Formation of protein kinase C(epsilon)-Lck signaling modules confers cardioprotection

The epsilon isoform of protein kinase C (PKCepsilon) is a member of the PKC family of serine/threonine kinases and plays a critical role in protection against ischemic injury in multiple organs. Functional proteomic analyses of PKCepsilon signaling show that this isozyme forms multiprotein complexes in the heart; however, the precise signaling mechanisms whereby PKCepsilon orchestrates cardioprotection are poorly understood. Here we report that Lck, a member of the Src family of tyrosine kinases, forms a functional signaling module with PKCepsilon. In cardiac cells, PKCepsilon interacts with, phosphorylates, and activates Lck. In vivo studies showed that cardioprotection elicited either by cardiac-specific transgenic activation of PKCepsilon or by ischemic preconditioning enhances the formation of PKCepsilon-Lck modules. Disruption of these modules, via ablation of the Lck gene, abrogated the infarct-sparing effects of these two forms of cardioprotection, indicating that the formation of PKCepsilon-Lck signaling modules is required for the manifestation of a cardioprotective phenotype. These findings demonstrate, for the first time to our knowledge, that the assembly of a module (PKCepsilon-Lck) is an obligatory step in the signal transduction that results in a specific phenotype. Thus, PKCepsilon-Lck modules may serve as novel therapeutic targets for the prevention of ischemic injury.     

Efficacy and safety of ketoprofen lysine salt mouthwash versus benzydamine hydrochloride mouthwash in acute pharyngeal inflammation: a randomized, single-blind study

BACKGROUND: Pharyngodynia, or sore throat, is one of the symptoms most frequently reported by patients to primary care physicians. OBJECTIVE: The purpose of this study was to compare the efficacy and tolerability of mouthwash formulations of ketoprofen lysine salt (KLS), an anti-inflammatory agent, and benzydamine hydrochloride (BH), a local anesthetic, in patients with acute inflammation of the pharyngeal cavity. METHODS: In this randomized, multicenter, parallel-group, single-blind study, patients (who were blinded) were assigned to receive undiluted BH 15 mL (22.5 mg) or KLS 10 mL (160 mg) diluted in 100 mL of water. Both agents were gargled twice daily until pain remission or up to 7 days. A physical examination of the oropharyngeal cavity was performed, and severity of edema and hyperemia was assessed after 3 days of treatment and, if symptoms had not resolved, after pain remission. RESULTS: Of the 241 patients (120 KLS, 121 BH), 239 were included in the safety analysis and 232 were in the intent-to-treat population. The differences between groups in the duration of analgesic effect after the first dose of drug and the time course of pain were found to be statistically significant (P = 0.006 and P = 0.017, respectively), favoring KLS. Adverse drug-related effects reported included numbness of the tissues in the oral cavity, sensation of tingling in the tissues in the oral cavity, dry mouth, thirst, and nausea. A significantly greater proportion of BH-treated patients reported adverse events (P = 0.001 for all adverse events and drug-related adverse events). CONCLUSIONS: KLS mouthwash exerts a significantly longer first-application analgesic action with significantly greater local tolerability than BH in patients with pharyngeal pain of inflammatory and/or infectious origin.     

Treatment of inferior turbinate hypertrophy: a randomized clinical trial

In the past 130 years, many surgical procedures for turbinate reduction have been developed. We analyzed the long-term efficacy of 6 of these surgical techniques (turbinectomy, laser cautery, electrocautery, cryotherapy, submucosal resection, and submucosal resection with lateral displacement) over a 6-year follow-up period. We randomly divided 382 patients into 6 therapeutic groups and surgically treated them at the Department of Otorhinolaryngology of the University of Siena. After 6 years, only submucosal resection resulted in optimal long-term normalization of nasal patency and in restoration of mucociliary clearance and local secretory IgA production to a physiological level with few postoperative complications (p < .001). The addition of lateral displacement of the inferior turbinate improved the long-term results. We recommend, in spite of the greater surgical skill required, submucosal resection combined with lateral displacement as the first-choice technique for the treatment of nasal obstruction due to hypertrophy of the inferior turbinates.     

Torsade de pointes in a child with acute rheumatic fever

Ventricular arrhythmias are uncommon in acute rheumatic carditis. We report the case of a child who presented with rheumatic carditis, prolonged corrected QT interval, and torsade de pointes. The episodes of torsade were controlled with beta-blockade and cardiac pacing. The child subsequently died as a result of brain injury; the autopsy revealed classic findings of acute rheumatic carditis.     

Aberrant methylation and simian virus 40 tag sequences in malignant mesothelioma

Aberrant promoter methylation and resultant silencing of several genes plays an important role in the pathogenesis of many tumor types. We compared the methylation profile of 66 malignant mesotheliomas (MMs) and 40 lung adenocarcinomas using methylation-specific PCR for seven genes frequently methylated in lung cancer. We also compared the methylation frequencies of these genes as well as the methylation index, a reflection of all of the gene frequencies, with the presence of SV40 large T-antigen (Tag) sequences, histological subtype, and patient survival. Our major findings are: (a) with the exception of the RASSF1A promoter of the RASSF1 gene, frequencies of aberrant methylation were significantly lower in MMs than in adenocarcinomas; (b) the frequency of RASSF1A aberrant methylation and the value of the methylation index were significantly higher in SV40 sequence positive MM than in negative MM; and (c) the methylation index was higher in epithelial MM than in sarcomatous/mixed MM. Our results demonstrate a relationship between SV40 and aberrant methylation in MMs.     

Novel molecular and immunotherapeutic strategies for lung cancer

Lung cancer therapy in the future will be guided by specific characteristics of the individual tumor specimens. The molecular cancer phenotyping will allow for targeted approaches based on the amplification of oncogenes, lack of tumor suppressor genes, dysregulation of growth factors, and angiogenesis or matrix metalloproteinases. Specific immunotherapeutic approaches based on.     

Longitudinal investigation of hearing disorders in children with congenital cytomegalovirus

This investigation consisted of a longitudinal study of the effects of congenital cytomegalovirus (CMV) infection on hearing sensitivity in 860 children with documented asymptomatic or symptomatic congenital CMV infection. Of the 651 children with asymptomatic CMV infection, 48 (7.4%) developed sensorineural hearing loss (SNHL), compared to 85 (40.7%) of the children with symptomatic CMV infection. Children in both groups experienced latent effects consisting of delayed onset of loss, threshold fluctuations, and/or progressive loss of hearing. It can be concluded that congenital CMV infection is a leading cause of SNHL in children. The late onset and progression of loss necessitates continued monitoring of hearing sensitivity in this population.     

Radiology of the orbital apex

The orbital apex, formed by the superior orbital fissure and optic canal, is the cross-road between the orbit and the intracranial structures. Pathological processes may extend intracranially via the superior orbital fissure and vice versa. In addition to intrinsic soft tissue lesions, various pathological processes may involve the surrounding osseous anatomy. Malignant lesions arising from adjacent structures or from haematogeneous metastasis may also infiltrate this region.     

Comparative study of diagnostic procedures for congenital cytomegalovirus infection

In a prospective study the incidence of congenital cytomegalovirus (CMV) infection was 2.2% (31 OF 1,412) as evidenced by viruria during the first week of life. Among immunoserologic methods used to screen these neonates, the rheumatoid factor test, although non-specific, proved to be the most convenient; its sensitivity for identifying infants with CMV infection was 35% to 45% with no false-positives. The rates for correct and incorrect identification of neonates at risk was, respectively, 33% and 3.1% when testing for increased levels of IgM; 5% and 10% when testing for increased levels of IgA; 76% and 21% when testing for IgM anti-CMV (IgM immunofluorescent test) antibody, and 0% when testing for IgA anti-CMV antibody. Rapid virologic diagnosis was achieved by assessing urine specimens. Confirmation by electron microscopy was possible in less than one hour in 92% of cases. The detection of early induced CMV-specific nuclear antigens by anticomplement immunofluorescence was diagnostic in 91% of cases within one day of inoculation of specimens in tissue culture. Infectivity of CMV in urine was well preserved for a least seven days at 4 C. Thus, in order to achieve a rapid diagnosis of congenital CMV infection, in sick as well as asymptomatic neonates, urine specimens may, if necessary, be transported at 4 C to distant laboratories.