Efficacy of MLC based cobalt-60 plans: A DVH comparison and analysis with 6 MV plans.

The purpose of this study was to compare 3D treatment plans implemented using 6 MV Linac with a retrofitted multileaf collimator (MLC) based cobalt-60 plans. In this retrospective study, DVH analysis was used to compare homogeneity of dose within the target and the dose received by critical organs. A prototype MLC designed and developed as a retrofit to current cobalt-60 teletherapy machines with a dedicated 3D treatment planning system was used. Cases representing 5 tumor sites like head & neck, glottis, lung, gall bladder, stomach were taken for the study, which were planned using Eclipse treatment planning system and treated with 6 MV photon beams. The plans were re-planned using the retrofit cobalt-60 MLC with same beam arrangement and dose prescription in Radiation Oncology planning system (ROPS). For each case, DVH data was evaluated for both types of beam energies. Conformity index (CI) and homogeneity index (HI) for target were calculated and compared. The conformal plans created using cobalt MLC for five sites were found to be similar to those planned using 6 MV photon beams. CI values close to unity reflected dose uniformity in the target volume while HI evaluated the hotspots in the target volume. It was concluded that plans created using retrofit prototype MLC developed for cobalt-60 teletherapy machines can provide dose distributions comparable to 6 MV photon beams. The prototype MLC developed can provide a promising treatment option for existing telecobalt machines in implementing conformal therapy in developing countries.

Estimation of Skin doses for Retrofit Prototype Multileaf Collimators Designed for Telecobalt Therapy Machine.

AIM: The objective of this study was to evaluate skin dose based on retrofit prototype multileaf collimators (MLCs), designed for cobalt-60 teletherapy machine. Since patient's skin is sensitive to radiation, evaluation of skin dose is of utmost importance for investigating the risk of late effects. MATERIALS AND METHODS: Measurements were performed with a Phoenix cobalt-60 teletherapy machine and the detector used was EBT3 radiochromic film. The experiments were performed in a solid water phantom with two prototype MLCs mounted to the machine. Dose readings were taken by placing the films at source-to-surface distance (SSD) of 60 cm, 65 cm, 70 cm, 75 cm, 80 cm, 85 cm, and 90 cm for various MLC-generated field sizes starting from 2 cm × 2 cm to 14 cm × 14 cm. The films were analyzed using custom made programs. The measured doses were normalized to the dose at dmax for that particular measurement of SSD. RESULTS: The skin dose is expressed as a percentage of dose at dose maximum. In general, the skin dose increases with field size and decreases with SSD. The measurements indicate surface doses within 20%-60% for the investigated SSD range. Furthermore, there is no significant difference between the surface doses of two prototype MLCs studied. CONCLUSIONS: From the measurements, it can be concluded that there is good skin sparing even at close distance to the MLCs. The skin dose is <50% for SSDs >65 cm. A minimum gap of 5 cm is required to produce acceptable skin dose.

Comparison of adductor canal block and IPACK block (interspace between the popliteal artery and the capsule of the posterior knee) with adductor canal block alone after total knee arthroplasty: a prospective control trial on pain and knee function in immediate postoperative period.

BACKGROUND: Adductor canal block (ACB) is a peripheral nerve blockade technique that provides good pain control in patients undergoing total knee arthroplasty which however does not relieve posterior knee pain. The recent technique of an ultrasound-guided local anesthetic infiltration of the interspace between popliteal artery and the capsule of posterior knee (IPACK) has shown promising results in providing significant posterior knee analgesia without affecting the motor nerves. MATERIALS AND METHODS: A prospective study was conducted from September 2016 to March 2017 in a total of 120 patients undergoing unilateral total knee arthroplasty. The initial 60 consecutive patients received ACB + IPACK (Group 1, n = 60), and the subsequent 60 patients received ACB alone (Group 2, n = 60). All patients were evaluated with VAS score for pain recorded at 8 h, postoperative day (POD) 1 and POD 2 after the surgery. The secondary outcome measures assessed were the range of movement (ROM) and ambulation distance. RESULTS: VAS score showed significantly (p < 0.005) better values in ACB + IPACK group compared to the ACB group. The mean ROM of knee and ambulation distance also showed significantly better values in ACB + IPACK group compared to the ACB group. CONCLUSION: ACB + IPACK is a promising technique that offers improved pain management in the immediate postoperative period without affecting the motor function around the knee joint resulting in better ROM and ambulation compared to ACB alone.

Comparative analysis of influence of adductor canal block and multimodal periarticular infiltration versus adductor canal block alone on pain and knee range of movement after total knee arthroplasty: a prospective non-randomised study.

PURPOSE: Pain management after total knee arthroplasty has seen many recent advances such as peripheral nerve blocks in order to improve the functional outcome and reduce morbidity after surgery. Adductor canal block (ACB) and multimodal periarticular infiltration (MPI) are two techniques that have been proven to be efficacious individually. We hypothesized that the combination of ACB with MPI would reduce pain and improve knee range of movement (ROM) compared to ACB alone. METHODS: A prospective non-randomized study was conducted from July 2015 to December 2015 in our institution in a total of 200 consecutive patients undergoing unilateral total knee arthroplasty who were either given ACB alone (Group 1, n = 100 patients) or ACB + MPI (Group 2, n = 100 patients). All the patients were assessed for severity of pain by Visual Analogue Scale (VAS) at 8, 24, 48 h postoperatively and knee ROM after 48 h. RESULTS: Patients in ACB + MPI group had significantly better VAS scores at 8 h postoperatively but showed no significant difference at 24 and 48 h compared to ACB group. Patients in ACB + MPI group showed significantly better knee ROM after 48 h. CONCLUSIONS: Our study concludes that patients receiving ACB + MPI have demonstrated better VAS scores in the immediate postoperative period but have no significant difference at the time of discharge.

Monte Carlo study of MLC fields for cobalt therapy machine.

An automated Multi-Leaf Collimator (MLC) system has been developed as add-on for the cobalt-60 teletherapy machines available in India. The goal of the present computational study is to validate the MLC design using Monte Carlo (MC) modeling. The study was based on the Kirloskar-supplied Phoenix model machines that closely match the Atomic Energy of Canada Limited (AECL) theratron-80 machine. The MLC is a retrofit attachment to the collimator assembly, with 14 non-divergent leaf pairs of 40 mm thick, 7 mm wide, and 150 mm long tungsten alloy plates with rounded edges and 20 mm tongue and 2 mm groove in each leaf. In the present work, the source and collimator geometry has been investigated in detail to arrive at a model that best represents the measured dosimetric data. The authors have studied in detail the proto-I MLC built for cobalt-60. The MLC field sizes were MC simulated for 2 × 2 cm(2) to 14 × 14 cm(2) square fields as well as irregular fields, and the percent depth dose (PDD) and profile data were compared with ROPS(†) treatment planning system (TPS). In addition, measured profiles using the IMATRIXX system(‡) were also compared with the MC simulations. The proto-I MLC can define radiation fields up to 14 × 14 cm(2) within 3 mm accuracy. The maximum measured leakage through the leaf ends in closed condition was 3.4% and interleaf leakage observed was 7.3%. Good agreement between MC results, ROPS and IMATRIXX results has been observed. The investigation also supports the hypothesis that optical and radiation field coincidence exists for the square fields studied with the MLC. Plots of the percent depth dose (PDD) data and profile data for clinically significant irregular fields have also been presented. The MC model was also investigated to speed up the calculations to allow calculations of clinically relevant conformal beams. (†)Radiation Oncology Planning System (ROPS) is supplied by Tirumala Jyothi Computer Systems described at https://sites.google.com/site/tjcsrops/ (‡)IMATRIXX is supplied by IBA Dosimetry described at HYPERLINK http://www.iba-dosimetry.com.

Perspectives of Indian traditional and allopathic professionals on religion/spirituality and its role in medicine: basis for developing an integrative medicine program.

Allopathic medical professionals in developed nations have started to collaborate with traditional, complementary, and alternative medicine (TCAM) to enquire on the role of religion/spirituality (r/s) in patient care. There is scant evidence of such movement in the Indian medical community. We aim to understand the perspectives of Indian TCAM and allopathic professionals on the influence of r/s in health. Using RSMPP (Religion, Spirituality and Medicine, Physician Perspectives) questionnaire, a cross-sectional survey was conducted at seven (five TCAM and two allopathic) pre-selected tertiary care medical institutes in India. Findings of TCAM and allopathic groups were compared. Majority in both groups (75% of TCAM and 84.6% of allopathic practitioners) believed that patients' spiritual focus increases with illness. Up to 58% of TCAM and allopathic respondents report patients receiving support from their religious communities; 87% of TCAM and 73% of allopaths believed spiritual healing to be beneficial and complementary to allopathic medical care. Only 11% of allopaths, as against 40% of TCAM, had reportedly received 'formal' training in r/s. Both TCAM (81.8%) and allopathic (63.7%) professionals agree that spirituality as an academic subject merits inclusion in health education programs (p = 0.0003). Inclusion of spirituality in the health care system is a need for Indian medical professionals as well as their patients, and it could form the basis for integrating TCAM and allopathic medical systems in India.

The use of propranolol in the management of periocular capillary haemangioma--a systematic review.

Capillary haemangioma or infantile haemangioma (IH) is the most common congenital vascular tumour in the periocular region. Several treatment modalities have been documented, with variable degree of success. Propranolol has recently been reported to be an effective and safe alternative. The aim of this systematic review is to examine the evidence base for the use of propranolol administered orally in the management of periocular capillary haemangioma, and use this information to guide future research. A systematic review of literature was carried out by two independent reviewers using the search strategies highlighted below. A total of 100 cases of oral propranolol use in periorbital or orbital capillary haemangiomas have been documented in the literature. Of the 85 cases that had details of previous treatment, it was used as first-line treatment in 50 (58.8%). The commonest dose used was 2 mg/kg/day. Adverse events were documented in one-third of cases; in most cases these were minor. Improvement or complete resolution of the lesions occurred in 96% of cases. Recurrence was noted in one-fifth of cases. Propranolol has shown a lot of promise in the therapy of IH and further research in the form of properly designed randomized trials is certainly warranted. Treatment guidelines based on literature available to date is included in this review.

Wavelength dependant quenching of 2,5-diphenyloxazole fluorescence by nucleotides.

The quenching of 2,5-diphenyloxazole (PPO) fluorescence by nucleotides has been investigated by electronic absorption and steady state fluorescence spectra. Five purine nucleotides AMP, ADP, ATP, GMP and dGMP, one pyrimidine nucleotide UMP and one dinucleotide NAD have been employed in the present study. Electronic absorption studies indicate that there is no ground state complexation between the nucleotides and PPO. The quenching of PPO fluorescence was investigated at two different wavelengths. When excited at 304 nm, the lambda(max) of PPO, the fluorescence spectra of PPO is quenched following Stern-Volmer kinetics. The quenching ability of nucleotides are in the order NAD>AMP>ADP>GMP>dGMP>UMP. The K(SV) and k(q) values obtained indicate that AMP is a better quencher of PPO fluorescence than GMP, which is contrary to commonly observed pattern. The quenching is found to be dynamic in nature. However, when excited at 260 nm, the absorption maximum of the nucleotides, the fluorescence intensity of PPO is reduced with increase in the concentration of the nucleotide. This is attributed to the primary inner filter effect arising due to the absorption of the incident radiation by the nucleotides. Thus the inner filter effect phenomenon can be employed to assay the non-fluorescent molecules by fluorimetry.

Contraceptive, cerebral vein thrombosis and choked discs.

PURPOSE: To raise awareness of the importance of prompt and appropriate imaging in patients presenting with signs and symptoms suggestive of idiopathic intracranial hypertension. METHODS: Case report with diagnostic tests and discussion of management options. RESULTS: A 15-year-old girl presenting with bilateral optic disc swelling was noted to have extensive thrombosis of intracerebral venous sinuses with the clot extending along the internal jugular vein as inferior as the root of the neck demonstrable on magnetic resonance venography. CONCLUSIONS: Ophthalmologists should be vigilant in obtaining appropriate imaging in cases of optic disc swelling.

Tuberculosis: an under-diagnosed aetiological agent in uveitis with an effective treatment.

PURPOSE: To highlight the diversity of clinical presentations with tubercular uveitis in a nonendemic setting, and discuss the diagnostic approach and an effective treatment. METHOD: Descriptive case series. RESULTS: A total of 12 cases of varied presentations of tubercular uveitis diagnosed over a period of 1 year of which six cases are described in detail. Presentations included choroidal tuberculomas, multifocal choroiditis, recurrent granulomatous uveitis, panuveitis with cystoid macular oedema, and serpiginous choroiditis. All cases had a chronic or recurrent course and responded very well to antitubercular treatment. Diagnosis was mainly assisted by positive tuberculin testing. CONCLUSION: A high index of suspicion helps diagnose ocular tuberculosis in areas of low prevalence of the disease. It forms part of the differential diagnosis of any chronic or recurrent uveitis, especially in an at-risk patient. Antitubercular treatment seems highly effective.

Structural characterization of impurities in pioglitazone.

In the pioglitazone bulk drug three prominent impurities I-III were detected up to concentrations of 0.1% (ranging from 0.05-0.1%) by reversed phase HPLC. These impurities were isolated from enriched mother liquor samples and characterized as 5-(4-hydroxybenzyl)-1,3-thiazolidine-2,4-dione (I) 5-(4-fluorobenzyl)-1,3-thiazolidine-2,4-dione (II), 2-[2-(4-bromophenoxy) ethyl-5-ethyl pyridine (III) based on their 1H, and 13C NMR, DEPT, Mass and IR spectral data. Structure elucidation and synthesis of these impurities is discussed.

The cell morphogenesis gene ANGUSTIFOLIA encodes a CtBP/BARS-like protein and is involved in the control of the microtubule cytoskeleton.

The ANGUSTIFOLIA (AN) gene is required for leaf hair (trichome) branching and is also involved in polarized expansion underlying organ shape. Here we show that the AN gene encodes a C-terminal binding proteins/brefeldin A ADP-ribosylated substrates (CtBP/BARS) related protein. AN is expressed at low levels in all organs and the AN protein is localized in the cytoplasm. In an mutant trichomes, the organization of the actin cytoskeleton is normal but the distribution of microtubules is aberrant. A role of AN in the control of the microtubule cytoskeleton is further supported by the finding that AN genetically and physically interacts with ZWICHEL, a kinesin motor molecule involved in trichome branching. Our data suggest that CtBP/BARS-like protein function in plants is directly associated with the microtubule cytoskeleton.

Requirements for double-strand cleavage by chimeric restriction enzymes with zinc finger DNA-recognition domains.

This study concerns chimeric restriction enzymes that are hybrids between a zinc finger DNA-binding domain and the non-specific DNA-cleavage domain from the natural restriction enzyme FOK:I. Because of the flexibility of DNA recognition by zinc fingers, these enzymes are potential tools for cleaving DNA at arbitrarily selected sequences. Efficient double-strand cleavage by the chimeric nucleases requires two binding sites in close proximity. When cuts were mapped on the DNA strands, it was found that they occur in pairs separated by approximately 4 bp with a 5' overhang, as for native FOK:I. Furthermore, amino acid changes in the dimer interface of the cleavage domain abolished activity. These results reflect a requirement for dimerization of the cleavage domain. The dependence of cleavage efficiency on the distance between two inverted binding sites was determined and both upper and lower limits were defined. Two different zinc finger combinations binding to non-identical sites also supported specific cleavage. Molecular modeling was employed to gain insight into the precise location of the cut sites. These results define requirements for effective targets of chimeric nucleases and will guide the design of novel specificities for directed DNA cleavage in vitro and in vivo.

Aldose reductase in rice (Oryza sativa L.): stress response and developmental specificity.

Aldose reductase (AR) protein and enzyme (alditol: NAD (P)(+) 1-oxidoreductase, EC 1.1.1.21) activity have been identified in mature seeds of indica rice cultivars. The protein begins to accumulate 15 days after pollination, reaches a peak at seed maturity and disappears upon imbibition. Furthermore, AR is induced in vegetative tissues in response to exogenous ABA application and other stress conditions, such as PEG mediated water stress and salinity. Increase in AR protein levels upon stress are in close agreement with a similar increase in enzyme activity. Varietal differences in AR levels have been demonstrated. Interestingly, all tested tolerant cultivars (as denoted by breeders) accumulate AR in vegetative tisssue in response to ABA application, while the sensitive line, Hamsa, does not do this under similar stress conditions, suggesting that AR may be associated with stress tolerance. Furthermore, AR protein has been identified in mature seeds of some selected cereals indicating the conserved nature of AR across grasses.

Photosynthesis and kinetic characteristics of rubisco in Hibiscus cannabinus L.

Photosynthetic characteristics in kenaf (Hibiscus cannabinus L.), a C3 plant, were compared with Abelmoschus esculentus (L.) Moench, another member of Malvaceae. Kenaf leaves exhibited significantly higher rate of photosynthesis (40 mg CO2 dm(-2) hr(-1)) which was 24.6 mg dm(-2) hr(-1) in A. esculentus. Rate of photo and dark respiration was similar in both the species. Kenaf leaf photosynthesis had a higher optimum temperature (32 degrees C) than that of A. esculentus (26 degrees C). Photosynthesis in kenaf leaves required higher saturation irradiance (1,600 micromole m(-2) sec(-1)). There was a significant correlation between photosynthetic rate and biomass yield in these species. The primary product of photosynthesis after 5 seconds of 14C-assimilation was 3-PGA in both the species. The kinetic properties of RuBP carboxylase/oxygenase were determined in the leaf extracts. Higher carboxylase activities were recorded with kenaf leaf extracts (245 pmole mg chl(-1) hr(-1)). Km (CO2) for kenaf leaf carboxylase was significantly lower (7.8 microM) than A. esculentus (13.5 microM) and corresponding difference in Vmax values of carboxylase was recorded between the two species. The kinetic characteristics of oxygenase were similar in both the extracts. These results indicated the variation in carboxylase activity and its kinetic characteristics reflected a significant difference in CO2 assimilation in C3 plants.

A bifunctional luminogenic substrate for two luminescent enzymes: firefly luciferase and horseradish peroxidase.

Horseradish peroxidase (HRP) catalyzes the oxidative chemiluminescent reaction of luminol, and firefly luciferase catalyzes the oxidation of firefly D-luciferin. Here we report a novel substrate, 5-(5'-azoluciferinyl)-2,3-dihydro-1,4-phthalazinedione (ALPDO), that can trigger the activity of HRP and firefly luciferase in solution because it contains both luminol and luciferin functionalities. It is synthesized by diazotization of luminol and its subsequent azo coupling with firefly luciferin. NMR spectral data show that the C5' of benzothiazole in luciferin connects the diazophthalahydrazide. The electronic absorption and fluorescence properties of ALPDO are different from those of its precursor molecules. The chemiluminescence emission spectra of the conjugate substrate display biphotonic emission characteristic of azophthalatedianion and oxyluciferin. It has an optimum pH of 8.0 for maximum activity with respect to HRP as well as luciferase. At pH 8.0 the bifunctional substrate has 12 times the activity of luminol but has 7 times less activity than the firefly luciferin-luciferase system. The specific enhancement of light emission from the cyclic hydrazide part of ALPDO helped in the sensitive assay of HRP down to 2.0 x 10(-13) M and of ATP to 1.0 x 10(-14) mol. Addition of enhancers such as firefly luciferin and p-iodophenol (PIP) to the HRP-ALPDO-H2O2 system enhanced the light output.

Opiate analgesics' dual role in firefly luciferase activity.

The effects of three opiate analgesics, isolated from opium, on the firefly luciferase enzyme have been studied. Morphine (MN), 6-acetylmorphine (MAM), and diacetylmorphine (DAM) inhibited the enzyme activity at different levels. At lower concentrations, MN and MAM enhanced enzyme activity, effecting inhibition at higher concentrations. However, DAM inhibited the enzyme activity at all concentrations investigated. The stimulating activity of MN and MAM is attributed to the hydrophilic interaction of the proton donor-acceptor type with the polar regions of the luciferase located outside the binding pocket of the active site. The inhibition at higher concentrations of MN and MAM and at all concentrations of DAM is found to be competitive in nature, with the analgesics competing for the binding of the enzyme's natural substrate luciferin. The binding site of the luciferase could accommodate only one analgesic molecule. Binding constants determined from bioluminescence studies showed that the inhibitor binding site is hydrophobic in nature. The inhibition constants of analgesics are in the order MN > MAM > DAM. The greater binding of DAM to luciferase is attributed to its ability to form a ground state complex with ATP and greater hydrophobicity. At higher concentrations of ATP, the binding constants increased. The results obtained are explained assuming that the firefly luciferase acts as a subtype mu-opioid receptor model.

DNA helix destabilization by proline and betaine: possible role in the salinity tolerance process.

Evidence is provided for the ability of proline, a salinity induced osmoprotectant, to destabilize the double helix and lower the Tm of DNA in a concentration dependent manner. At the reported salinity-adaptive bio-accumulation of 1 M and above, proline could considerably decrease the Tm and partially counteract the effect of sodium chloride and spermidine on DNA stability. On the contrary, several other amino acids tested did not show any such destabilizing effect on DNA helix. Enhanced susceptibility to S1 nuclease and insensitivity to DNase I in presence of increasing proline concentrations have further suggested a clear destabilization of the double helix. Such an effect is somewhat reminiscent of the interaction between betaine, another salinity induced osmolyte, and DNA resulting in decreased Tm values. These interactions may be significant in view of the abundance of such osmolytes in cells under salinity stress-adapted conditions, with many a bacterial mutant accumulating them exhibiting improved tolerance to salinity.