Burden of an educational program on end of life management in a Internal Medicine ward: a real life report.

BACKGROUND AND AIM: Appropriate end of life (EOL) management in Internal Medicine wards is challanging. The aim of this study was to analyze the burden of an educational program on EOL management in a Internal Medicine ward. Materials and methods: We retrospectively analysed characteristics and management of patients consecutively died in an italian Internal Medicine ward along one year. We compared demographic, co-morbidity, pharmacological treatment in the last 48-hours of life and procedures during hospital stay in patients died six months before and after an educational program on palliative cares and EOL management addressed to a team of physicians and nurses. RESULTS: Study population was composed by 354 patients (190 females), with mean age ± DS 83.5 ± 10.6 years, one half admitted after the educational program. Eighty-four percent of deaths was exepected in the last 48 hours before exitus. Demographic characteristics and causes of hospitalization were not different before and after educational program. After the educational program the sharing of palliative care program with patient, relatives and/or caregivers (97.7% vs 85.8%, p=0.0001) and written order to withdrawal vital parameters relevation (39.5% vs 22%, p=0.0005) significantly increased, while difference in pharmacological classes prescribed in the last 48 hours of life was not find. Blood (54.8% vs 67.2%, p=0.0219) and arterial gas analysis (28.8% vs 39.5%, p=0.0435) samples in the last 48 hours of life were significantly reduced. Radiological and/or endoscopic examinations, red cells or platelets transfusion were reduced and palliative therapy was increased, despite difference between the two periods was not statistically significant. CONCLUSION: Educational program in Internal Medicine wards aimed to improve skills could contribute to make EOL management more appropriate and patient-oriented and it should be strongly encour-aged.

Fasitibant prevents the bradykinin and interleukin 1ß synergism on prostaglandin E2 release and cyclooxygenase 2 expression in human fibroblast-like synoviocytes.

This study investigates the effect of the selective and potent B(2) receptor antagonist fasitibant (MEN16132) on the proinflammatory effect of bradykinin (BK) and its interaction with interleukin 1ß (IL-1ß) in human synoviocytes. PGE(2) content was detected in the surnatants and COX-2 and COX-1 gene and protein expression determined in the cells. Radioligand binding ([(3) H]BK) and BK-induced inositolphosphate experiments were performed. Incubation of synoviocytes with BK induced a sustained production of PGE(2) and transient COX-2 gene expression that were prevented by pretreatment with fasitibant (1 µM, 30 min preincubation). IL-1ß increased PGE(2) release and COX-2 expression more than BK alone. The combined treatment of cells with BK and IL-1ß induced an even increase of released PGE(2) and COX-2 gene and protein expression indicating a synergistic rather than an additive effect, not related to an increase of B(2) receptors density or its coupling. These potentiating effects of BK on PGE(2) production and increased COX-2 expression produced by IL-1ß were B(2)-receptor-mediated as fasitibant could prevent them. None of the treatments induced changes in the COX-1 expression. The synergistic PGE(2) production was abolished by the specific NF-kappaB inhibitor (BAY-117085), whereas specific inhibitors for the p38 (SB203580), JNK (SP600125), and ERK1/2 (PD98059) mitogen-activated protein kinases could prevent the prostanoid release. BK can potentiate the COX-2 gene expression and consequent prostanoid production induced by IL-1ß. The prevention of this synergism by fasitibant indicates BK B(2) receptor blockade as an alternative symptomatic therapy for osteoarthritis.

Inhibitory effect of synthetic cannabinoids on cytokine production in rheumatoid fibroblast-like synoviocytes.

OBJECTIVE: To verify whether synthetic cannabinoids (CP55,940 and WIN55,212-2) are able to exert an anti-inflammatory effect on rheumatoid fibroblast-like synoviocytes (FLS) by down-regulating cytokine production, and determine whether this effect could be mediated by CB1/CB2 cannabinoid receptors. METHODS: Interleukin-6 (IL-6) and interleukin-8 (IL-8) were assayed in the supernatant from cultured FLS by ELISA method before and after 3 hours of incubation with CP55,940 (10 microM) and WIN55,212-2 (10 microM). Co-stimulation of cells with the cannabinoid receptor antagonists was performed to evaluate receptor involvement in cytokine modulation. All the experiments were conducted in basal conditions and after 1 hour pre-incubation with 0.1 ng/ml IL-1beta. FLS expression of CB1 and CB2 receptor was studied by Western Blot analyses. RESULTS: Both CP55,940 and WIN55,212-2 induced a potent and significant reduction in IL-6 and IL-8 secretion from IL-1beta. stimulated FLS. Although FLS express CB1 and CB2 receptor, cannabinoid receptor antagonists did not significantly modify the inhibition of cytokines secretion induced by CP55,940 and WIN55,212-2. CONCLUSIONS: In vitro, CP55,940 and WIN55,212-2 exert a potent anti-inflammatory effect on rheumatoid FLS via a non-CB1/CB2 receptor mediated mechanism.

[Anabolic effects and inhibition of interleukin 6 production induced by neridronate on human osteoblasts]. / Effetti anabolici e di inibizione della produzione di interleuchina 6 indotti dal neridronato in colture di osteoblasti umani.

UNLABELLED: Bisphosphonates (BPs) are pharmacological compounds widely used in the treatment of a variety of bone-related diseases, particularly where the bone-turnover is skewed in favour of osteolysis. The mechanisms by which BPs reduce bone-resorption directly acting on osteoclasts (OCs) are now largely clarified even at molecular level. The researches concerning the BPs effects on osteoblasts (OBs) have instead shown variable results. OBJECTIVES: We have investigated the efficacy of neridronate (NER), an amino-BP, as anabolic agent on human OBs. Moreover, we have tried to verify if NER is able to negatively modulate the production of IL-6 on OBs stimulated or not by the pro-inflammatory cytokine IL-1beta. METHODS: We have tested if different concentrations of NER (from 10-11 M to 10-3 M), added to primary human OB cultures, could affect the cells number, the endogenous cellular alkaline phosphatase (ALP) activity, the collagen I (COL-I) synthesis, the formation of mineralized nodules and the IL-6 production. Our experimental approach was performed testing a wide range of NER concentrations because, under physiological conditions, OBs seems to be exposed to variable and transient levels of the drug. RESULTS: Our results show that NER doesn't negatively affect in vitro the viability, proliferation and cellular activity of human OBs, even after 20 days of exposure to concentrations < or =10-5 M (therapeutic dose). In addition, NER seems to enhance the differentiation of cultured OBs in mature bone-forming cells. A maximum increase of COL-I synthesis (+25% after 4 days; p < 0.05), ALP activity (+50% after 10 days; p < 0.01) and mineralized nodules (+48% after 20 days; p < 0.05) was observed in cultures treated with NER 10-8 M. A maximal reduction of IL-6 secretion (-24% on IL-1beta stimulated cultures and -29% on unstimulated cultures) was observed for NER 10-9 M. CONCLUSIONS: These results encourage the use of neridronate in therapy of demineralizing metabolic bone disorders.

[Complete neurologic recovery after prolonged cardiac arrest caused by refractory ventricular fibrillation. Clinical case]. / Completo recupero neurologico dopo arresto cardiaco prolungato da fibrillazione ventricolare refrattaria. Caso clinico.

The clinical case of a 45-year-old patient referred to us for chest pain and with clinical examination and ECG negative for ischaemic damage, is reported. The patient, hospitalised in a bed without an ECG monitor, presented heart failure due to ventricular fibrillation. He was re-examined first with ventilation and EMC and then with defibrillation. Reanimation continued for about 70 minutes. Administration of high doses of adrenalin (0.2 mg/kg) and 9 defibrillations failed to resolve the refractory VF; nor did i.v. lidocaine administration resolve the situation. Echocardiogram did not reveal cardiac tamponade. Administration of 4 g of magnesium sulphate followed by adrenalin and defibrillation, led to asystole with subsequent restoration of sinus rhythm. The patient was then transferred to Intensive Care where he was sedated and curarized for 48 hours. The clinical course was characterised from the start by positive aspects that excluded the need to carry out instrumental investigations such as evoked somatosensory potentials, in the formulation of a prognosis. The patient was transferred to the Hospital Cardiology Unit 72 hours after admission. Two weeks later the patient was discharged with a complete recovery of neurological functions and with no metabolic or thoracopulmonary changes. It can be concluded from this experience that prognosis during CPR may not be reliable. So the factors that should lead us to carry out prolonged reanimation are the age of the patient, his pre-existing clinical conditions, the speed of our actions and correct performance of reanimation.