A single-centre, before-after study of the short- and long-term efficacy of Narivent(®) in the treatment of nasal congestion.

OBJECTIVE: Nasal congestion is a common symptom in allergic and nonallergic rhinitis, rhinosinusitis and nasal polyposis. The present study evaluated the clinical effectiveness of Narivent(®), an osmotically-acting medical device with anti oedematous and anti-inflammatory effects, in nasal congestion. METHODS: A single-centre, prospective study with a pre- post design and consecutive patient enrolment was conducted in an Italian otolaryngology department. Patients with persistent nasal congestion were allocated to treatment groups as follows: group 1 (n = 36) treated for 7 days; group 2 (n = 56) treated for 30 days. In each group, patients received two puffs of Narivent(®) into each nostril twice daily. Symptom severity was assessed subjectively on a 0-10 visual analogue scale, and objectively by the presence/absence of signs and symptoms. Differences in subjective and objective severity measures before and after treatment were compared using Wilcoxon's signed rank test. RESULTS: All symptoms and objective scores improved after treatment with Narivent(®) for 7 or 30 days and no adverse effects were reported by the patients in either group. CONCLUSION: Narivent(®) appears to be efficacious in treating nasal congestion over a 7- or a 30-day period.

Thymoquinone, a potential therapeutic agent of Nigella sativa, binds to site I of human serum albumin.

Thymoquinone (TQ) is the main constituent of Nigella sativa essential oil which shows promising in vitro and in vivo antineoplastic growth inhibition against various tumor cell lines. Because of the increasing interest to test it in pre-clinical and clinical researches for assessing its health benefits, we here evaluate the interactions between TQ and human serum albumin (HSA), a possible carrier of this drug in vivo. Binding to HSA was studied using different spectroscopic techniques. Fourier transform infrared (FT-IR) and circular dichroism (CD) spectroscopies suggest that the association between TQ and HSA does not affect the secondary structure of HSA. Using fluorescence spectroscopy, one mole of TQ was found to bind one mole of HSA with a binding constant of 2.39 +/- 0.2 10(4)M(-1). At 25 degrees C (pH 7.4), van't Hoff's enthalpy and entropy that accompany the binding were found to be -10.24 kJ/mol(-1) and 45 J/mol(-1)K(-1) respectively. The thermodynamic analysis of the TQ-HSA complex formation shows that the binding process is enthalpy driven and spontaneous, and that hydrophobic interactions are the predominant intermolecular forces stabilizing the complex. Furthermore, displacement experiments using warfarin and ibuprofen indicate that TQ could bind to site I of HSA, which is also in agreement with the results of the molecular modeling study.

Topological insight into the non-arrhenius mode hopping of semiconductor ring lasers.

We investigate both theoretically and experimentally the stochastic switching between two counterpropagating lasing modes of a semiconductor ring laser. Experimentally, the residence time distribution cannot be described by a simple one-parameter Arrhenius exponential law and reveals the presence of two different mode-hop scenarios with distinct time scales. In order to elucidate the origin of these two time scales, we propose a topological approach based on a two-dimensional dynamical system.

Theory of collective firing induced by noise or diversity in excitable media.

Large variety of physical, chemical, and biological systems show excitable behavior, characterized by a nonlinear response under external perturbations: only perturbations exceeding a threshold induce a full system response (firing). It has been reported that in coupled excitable identical systems noise may induce the simultaneous firing of a macroscopic fraction of units. However, a comprehensive understanding of the role of noise and that of natural diversity present in realistic systems is still lacking. Here we develop a theory for the emergence of collective firings in nonidentical excitable systems subject to noise. Three different dynamical regimes arise: subthreshold motion, where all elements remain confined near the fixed point; coherent pulsations, where a macroscopic fraction fire simultaneously; and incoherent pulsations, where units fire in a disordered fashion. We also show that the mechanism for collective firing is generic: it arises from degradation of entrainment originated either by noise or by diversity.

Structural basis of the destabilization produced by an amino-terminal tag in the beta-glycosidase from the hyperthermophilic archeon Sulfolobus solfataricus.

We have previously shown that the major ion-pairs network of the tetrameric beta-glycosidase from the hyperthermophilic archeon Sulfolobus solfataricus involves more than 16 ion-pairs and hydrogen bonds between several residues from the four subunits and protects the protein from thermal unfolding by sewing the carboxy-termini of the enzyme. We show here that the amino-terminal of the enzyme also plays a relevant role in the thermostabilization of the protein. In fact, the addition of four extra amino acids at the amino-terminal of the beta-glycosidase, though not affecting the catalytic machinery of the enzyme and its thermophilicity, produced a faster enzyme inactivation in the temperature range 85-95 degrees C and decreased the Tm of the protein of 6 degrees C, measured by infrared spectroscopy. In addition, detailed two-dimensional IR correlation analysis revealed that the quaternary structure of the tagged enzyme is destabilized at 85 degrees C whilst that of the wild type enzyme is stable up to 98 degrees C. Molecular models allowed the rationalization of the experimental data indicating that the longer amino-terminal tail may destabilize the beta-glycosidase by enhancing the molecular fraying of the polypeptide and loosening the dimeric interfaces. The data support the hypothesis that fraying of the polypeptide chain termini is a relevant event in protein unfolding.

Alternate oscillations in semiconductor ring lasers.

We report on fabrication and characterization of single-longitudinal- and transverse-mode semiconductor ring lasers. A bifurcation from bidirectional stable operation to a regime with alternate oscillations of the counterpropagating modes was observed experimentally and is theoretically explained through a two-mode model. Analytical expressions for the onset and the frequency of the oscillations are derived, and L-I curves numerically evaluated. Good quantitative agreement between theory and measurements made over a large number of tested devices is obtained.

Salts induce structural changes in elongation factor 1alpha from the hyperthermophilic archaeon Sulfolobus solfataricus: a Fourier transform infrared spectroscopic study.

Elongation factor 1alpha from the hyperthermophilic archaeon Sulfolobus solfataricus (SsEF-1alpha) carries the aminoacyl tRNA to the ribosome; it binds GDP or GTP, and it is also endowed with an intrinsic GTPase activity that is triggered in vitro by NaCl at molar concentrations [Masullo, M., De Vendittis, E., and Bocchini, V. (1994) J. Biol. Chem. 269, 20376-20379]. The structural properties of SsEF-1alpha were investigated by Fourier transform infrared spectroscopy. The estimation of the secondary structure of the SsEF-1alpha*GDP complex, made by curve fitting of the amide I' band or by factor analysis of the amide I band, indicated a content of 34-36% alpha-helix, 35-40% beta-sheet, 14-19% turn, and 7% unordered structure. The substitution of the GDP bound with the slowly hydrolyzable GTP analogue Gpp(NH)p induced a slight increase in the alpha-helix and beta-sheet content. On the other hand, the alpha-helix content of the SsEF-1alpha*GDP complex increased upon addition of salts, and the highest effect was produced by 5 M NaCl. The thermal stability of the SsEF-1alpha*GDP complex was significantly reduced when the GDP was replaced with Gpp(NH)p or in the presence of NaBr or NH4Cl, whereas a lower destabilizing effect was provoked by NaCl and KCl. Therefore, the extent of the destabilizing effect of salts depended on the nature of both the cation and the anion. The data suggested that the sodium ion was responsible for the induction of the GTPase activity, whereas the anion modulated the enzymatic activity through destabilization of particular regions of SsEF-1alpha. Finally, the infrared data suggested that, in particular region(s) of the polypeptide chain, the SsEF-1alpha*Gpp(NH)p complex possesses structural conformations which are different from those present in the SsEF-1alpha*GDP complex.

Effects of Fe(III) binding to the nucleotide-independent site of F1-ATPase: enzyme thermostability and response to activating anions.

Mitochondrial F1-ATPase was induced in different conformations by binding of specific ligands, such as nucleotides. Then, Fourier transform infrared spectroscopy (FT-IR) and kinetic analyses were run to evaluate the structural and functional effects of Fe(III) binding to the nucleotide-independent site. Binding of one equivalent of Fe(III) induced a localised stabilising effect on the F1-ATPase structure destabilised by a high concentration of NaCl, through rearrangements of the ionic network essential for the maintenance of enzyme tertiary and/or quaternary structure. Concomitantly, a lower response of ATPase activity to activating anions was observed. Both FT-IR and kinetic data were in accordance with the hypothesis of the Fe(III) site location near one of the catalytic sites, i.e. at the alpha/beta subunit interface.

Specific interaction of cytosolic and mitochondrial glyoxalase II with acidic phospholipids in form of liposomes results in the inhibition of the cytosolic enzyme only.

Kinetics of cytosolic recombinant human glyoxalase II and bovine liver mitochondrial glyoxalase II were studied in the presence of liposomes made of different phospholipids (PLs). Neutral PLs such as egg phosphatidylcholine or dipalmitoylphosphatidylcholine did not affect the enzymatic activity of either enzymatic form. Liposomes made of dioleoyl phosphatidic acid or cardiolipin or phosphatidylserine also did not affect the enzymatic activity of mitochondrial glyoxalase II. Conversely, these negatively charged PLs exerted noncompetitive inhibition on cytosolic glyoxalase II only, dioleoyl phosphatidic acid and bovine brain phosphatidylserine exerting the highest and lowest inhibition, respectively. Binding studies, carried out by using a resonant mirror biosensor, revealed that liposomes made of negatively charged PLs interact specifically with both enzymatic forms of glyoxalase II, whereas interactions were not detected with neutral PLs. Once bound on glyoxalase II, negatively charged liposomes could not be removed by 3 M NaCl, suggesting that interactions between glyoxalase II and negatively charged PLs, besides ionic, may be also hydrophobic. These data suggest a possible role of negatively charged phospholipids in the regulation of level of lactoylglutathione in the cell. The data are also discussed in terms of a possible regulation of reduced glutathione supply to mitochondria.

Interaction between exercise training and ejection fraction in predicting prognosis after a first myocardial infarction.

BACKGROUND: Although recent meta-analysis trials have shown that exercise training may improve survival after myocardial infarction, the mechanism of this beneficial effect is still unknown. The purpose of this study was to detect possible interactions between exercise training and predictors of prognosis after a first myocardial infarction. METHODS AND RESULTS: Patients with uneventful clinical courses after a first myocardial infarction were randomly assigned to a 4-week training period (125 patients, group 1) or to a control group (131 patients, group 2). Before randomization, all patients underwent a symptom-limited exercise test (28 +/- 2 days after myocardial infarction), 24-hour Holter monitoring, and coronary arteriography (31 +/- 3 days after the acute episode). After a mean follow-up period of 34.5 months, 18 patients had cardiac deaths (5 in group 1 and 13 in group 2). Multivariate analysis by Cox regression model showed that ejection fraction was the only independent prognostic indicator (P = .03). Evidence existed of an interaction between ejection fraction and exercise training, showing an effect of physical training on survival that depended on the patient's ejection fraction. Among patients with ejection fractions < 41%, the relative risk for an untrained patient was 8.63 times higher than for a trained patient (P = .04), whereas for ejection fractions > 40%, the estimated risks for trained and untrained patients were similar. CONCLUSIONS: These data show that exercise training may prolong survival in post-myocardial infarction patients with depressed left ventricular function. A randomized trial in such patients seems warranted.

Long-term survival and risk stratification in patients with angina at rest undergoing medical treatment.

In order to determine those factors which influence long-term prognosis in patients with angina at rest associated with transient ST-segment changes, 217 patients undergoing medical treatment were followed for a mean of 39 months. All patients underwent coronary arteriography. Univariate analysis identified 12 variables significantly related to prognosis. These were disease of the left main coronary artery; the number of diseased vessels; left ventricular end-diastolic pressure; ejection fraction; baseline electrocardiogram; presence of prior myocardial infarction; ST-segment depression and ventricular arrhythmias during pain; disease of the proximal anterior descending coronary artery; crescendo angina; hypertension; and age. Use of the Cox regression model for survival analysis revealed only 3 variables which were independent predictors of prognosis. They were disease of the left main coronary artery; the number of diseased vessels and left ventricular end-diastolic pressure. The model allowed stratification of patients into 3 groups. Survival at 3 years was 98% in the low risk group; 82% in the intermediate risk group; and 58% in the high risk group. These data indicate that disease of the left main coronary artery, the number of diseased vessels and left ventricular end-diastolic pressure are the independent predictors of prognosis in angina at rest. These variables may allow stratification of patients into groups having different long-term survivals.

Effects of surgical versus medical treatment on long-term prognosis in angina at rest: an observational non-randomized study of 400 patients.

The effect of surgical versus medical treatment on long-term prognosis in angina at rest was assessed using the Cox regression model for survival analysis in 400 patients complaining of recurrent episodes of resting chest pain associated with transient repolarization changes. The surgical group included 185 patients, and the medical group 215. Surgically treated patients more frequently had two- and three-vessel disease, while single-vessel disease prevailed in medically treated patients (P less than 0.01). No difference between the two groups was found in mean values of left ventricular end diastolic pressure and ejection fraction. Three variables were identified as independent predictors of prognosis in all patients: left ventricular end-diastolic pressure (P less than 0.001), age greater than 45 years (P less than 0.05), and number of diseased vessels (P less than 0.05). Treatment modality did not result in different long-term survival in the entire population. However, patients with three-vessel disease had a better outcome with surgical than with medical therapy (P less than 0.05). Although our conclusions must be tempered by consideration of the limitations of non-randomized studies, these results show that surgical treatment may improve survival in patients with angina at rest and three-vessel disease.

Clinical significance of mitral regurgitation in patients with recent myocardial infarction.

The prognostic implications of the presence of mitral regurgitation (MR) in patients with recent myocardial infarction has not been clarified yet. In March 1983, we undertook a prospective study in patients surviving a first episode of acute myocardial infarction. Over a 4-year period, 266 patients entered the study. Left ventriculography documented the presence of MR in 51 patients, while 215 did not have angiographic evidence of MR. The presence of MR was associated with larger infarcts, as shown by greater values of peak CK (P less than 0.05) and by the prevalence of Q-wave vs non-Q-wave infarctions (P less than 0.05). Transient left ventricular failure during hospitalization was more frequent in patients with MR (P less than 0.05), while the occurrence of early post-infarction angina was similar in the two groups of patients. No difference was found in the extent of coronary disease, yet patients with MR had higher values of left ventricular end diastolic pressure (LVEDP) (P less than 0.005) and a lower ejection fraction (EF) (P less than 0.001). Patients with MR had a reduced exercise capacity (P less than 0.005), but signs of myocardial ischaemia were similarly distributed in the two groups. Patients with anterior infarcts and MR had higher left ventricular volumes than patients without MR, while no difference was found between patients with and patients without MR and inferior infarction, suggesting that left ventricular dilatation may play an important role in the pathogenesis of MR in patients with anterior but not in those with inferior infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Unstable angina.

Patients with unstable angina, defined as resting chest pain associated with transient repolarization changes on the electrocardiogram, represent a high risk subset among the clinical manifestations of ischemic heart disease. Pathogenetic mechanisms include coronary spasm and vasoconstriction, coronary thrombosis and platelet aggregation. Early prognosis is related to the degree of activity of the disease while long-term outcome depends on the extent of the coronary disease and the degree of left ventricular dysfunction. Medical treatment should include the combination of beta-blockers, nitrates and calcium antagonists as well as the use of heparin and aspirin. Despite such an aggressive treatment, attacks of resting chest pain persist in almost 30 per cent of patients. In these cases emergency revascularization may be achieved by either coronary angioplasty or bypass surgery. The latter operation may result in improved survival in patients with impaired left ventricular function and triple vessel disease.

Adolescent medicine education in pediatric residency programs following the 1978 Task Force on Pediatric Education report.

In 1982, the Society for Adolescent Medicine initiated a survey of all pediatric residencies in the United States and Canada to determine: if there had been an increase in the amount and quality of adolescent medicine training since the 1978 report by the Task Force on Pediatric Education; if pediatric departments were assuming responsibility for the care of adolescents; and the curriculum objectives for adolescent medicine (AM), the educational methods used, and whether program graduates (PGs) felt competent to care for adolescents. One hundred directors and 72 recent graduates completed an initial questionnaire. A follow-up telephone survey of program directors (PDs) who did not respond resulted in 109 completed interviews. The survey results suggest a favorable trend in AM training. Evidence of this favorable trend includes: a 10% increase (p less than 0.05) in the number of AM wards, and a 33% increase (p less than 0.01) in clinics; a 29% increase (p less than 0.01) in programs having a block of time devoted to AM; increased time spent caring for adolescents at all resident levels; and an increase in adolescent inpatients of 32% and outpatients of 45% (p less than 0.01). An increase in the number of and time for mastery of curriculum objectives and educational methods was reported by PDs.

Clinical significance of exercise-induced silent myocardial ischemia in patients with coronary artery disease.

Exercise-induced silent myocardial ischemia is a frequent feature in patients with coronary artery disease. The purpose of this study was to compare the clinical and angiographic characteristics of 269 patients who complained of chest pain during an exercise test (group I) with those of 204 who developed exercise-induced silent myocardial ischemia (group II). Group I patients more frequently had anginal symptoms of class III and IV of the Canadian Cardiovascular Society than did group II patients, who had milder symptoms (p less than 0.001). The only angiographic difference observed between the two groups was a slightly but significantly higher left ventricular end-diastolic pressure in group II patients (p less than 0.05), who also showed a longer exercise duration (p less than 0.01) with a higher heart rate-systolic pressure product (p less than 0.01) and more pronounced ST segment depression at peak exercise (p less than 0.001). Moreover, ventricular ectopic beats during exercise were more frequently observed in group II patients (p less than 0.05). Coronary bypass surgery was performed in 45% of patients of group I and in 24% of patients of group II (p less than 0.05). Survival curves of medically treated patients did not show any statistically significant difference between the two groups. Thus, although patients with a defective anginal warning system may have more pronounced signs of myocardial ischemia and a greater incidence of ventricular arrhythmias during exercise, their long-term prognosis is not different from that of patients who are stopped by angina from the activity that is inducing myocardial ischemia.

[Different clinical and prognostic aspects of angina pectoris in unstable phase]. / Differenti aspetti clinici e prognostici dell'angina pectoris in fase instabile.

The purpose of this study was to focus on the clinical and angiographic characteristics of 113 patients with crescendo angina (Group I) as compared to 187 patients with angina of new onset (Group II), selected from a series of 474 consecutive subjects, admitted to our clinic between January 1976 and July 1983 because of recurrent episodes of spontaneous angina, who underwent cardiac catheterization and coronary angiography within one month of hospitalization. Group I patients showed a greater incidence of prior transmural myocardial infarction (p less than 0.01), arterial hypertension (p less than 0.01), multivessel disease (p less than 0.01) and a lower value of left ventricular ejection fraction (p less than 0.01) than Group II patients. In the latter group of patients anginal episodes were more frequently associated with S-T segment elevation than with S-T segment depression (p less than 0.001), while the opposite was found in patients with crescendo angina. Survival curves up to five years showed that medically treated patients with crescendo angina had a worse long-term prognosis than patients with unstable angina of new onset (p less than 0.01). On the contrary no difference was found between the surgically treated patients of the two groups. Our data suggest that the more diffuse involvement of the coronary tree associated with a more depressed left ventricular function may result in an unfavorable long-term prognosis in patients with crescendo angina as compared to those with unstable angina of new onset. Such a difference between the two groups was abolished by surgical treatment.