Pharmacodynamic profile of isbufylline, a new antibronchospastic xanthine devoid of central excitatory actions.

1,3-Dimethyl-7-isobutylxanthine (isbufylline, TE/06; CAS 90162-60-0) is a newly synthetized xanthine derivative. This compound exhibits remarkable antibronchospastic properties both in in vitro and in vivo (after oral or intravenous administration) experimental models. Isbufylline is significantly more effective than theophylline in antagonizing bronchospasms elicited by spasmogens (capsaicin, arachidonic acid, PAF and antigen) which mainly act by a local release of biologically active substances proposed to be involved in the pathogenesis of asthma. Isbufylline, unlike theophylline, possesses little or no CNS excitatory properties. This reduced neuroexcitatory action is probably related to the poor affinity of isbufylline, as compared to theophylline, to A1 purinoceptor. Indeed, isbufylline is ineffective in antagonizing 2Cl-adenosine-induced EEG synchronization. In normotensive and hypertensive rats oral administration of isbufylline resulted in small and transient positive chronotropic and hypotensive response, markedly lower than those elicited by theophylline or enprofylline. Finally isbufylline exhibits phosphodiesterase inhibitory properties, although at concentration 50-100 times higher than those exerting spasmolytic effects in isolated bronchial tissues. As a whole the pharmacodynamic profile of isbufylline is promising and, in the clinical setting, this compound might exert enhanced antiasthma effects coupled to a low incidence of central and cardiovascular adverse effects.     

Malignant Myoepithelioma of the Rhinopharynx: Case Report

Malignant myoepitheliomas are rare tumors of salivary glands. Most occur in the parotid gland; few other sites of origin are described. Malignant myoepithelioma of the rhinopharynx has only been reported twice. Because the lesion is so rare, there are no specific indications for its treatment. We present a third case of malignant myoepithelioma in the rhinopharynx and discuss its diagnostic and therapeutic aspects.     

Effects of atorvastatin on arterial endothelial function in coronary bypass surgery

Objective: Endothelial dysfunction represents a critical early component of organ injury following cardiopulmonary bypass. Recent studies demonstrate that the treatment with atorvastatin is associated with a significant improvement of endothelial function independently of its efficacy on cholesterol levels. Therefore, we investigated the effects of preoperative atorvastatin treatment on endothelium function after coronary surgery. Methods: Forty patients undergoing coronary surgery were randomized to treatment with atorvastatin (20 mg/die; N = 20) or placebo (N = 20) 3 weeks before surgery. Twenty normal patients served as control group. The flow-mediated dilations (FMD) of the brachial artery after both reactive hyperemia (endothelium dependent) and nitroglycerin administration (endothelium independent) were evaluated at baseline, at 48 h, and 5 days postoperatively. Results: At baseline, the endothelium-dependent FMD was significantly attenuated in coronary versus normal patients (normal 10.3 ± 1.8% vs coronary 4.1 ± 1.6%, p < 0.01). At 48 h postoperatively all patients exhibited a reduced FMD compared with baseline values: the endothelium-dependent dilatation showed a drop of 60.1 + 15% in the patients of the placebo group compared with 45.8 + 16.6% (p < 0.05) those in the atorvastatin group. At the univariate analysis, no significant correlation was found between serum levels of either total cholesterol or HDL cholesterol and FMD. The nitroglycerin-induced dilation was not significantly influenced by extracorporeal circulation as well as by atorvastatin treatment. Conclusions: The endothelial dysfunction following cardiopulmonary bypass is improved by the treatment with atorvastatin, by a mechanism unrelated to the drug efficacy of controlling serum cholesterol levels.     

Increased external tibial torsion in Osgood-Schlatter disease

We studied the relationship between Osgood-Schlatter disease and torsional abnormalities of the lower limb in 21 boys with this condition and 20 age- and sex-matched controls. 3 groups of knees (20 control knees, 21 symptomatic and 21 asymptomatic or less symptomatic knees) were subjected to clinical, radiographic and CT evaluation. We found no statistically significant differences between patients and controls, as regards femoral anteversion, patellar congruence angle, patellar tilt angle and anterior tibial tuberosity-trochlear groove distance, but the condylomalleolar angle and tibial torsion angle were greater in patients. We found no differences between symptomatic and asymptomatic or less symptomatic knees in any of the parameters. All the symptomatic knees were on the side preferentially involved in jumping and sprinting. This increase in external tibial torsion may play a role as a predisposing mechanical factor in the onset of Osgood-Schlatter disease in male athletes.     

The role of IFN-alpha as homeostatic agent in the inflammatory response: a balance between danger and response?

Interferon-alpha (IFN-alpha) is thought of by most immunologists as a fundamental component of the antiviral innate immune response, with other, accessory properties. Several lines of evidence point to a fundamental reappraisal of this conceptual framework because it may neglect other crucial functions of this cytokine under both health and disease conditions. Among these, a regulatory role in the inflammatory response is probably of paramount importance, as shown by in vivo and in vitro studies on humans, pets, and farm and laboratory animals. This role would not conflict with the main functions of IFN-alpha in the innate immune system and would complement these in line with major, evolution-based needs of the host. A hinge role of IFN-alpha between innate and adaptive immunity was recognized in the past on the basis of compelling evidence. This concept should now be widened; not only does IFN-alpha act to trigger, amplify, and sustain the different phases of the immune response, but it could also promote a substantial balance between danger and inflammatory response when an infectious challenge is either declining or completely over.     

Early and late onset bacteremia have different risk factors in trauma patients

Objective The aim of this study was to identify risk factors and to describe epidemiological patterns for early—(EOB) and late—onset bacteremias (LOB) after trauma.Design A prospective study conducted on 141 consecutive trauma patients.Setting A general intensive care unit (ICU) of a university hospital.Patients All multiple trauma patients admitted to our general intensive care unit (ICU) from December 1990 to May 1992 were prospectively enrolled in the study. The following information was collected for each patient and recorded in a computer database: demography, severity of trauma according to the Abbreviated Injury Scale (AIS), severtity of trauma according to the Glasgow Coma Scale (GCS), presence of pneumothorax, pulmonary contusion, rib fractures, hemothorax, and abdominal trauma, use of mechanical ventilation, and placement of central venous catheters. Bacteremias were defined as EOB when onset occurred within 96 h after trauma, and as LOB when appearing after 96 h from trauma.Results Thirty-seven patients developed bacteremia during their ICU stay (26%): 11 (29.7%) EOB and 26 (70.3%) LOB. Gram-positive cocci were isolated more frequently in EOB than in LOB (x ²=4.1,P=0.04). The risk of EOB was significantly increased by the presence of pulmonary contusion [relative risk (RR) 15.0; confidence interval (CI) 1.99-113.25], pneumonia before the onset of bacteremia (RR 3.56; CI 1.17-10.69), AIS score greater than 32 and an abdominal injury score greater than 9 (RR 3.11; CI 1.02-9.49), while intravascular catheters and mechanical ventilation did not represent risk factors for EOB. LOB had a very different pattern and their risk was significantly increased by exposure to intravascular catheters (RR 4.96; CI 1.23-19.94) and to mechanical ventilation lasting more than 7 days (RR 3.6; CI 1.6-8.1).Conclusions Scoring with the AIS of the abdominal and thoracic trauma at admission to the ICU appears a useful tool for identifying trauma patients at increased risk of EOB. A rigorous policy of catheter placement and maintenance as a means of reducing late bacteremias in trauma patients is essential.     

Transposition of the great arteries and isolated origin of the sinus node artery

We report the cases of 2 newborns who underwent at 7 days of age an arterial switch operation for transposition of the great arteries with a rare coronary anomaly: the left and right coronary arteries originated with a single ostium from sinus 1 and the sinus node artery had an isolated origin from sinus 2. The sinus node artery was reimplanted into the new aorta in both patients. Both babies were discharged in sinus rhythm. Preserving the vascularization of the sinus node may avoid the occurrence of postoperative atrial rhythm disturbances.