Dysregulation of miR-31 and miR-375 expression is associated with clinical outcomes in oral carcinoma.

OBJECTIVES: To identify differentially expressed miRNA between oral squamous cell carcinoma (OSCC) and non-cancer (NC) and to associate these with clinico-pathological parameters. MATERIALS AND METHODS: miRNA microarray profiling was utilized to obtain the expression profile of miRNAs in four OSCC and four NC samples. The expression of miR-31 and miR-375 was further validated in 26 OSCC and three NC samples using real-time-PCR. The association between miRNA expression and clinico-pathological parameters was tested by univariate and multivariate analyses. RESULTS: Microarray profiling demonstrated that 15 and four miRNAs were up-regulated and down-regulated, respectively, in OSCC as compared with NC. miR-31 and miR-375 were validated as up- and down-regulated miRNAs, respectively. In univariate analyses, expression of miR-31 was significantly elevated in early stage, tumours with no metastatic nodes and those from the buccal mucosa. By contrast, low miR-375 expression was significantly associated with late stage disease, larger tumour size and the non-cohesive type of pattern of invasion in OSCC. The association between miR-31 expression with tumour staging and site and miR-375 with tumour staging remained significant in multivariate analyses. CONCLUSIONS: This study has identified 19 miRNAs significantly associated with OSCC, and expressions of miR-31 and miR-375 were significantly related with clinico-pathological parameters suggesting they could be important in driving oral tumourigenesis.

Seropositivity of HPV 16 E6 and E7 and the risk of oral cancer.

OBJECTIVES: The objective of the study was to determine the prevalence of HPV seropositivity among patients with oral squamous cell carcinoma (OSCC) and healthy individuals and to correlate the association between HPV 16 seropositivity and risk of OSCC. MATERIALS AND METHODS: HPV 16 E6 and E7 plasmids were constructed for the production of recombinant protein, which was used as the antigen in ELISA. HPV ELISA was performed on serum samples from 50 healthy individuals and 50 patients with OSCC. RESULTS: Using the HPV ELISA, 30% (OR = 2.25, 95% CI = 0.85-5.93) and 18% (OR = 1.61, 95% CI = 0.53-4.92) of patients with oral cancer were found to be HPV 16 E6 and E7 seropositive, respectively. Significant association was found between HPV 16 seropositivity and increased risk of OSCC in men, but not in male subjects. A similar trend was observed in non-betel quid chewers. CONCLUSIONS: Potential associations between HPV 16 E6/E7 seropositivity and oral cancer were revealed in men and non-betel quid chewer subjects, suggesting a possible etiological role of HPV 16 in subgroup of patients with OSCC in Malaysia.

[Endoscopic brow lift]. / Endoskopisches Brauenlift.

Endoscopic surgical techniques have greatly increased in popularity with the advent of modern endoscopes. Endoscopic brow lifting has largely replaced older, more invasive procedures. With this technique a skilled surgeon can identify and treat a ptotic eyebrow by addressing the relevant anatomy, including the frontalis, corrugator, procerus and orbicularis oculi muscles. The frontalis muscle can then be permanently fixed into a predesignated position using titanium screws and permanent sutures. This approach has allowed facial plastic surgeons to address the ptotic brow with decreased rates of edema, hematoma, hypesthesia, alopecia and scarring.

Genome-wide analysis of oral squamous cell carcinomas revealed over expression of ISG15, Nestin and WNT11.

BACKGROUND: Multistep pathways and mechanisms are involved in the development of oral cancer. Chromosomal alterations are one of such key mechanisms implicated oral carcinogenesis. Therefore, this study aims to determine the genomic copy number alterations (CNAs) in oral squamous cell carcinoma (OSCC) using array comparative genomic hybridization (aCGH) and in addition attempt to correlate CNAs with modified gene expression. MATERIALS AND METHODS: Genome-wide screening was performed on 15 OSCCs using high-density aCGH. On the basis of pathway analysis, three genes (ISG15, Nestin and WNT11) which mapped to CNA regions were selected for further evaluation of their mRNA expression using quantitative reverse transcriptase PCR (qRT-PCR). RESULTS: Copy number alterations were observed on multiple genomic regions, including amplifications on 1p, 3q, 5p, 6p, 7p, 8q, 9q, 11q, 12q, 16p, 18p and deletions on 3p, 7q, 8p, 11q, 19q and 20q. Among the three selected genes, ISG15 had the highest mRNA expression level with a 22.5-fold increase, followed by Nestin with a 4.5-fold increase and WNT11 with a 2.5-fold increase. CONCLUSIONS: This study has identified several major CNAs in oral cancer genomes and indicated that this correlates with over expression of the ISG15, WNT11, and Nestin genes.

Transcriptional profiling of oral squamous cell carcinoma using formalin-fixed paraffin-embedded samples.

Despite the advances in cancer treatment, the 5-year survival rate for oral cancer has not changed significantly for the past 40 years and still remains among the worst of all anatomic sites. Gene expression microarrays have been used successfully in the identification of genetic alterations in cancer development, however, these have hitherto been limited by the need for specimens with good quality intact RNA. Here, we demonstrated the use of formalin-fixed paraffin-embedded tissues in microarray experiments to identify genes differentially expressed between cancerous and normal oral tissues. Forty-three tissue samples were macrodissected and gene expression analyses were conducted using the Illumina DASL assay. We report RNA yield of 2.4 and 0.8 microg/mm(3) from tumour and normal tissues, respectively and this correlated directly with the tissue volume used for RNA extraction. Using unsupervised hierarchical clustering, distinct gene expression profiles for tumour and normal samples could be generated, and differentially expressed genes could be identified. The majority of these genes were involved in regulation of apoptosis and cell cycle, metastasis and cell adhesion including BCL2A1, BIRC5, MMP1, MMP9 and ITGB4. Representative genes were further validated in independent samples suggesting that these genes may be directly associated with oral cancer development. The ability to conduct microarrays on formalin-fixed paraffin-embedded specimens represents a significant advancement that could open up avenues for finding genes that could be used as prognostication and predictive tools for cancer.

Coronary artery disease among diabetic and non-diabetic patients with end stage renal disease.

Cardiovascular disease is the major cause of death among patients with end stage renal disease and accounts for about half the deaths among the dialysis population. Several researchers have reported a high prevalence of coronary artery disease among diabetic patients with renal failure and coronary arteriography is often considered an integral part of the pre-transplant evaluation of diabetic patients with end stage renal disease. However, very few reports have addressed the question of coronary disease in non-diabetic patients, and the pattern and prevalence of coronary artery disease in non-diabetic patients with end stage renal disease are not well defined. We evaluated the clinical and coronary angiographic findings in 158 consecutive patients (84 diabetic and 74 non-diabetic) with end stage renal disease. The coronary arteries were divided into 16 segments and each segment was analyzed for the presence of coronary disease, which was defined as the presence of > or = 50% luminal diameter stenosis. Diabetic patients had more adverse risk factors for coronary artery disease, yet there was no significant difference in the prevalence of coronary artery disease between the diabetic and non-diabetic patients (67% vs. 55%, p = 0.15), or in the number of affected coronary artery segments (2.0 vs. 1.4, p = 0.05). Triple vessel coronary artery disease was however, significantly more common among the diabetic subjects (27% vs. 12%, p = 0.005). Non-diabetic patients with end stage renal disease also have a high prevalence of coronary artery disease and may merit as careful investigation of their coronary status as their diabetic counterparts.

Motility-related proteins as markers for head and neck squamous cell cancer.

HYPOTHESIS: Increased cell motility is a hallmark of cancer cells. Proteins involved in cell motility may be used as molecular markers to characterize the malignant potential of tumors. METHODS: Molecular biology and immunohistochemistry techniques were used to investigate the expression of a selected panel of motility-related proteins (Rho A, Rac 2, Cdc42, PI3K, 2E4, and Arp2) in normal, premalignant, and squamous cell cancer cell lines of human head and neck origin. To assess the clinical potential of these proteins as molecular markers for cancer, immunohistochemistry was performed on paraffin-fixed head and neck cancer specimens (n = 15). RESULTS: All six motility-associated proteins were overexpressed in the premalignant and squamous cell cancer cell lines relative to normal keratinocytes. Immunohistochemistry with Rho A and Rac 2 showed increased staining in areas of cancer but not in normal tissue. CONCLUSION: Proteins involved in cell motility can be used as markers for head and neck squamous cell carcinoma. The head and neck cell lines used in this study may be used as a model to further investigate cell motility. Molecular markers of motility could have a significant impact on the diagnosis and staging of cancers originating from differentiated non-motile cells.

Complications of type I thyroplasty and arytenoid adduction.

OBJECTIVES/HYPOTHESIS: Unilateral vocal fold paralysis resulting in glottal incompetence can cause significant morbidity attributable to impaired speech, swallowing, and ability to protect the airway. Type I thyroplasty in combination with arytenoid adduction is a proven technique for medialization of the paralyzed vocal fold but must be evaluated in light of potential complications following laryngeal framework surgery. STUDY DESIGN AND METHODS: The charts of 237 patients who underwent unilateral vocal fold medialization surgery between July 1, 1991, and August 30, 1999, at a tertiary care cancer referral center were retrospectively reviewed. RESULTS: There were 98 cases of type I thyroplasty alone and 96 cases of type I thyroplasty with arytenoid adduction. The two groups had similar patient characteristics. Mean time of surgery (45 vs. 73 min, P <.0001) and length of hospital stay (1.1 vs. 1.8 d, P <.0001) were increased when arytenoid adduction was performed. Overall improvement of symptoms was similar in both groups (93%-94%), but posterior glottic closure appeared subjectively improved when arytenoid adduction was used (P =.0054). Overall complication rates were slightly higher in the arytenoid adduction group (14% vs. 19%), primarily because of transient vocal fold edema and wound complications (9 vs. 19 cases), but the increase was not statistically significant (P =.1401). Complications warranting medical or surgical intervention occurred in 8% of cases. Two patients who underwent type I thyroplasty with arytenoid adduction required tracheotomy as a consequence of postoperative complications. The three patients who had extrusion of the implant underwent type I thyroplasty alone. CONCLUSION: Using the appropriate technique, the potential benefits of improved glottic function following type I thyroplasty with arytenoid adduction outweigh the small risk of significant complications observed.

A randomized study of the safety and efficacy of reused angioplasty balloon catheters.

BACKGROUND: To lower costs, many centers around the world utilize previously used, resterilized balloon catheters to perform coronary angioplasty There are no controlled trials regarding their safety and efficacy. METHODS AND RESULTS: We performed the first randomized, double-blind, controlled, single-center clinical trial comparing the safety (clinical success) and efficacy (angiographic success) of reused versus new coronary angioplasty balloon catheters. A total of 377 procedures were included, 178 in the reused catheter arm and 199 in the new catheter arm. There were no significant differences in clinical or lesion characteristics among the two arms. The incidence of first balloon failure in the reused catheter arm was similar to that of the new catheter arm (12 cases [7%] v. 10 cases [5%], respectively). The angiographic success rate was also similar-176 cases (98.9%) in the reused catheter arm and 196 cases (98.5%) in the new catheter arm. The number of balloon catheters used per lesion, amount of contrast, and procedural and fluoroscopy time were similar in the two arms. At 30 days, the incidence of major adverse cardiac events was similar in both arms, 8 cases (4.5%) in the reused catheter arm and 10 cases (5%) in the new catheter arm. The incidence of fever was also similar. CONCLUSIONS: When performing coronary angioplasty, reused catheters are as effective (similar angiographic success) and safe (similar clinical success) as new catheters.

Clinical and angiographic features in patients under 35 years with a first Q wave acute myocardial infarction.

Sixty patients less than 35 years with a first Q wave acute myocardial infarction were prospectively studied to evaluate their features, risk factors and evidence of any viral infection. Typical chest pain was present in 98.3% with Q waves and ST segment elevation in all. None had hypotension or cardiogenic shock. Smoking was the most common risk factor (81.7%). Mean total cholesterol was 5.74 (+/-1.42) mmol/l. History of a viral illness was present in 28.3%, severe emotional stress in 21.7% and exhausting physical activity in 18.3%. Mean left ventricular diastolic and end systolic volumes were increased (90.11+/-22.5 ml/m2) and (46.62+/-20.46 ml/m2), respectively. The ejection fraction was depressed (49.71+/-1.6%). Triple vessel disease was seen only in 6.8 and 26.7% had insignificant or no coronary artery disease. Left anterior descending artery was most frequently involved (66%). None had left main involvement. Coronary ectasia was present in 11.7%, intracoronary thrombus in 28.3% and 40% had collaterals. Patients with no significant disease had no diabetes, a smaller number had a raised total cholesterol or smoked and had a lower ejection fraction. Patients from the Indian subcontinent who had fewer conventional risk factors, had more severe disease than those from the Arab world suggesting that other etiological factors need investigation.

2E4 (kaptin): a novel actin-associated protein from human blood platelets found in lamellipodia and the tips of the stereocilia of the inner ear.

Platelet activation, crucial for hemostasis, requires actin polymerization, yet the molecular mechanisms by which localized actin polymerization is mediated are not clear. Here we report the characterization of a novel actin-binding protein, 2E4, originally isolated from human blood platelets and likely to be involved in the actin rearrangements occurring during activation. 2E4 binds to filamentous (F)-actin by F-actin affinity chromatography and is eluted from F-actin affinity columns and extracted from cells with ATP. Its presence at the leading edge of platelets spread on glass and in the lamellipodia of motile fibroblasts suggests a role in actin dynamics. Using localization to obtain clues about function, we stained the sensory epithelium of the embryonic inner ear to determine whether 2E4 is at the barbed end of actin filaments during their elongation. Indeed, 2E4 was present at the tips of the elongating stereocilium. 2E4 is novel by DNA sequence and has no identifiable structural motifs. Its unusual amino acid sequence, its ATP-sensitive actin association and its location at sites of actin polymerization in cells suggest 2E4 plays a unique role in the actin rearrangements that accompany platelet activation and stereocilia formation.

Angioplasty in the stent era: results of a consecutive series of patients undergoing coronary angioplasty without surgical backup.

UNLABELLED: We prospectively studied the angiographic and clinical outcome in a group of 117 consecutive patients (140 vessels) undergoing coronary angioplasty in the stent ERA without surgical backup. There were no exclusion criteria. Intracoronary stents were deployed in 36 vessels (26%) either as a bailout procedure or for a suboptimal result following balloon angioplasty. Procedural success was achieved in 126 vessels in 108 patients (90%). Two patients developed Q-wave myocardial infarction and another two developed nonQ myocardial infarction. One patient died suddenly 2 days following an initially successful procedure. No patient was referred for emergency coronary artery bypass grafting and there were no vascular complications. Clinical or angiographic follow up was available in 87% of the patients and an angiographic follow up in 50% of the patients. At a median angiographic follow up of 210 days restenosis was seen in 34% of the vessels. Restenosis occurred in three of the 21 (14%) stented vessels and in 18 of the 41 (44%) nonstented vessels (P<0.02). CONCLUSION: In the stent era, coronary angioplasty can be safely performed without surgical backup. A satisfactory immediate and long-term result could be achieved by stenting 26% of the vessels.

Rerouting of the intratemporal facial nerve: an analysis of the literature.

Anterior rerouting of the intratemporal facial nerve in the infratemporal fossa approach is employed to access to the jugular bulb, hypotympanum, and lateral skull base, whereas posterior rerouting of the facial nerve, as employed in the transcochlear craniotomy, is most frequently used for surgery of the posterior fossa, cerebellopontine angle, prepontine region, and petrous apex. Facial nerve rerouting may lead to facial paresis or paralysis. This review of the literature is intended to define the physiologic "cost" of these procedures, so that the neurotologic surgeon can determine if the morbidity incurred in these techniques is worth the resultant exposure. Inconsistencies in reporting facial function places into question the validity of some of the cumulative data reported. Postoperatively, grades I-II facial nerve function was seen in 91% of patients undergoing short anterior rerouting, 74% of patients undergoing long anterior rerouting, and 26% of patients undergoing posterior complete rerouting. Although facial nerve rerouting allows unhindered exposure to previously inaccessible regions, it is achieved at the cost of facial nerve function. Facial nerve dysfunction increases with the length of facial nerve rerouted.

Primary pulmonary hypertension

Os autores apresentam resultados de uma serie de 91 pacientes com hipertensao pulmonar primaria observada em area tropical.Havia predominancia de doentes do sexo masculino, ao contrario do constatado em regioes nao tropicais. Praticamente, todos os pacientes apresentavam dispneia de esforco. Alteracoes eletrocardiograficas com aumento de voltagem de onda R em V1 tinham forte correlacao positiva com o nivel de pressao arterial pulmonar. Alteracoes da conducao de estimulo eletrico eram pouco frequentes. Era destacada em 90% dos casos o aumento de tamanho das arterias pulmonares, apreciado sob o aspecto radiologico.Pressao arterial pulmonar sistolica superior a 90 mmHg foi registrada em cerca de 70% dos doentes, sendo que em cerca de 49% ela superava o nivel sistemico. De um total de 58 pacientes seguidos, 34 morreram dentro de um periodo medio de 20 meses.Nao se podem determinar as razoes para o maior grau de severidade observado nesta serie, sendo possivel a participacao de um fator etnico