Evaluation of two internal fixation techniques for mandibular parasymphyseal fractures comparing conventional titanium miniplates with customised titanium CRB omega miniplates: a prospective study.

Our aim was to compare the efficacy and outcome of customised, titanium, CRB (Chandrashekhar Rushiji Bande), omega miniplates with those of conventional titanium miniplates in the management of parasymphyseal fractures of the mandible, with or without involvement of the mental nerve, after clinical and radiographic evaluation. A total of 252 parasymphyseal fractures in 200 patients were selected for the study over the period of seven years (January 2010-January2017) and divided randomly into two groups. The first group included 126 fractures treated with two conventional titanium miniplates (conventional group) and the second 126 fractures treated with one customised, titanium, CRB, omega miniplate (customised group). All operations were done by the same surgeon. Duration of operation (from placement of incision to closure of the defect) was recorded. Postoperative paraesthesia, infection, and acceptability of the plate to patients were also recorded. Postoperative healing was evaluated radiologically at one week and six months postoperatively. Operations were significantly shorter, and significantly fewer patients developed paraesthesia or infection, in the customised group. These patients were also happier with their miniplates, and had good radiological bony healing. In conclusion, a single customised, titanium, CRB, omega miniplate is an effective and economical alternative to two conventional titanium miniplates in the management of parasymphysis fractures of the mandible.

Hyaline Fibromatosis Syndrome: A Rare Inherited Disorder.

Hyaline fibromatosis syndrome (HFS) is rare autosomal recessive disease characterized by the deposition of amorphous hyaline material in skin and visceral organs. It represents a disease spectrum with infantile systemic hyalinosis (ISH) being the severe form and juvenile hyaline fibromatosis (JHF) being the mild form. Dermatologic manifestations include thickened skin, perianal nodules, and facial papules, gingival hyperplasia, large subcutaneous tumors on the scalp, hyperpigmented plaques over the metacarpophalangeal joints and malleoli, and joint contractures. ISH shows a severe visceral involvement, recurrent infections, and early death. We report a case of 2.5-year-old female patient who presented with HFS who had overlapping features of both ISH and JHF. To the best of our knowledge, very few cases of HFS have been reported in Indian literature till date.

Cardiopulmonary functions and adenotonsillectomy: surgical indications need revision.

OBJECTIVE: To assess cardiac functions in adenotonsillar or tonsillar hypertrophy. METHODS: A prospective, interventional, academic centre based study was conducted on 25 children with adenotonsillar or tonsillar hypertrophy. All patients underwent pulsed 2-dimensional Doppler echocardiography, pulse oximetry and 12-lead electrocardiography. These assessments were repeated three months later to determine the impact of adenotonsillectomy. RESULTS: There were significant differences in mean arterial oxygen saturation, pulmonary flow acceleration time and mean pulmonary artery pressure post-operatively. Adenotonsillectomy led to significant improvements in pulmonary flow acceleration time and pulmonary flow velocity time index, while tonsillectomy resulted in right ventricular early and late diastolic velocity index improvement. CONCLUSION: Upper airway obstruction in children affects cardiac functioning and this can subsequently lead to morbidity and delayed growth. Hence, revision of surgical indications is advocated in adenotonsillar hypertrophy to avoid irreversible damage to cardiopulmonary functions.

Analysis of exome sequence in 604 trios for recessive genotypes in schizophrenia.

Genetic associations involving both rare and common alleles have been reported for schizophrenia but there have been no systematic scans for rare recessive genotypes using fully phased trio data. Here, we use exome sequencing in 604 schizophrenia proband-parent trios to investigate the role of recessive (homozygous or compound heterozygous) nonsynonymous genotypes in the disorder. The burden of recessive genotypes was not significantly increased in probands at either a genome-wide level or in any individual gene after adjustment for multiple testing. At a system level, probands had an excess of nonsynonymous compound heterozygous genotypes (minor allele frequency, MAF ⩽ 1%) in voltage-gated sodium channels (VGSCs; eight in probands and none in parents, P = 1.5 × 10(-)(4)). Previous findings of multiple de novo loss-of-function mutations in this gene family, particularly SCN2A, in autism and intellectual disability provide biological and genetic plausibility for this finding. Pointing further to the involvement of VGSCs in schizophrenia, we found that these genes were enriched for nonsynonymous mutations (MAF ⩽ 0.1%) in cases genotyped using an exome array, (5585 schizophrenia cases and 8103 controls), and that in the trios data, synaptic proteins interacting with VGSCs were also enriched for both compound heterozygosity (P = 0.018) and de novo mutations (P = 0.04). However, we were unable to replicate the specific association with compound heterozygosity at VGSCs in an independent sample of Taiwanese schizophrenia trios (N = 614). We conclude that recessive genotypes do not appear to make a substantial contribution to schizophrenia at a genome-wide level. Although multiple lines of evidence, including several from this study, suggest that rare mutations in VGSCs contribute to the disorder, in the absence of replication of the original findings regarding compound heterozygosity, this conclusion requires evaluation in a larger sample of trios.

Occupational radiation exposure from C arm fluoroscopy during common orthopaedic surgical procedures and its prevention.

BACKGROUND: Image intensifiers have become popular due to the concept of minimally invasive surgeries leading to decreasing invasiveness, decreased operative time, and less morbidity. The drawback, however, is an increased risk of radiation exposure to surgeon, patient and theatre staff. These exposures have been of concern due to their potential ability to produce biological effects. The present study was embarked upon to analyse the amount of radiation received by orthopedic surgeons in India using standard precautionary measures and also to bring awareness about the use of image intensifier safety in everyday practice. MATERIALS AND METHODS: Twelve right-handed male orthopedic surgeons (4 senior consultants, 5 junior consultants and 3 residents) were included in a three month prospective study for radiation exposure measurement with adequate protection measures in all procedures requiring C Arm fluoroscopy. Each surgeon was provided with 5 Thermo Luminescent Dosimeter (TLD) badges which were tagged at the level of neck, chest, gonads and both wrists. Operative time and exposure time of each procedure was recorded. Exposure dose of each badge at the end of the study was obtained and the results were analysed. RESULTS: Mean radiation exposure to all the parts were well within permissible limits. There was a significantly positive correlation between the exposure time and the exposure dose for the left wrist (r=0.735, p<0.01) and right wrist (r=0.58, p<0.05). The dominant hand had the maximum exposure overall. CONCLUSION: Orthopaedic surgeons are not classified radiation workers. The mean exposure doses to all parts of the body were well within permissible limits. Nothing conclusive, however, can be said about the stochastic effects (chance effects like cancers). Any amount of radiation taken is bound to pose an additional occupational hazard. It is thus desirable that radiation safety precautions should be taken and exposures regularly monitored with at least one dosimeter for monitoring the whole-body dose.

Early hematological effects of chemo-radiation therapy in cancer patients and their pattern of recovery - A prospective single institution study.

UNLABELLED: The purpose of this prospective study is to understand the early hematological effects of chemo-radiation therapy in cancer patients, their pattern of recovery and to ascertain their prognostic value. METHODS: 255 diagnosed cancer patients planned for definitive treatment with radiation therapy alone or with chemotherapy were included in this two year prospective study. A complete blood count was done at baseline, weekly during the course of therapy and thereafter, monthly for a period of 6 months. For the purpose of grading clinical toxicity, the Common Toxicity Criteria, CTCAE v2.0 was used while RECIST criteria was used to define the tumor response rates. This study was statistically analyzed using SPSS software. RESULTS: 255 patients were included in the study wherein head and neck cancers comprised the major patient population (28.6%) followed by cervix (18.8%) and breast (15.7%). Out of these, 37% in head-and-neck cancer subgroup, and 58.3% in cervix had anemia at start of treatment. 92.2% cases with chemoradiation developed anemia during treatment, while with radiation alone it was 95.5%. This was statistically significant in patients with cancer uterine cervix (p 〈 0.01). At the end of treatment 65% patients with normal hemoglobin had complete responses (CR), while 58.3% with mild anemia and 33.3% with moderate anemia had CR (p=0.1). CONCLUSIONS: Severe anemia during treatment is a poor prognostic indicator and is usually a sign of advanced disease. Leucopenia and thrombocytopenia occur more commonly during chemoradiotherapy as against radiotherapy alone, but improves with supportive management.

Carcinoma base of tongue: single institution 15 year experiences.

AIMS: To report the outcome with radiotherapy and concomitant chemoradiotherapy in patients with locally advanced squamous cell carcinoma base of tongue treated and followed up at single institution over a period of 15 years. MATERIALS AND METHODS: This study was carried out by auditing the medical records of 103 patients treated at our institution between 1991 and 2006. Mean age with standard deviation of patients in the Radiotherapy only (group I) and chemoradiotherapy (group II) was 55.26 ± 14.16 and 49.81 ± 12.16 years. 46 patients were treated with radiotherapy alone and 57 patients were treated with concurrent chemo radiotherapy using infusion cisplatinum 3 weekly and 5 fluorouracil twice weekly. Mean follow up was 13.35 months. All the patients characteristic and treatment characteristics were recorded. RESULTS: There were 81 men and 22 women in the study. Group I contains 15 and 31 cases of stage III and IV tumors while group II contains 19 and 38 cases of stage III and IV respectively. Group II has shown improved loco regional control rate for the T3 and T4 tumors as compared to group I. Disease free survival and overall survival in the group II is 25.51 months and 22.53 months while group I has 8.67 months and 6.74 months respectively. Grade III mucosal toxicity incidence was higher in group II as compared to group I. CONCLUSIONS: In locally advanced squamous cell carcinoma of base of tongue tumors concomitant chemoradiotherapy with infusional cisplatinum and 5 fluorouracil results in higher disease free and overall survival as compared to radiotherapy as single modality. This better tumor response with chemoradiotherapy comes at cost of higher incidence of mucosal toxicity.

Increase in flavan-3-ols by silencing flavonol synthase mRNA affects the transcript expression and activity levels of antioxidant enzymes in tobacco.

Flavonoids are plant secondary metabolites widespread throughout the plant kingdom involved in many physiological and biochemical functions. Amongst the flavonoids, flavan-3-ols (catechin and epicatechin) are known for their direct free radical scavenging activity in vitro, but studies on their antioxidant potential and interaction with antioxidant enzymes in vivo are lacking. Here, the flavonoid pathway was engineered by silencing a gene encoding flavonol synthase (FLS) in tobacco to direct the flow of metabolites towards production of flavan-3-ols. FLS silencing reduced flavonol content 17-53%, while it increased catechin and epicatechin content 51-93% and 18-27%, respectively. The silenced lines showed a significant increase in expression of genes for dihydroflavonol reductase and anthocyanidin synthase, a downstream gene towards epicatechin production, with no significant change in expression of other genes of the flavonoid pathway. Effects of accumulation of flavan-3-ols in FLS silenced lines on transcript level and activities of antioxidant enzymes were studied. Transcripts of the antioxidant enzymes glutathione reductase (GR), ascorbate peroxidase (APx), and catalase (CAT) increased, while glutathione-S-transferase (GST), decreased in FLS silenced lines. Enhanced activity of all the antioxidant enzymes was observed in silenced tobacco lines. To validate the affect of flavan-3-ols on the antioxidant system, in vitro experiments were conducted with tobacco seedlings exposed to two concentrations of catechin (10 and 50 µm) for 2 days. In vitro exposed seedlings produced similar levels of transcripts and activity of antioxidant enzymes as FLS silenced seedlings. Results suggest that flavan-3-ols (catechin) might be increasing activity of GR, Apx and CAT by elevating their mRNAs levels. Since these enzymes are involved in scavenging of reactive oxygen species, this strategy would help in tailoring crops for enhanced catechin production as well as making them tolerant to oxidative stresses.

Whole saliva physico-biochemical changes and quality of life in head and neck cancer patients following conventional radiation therapy: a prospective longitudinal study.

BACKGROUND: We investigated the physico-biochemical changes in saliva and its relation to quality of life (QOL) in head and neck cancer patients following conventional radiation therapy (RT). MATERIALS AND METHODS: 53 consecutive head and neck cancer patients underwent conventional RT using telecobalt photons. We analyzed objective sialometry and sialochemical parameters of salivary gland function and a physician reported Oral Assessment Protocol to assess the patients' QOL during (baseline, 3 and 6 weeks) and post RT (3 and 6 months). Statistical analysis was done using SPSS software (version 15.0; SPSS, Inc., Chicago, IL, USA). RESULTS: Stimulated salivary flow rates had shown a consistent decline during and in post-RT analysis (P < 0.001). A significant correlation was seen between mean salivary flow rates at 6 months post-RT and mean salivary electrolytes and amylase levels during the same period (P < 0.001). Mean global QOL scores had significantly worsened during RT and were still significantly poorer at 6 months than initial pre-RT levels (P < 0.001). Further, significant correlation was established between salivary pH values with global QOL scores at 6 months (P = 0.05). CONCLUSIONS: Radiation-induced hyposalivation invariably persists and correlates with poor global QOL scores seen during and following conventional RT. Post RT, there is a trend for biochemical reversal toward pre-irradiation levels suggesting a subsiding inflammation or a probable functional recovery.

Thyroid diseases as a sequelae following treatment of head and neck cancer.

AIMS: To evaluate the radiation-induced sequelae on thyroid gland and influence of concomitant chemotherapy. MATERIALS AND METHODS: This prospective study was carried out on 53 patients of head and neck carcinoma in the age group of 30-75 years (55.9 years). Patients were treated with external beam radiotherapy (52.8%) or concurrent chemo-radiotherapy with 5-flourouracil and cisplatinum (47.1%). The target volume included the thyroid gland, which received an average dose of 60 Gy in 30 fractions. Thyroid function tests were done at the start of radiotherapy. Follow up thyroid function tests were done on completion of radiotherapy treatment, at 3 months, at 6 months after treatment, and then every 6 months. Follow up ranges from 3-51 months (median: 27 months). RESULTS: Subclinical hypothyroidism was seen in 4 (7.5%) of the 53 patients. In three patients, the incidence was seen after a gap of 12 months and in one patient after a gap of 35 months. Of the four patients, three were of age ≤41 years and 1 was of age 66 years. In younger age group (30-39 years) patients, TSH shows statistically significant (P < 0.05) increase in TSH values. No significant difference was observed in radiation and chemo-radiation treatment groups (P > 0.10). CONCLUSIONS: Subclinical hypothyroidism is an important sequelae seen in the treated patients of head and neck when thyroid is in the radiation field. The patients with age less than 45 years are more prone to develop hypothyroidism. Chemotherapy has not affected the incidence of hypothyroidism significantly. Also, the dose of radiation has not shown any statistically significant difference.

Synthesis and in vitro cytotoxic evaluation of N-alkylbromo and N-alkylphthalimido-isatins.

The manuscript pertains to the synthesis and in vitro cytotoxic evaluation of a series of N-alkylbromo and N-alkylphthalimido-isatins against four different human cancer cell lines namely Colon: HCT-15; Liver: Hep-2; Lung: A-549 and Leukemia: THP-1 at 10 and 100 µM concentrations. The active compounds based on preliminary studies were evaluated for their IC(50) value against six cell lines viz. Colo-205, HCT-15 (Colon), THP-1 (Leukemia), A-549 (Lung), PC-3 (Prostate) and HeLa (Cervix). The active analogue IS-4 exhibited IC(50) values of 4.57, 10.90, 11.75, 12.40 and 54.20 µM against HeLa, PC-3, HCT-15, THP-1 and Colo-205, respectively.

Molecular detection of meat animal species targeting MT 12S rRNA gene.

The efficacy of PCR-RFLP analysis of mt 12S rRNA gene in identification of animal species from meat samples of known and unknown origin and adulterated meat samples was evaluated. In PCR, all the samples generated an amplicon of 456 bp. Restriction enzyme digestion of the PCR product with AluI, HhaI, BspTI and ApoI revealed characteristic RFLP patterns. Of the samples of unknown origin few were identified as cattle, few as buffalo and some were admixtures of two, suggesting adulteration. The RFLP pattern of one did not match any of species included in the study, which on sequencing was confirmed as camel meat. Application of this technique on adulterated meat samples could detect both animal species in proportion of 50:50 and 75:25 (except in case of goat+cattle). The technique however could not detect any of the two species when proportion of mixture was 90:10 (except in case of cattle+buffalo).

Role of the APOB Gene Polymorphism (c.12669G>A, p. Gln4154Lys) in Coronary Artery Disease in the Indian Punjabi Population.

High concentration of apolipoprotein B (apoB) is a risk factor for coronary artery disease (CAD). The association of the APOB gene polymorphism c.12669G>A, p.Gln4154Lys with the risk of CAD varies considerably in different populations. The present study represents the first investigation regarding the role of this APOB gene polymorphism with CAD in the Indian Punjabi population. We have studied the APOB gene polymorphism c.12669G>A, p.Gln4154Lys and its relationship with lipid, apoB, low-density lipoprotein (LDL) heterogeneity and oxidation in subjects suffering from CAD. The study was conducted on 87 patients with CAD; 75 healthy subjects served as controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the DNA polymorphism in the APOB gene. Frequency of R- (mutant) allele was significantly high (p <0.05) in CAD patients when compared to controls. Variations in serum lipid levels in the R+R+ and R+R- APOB genotypes were insignificant (p >0.05). However, serum apoB levels were significantly raised (p <0.05) in CAD patients with the R+R- genotype as compared to those with the R+R+ APOB genotype. Coronary artery disease patients had raised significantly raised (p <0.01) Log triglyceride/high density lipoprotein-cholesterol (HDL-C) ratio, apoB carbonyl content and increased malondialdehyde-low density lipoprotein (MDA-LDL levels, irrespective of APOB genotype as compared to controls. Carriers of the R- allele are at higher risk of CAD, probably because of elevated serum apoB levels in the Indian Punjabi population. Overall, it may be concluded that the R- allele might be associated with increased susceptibility towards CAD development in the Indian Punjabi population, and one of the linking factor is the elevation in serum apoB levels. However, this association needs further evaluation in a larger population. Secondly, the robust mechanism behind the positive association of the R- allele with raised serum apoB levels needs to be explored, which might be helpful in the strengthening the observed results.

Proteomics-based approach for identification and purification of human phosphate binding apolipoprotein from amniotic fluid.

Human amniotic fluid is of both maternal and fetal origin; it protects the fetus and provides the environment for growth and development of the fetus. We used a proteomics-based approach for targeting and purifying human phosphate binding protein, a member of the DING family of proteins from amniotic fluid, using Blue Sepharose CL-6B, DEAE-Sephacel and gel filtration chromatography. The protein had earlier been reported to be serendipitously purified along with PON1 (paraoxonase 1). It was identified using electro-spray-ionization-time-of-flight mass spectrometry and was found to be human phosphate binding protein. Human phosphate binding proteins have been reported to play a role as phosphate scavengers and may have a protective function against phosphate-related disorders, such as atherosclerosis, diabetes and kidney stones.

Identification of lysine positive non-fermenting gram negative bacilli (Stenotrophomonas maltophilia and Burkholderia cepacia complex).

BACKGROUND: The Burkholderia cepacia complex (BCC) and Stenotrophomonas maltophilia are closely related groups of non-fermenting gram-negative bacilli (NFGNBs) having a similar spectrum of infections ranging from superficial to deep-seated and disseminated infections. Identification of these lysine decarboxylase-positive NFGNBs lags behind in most Indian laboratories. A simplified identification scheme was devised for these two pathogens that allowed us to isolate them with an increasing frequency at our tertiary care institute. MATERIALS AND METHODS: A simple five-tube conventional biochemical identification of these bacteria has been standardized. In the beginning, some of the isolates were confirmed from the International B. cepacia Working group, Belgium. Molecular identification and typing using recA polymerase chain reaction-restriction fragment length polymorphism was also standardized for BCC. For short-term preservation of BCC, an innovative method of preserving the bacteria in Robertson's cooked medium tubes kept in a domestic refrigerator was developed. RESULTS: Thirty-nine isolates of BCC isolates were obtained from various specimens (30 from blood cultures) and 22 S. maltophilia (13 blood cultures and 9 respiratory isolates) were isolated during the year 2007 alone. CONCLUSIONS: BCC and S. maltophilia can be identified with relative ease using a small battery of biochemical reactions. Use of simplified methods will allow greater recognition of their pathogenic potential and correct antimicrobials should be advised in other clinical laboratories and hospitals.

Development of a minimally invasive epidermal abrasion device for clinical skin sampling and its applications in molecular biology.

A new abrasion tool (US patent US7087063 B2) has been developed for collecting skin epidermal samples. This device includes a central shaft that holds the probe in a split chuck. Of the variety of probe designs tested, the laser-cut hollow tube (HT) probe abraded the basal layer of the epidermis most consistently, resulting in representative epidermal skin samples. Compared with traditional clinical methods, the abrasion method allows for high-throughput epidermal skin collection with minimal invasiveness to the volunteer subjects. A large number of abrasion samples have been collected in various clinical studies with no adverse effects observed. Epidermal abrasion, when used appropriately and with the optimized probes, can yield high quality tissue samples that are representative of the epidermis. A sufficient quantity of RNA and protein can be obtained for many subsequent molecular and biochemical applications. Because of its minimal invasiveness and high-throughput nature, the abrasion method can be a valuable tool used to investigate the efficacy of topical applications of skin care products.

Hypocholesterolemic activity of some novel azetidin-2-ones in diet and diabetes induced hypercholesterolemia in rats.

Some novel substituted azetidin-2-ones (5-8) were synthesized via [2 + 2] cycloaddition reactions of imines and ketenes and evaluated for their ability to prevent diet and diabetes induced hypercholesterolemia. The test compounds 5a and 7a significantly (p < 0.01) inhibited the rise in serum total cholesterol induced by peanut oil (5.5%), cholesterol (1.5%) and cholic acid (0.5%) diet in both acute and chronic models in a dose dependent manner. Compound 5a also raised the high density lipoprotein-cholesterol levels in chronic diet models by peanut oil (5.5%), cholesterol (1.5%) and cholic acid (0.5%). In a diabetes induced model of hypercholesterolemia, the test compounds were evaluated for preventing diabetes-induced hypercholesterolemia (protocol 1) as well as for lowering post diabetic hypercholesterolemia (protocol 2). Test compounds 5a-g and 7a-d significantly (p < 0.05) reduced serum total cholesterol with a greater reduction in protocol 1 as compared with protocol 2. Based on SAR studies, the substituents that favor hypocholesterolemic activity around the azetidin-2-one nucleus are discussed and a possible mechanism of action is proposed on the basis of their differential effects in two protocols of diabetes-induced hypercholesterolemia.

Quinazolines revisited: search for novel anxiolytic and GABAergic agents.

A systematic approach through computer assisted design to identify novel quinazolines having anxiolytic and GABAergic activity has been reported.