Resting and stimulated human polymorphonuclear leucocytes from type-2 diabetic patients: change in purine nucleotide pattern

It is known that polymorphonuclear leucocytes are deeply involved in the inflammatory complications of diabetes mellitus, showing many functional and biochemical abnormalities. Because adenine and guanine metabolites exert an important role in many metabolic aspects of phagocytic cells, we have investigated the pattern of purine metabolites during the respiratory burst of polymorphonuclear leucocytes in order to characterize any difference that may be significantly correlated with the abnormal neutrophil function of diabetic patients. The results obtained show clearly that polymorphonuclear leucocytes from diabetic patients are characterized by an abnormal pattern of purine nucleotides and their metabolites. In particular, the concentration of adenine and guanine triphosphates and the net amount of adenosine triphosphate hydrolysed during neutrophil stimulation by phorbol ester is higher in diabetic than in control cells. Moreover, higher values of adenosine monophosphate, inosine monophosphate and inosine have been found in diabetic cells. The behaviour of guanosine triphosphate is highly interesting. In fact, in addition to the higher concentration found in diabetic polymorphonuclear leucocytes, stimulation by phorbol ester induces a net decrease in guanosine triphosphate whereas control neutrophils show a slight increase. These findings have been associated with the ease with which diabetic neutrophils undergo metabolic activation and sustain an inflammatory response.     

Adverse drug reactions related to amoxicillin alone and in association with clavulanic acid: data from spontaneous reporting in Italy

OBJECTIVES: To analyse an Italian database of spontaneous reporting of suspected adverse drug reactions in order to compare the safety profile of amoxicillin and amoxicillin/clavulanic acid. METHODS: Data were retrieved from the spontaneous reports collected by six Italian regions (the GIF database) from January 1988 to June 2005. Drug utilization data were also available for the two drugs. The comparison between amoxicillin and amoxicillin/clavulanic acid was made using the chi(2) or Student's t-test, when appropriate. Disproportionality in reporting of adverse events was assessed using reporting odds ratio methodology. RESULTS: Up to June 2005, the GIF database collected 37 906 reports, of which 1088 were related to amoxicillin/clavulanic acid and 1095 to amoxicillin. The percentage of skin reactions was statistically higher for amoxicillin (82%) than for amoxicillin/clavulanic acid (76%); on the contrary, the percentage of gastrointestinal, hepatic and haematological reactions was significantly higher for amoxicillin/clavulanic acid (13%, 4% and 2%, respectively) than for amoxicillin (7%, 1% and 1%, respectively). Amoxicillin/clavulanic acid seems to be associated with a higher risk of Stevens-Johnson syndrome, purpura and hepatitis than amoxicillin alone. In particular, the reporting rate of hepatitis is on average 9-fold higher for amoxicillin/clavulanic acid than for amoxicillin. CONCLUSIONS: Analysis shows a different safety profile for the two selected drugs. The combination of amoxicillin/clavulanic acid has been increasingly used in Italy and now represents the most frequently antibiotic prescribed by Italian general practitioners. Given the documented level of inappropriate use of beta-lactams in Italy, these results should be taken into account by physicians before prescribing amoxicillin/clavulanic acid to patients.     

Myocarditis: basic and clinical aspects

Myocarditis represents a heterogeneous final common pathway for myocardial inflammation of diverse etiologies and accounts for up to one-third of cases of dilated cardiomyopathy. The pathophysiology of viral myocarditis can be disaggregated into the effects of direct viral mediated injury, triggered acute and chronic autoimmune responses, and subsequent adverse remodeling. Recent research highlights the pathogenic role of persistent viral genome expression, Fas-ligand, tumor necrosis factor-alpha receptor 1, and antimyosin autoantibodies in the evolution of chronic systolic and diastolic heart failure. Recent refinements in endomyocardial biopsy evaluation, cardiac magnetic resonance imaging, and cytokine assays augment existing diagnostic modalities. Novel specific immunosuppressive targets aimed at interrupting myocyte injury and apoptosis, including interferon-beta seem promising to date in small clinical studies performed on selected patients.     

Efficacy of traditional and biologic agents in different clinical phenotypes of adult‐onset Still's disease

Objective

To evaluate the efficacy of antiinflammatory agents, steroids, immunosuppressants, and biologic agents in patients with adult‐onset Still's disease (AOSD) who have either chronic articular disease or nonchronic disease.

Methods

Forty‐five patients with AOSD were seen and followed up for at least 2 years at our institution, from 1991 to 2008. The majority of patients were treated with several therapeutic regimens; a total of 152 efficacy trials were administered. Data regarding the type of medication, the dosage used, and the outcome of these trials were collected and analyzed.

Results

Our data showed that the efficacy of monotherapy with a nonsteroidal antiinflammatory drug was very low (16%) and confirmed good efficacy of steroid therapy (63%), particularly in patients without chronic articular disease (78%). Patients whose disease did not respond to steroid therapy at the time of disease onset were at risk of the subsequent development of chronic arthritis. Disease‐modifying antirheumatic drug (DMARD) monotherapy was successful in controlling steroid‐resistant or steroid‐dependent disease in 60% of patients. Methotrexate and cyclosporine showed the best response rates. The combination of high‐dose steroids and cyclosporine was administered to successfully control some acute life‐threatening complications. Only 6 patients had disease that was both steroid resistant and DMARD resistant. Treatment with biologic agents eventually led to satisfactory control of disease manifestations in 5 (83%) of these 6 patients.

Conclusion

Steroids were less effective in patients with chronic articular disease than in those with nonchronic disease. The administration of DMARDs early after disease onset could be beneficial in patients with steroid‐resistant disease who are at risk of the development of chronic articular disease. Biologic agents proved to be highly effective in both steroid‐resistant and DMARD‐resistant AOSD.

     

Does the Italian pediatric anesthesia training program adequately prepare residents for future clinical practice? What should be done?

BACKGROUND: Pediatric anesthesia should be considered a subspecialty addressing the complete pediatric population (from preterm to teenager) and requiring particular anatomical, pathophysiological, pharmacological and anesthesiological knowledge. A survey was conducted to evaluate the training in pediatric anesthesia performed by Medical Schools of Anesthesia in Italy and to assess if the European Federation of Associations of Pediatric Anesthesia (FEAPA) guidelines for training in pediatric anesthesia had been adopted. METHODS: The survey was addressed to the Directors of the Departments of Anesthesia and Intensive Care of the Medical Schools throughout Italy using a questionnaire. RESULTS: We contacted all 37 Schools of Anesthesia, but only 26 of these (70 %) answered all the questions. A specific training program exists in 24 (92%). The duration of the training is variable: in 40% of the schools it lasts 2 months, in 27% 3 months and in 33% more than 3 months (3-6 months). Only 29% of the Schools required a minimum number of procedures to be performed during the training period. A final test is performed in 46% of the Schools. A dedicated staff for pediatric anesthesia exists in 70% of the Italian Schools. CONCLUSIONS: In Italy, the FEAPA guidelines have not yet been completely adopted. The experience of a dedicated unit for pediatric anesthesia will be invaluable to define operative guidelines, courses and to establish the minimum equipment necessary for pediatric management in nonspecialist hospitals.