Gamma radiation induced changes in expression of heat shock proteins (Hsc70 and Hsp83) in the dengue vector Aedes aegypti (L.)

We aimed to assess the effect of gamma radiation on the expression of heat shock proteins Hsc70 and Hsp83 in Aedes aegypti. Adult males were irradiated with 50Gy of gamma radiation, and changes in the expression of proteins in SDS-PAGE gel bands corresponding to molecular weights ~60–75kDa and ~80–95kDa were analyzed at two different time points 6 and 12-hour post-irradiation, using a temporal mass spectrometry based semi-quantitative analysis. A 2-3-fold increase was observed in both proteins Hsc70 and Hsp83, at both time points. In addition, the experiment also revealed the overexpression of several other molecules such as Arginine Kinase - known to be upregulated in certain insects during stress, Esterase B1- implicated in insecticide resistance, and also down-regulation of the 26S proteasome non-ATPase regulatory subunit 1 and ubiquitin-activating enzyme E1 - both known to be involved in ubiquitin-mediated protein degradation. The results taken together with existing data on Hsp83 and Hsc70, indicate that these proteins may enhance the survival of Ae. aegypti following gamma radiation and could serve as molecular markers for the detection of radiation-induced stress.

Experience with non-cremophor-based paclitaxel-gemcitabine regimen in advanced pancreatic cancer: Results from a single tertiary cancer centre

Background & objectives: Gemcitabine combined with non-cremophor-based paclitaxel is one of the standards of care in advanced inoperable pancreatic cancer. This study was undertaken to retrospectively evaluate real world non-trial outcomes with this combination. Methods: Patients with histologically proven advanced inoperable pancreatic adenocarcinoma (PDAC), treated with non-cremophor-based paclitaxel-gemcitabine combination (PG) (gemcitabine-nanoxel or gemcitabine-abraxane) between January 2012 and June 2015, were retrospectively analyzed. Response assessment was done every 8-12 wk with computed tomography scan and responses were measured as per the Response Evaluation Criteria in Solid Tumours 1.1 criteria where feasible. Toxicity was recorded as per the Common Terminology Criteria for Adverse Events (CTCAE) v4 criteria. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results: A total of 78 patients with PDAC were treated with the combination. Of these, 83.3 per cent of patients had metastatic disease. The median number of chemotherapy cycles administered was three. The objective response rate for the whole group was 30.8 per cent. Grade III/IV toxicities were seen in 35.9 per cent of patients. Median PFS was 5.6 months and median OS was 11.6 months. Interpretation & conclusions: Non-cremophor-based paclitaxel in combination with gemcitabine appeared efficacious for advanced pancreatic cancers in routine clinical practice. Within the confines of a single-centre retrospective analysis, gemcitabine-nanoxel and gemcitabine-abraxane appeared to have similar efficacy and toxicity in advanced pancreatic cancers.

Epidemiology of male seminomatous and nonseminomatous germ cell tumors and response to first‑line chemotherapy from a tertiary cancer center in India.

INTRODUCTION: Unlike the developed countries, there is a lack of good epidemiologic data for testicular germ cell tumors (GCTs) in India with majority presenting in advanced stage. This study aims to elaborate on the epidemiology of testicular GCTs and response to standard first‑line chemotherapy (CT). METHODS: GCTs treated at our center from January 2013 to June 2014 were retrospectively analyzed. Patients underwent orchidectomy either outside or at our hospital. Based on stage and risk group, standard CT (bleomycin, etoposide, and cisplatin/etoposide and cisplatin/carboplatin AUC7) and radiotherapy were given as appropriate. Response was calculated based on the Response Evaluation Criteria in Solid Tumors. Statistical analysis was performed using SPSS 18 software. RESULTS: Fifty nonseminomatous germ cell tumor (NSGCT) and 36 of SGCT cases were studied. 30%, 46%, and 64% of NSGCT and 11%, 28%, and 22% of SGCT had N2, N3, and M1 diseases, respectively. The mean nodal size was 7 cm (1.5–19) in NSGCT and 5.5 cm (1.3–11) in SGCT. As per the International Germ Cell Cancer Collaborative Group classification, in patients with metastatic disease, 9% of NSGCT were good, 53% were intermediate, and 38% were poor risk whereas 75% of SGCT were good and 25% were intermediate risk. Following CT among NSGCT, 5% and 71% had radiologic complete response (CR) and partial response (PR), respectively. Among SGCT, 46% and 38% had radiologic CR and PR, respectively. 22%, 53%, and 13% of NSGCT and 12%, 24%, and 20% of SGCT developed febrile neutropenia, Grade 3 or 4 hematological and nonhematological toxicities, respectively, after standard chemotherapy. CONCLUSIONS: GCTs in India present with high nodal and high‑risk diseases wherein the standard first‑line CT may not be adequate as curative therapy; however, significant chemotoxicity is also a hindrance.

Treatment of patients with metastatic pancreatic cancer: Experience from a tertiary Indian cancer center.

BACKGROUND: The aim of this study was to look at the outcome of patients with metastatic pancreatic cancer treated at a tertiary cancer center in India. PATIENTS AND METHODS: A total of 101 patients with locally advanced and metastatic pancreatic cancer diagnosed between May 2012 and July 2013 were identified from a prospectively maintained database at the tertiary cancer center. Overall survival (OS) was computed using the Kaplan–Meir product limit method and compared across groups using the log‑rank statistics. Cox proportional hazards model, adjusted for a number of patient and tumor characteristics, was then used to determine factors prognostic for OS. RESULTS: Median age at diagnosis was 55 years (range: 21–81 years). 57.4% (n = 58) of patients were male, 22% (n = 22) had performance status (PS) of <2 at diagnosis and 89% received first‑line chemotherapy, while the rest received best supportive care. For the whole cohort, 6 month and 1‑year OS was 57% (95% confidence interval [CI]: 46–66%) and 47% (95% CI: 35–57%), respectively. In a multivariable model, PS <2 and oligometastatic disease were associated with a significantly decreased risk of death. CONCLUSION: Results from our analysis indicate that the prognostic outcome among Indian patients with metastatic pancreatic cancer is poor with survival outcomes similar to those reported in North America and Europe.

Comparison of isolates and antibiotic sensitivity pattern in pediatric and adult cancer patients; is it different.

BACKGROUND: Infection is a common cause of mortality and morbidity in cancer patients. Organisms are becoming resistant to antibiotics; age appears to be one of the factors responsible. We analyzed common organisms and their antibiotic sensitivity pattern in the correlation with age. METHODS: This is a single institutional, retrospective analysis of all culture positive adult and pediatric cancer patients from January 2007 to December 2007. For statistical analysis, Chi‑square test for trend was used and P values were obtained. Of 1251 isolates, 262 were from children <12 years of age and 989 were from adolescents and adults (>12 years of age). Gram‑negative organisms were predominant (64.95) while Gram‑positive constituted 35.09% of isolates. RESULTS: The most common source in all age groups was peripheral‑blood, accounting to 47.8% of all samples. The most common organisms in adults were Pseudomonas aeruginosa (15.3%) while in children it was coagulase negative Staphylococcus aureus (19.8%). Antibiotic sensitivity was different in both groups. In pediatric group higher sensitivity was seen for Cefoparazone‑sulbactum, Cefipime, Amikacin, and Tobramycin. No resistance was found for Linezolid. CONCLUSIONS: The isolates in both children and adults were predominantly Gram‑negative though children had proportionately higher Gram‑positive organisms. High‑dose cytarabine use, cotrimoxazole prophylaxis, and frequent use of central lines in children especially in hematological malignancies could explain this observation. Children harbor less antibiotic resistance than adults; Uncontrolled, cumulative exposure to antibiotics in our community with increasing age, age‑related immune factors and variable bacterial flora in different wards might explain the higher antibiotic resistance in adults. Thus age is an important factor to be considered while deciding empirical antibiotic therapy.

Management of febrile neutropenia in malignancy using the MASCC score and other factors: Feasibility and safety in routine clinical practice.

BACKGROUND: The current standards for empirical broad‑spectrum intravenous antibiotic (AB) treatment, combined with hospitalization, are cautious and safe, but lead to over‑treatment of a substantial group of patients. We need to validate parameters to identify these low‑risk febrile‑neutropenia (FN) patients, who could then be safely treated in an outpatient setting with minimal/no AB treatment. MATERIALS AND METHODS: A retrospective analysis for validation of a risk‑assessment model in FN patients was done on a patient population from January 2007 to December 2008. Inclusion criteria were a histological diagnosis of malignancy, FN secondary to chemotherapy, absolute‑neutrophil‑count of ≤500/μl, axillary temperature of ≥38°C, and age ≥14 years. Other clinical and laboratory parameters were explored for risk stratification during the FN episodes. Receiver‑operating characteristic curves were used to find the threshold value, and Chi‑square analysis was done to find the association between the outcome and the parameters. RESULTS: A total of 178 FN episodes were documented; 22 in solid tumors and 156 in hematolymphoid malignancies. Culture positivity was documented in 59 episodes; peripheral blood was the most common source, with Escherichia coli being the most common organism identified. Risk stratification was done using the Multinational Association of Supportive Care in Cancer (MASCC) risk‑index score. The association between the MASCC score and risk stratification could not be established (P = not significant) at a score of ≤21; however, it was found to be significant at a score of ≤18. The total number of complications was 23 (sepsis 22, mortality 23). Other factors found to be significantly associated with a high risk of complications in the univariate analysis were, mucositis (P = 0.03), maximum temperature ≥103°F (P = 0.01), tachycardia (P < 0.001), tachypnea (P = <0.001), age (P = 0.006), high dose of steroid (P < 0.001), total duration of fever (≥2.5 days (for which sensitivity (S) and specificity (Sp) were 87 and 81%, respectively), serum‑creatinine (≥0.45 mg%, S = 100%, Sp = 97%), serum‑bilirubin (≥0.5 mg/dl, S = 100%. Sp = 90%), requirement of second‑line antibiotics (P = 0.02), intensive‑care (P ≤ 0.001), ventilatory support (P < 0.001), and requirement of packed cell (PC) transfusion (P = 0.02). In the multivariate analysis, mucositis (P = 0.02), HD steroid use (P = 0.026), and PC requirement (0.026) were identified as independent variables. CONCLUSIONS: The MASCC risk‑index score was found to be meaningful at a score of ≤18. Other clinical and laboratory parameters were found to have a strong association with risk stratification in cancer patients during FN episodes.

Comparative study to evaluate the accuracy of polyether occlusal bite registration material and occlusal registration wax as a guide for occlusal reduction during tooth preparation.

Introduction: The use of different materials and techniques has been studied to decide the safest quantum of reduction of the occlusal surfaces. However, these methods provide limited information as to the actual amount of reduction with limitations in accuracy, accessibility and complexity. Objective: The objective of this study was to compare and evaluate the reliability of the most commonly used occlusal registration wax that with polyether bite registration material as a guide for occlusal reduction required during tooth preparations. Materials and Methods: For the purpose of this study, 25 abutment teeth requiring tooth preparation for fixed prosthesis were selected and tooth preparations carried out. Modeling wax strips of specific dimensions were placed onto the cast of prepared tooth, which was mounted on maximum intercuspation on the articulator and the articulator was closed. The thickness of the wax registration was measured at three zones namely two functional cusps and central fossa. Similar measurements were made using the polyether bite registration material and prosthesis at the same zones. The data was tabulated and was subjected to statistical analysis using anova test and Tukey honestly significant difference test. Results: The differences in thickness between wax record and prosthesis by 0.1346 mm, whereas the difference between polyether and prosthesis was 0.02 mm with a P value of 0.042, which is statistically significant. This means that the wax record was 8.25% larger than the prosthesis while polyether was just 1.27% larger than the prosthesis. Conclusion: The clinical significance of the above analysis is that Ramitec polyether bite registration material is most suitable material when compared with commonly used modeling wax during the tooth preparation.

The genetics of green thorax, a new larval colour mutant, non-linked with ruby-eye locus in the malaria mosquito, Anopheles stephensi Liston.

Background & objectives: Anopheles stephensi, an important vector of malaria continues to be distributed widely in the Indian subcontinent. The natural vigour of the species combined with its new tolerance, indeed resistance to insecticides has made it obligatory that we look for control methods involving genetic manipulation. Hence, there is an immediate need for greater understanding of the genetics of this vector species. One of the requirements for such genetic studies is the establishment of naturally occurring mutants, establishment of the genetic basis for the same and use of such mutants in the genetic transformation studies and other genetic control programme(s). This paper describes the isolation and genetic studies of a larval colour mutant, green thorax (gt), and linkage studies involving another autosomal recessive mutant ruby-eye (ru) in An. stephensi. Methods: After the initial discovery, the mutant green thorax was crossed inter se and pure homozygous stock of the mutant was established. The stock of the mutant ruby-eye, which has been maintained as a pure stock in the laboratory. Crosses were made between the wild type and mutant, green thorax to determine the mode of inheritance of green thorax. For linkage studies, crosses were made between the mutant green thorax and another autosomal recessive mutant ruby-eye. The percentage cross-over was calculated for the genes linkage relationship for gt and gt ru. Results: Results of crosses between mutant and wild type showed that the inheritance of green thorax (gt) in An. stephensi is monofactorial in nature. The gt allele is recessive to wild type and is autosomal. The linkage studies showed no linkage between ru and gt. Interpretation & conclusion: The mutant gt represents an excellent marker for An. stephensi as it is expressed in late III instar stage of larvae and is prominent in IV instar and pupal stages with complete penetrance and high viability. The said mutant could be easily identified without the aid of a microscope. This mutant can be used extensively to conduct basic and applied research. The mutant has been maintained in two large cages in our laboratory.

Dark larva a new autosomal larval colour mutant in the malaria mosquito, Anopheles stephensi Liston.

Anopheles stephensi is an important urban malaria vector, which is widely distributed throughout the Indian subcontinent. The said vector species has developed resistance to various insecticides and therefore, it is desirable to develop alternative strategies including genetic methods for its control. One of the requirements for such strategy is to establish morphological mutants and to establish the genetic basis of the same. Such mutant markers could be used in the construction of genetically modified strain/s in the genetic control programme of An. stephensi. The dark colour expresses in all larval stages and pupae with full penetarence and uniform expression in both the sexes. The viability of the mutant is as good as the wild type. The genetic studies of the dark larva revealed that the gene da is mono-factorial, autosomal and recessive to the wild type. The gene da is an excellent marker for An. stephensi.

An integrated treatment approach: a case report for dentinogenesis imperfecta type II.

Dentinogenesis imperfecta type II or hereditary opalscent dentin is one of the most common autosomal dominant anomaly of dentin that occurs in both sex affecting approximately 1:8000 persons. Clinically this disorder is characterized by variable blue gray to yellow brown teeth, with fracture of enamel and excessive wear. The treatment strategy is focused towards protecting teeth from further wear and tear and total oral rehabilitation of patient with paramount importance to aesthetics, obtaining an appropriate vertical dimension and providing soft tissue support which will help to return the facial profile to a more normal appearance. A multidisciplinary treatment planning is required for treatment of these individuals.

Hyperammonemia: an unusual presenting feature of multiple myeloma.

A 76 year old lady presented with altered sensorium and was found to have hyperammonemia on evaluation. She had no evidence of liver disease. For her symptomatology of backache, evaluation by bone marrow study showed evidence of multiple myeloma. She was given chemotherapy for multiple myeloma, which resulted in improvement in her sensorium, along with this there was also a rapid decline in serum ammonia levels. Hyperviscosity and hypercalcemia are common causes of altered sensorium in a patient with myeloma but in this case hyperammonemia was the likely cause.

Giant lesions in histoid leprosy--an unusual presentation.

A forty-year-old man presented with multiple, asymptomatic, raised lesions of one-year duration. Well-defined, non-tender papules and nodules were seen on the normal looking skin. Few giant lesions were seen over the lower legs and feet. Diffuse infiltration of the face and ears was present. Bilateral ulnar, radial cutaneous, sural and right superficial peroneal nerves were thickened. Slit-skin smear from a nodule had a BI of 6+. Biopsy showed features of histoid leprosy. The lesions had developed de novo, without previous dapsone monotherapy.

An evaluation of clinical and histopathological status in paucibacillary leprosy patients after completion of fixed duration therapy.

The present study was carried out involving 25 patients with paucibacillary leprosy who attended the outpatient department of dermatology of Father Muller's Medical College Hospital during the period January 2001 to March 2002. All the patients were examined clinically and histopathologically at the beginning and at the end of six months of MDT and relevant data recorded. Clinicopathological correlation with histopathological classification before MDT was 72% and 68% at the end of MDT in our study. At the end of treatment 4 (16%) cases were clinically active and 8 (32%) were histopathologlcally active. The study showed that active cases were significantly reduced as a result of MDT, both clinically and histopathologically. The histopathological activity that outlasts MDT may be due to the bacillary fragments that persist; but clinical activity coupled with histopathological activity seen in 2 patients at the end of 6 months of MDT was possibly an indicator of relapse and these patients and similar others need to be followed up for a longer duration. In this study, resolution of granuloma and clinical activity after completion of MDT were assessed.

The effect of 0.5% sodium hypochlorite and 2% glutaraldehyde spray disenfectants on irreversible hydrocolloid impression material.

Infection control has assumed prime importance in dentistry. It is a prime concern in prosthodontics as well, where impressions materials are most commonly used. Impression materials can act as a medium for cross infection. To prevent cross infection many products are being developed. Among them 0.5% Sodium hypochlorite and 2% Glutaraldehyde are considered effective. This study was done to asses the efficacy of 0.5% Sodium hypochlorite and 2% Glutaraldehyde on irreversible hydrocolloid impression material. The result of the study indicated that they are effective against both Gram positive and Gram negative organisms and their use is recommended.

Ruby-eye, a new autosomal mutant in the malaria mosquito, Anopheles stephensi Liston.

BACKGROUND & OBJECTIVES: Anopheles stephensi, an important vector of malaria continues to be distributed widely in the Indian subcontinent. This vector species has developed resistance for various insecticides. Therefore, it is desirable to develop alternate strategy, which does not involve resistance. In order to develop such strategy, it is mandatory that genetic studies of concerned vector species should be established. This paper describes the isolation and genetic studies of an eye colour mutant, ruby-eye (ru), and linkage studies involving another autosomal recessive mutant greyish brown larva (grb ru) in A. stephensi. METHODS: The stocks of mutants ruby-eye (ru), greyish brown (grb ru) and wild type mosquitoes were maintained in the laboratory. Crosses were made between the wild type and mutant to determine the mode of inheritance of ruby-eye. For linkage studies crosses were made between the mutant ruby-eye and another autosomal recessive mutant greyish brown larva. The percentage cross over was calculated for the genes linkage relationship for ru and grb ru. RESULTS: Results of crosses between mutant and wild type show that the inheritance of ruby-eye in A. stephensi is monofactorial in nature. The ru allele is recessive to wild type and is autosomal. The linkage studies showed no linkage between grb and ru. INTERPRETATION & CONCLUSION: The mutant ru represents an excellent marker for A. stephensi as it expresses in all the life stages with complete penetrance and high viability. This mutant can be used extensively to conduct basic and applied research.

Sclerosing mediastinitis: a case report.

A rare case of sclerosing mediastinitis in a 38 year old male is described. This interesting case illustrates how a seemingly benign fibrosing condition may lead to disastrous and fatal complications.

Congenital retinoschisis: successful collapse with photocoagulation.

We report a case of progressive congenital retinoschis is where the schisis cavity collapsed following argon laser photocoagulation. Despite reports to the contrary, we feel that in the absence of significant vitreous or inner layer traction, photocoagulation applied as light burns in the schisis cavity may be beneficial in collapsing the cavity. Whether or not this collapse of the schisis cavity reduces the risk of rhegmatogenous retinal detachment is unclear.