A study of recurrence, complication and survival rates in patients with early stage vulval cancer undergoing sentinel lymph node sampling: a single-centre experience.

PURPOSE: Groin sentinel lymph node (SLN) identification and removal has become a standard of care for women with clinical early stage vulval cancer. There is evidence to support safe detection of the SLN with minimal morbidity. The purpose of this study is to report our experience of managing patients focusing on patient selection, adverse events, quality assurance of the procedure and any benefits and/or disadvantages to patients. METHODS: This was a retrospective study of patients with clinical early stage vulval cancer in a cancer centre over 5 years. Notes and hospital data were reviewed including admissions to emergency departments. Statistical software was used for the statistical analysis and the Kaplan Meier survival curve was generated to present survival rates. RESULTS: 61 cases were analysed. A total of 156 nodes have been removed and positive nodes were identified in 14 cases. In total, 9 women (14.75%) had disease recurrence within 5 years from primary surgery. Overall, 4 patients (6.5%) developed groin recurrence. In 3 of these patients there was isolated groin recurrence (4.9%). The median length of admission was 3 days and 6 cases were managed as day cases. CONCLUSIONS: Since the closure of the GROINNS-2 trial we have continued the procedure of SLN identification for women with clinical early stage vulval cancer. We have shown high level of adherence to our protocol and survival and complication rates comparable to other studies on the same field. There were a few patients managed as day-case which was of benefit to the patients.

Selectivity among Anti-σ Factors by Mycobacterium tuberculosis ClpX Influences Intracellular Levels of Extracytoplasmic Function σ Factors.

Extracytoplasmic function σ factors that are stress inducible are often sequestered in an inactive complex with a membrane-associated anti-σ factor. Mycobacterium tuberculosis membrane-associated anti-σ factors have a small, stable RNA gene A (ssrA)-like degron for targeted proteolysis. Interaction between the unfoldase, ClpX, and a substrate with an accessible degron initiates energy-dependent proteolysis. Four anti-σ factors with a mutation in the degron provided a set of natural substrates to evaluate the influence of the degron on degradation strength in ClpX-substrate processivity. We note that a point mutation in the degron (X-Ala-Ala) leads to an order-of-magnitude difference in the dwell time of the substrate on ClpX. Differences in ClpX/anti-σ interactions were correlated with changes in unfoldase activities. Green fluorescent protein (GFP) chimeras or polypeptides with a length identical to that of the anti-σ factor degron also demonstrate degron-dependent variation in ClpX activities. We show that degron-dependent ClpX activity leads to differences in anti-σ degradation, thereby regulating the release of free σ from the σ/anti-σ complex. M. tuberculosis ClpX activity thus influences changes in gene expression by modulating the cellular abundance of ECF σ factors.IMPORTANCE The ability of Mycobacterium tuberculosis to quickly adapt to changing environmental stimuli occurs by maintaining protein homeostasis. Extracytoplasmic function (ECF) σ factors play a significant role in coordinating the transcription profile to changes in environmental conditions. Release of the σ factor from the anti-σ is governed by the ClpXP2P1 assembly. M. tuberculosis ECF anti-σ factors have an ssrA-like degron for targeted degradation. A point mutation in the degron leads to differences in ClpX-mediated proteolysis and affects the cellular abundance of ECF σ factors. ClpX activity thus synchronizes changes in gene expression with environmental stimuli affecting M. tuberculosis physiology.

Can image enhancement allow radiation dose to be reduced whilst maintaining the perceived diagnostic image quality required for coronary angiography?

OBJECTIVE: The aim of this research was to quantify the reduction in radiation dose facilitated by image processing alone for percutaneous coronary intervention (PCI) patient angiograms, without reducing the perceived image quality required to confidently make a diagnosis. METHODS: Incremental amounts of image noise were added to five PCI angiograms, simulating the angiogram as having been acquired at corresponding lower dose levels (10-89% dose reduction). 16 observers with relevant experience scored the image quality of these angiograms in 3 states-with no image processing and with 2 different modern image processing algorithms applied. These algorithms are used on state-of-the-art and previous generation cardiac interventional X-ray systems. Ordinal regression allowing for random effects and the delta method were used to quantify the dose reduction possible by the processing algorithms, for equivalent image quality scores. RESULTS: Observers rated the quality of the images processed with the state-of-the-art and previous generation image processing with a 24.9% and 15.6% dose reduction, respectively, as equivalent in quality to the unenhanced images. The dose reduction facilitated by the state-of-the-art image processing relative to previous generation processing was 10.3%. CONCLUSION: Results demonstrate that statistically significant dose reduction can be facilitated with no loss in perceived image quality using modern image enhancement; the most recent processing algorithm was more effective in preserving image quality at lower doses. Advances in knowledge: Image enhancement was shown to maintain perceived image quality in coronary angiography at a reduced level of radiation dose using computer software to produce synthetic images from real angiograms simulating a reduction in dose.

A cross-sectional study to compare intraocular pressure measurement by sequential use of Goldman applanation tonometry, dynamic contour tonometry, ocular response analyzer, and Corvis ST.

OBJECTIVE: To study the correlation and effect of sequential measurement of intraocular pressure (IOP) with Goldmann applanation tonometer (GAT), ocular response analyzer (ORA), dynamic contour tonometer (DCT), and Corvis ST. SETTING AND DESIGN: Observational cross-sectional series from the comprehensive clinic of a tertiary eye care center seen during December 2012. METHODS: One hundred and twenty-five study eyes of 125 patients with normal IOP and biomechanical properties underwent IOP measurement on GAT, DCT, ORA, and Corvis ST; in four different sequences. Patients with high refractive errors, recent surgeries, glaucoma, and corneal disorders were excluded so as to rule out patients with evident altered corneal biomechanics. STATISTICAL ANALYSIS: Linear regression and Bland-Altman using MedCalc software. RESULTS: Multivariate analysis of variance with repeated measures showed no influence of sequence of device use on IOP (P = 0.85). Linear regression r2 between GAT and Corvis ST, Corvis ST and Goldmann-correlated IOP (IOPg), and DCT and Corvis ST were 0.37 (P = 0.675), 0.63 (P = 0.607), and 0.19 (P = 0.708), respectively. The Bland-Altman agreement of Corvis ST with GAT, corneal compensated IOP, and IOPg was 2 mmHg (-5.0 to + 10.3), -0.5 mmHg (-8.1 to 7.1), and 0.5 mmHg (-6.2 to 7.1), respectively. Intraclass correlation coefficient for repeatability ranged from 0.81 to 0.96. CONCLUSIONS: Correlation between Corvis ST and ORA was found to be good and not so with GAT. However, agreement between the devices was statistically insignificant, and no influence of sequence was observed.

Estimation of serum lipids in patients with Oral Submucous Fibrosis in India.

OBJECTIVES: Oral submucous fibrosis (OSMF) is the most prevalent precancerous condition in India. Low levels of lipids serves as a marker and prognostic indicator in the early detection of oral precancerous and cancerous states. In spite of the high prevalence and its potential to undergo malignant transformation, this condition has not widely been investigated with respect to the serum lipid levels. In the present study, an attempt was made to analyze the complete serum lipid profile, total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and very low density lipoprotein (VLDL) cholesterol in OSMF and controls. MATERIAL AND METHODS: The study was conducted in 45 clinically and histopathologically diagnosed cases of OSMF and 45 age and sex matched controls. The complete lipid profile including TC, TG, HDL cholesterol, LDL cholesterol and VLDL cholesterol was analyzed. RESULTS: The serum lipid levels were significantly lower in the patients with OSMF than in the controls. When the values were compared between different disease stages, the maximum reduction of lipids was evident for stage 3 OSMF. From the present results, it is evident that the level of serum lipids decreases with progression of the disease. CONCLUSIONS: From these findings, it appears that the decrease in the lipid levels may be considered as a useful marker in the early diagnosis of oral premalignant condition like OSMF. Key words:Oral submucous fibrosis, lipids, premalignant condition.

The 2014 Academic College of Emergency Experts in India's INDO-US Joint Working Group (JWG) White Paper on "Developing Trauma Sciences and Injury Care in India".

It is encouraging to see the much needed shift in the understanding and recognition of the concept of "burden of disease" in the context of traumatic injury. Equally important is understanding that the impact of trauma burden rivals that of nontraumatic morbidities. Subsequently, this paradigm shift reinstates the appeal for timely interventions as the standard for management of traumatic emergencies. Emergency trauma care in India has been disorganized due to inadequate sensitivity toward patients affected by trauma as well as the haphazard, nonuniform acceptance of standardization as the norm. Some of the major hospitals across various regions in the country do have trauma care units, but even those lack protocols to ensure that all trauma cases are handled by those units, largely owing to lack of structured referral system. As a first step to reform the state of trauma care in the country, a detailed overview is needed to gain insight into the prevailing reality. The objectives of this paper are to thus weave a foundation based on the statistical and qualitative burden of trauma in the country; the available infrastructure of trauma care centers equipped to deal with trauma; the need and scope of standardized protocols for intervention; and most importantly, the application of these in shaping educational initiatives in advancing emergency trauma care in the country.

Effect of concomitant administration of L-glutamine and cycloart-23-ene-3ß, 25-diol (B2) with sitagliptin in GLP-1 (7-36) amide secretion, biochemical and oxidative stress in streptozotocin - nicotinamide induced diabetic Sprague Dawley rats.

Previously we have reported that, cycloart-23-ene-3ß, 25-diol (called as B2) and L-glutamine stimulated glucagon like peptide-1 (GLP-1) (7-36) amide secretion diabetic rats. The objective of present investigation was to investigate the concomitant administration of cycloart-23-ene-3ß, 25-diol+sitagliptin and L-glutamine+sitagliptin in streptozotocin - nicotinamide induced diabetic Sprague Dawley. Type 2 diabetes was induced in overnight fasted male Sprague Dawley rats pre-treated with nicotinamide (100 mg/kg, i.p.) followed by administration of streptozotocin (55 mg/kg, i.p.) 20 min after. The rats were divided into; I- non-diabetic, II- diabetic control, III- Sitagliptin (5 mg/kg, p.o.)+cycloart-23-ene-3ß, 25-diol (1 mg/kg, p.o.), IV- Sitagliptin (5 mg/kg, p.o.)+L-glutamine (1000 mg/kg, p.o.). The concomitant treatment of cycloart-23-ene-3ß, 25-diol and L-glutamine with sitagliptin was 8 weeks. Plasma glucose, body weight, food and water intake were determined every week. Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7-36) amide, plasma and pancreatic insulin, histology of pancreata and biomarkers of oxidative stress were measured after 8(th) week treatment. Concomitant administration of cycloart-23-ene-3ß, 25-diol and L-glutamine with sitagliptin significantly (p<0.001) reduced plasma glucose, glyoxylated haemoglobin, lipid profile and oxidative stress parameters compared to diabetic control groups. Both concomitant treatment increased plasma and pancreatic insulin as well as plasma and colonic active (GLP-1) (7-36) amide secretion. Histological analysis by Gomori staining observed less destruction of pancreatic ß cells. The result obtained from this study; it is concluded that concomitant administration of cycloart-23-ene-3ß, 25-diol+sitagliptin and L-glutamine+sitagliptin showed additive antihyperglycaemic effect in diabetic rats.

Academic College of Emergency Experts in India's INDO-US Joint Working Group (JWG) White Paper on the Integrated Emergency Communication Response Service in India: Much more than just a number!

The proposal for an integrated national emergency number for India is garnering a lot of enthusiasm and stimulating debate. This ambitious project has a two-part paradigm shift to set in; the first being the integration into a single number and the infrastructure required for setting up and operating this number such that a call can be received and identified. The second is the submerged part of the iceberg: That of the ability to respond to a call and deliver the appropriate emergency service. The first part is more technical and has potential precedents like the 911 phone hotline, for example, to emulate. The main premise of this paper is that the second part is a rather subjective exercise largely determined by the realities of existing public infrastructure in a specific geographical area with respect to emergency services management, especially medical care. Consequently, we highlight the key areas of both precall preparedness and postcall execution that need to be reviewed prior to going live with an integrated number on a national scale.

Oral L-glutamine increases active GLP-1 (7-36) amide secretion and improves glycemic control in stretpozotocin-nicotinamide induced diabetic rats.

L-glutamine is a non-essential amino acid. It decreased blood sugar, stimulated insulin secretion in type 2 diabetic patients. The objective of the present investigation was to evaluate L-glutamine increases glucagon like peptide-1 (GLP-1) (7-36) amide secretion in streptozotocin-nicotinamide (STZ-NTM) induced diabetic Sprague Dawley rats. Molecular docking study was performed to elucidate the molecular basis for GLP-1 receptor agonistic activity. Type 2 diabetes was induced in overnight fasted Sprague Dawley rats pre-treated with nicotinamide (100 mg/kg, i.p.) followed by 20 min after administration of streptozotocin (55 mg/kg, i.p.). The rats were divided into; I - nondiabetic, II - diabetic control, III - sitagliptin (5 mg/kg, p.o.), IV - L-glutamine (250 mg/kg, p.o.), V - L-glutamine (500 mg/kg, p.o.) and VI - L-glutamine (1000 mg/kg, p.o.). The L-glutamine and sitagliptin treatment was 8 week. Plasma glucose was estimated every week. Body weight, food and water intake were recorded daily. Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7-36) amide, mRNA expression of proglucagon GLP-1, plasma and pancreatic insulin, histology of pancreata and biomarkers of oxidative stress (superoxidase dismutase, reduced glutathione, malondialdehyde, glutathione peroxidase, glutathione S transferase) were measured after 8 week. In acute study, the rats were divided into I - glucose (2.5 g/kg, p.o.), II - sitagliptin (5 mg/kg, p.o.), III - L-glutamine (250 mg/kg, p.o.), IV - L-glutamine (500 mg/kg, p.o.) and V - L-glutamine (1000 mg/kg, p.o.). Plasma glucose, active GLP-1 (7-36) amide concentration and insulin levels were measured after glucose loading. The docking data indicated that l-glutamine bind to the GLP-1 receptor. L-glutamine decreased plasma glucose, increased plasma and pancreatic insulin, increased plasma and colonic active GLP-1 (7-36) amide secretion as well as decreased oxidative stress in streptozotocin-nicotinamide induced diabetic rats.

Cycloart-23-ene-3ß, 25-diol stimulates GLP-1 (7-36) amide secretion in streptozotocin-nicotinamide induced diabetic Sprague Dawley rats: a mechanistic approach.

In previous study, we have reported cycloart-23-ene-3ß, 25-diol is an active antidiabetic constituent isolated from stem bark of Pongamia pinnata (Linn.) Pierre. The objective of the present investigation was to evaluate cycloart-23-ene-3ß, 25-diol stimulates glucagon like peptide-1 (GLP-1) (7-36) amide secretion in streptozotocin-nicotinamide induced diabetic Sprague Dawley rats. Molecular docking studies were performed to elucidate the molecular basis for GLP-1 receptor agonistic activity. Type 2 diabetes was induced in overnight fasted Sprague Dawley rats pre-treated with nicotinamide (100mg/kg, i.p.) followed by administration of streptozotocin (55 mg/kg, i.p.) 20 min after. The rats were divided into following groups; I- non-diabetic, II- diabetic control, III- sitagliptin (5mg/kg, p.o.), IV- cycloart-23-ene-3ß, 25-diol (1mg/kg, p.o.). The cycloart-23-ene-3ß, 25-diol and sitagliptin treatment was 8 week. Plasma glucose was estimated every week (week 0 to week 8). Body weight, food and water intake were recorded daily. Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7-36) amide, mRNA expression of proglucagnon GLP-1, plasma and pancreatic insulin, histology of pancreata as well as biomarkers of oxidative stress (superoxidase dismutase, reduced glutathione, malondialdehyde, glutathione peroxidase, glutathione S transferase) were measured after 8th week treatment. In acute study, active GLP-1 (7-36) amide release, plasma glucose and insulin were measured during oral glucose tolerance test. The docking data clearly indicated cycloart-23-ene-3ß, 25-diol bind to the GLP-1 receptor. It decreased plasma glucose level, increased plasma and pancreatic insulin level as well as increased plasma and colonic active GLP-1 (7-36) amide secretion in streptozotocin-nicotinamide induced diabetic Sprague Dawley rats.

Extensive neonatal dermatophytoses.

We report a 25-day-old boy who was referred to our dermatology unit for evaluation of extensive annular erythematous lesions on his body. We initially considered the differential diagnoses of candidiasis and neonatal lupus erythematosus but investigations revealed the case as tinea corporis due to a relatively uncommon causative agent, Microsporum gypseum. To the best of our knowledge it is the first case of extensive neonatal dermatophytoses caused by this organism. The possible causes and the role of steroids in producing the clinical picture in our patient are discussed.