Definitive radiotherapy for early stage glottic cancer by 6 MV photons

Purpose: To evaluate the clinical outcome of early glottic cancer (GC) treated by primary radiotherapy (RT) with 6 MV photons. Methods and materials: We retrospectively reviewed the medical records of 695 consecutive patients with T1N0 and T2N0 GC treated between 1983 and 2005 by RT in our institution. Clinical outcome in terms of local control (LC), overall survival (OS) and cause- specific survival (CSS) rate were evaluated. Results: The median follow-up time was 10.5 years.The 10-year actuarial LC rates were as follows: T1A, 91%; T1B, 87%; T2, 77%. The 10-year OS were as follows: T1, 74.2%; T2, 70.7%. The 10-year CSS were as follows: T1, 97.7%; T2, 97.1%. Poorly differentiated histology and tumor biologically effective dose < 65 Gy.© 2012 Tong et al.; licensee BioMed Central Ltd.Link_to_subscribed_fulltex

A Gramaticalização do Verbo Ir e a Variação de Formas para Expressar o Futuro do Presente: uma Fotografia Capixaba

Esta pesquisa verifica o estágio do processo de gramaticalização do verbo IR, que tem assumido a função de auxiliar em construções perifrásticas para expressar tempo. Para isso, investiga-se a variação entre as formas sintética e perifrástica com IR para expressão do futuro do presente. Temos por hipótese que a forma perifrástica já atinge todos os gêneros das duas modalidades da língua, uma vez que já se especializou para codificar tempo. São examinados dois gêneros, tomando-os como prototípicos do continuun oral/escrito: entrevistas com informantes universitários e editoriais de jornal. Partindo de uma orientação teórica Funcionalista, num quadro mais geral, concebe-se a língua como flexível ao uso, passível de influências cognitivas, sociais e também individuais, embora haja nela forças que atuam no sentido de regularizar a estrutura. Seguindo algumas pesquisas que têm se mostrado frutíferas, o modelo funcionalista estará em diálogo com outro modelo que procura dar conta da heterogeneidade estruturada da língua e de seus processos de mudança: a Teoria Variacionista. Num quadro mais específico, os fundamentos que orientam a pesquisa são os da Gramaticalização. Os dados extraídos dos gêneros selecionados serão submetidos ao programa computacional GOLDVARB 2001 e, em seguida, interpretados à luz das teorias lingüísticas que fundamentam esta pesquisa

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Clinical metabonomics for advanced laboratory medicine

Metabonomics is an unbiased and comprehensive quantitative study of metabolomes in a biological system. Using a metabonomics approach, new insight in disease pathogenesis and novel diagnostic biomarkers with improved accuracy can be identified with clinical impact. This PhD study focused on clinical metabonomics in advanced laboratory medicine. In part I, it was focused on the biomarker discovery for urinary tract infection (UTI) using nuclear magnetic resonance (NMR)-based metabonomics. Urine acetic acid and trimethylamine (TMA) were determined to be the best biomarker for diagnosing bacterial and Escherichia coli (EC)-associated UTI respectively. The area-under-curve (AUC) for acetic acid was 0.97 (95% confidence interval (CI): 0.94 – 1.00) and that for TMA was 0.85 (95% CI: 0.76 – 0.92). The performances were superior to conventional laboratory tests, i.e. dipstick urinalysis and urine microscopy. The high urine acetic acid was secondary to bacterial anaerobic respiration whereas TMA was a microbial-mammalian co-metabolite which was converted from trimethylamine N-oxide (TMAO), a human metabolite by EC TMAO reductase. In part II, the diagnostic application of acetic acid in bacterial UTI was extend to spontaneous bacterial peritonitis (SBP). Rapid diagnosis for SBP is vital because antibiotics treatment could dramatically reduce morbidity and mortality. Using NMR-based metabolomics approach, peritoneal fluid acetic acid was significantly elevated in SBP patients but undetected in controls. This finding echoed the results in part I and supported acetic acid as a biomarker for active bacterial infection. In part III, it was focused on the classification of pleural effusions (PE) using NMR-based metabonomics. PE lipoprotein was determined to be the best biomarker to differentiate exudates from transudates with an AUC of 0.96 (95% CI: 0.89 – 0.99). The diagnostic performance was superior to the Light's criteria recommended by International guideline. Elevated lipoprotein in exudates was secondary to increased capillary pore-size of the inflamed pleura. Therefore, quantification of PE lipoprotein will help assessing disease severity which is a novel and only clinical test for in vivo pleural permeability measurement. To determine the aetiology of exudates, liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabonomics was applied for cancerous and tuberculous PE, the two major causes of exudates. High levels of PE oleic acid and ceramide (d18:1/16:0) were found in cancerous and tuberculous PE respectively. The high oleic acid was secondary to fatty acid synthase (FASN) over-expression in cancer cells while the high ceramide was secondary to host immune response. Using a ratio of the two to predict cancerous and tuberculous PE, the AUC was increased to 0.99 (95% CI: 0.91 – 1.00). In part IV, it was focused on the rapid diagnosis of inborn errors of metabolism (IEM) using NMR spectroscopy. Patients with IEM can present with acute metabolic decompensation. Currently, most clinical laboratories rely on gas chromatography-mass spectrometry (GC-MS) for the diagnosis of IEM which usually takes a considerable time, i.e. day(s). The feasibility of NMR spectroscopy as a rapid diagnostic test was evaluated using various IEM conditions. Pathognomonic metabolites were identified using NMR-based urinalysis in <15 minutes. This supports the essential clinical role of NMR spectroscopy for rapid diagnosis of IEM.published_or_final_versionPathologyDoctoralDoctor of Philosoph

Emphysematous pyelonephritis: An 8-year retrospective review across four acute hospitals

To retrospectively review our experience of managing patients with emphysematous pyelonephritis (EPN). Case notes of patients with EPN were reviewed. The patients' demographic data, clinical presentation, investigation findings, treatment, and outcome were studied. Twelve patients were diagnosed with EPN. Majority (66.7%) of them had diabetes mellitus. All patients had been evaluated by computed tomography (CT). Using the classification proposed by Wan et al, five patients had type 1 EPN, whereas six, two, and four patients had Huang and Tseng CT class 2, 3a, and 3b EPN, respectively. Immediate nephrectomy was performed in six patients, whereas conservative treatment was adopted in the other six. In the nephrectomy group, one patient died of disseminated sepsis after a protracted course. Conservative treatment failed in three patients, who succumbed despite salvage nephrectomy in two of them. Analysis revealed that severe hyperglycemia and radiological CT class (both Wan and Huang systems) were significant predictors of mortality from EPN. Severe hyperglycemia and CT class of EPN are significant risk factors for death. CT is the investigation of choice for correct diagnosis of EPN. Additional intervention should be offered to EPN patients with Wan type 1 and Huang and Tseng class 3 CT features

Emphysematous pyelonephritis: An 8-year retrospective review across four acute hospitals

Objective: To retrospectively review our experience of managing patients with emphysematous pyelonephritis (EPN). Methods: Case notes of patients with EPN were reviewed. The patients' demographic data, clinical presentation, investigation findings, treatment, and outcome were studied. Results: Twelve patients were diagnosed with EPN. Majority (66.7%) of them had diabetes mellitus. All patients had been evaluated by computed tomography (CT). Using the classification proposed by Wan et al, five patients had type 1 EPN, whereas six, two, and four patients had Huang and Tseng CT class 2, 3a, and 3b EPN, respectively. Immediate nephrectomy was performed in six patients, whereas conservative treatment was adopted in the other six. In the nephrectomy group, one patient died of disseminated sepsis after a protracted course. Conservative treatment failed in three patients, who succumbed despite salvage nephrectomy in two of them. Analysis revealed that severe hyperglycemia and radiological CT class (both Wan and Huang systems) were significant predictors of mortality from EPN. Conclusion: Severe hyperglycemia and CT class of EPN are significant risk factors for death. CT is the investigation of choice for correct diagnosis of EPN. Additional intervention should be offered to EPN patients with Wan type 1 and Huang and Tseng class 3 CT features

Clinical whole-exome sequencing reveals a common pathogenic variant in patients with CoQ10 deficiency: An underdiagnosed cause of mitochondriopathy

[Background]: Primary CoQ deficiency occurs because of the defective biosynthesis of coenzyme Q, one of the key components of the mitochondrial electron transport chain. Patients with this disease present with a myriad of non-specific symptoms and signs, posing a diagnostic challenge. Whole-exome sequencing is vital in the diagnosis of these cases.[Case]: Three unrelated cases presenting as either encephalopathy or cardiomyopathy have been diagnosed to harbor a common pathogenic variant c.370G > A in COQ4. COQ4 encodes a key structural component for stabilizing the multienzymatic CoQ biosynthesis complex. This variant is detected only among East and South Asian populations.[Conclusions]: Based on the population data and our case series, COQ4-related mitochondriopathy is likely an underrecognized condition. We recommend including the COQ4 c.370G > A variant as a part of the screening process for mitochondriopathy in Chinese populations.This work was supported by the S.K. Yee Medical Foundation, Hong Kong

Acupuncture for Poststroke Dysphagia: A Pilot, Nonrandomized, Self-Controlled Trial

Objective. To evaluate the effectiveness and safety of acupuncture treatment for dysphagia as a complication of stroke. Methods and Design. This is a multicenter, pragmatic, nonrandomized, self-controlled clinical trial. A total of 39 patients were recruited from several Chinese medicine outpatient clinics and hospital-affiliated speech therapy outpatient clinics in Hong Kong. 26 patients completed all the 24 sessions of acupuncture treatment within two months, and only 12 of them were used as self-control. For the self-control group, the retrospective clinical data was taken from the electronic patient records with patient consent. The descriptive swallowing function data were converted into the quantitative Royal Brisbane Hospital Outcome Measure for Swallowing (RBHOMS) scores by two registered speech therapists through a validation process. And the data were validated by reaching consensus between the two speech therapists. All subjects underwent a baseline assessment before commencement of treatment, and outcome assessments were conducted upon the completion of treatment. The primary outcome measure is the RBHOMS score, which is a swallowing disability rating scale for monitoring difficulties in daily swallowing function. Secondary outcome measures include the Chinese version of the Swallow Quality-of-Life Questionnaire and adverse events. All the primary and secondary outcomes were assessed at baseline as well as at the end of acupuncture treatment (month 2). Results. A total of 39 participants aged 46 to 89 years were enrolled in the study, and the male-to-female ratio was 15 : 11. The mean baseline RBHOMS score of all 39 participants was 5.92 ± 2.23. The mean retrospective RBHOMS score of the 12 subjects who were used as self-control was 5.67 ± 1.72 before enrollment, while the mean RBHOMS score of the 26 participants who completed all the 24 sessions of treatment was 6.92 ± 2.07. There were statistically significant differences between the RBHOMS score at the completion of treatment and baseline (p=0.006), and retrospective data (p=0.042). Moreover, a significant difference was also found in terms of swallow quality-of-life score before and after acupuncture treatment (p<0.01). Conclusions. This pilot study provides preliminary evidence for the effectiveness of acupuncture for poststroke dysphagia. The findings from this trial can be used as a foundation for future full-scale randomized controlled clinical trials to assess the efficacy and safety of acupuncture for poststroke dysphagia. Ethics and Dissemination. The ethical approval of the clinical research study was granted by the Research Ethics Committee of both New Territories East and West Cluster of Hong Kong. Written informed consent was obtained from all participants, and the study was undertaken according to the ICH-GCP Guidelines. Trial Registration. This trial is registered with ChiCTR-TRC-12002621 and the registration date is 2012-10-26