence on global structural behaviour. Nevertheless, infill elements are not usually considered in the modelling process during the design phase. The present work investigates the effect of infill masonry walls on the dynamic characteristics of a R/C MRF building, designed according to a modern seismic building code, and on its seismic performance at different levels of seismic intensity. An analytical investigation is carried out through eigenvalue analysis on both bare and infilled structure, in order to calibrate the elastic properties of the concrete and infills according to in situ tests; nonlinear static analyses are also performed to characterize the inelastic behaviour. The infill system considerably affects the behaviour of the examined structure, in agreement with earlier studies related to very simple and usually ¿unrealistic¿ structures. This result becomes more reliable due to the consistency between the results of the eigenvalue analysis and the experimental dynamic data

Prevalence of Chronic Cancer and No-Cancer Pain in Elderly Hospitalized Patients: Elements for the Early Assessment of Palliative Care Needs

Summary: Background: We studied prevalence of chronic pain, related or not to cancer, in elderly patients, its correlation with socio-clinical factors, and its effects on daily living, to estimate feasibility of an early assessment of palliative care needs in a non-specialist hospital setting. Methods: In this prospective study, a questionnaire concerning pain and multidimensional assessment tools were administered to patients consecutively admitted to a Department of Internal Medicine comprising a Stroke Unit. Results: One hundred patients were recruited, 38 of whom experiencing pain, chronic in 26 patients (68%). A total of 34.3% of patients with pain and 12.5% of patients without pain suffered from depression (P = 0.013). Depressed patients showed significantly higher median values in all Brief Pain Inventory (BPI) scores and items. Depressed patients also obtained less pain relief from therapies. Patients with mild dementia showed, significantly or as a trend, a higher median least, average and "pain right now" pain values. Worst pain values in the previous 24 h increased with age. Only 42% of patients reported to be on pain therapy upon admission to hospital, whereas 62% were undergoing treatment at the time of discharge. A correlation was found between the pain value and the level of interference with daily activities. Pain was mentioned in the discharge letter in 36% of cases. Conclusion: Pain is a critical underestimated problem in elderly patients. A timely systematic evaluation of the pain would call attention to palliative care needs and reduce the negative effects of uncontrolled pain on the quality of life. Keywords: Pain assessment, Pain prevalence, Elderly patients, Pain and depression, Pain and activities of daily livin

UCN-01 enhances cytotoxicity of irinotecan in colorectal cancer stem-like cells by impairing DNA damage response

Colorectal cancer (CRC) is one of the most common and lethal cancers worldwide. Despite recent progress, the prognosis of advanced stage CRC remains poor, mainly because of cancer recurrence and metastasis. The high morbidity and mortality of CRC has been recently ascribed to a small population of tumor cells that hold the potential of tumor initiation, i.e. cancer stem cells (CSCs), which play a pivotal role in cancer recurrence and metastasis and are not eradicated by current therapy. We screened CRC-SCs in vitro with a library of protein kinase inhibitors and showed that CRC-SCs are resistant to specific inhibition of the major signaling pathways involved in cell survival and proliferation. Nonetheless, broad-spectrum inhibition by the staurosporin derivative UCN-01 blocks CRC-SC growth and potentiates the activity of irinotecan in vitro and in vivo CRC-SC-derived models. Reverse-Phase Protein Microarrays (RPPA) revealed that, albeit CRC-SCs display individual phospho-proteomic profiles, sensitivity of CRC-SCs to UCN-01 relies on the interference with the DNA damage response mediated by Chk1. Combination of LY2603618, a specific Chk1/2 inhibitor, with irinotecan resulted in a significant reduction of CRC-SC growth in vivo, confirming that irinotecan treatment coupled to inhibition of Chk1 represents a potentially effective therapeutic approach for CRC treatment

Effects of onabotulintoxinA on habituation of laser evoked responses in chronic migraine

Onabotulintoxin A (BontA) is an efficacious preventive treatment for chronic migraine, though the specific mechanism of action is still under discussion. The study aims: (1) To evaluate pain processing modifications in chronic migraine patients (CM) under single BontA administration in pericranial muscles, by means of CO2 Laser Evoked Potentials (LEPs) obtained by the stimulation of the skin over the right frontal and trapezius injection sites and hand dorsum, in a double blind placebo controlled crossover design. (2) To correlate main LEPs findings with clinical outcome after one year of BontA treatment. Twenty refractory CM patients were included in the analysis. The LEPs were recorded in basal conditions and seven days after BontA (PREEMPT protocol) and saline solution injection. The N1, N2 and P2 amplitude and latencies and N2P2 habituation index were evaluated and correlated with the percent change of headache frequency after one year of toxin treatment. After seven days of BontA treatment, a normalization of the trigeminal habituation index was observed, which was correlated with the clinical outcome after one year of BontA therapy. Patients displaying trigeminal LEPs facilitation at T0 time showed a more efficient therapeutic outcome. Neurotoxin may exert a modulating effect on trigeminal nociception, normalizing central neurotransmission

Persistent intraepithelial lymphocytosis in celiac patients adhering to gluten-free diet is not abolished despite a gluten contamination elimination diet

The gluten-free diet (GFD) is the only validated treatment for celiac disease (CD), but despite strict adherence, complete mucosal recovery is rarely obtained. The aim of our study was to assess whether complete restitutio ad integrum could be achieved by adopting a restrictive diet (Gluten Contamination Elimination Diet, GCED) or may depend on time of exposure to GFD. Two cohorts of CD patients, with persisting Marsh II/Grade A lesion at duodenal biopsy after 12–18 months of GFD (early control) were identified. Patients in Cohort A were re-biopsied after a three-month GCED (GCED control) and patients in Cohort B were re-biopsied after a minimum of two years on a standard GFD subsequent to early control (late control). Ten patients in Cohort A and 19 in Cohort B completed the study protocol. There was no change in the classification of duodenal biopsies in both cohorts. The number of intraepithelial lymphocytes, TCR + (T-Cell Receptor gamma delta) T cell and eosinophils significantly decreased at GCED control (Cohort A) and at late control (Cohort B), compared to early control. Duodenal intraepithelial lymphocytosis persisting in CD patients during GFD is not eliminated by a GCED and is independent of the length of GFD. [NCT 02711696

Methadone as First-line Opioid for the Management of Cancer Pain

Aim The aim of this study was to assess the efficacy and adverse effects of methadone when used as first-line therapy in patients that are either receiving low doses of opioids or none. Methods Patients with advanced cancer were prospectively assessed. Opioid-naive patients (L-group) were started with methadone at 6 mg/day. Patients receiving weak or other opioids in doses of &lt;60 mg/day of OME (H-group) were started with methadone at 9 mg/day. Methadone doses were changed according to the clinical needs to obtain the most favorable balance between analgesia and adverse effects. Edmonton Symptom Asssement Score (ESAS), Memorial Delirium Assessment Score (MDAS), doses of methadone, and the use of adjuvant drugs were recorded before starting the study treatment (T0), 1 week after (T7), 2 weeks after (T14), 1 month after (T30), and 2 months after (T60). Methadone escalation index percent (MEI%) and in mg (MEImg) were calculated at T30 and T60. Results Eighty-two patients were assessed. In both groups H and L, there were significant changes in pain and symptom intensity at the different times during the study. Adverse effects as causes of drop-out were minimal. Mean MEImg was 0.09 (SD 0.28) and 0.02 (SD 0.07) at T30 and T60, respectively. MEI% was 1.01 (SD 3.08) and 0.27 (SD 0.86) at T30 and T60, respectively. Conclusion Methadone used as a first-line opioid therapy provided good analgesia with limited adverse effects and a minimal opioid-induced tolerance

A Simple Pattern of Movement Is Not Able to Inhibit Experimental Pain in FM Patients and Controls: An sLORETA Study

Motor cortex activation seems to induce an analgesic effect on pain that would be different between patients with fibromyalgia (FM) and control subjects. This study was conducted to analyze the changes of the laser-evoked potentials (LEPs) induced during a finger tapping task in the FM patients and the controls employing a multi-dipolar analysis according to Standardized low resolution brain electromagnetic tomography (sLORETA) method. The LEPs from 38 FM patients and 21 controls were analyzed. The LEPs were recorded while subjects performed a slow and a fast finger tapping task. We confirmed that the difference between N1, N2 and P2 wave amplitudes between conditions and groups was not significant. In control subjects, the fast finger tapping task induced a modification of cortical source activation in the main areas processing laser stimulation from the moving hand independently from the movement speed. In summary, a simple and repetitive movement is not able to induce consistent inhibition of experimental pain evoked by the moving and the not moving hand in each group. It could interfere with LEP sources within the limbic area at least in control subjects, without inhibit cortical responses or explain the different pattern of motor and pain interaction in FM patients.The study was supported by the Bari Aldo Moro University Research fund