Physiological, anatomical and transcriptional alterations in a rice mutant leading to enhanced water stress tolerance.

Water stress is one of the most severe constraints to crop productivity. Plants display a variety of physiological and biochemical responses both at the cellular and whole organism level upon sensing water stress. Leaf rolling, stomatal closure, deeper root penetration, higher relative water content (RWC) and better osmotic adjustment are some of the mechanisms that plants employ to overcome water stress. In the current study, we report a mutant, enhanced water stress tolerant1 (ewst1) with enhanced water stress tolerance, identified from the ethyl methanesulfonate-induced mutant population of rice variety Nagina22 by field screening followed by withdrawal of irrigation in pots and hydroponics (PEG 6000). Though ewst1 was morphologically similar to the wild type (WT) for 35 of the 38 morphological descriptors (except chalky endosperm/expression of white core, decorticated grain colour and grain weight), it showed enhanced germination in polyethylene glycol-infused medium. It exhibited increase in maximum root length without any significant changes in its root weight, root volume and total root number on crown when compared with the WT under stress in PVC tube experiment. It also showed better performance for various physiological parameters such as RWC, cell membrane stability and chlorophyll concentration upon water stress in a pot experiment. Root anatomy and stomatal microscopic studies revealed changes in the number of xylem and phloem cells, size of central meta-xylem and number of closed stomata in ewst1. Comparative genome-wide transcriptome analysis identified genes related to exocytosis, secondary metabolites, tryptophan biosynthesis, protein phosphorylation and other signalling pathways to be playing a role in enhanced response to water stress in ewst1. The possible involvement of a candidate gene with respect to the observed morpho-physiological and transcriptional changes and its role in stress tolerance are discussed. The mutant identified and characterized in this study will be useful for further dissection of water stress tolerance in rice.

The efficacy and safety of amoxicillin-clavulanic acid 1000/125mg twice daily extended release (XR) tablet for the treatment of bacterial community-acquired pneumonia in adults.

This study was designed to demonstrate the efficacy and safety of pharmacokinetically enhanced amoxicillin/clavulanic acid 2000 mg/125 mg extended release formulation (ER), than conventional formulations against community-acquired respiratory tract pathogens, particularly Streptococcus pneumoniae, with reduced susceptibility to amoxicillin. This is an open labelled, multicentric, prospective, interventional study carried out across India from June 2008 to March 2009. The study included adult patients (>18 years), weighing between 40 to 60 kg with radiologically confirmed community-acquired pneumonia (CAP). Primary efficacy parameters were clinical response (fever, cough severity, sputum characteristics and improvement in dyspnoea grades) and laboratory parameters. Secondary efficacy parameters were radiological and bacteriological findings at the end of therapy. A total, 727 clinically and radiologically confirmed community-acquired pneumonia patients were enrolled in this study. Eighteen patients were lost to follow-up during study and 709 completed the study as per the study protocol. There was a significant improvement in clinical as well as laboratory parameters at the end of therapy. There was a significant improvement in fever, cough severity, sputum characteristic and dyspnoea grades from 101.88 +/- 1.55, 2.18 +/- 0.76, 1.75 +/- 0.77 and 1.91 +/- 1.23 to 98.14 +/- 0.87 (p < 0.0001), 0.24 +/- 0.45 (p < 0.0001), 0.14 +/- 0.39 (p < 0.0001) and 0.20 +/- 0.47 (p < 0.0001) respectively. Laboratory parameters such as total WBC count and neutrophil percentage decreased significantly from 15317 +/- 662 and 80 +/- 9 to 9067 +/- 558 (p < 0.0001) and 67 +/- 9 (p < 0.0001) respectively at the end of treatment. Bacteriological success and radiological success for amoxicillin-clavulanate 1,000/62.5 mg at the end of treatment was 94.33% (150 of 159) and 98.7% (700 of 709) respectively. Mild to moderate diarrhoea was reported in 61/709 patients (8.6%). Amoxicillin-clavulanate 1,000/62.5 mg given twice daily for ten days was shown to be clinically effective and safe in the treatment of community-acquired pneumonia in adult patients. Therapy was well tolerated. [J Indian Med Assoc 2011; 109: 124-7]

Childhood T-lineage acute lymphoblastic leukemia: management and outcome at a tertiary care center in North India.

OBJECTIVE: To assess the clinical features, prognostic factors and outcome of childhood T-ALL in comparison with B-lineage ALL, treated with a uniform treatment regimen (MCP 841). SETTING: Pediatric oncology division of a tertiary care institution in Northern India. DESIGN: Retrospective analysis of clinical data and survival outcome. PARTICIPANTS: 60 children with T-ALL and 139 with B- lineage ALL, and less than 15 years of age treated over 15 years. RESULTS: T-ALL was observed in 30%. High risk features at presentation (age >10 years, WBC >50,000/mm3, mediastinal mass, and CNS leukemia) were significantly more frequent in T-ALL as compared to B-lineage ALL (P=0.049, P<0.001, P<0.001 and P=0.02, respectively). Fifty five of 60 T-ALL patients (91.7%) achieved complete remission after induction therapy. There were 3 induction and 10 remission deaths while 11 (18.3%) relapsed. The overall survival and event-free survival of T-lineage ALL (61.5±7.6 and 49.9±7.4, respectively) were similar to that of B-lineage patients (68.7±4.7 and 47.1±5.1, respectively). National Cancer Institute risk groups emerged as significant prognostic factor for event free survival only in B-lineage patients. CONCLUSIONS: Even though high risk features were significantly more frequent in T-ALL, survival outcome was similar to that of B-lineage patients. None of the routinely described prognostic parameters significantly impacted survival.

Overt testicular disease at diagnosis in childhood acute lymphoblastic leukemia: prognostic significance and role of testicular irradiation.

OBJECTIVE: To analyze the prognostic impact of overt testicular disease (OTD) at diagnosis and role of testicular irradiation in the same. METHODS: Data of 579 boys treated at our center over 16 years was reviewed. RESULTS: Fourteen (2.4%) males had OTD. 10 (71.4%) of these had high-risk disease. Patients with OTD, had a significantly higher incidence of mediastinal-adenopathy (p=0.001), hyperleucocytosis (p=0.004) and CNS disease at presentation (p<0.0001) compared to patients in continuous complete remission (CCR). 4 of the 11 patients with OTD, who opted for therapy, had relapse; 2 are in CCR. Although, survival in patients with OTD was inferior (p=0.183) compared to patients without OTD, it was not an independent prognostic factor (p=0.47). In the entire study cohort, symptom-diagnosis interval (p=0.006), white cell (p=0.001) and platelet count (p=0.001) at presentation were significantly associated with survival (Cox multivariate regression analysis). CONCLUSIONS: OTD was not an independent prognostic factor, despite association with high-risk features. Survival outcome was inferior. The observations indicate the need of revaluation of the present protocol with incorporation of intermediate dose and subsequently high-dose methotrexate (after assessment for toxicity and tolerance), risk-stratified therapy and plausibly omission of testicular irradiation.

Testicular relapse in childhood acute lymphoblastic leukemia: the challenges and lessons.

BACKGROUND: Relapse of disease is documented in 15-20% of children with acute lymphoblastic leukemia (ALL). Although testicular relapse is rare with modern risk-adapted treatment protocols, earlier, the testes were a frequently encountered site of relapse and were designated as "drug sanctuaries". PURPOSE: This descriptive study was designed to assess the pattern of testicular relapse and to identify high-risk factors. MATERIALS AND METHODS: Data obtained from case records of 407 boys with ALL were analyzed. Fine needle aspiration cytology was carried out in children presenting with painless enlargement of testi(e)s. Bone marrow aspiration and cerebrospinal fluid examination were performed concomitantly to confirm or exclude disease at these sites. RESULTS: Testicular relapse was documented in 30 boys. It was isolated in 17 patients and associated with bone marrow and/or central nervous system relapse in 13. At relapse, nine boys were over the age of 10 years. The majority were very early and early relapsers. Hyperleucocytosis was documented in five of 30 and seven of 137 relapsers and nonrelapsers, respectively (P = 0.04). Twelve of the 30 boys with testicular relapse were treated with testicular irradiation, reinduction and maintenance therapy. The estimated median overall survival was 33 months. CONCLUSION: Testicular relapse, which depends on the therapy administered, may manifest several months/years after completion of treatment. The high incidence of testicular relapse in our series implicates the need of revaluation of our protocol and incorporation of high/intermediate dose methotrexate therapy upfront.

Pattern and implications of therapy abandonment in childhood acute lymphoblastic leukemia.

Abandonment of therapy is cited as an important factor contributory to inferior survival outcome in developing nations. In this communication we describe the pattern of therapy abandonment and its impact on survival of childhood acute lymphoblastic leukemia at a large tertiary care center in Northern India and discuss remedial measures.

Pattern of relapsed disease in childhood all: experience from a single tertiary care center in North India.

The study was designed to determine the pattern of relapsed disease and identify problem areas in management. Relapse occurred in 111 (23.9%) of the boys and 16 (13.0%) of the girls. The majority relapsed while on chemotherapy. Isolated relapse in the marrow and in the CNS was seen in 51 (40.8%) and 24 (18.9%) patients, respectively. Isolated testicular relapse was seen in 17 (15.3%) of the 111 boys who suffered a relapse. Age and TLC at initial presentation and gender in relapsers and nonrelapsers were compared. Multivariate regression analysis showed that gender (p = .03) and TLC (p = .001) were significant predictors of relapse. Relapse of disease while on chemotherapy and high incidence of CNS and testicular relapse indicate the need for reappraisal of treatment protocols.

Survival outcome in childhood ALL: experience from a tertiary care centre in North India.

BACKGROUND: Survival of children with ALL, in developing nations has not kept pace with cure rates in developed countries. Our study was designed to assess survival data and identify risk factors. PROCEDURE: Data of 762 patients with ALL were analyzed. Information regarding the clinical-demographic profile, therapy and course of illness were recorded. Status and duration at last follow-up were utilized to generate Kaplan-Meier survival curves. RESULTS: The mean age was 5.7 +/- 0.23 years (M/F, 3.2:1). Parents of 230 (30.2%) patients opted for no therapy. There were 68 and 60 deaths in induction and remission phases respectively. Besides these, 111 children either defaulted therapy or were lost to follow up. Relapsed disease was documented in 125 cases. The 5-year OS and EFS was 46% and 43% respectively. Survival analysis, using the Cox multivariate regression, for gender (P = 0.659, CI: 0.852-1.161), age (P = 0.943, CI: 0.725-1.225), symptom-diagnosis interval (P = 0.002, CI: 1.116-1.668), WCC (P < 0.001, CI: 1.353-1.814) and platelet count (P = 0.001, CI: 0.546-0.849) was performed. Bulk disease (P = 0.049, CI: 0.428-0.986), mediastinal adenopathy (P = 0.045, CI: 1.040-3.697), WCC (P = 0.016, CI: 1.395-2.691), platelet count (P = 0.031, CI: 0.431-0.967) and administration of 2 intensification blocks (P = 0.012, CI: 0.624-0.940) were found to be significant predictors of outcome by multivariate analysis. CONCLUSIONS: The management of ALL requires financial resources and access to quality supportive care. One third of our patients opted for no therapy. The other problem areas were a high proportion of therapy defaulters, lost to follow up and infection related deaths during induction and remission phases. The introduction of remedial measures for resolving the difficulties identified would hopefully improve cure rates in ALL in developing nations.

Efficacy and safety of oxum in treatment of chronic wounds.

Chronic wounds represent a major health burden contributing to substantial mortality, morbidity and costs. Several new treatment options are currently available, which has revolutionised the management of chronic wounds. The present study is a single centre, prospective, clinical trial comparing oxum (super oxidised water) and betadine as a topical treatment of chronic wounds conducted in 30 Indian patients, with 15 patients in each group. At the end of the study, there was a significant reduction in primary parameters such as wound area and microbial colony count in oxum treated group compared to betadine group. However, both the oxum and betadine treated group showed a similar results when the secondary parameters such as oedema, erythema and granulation tissue were considered. Oxum was better tolerated than betadine. It can be concluded that use of oxum (super oxidised water) is a novel technological innovation in the therapy of chronic wounds. Oxum has been shown to be effective, well tolerated and superior to betadine in wound care.

In vitro study to compare sensitivity of amoxicillin+clavulanic acid and cefpodoxime+clavulanic acid among beta-lactamase positive clinical isolates of gram-positive and gram-negative pathogens.

The present study was carried out to compare the in vitro sensitivity of cefpodoxime + clavulanic acid and amoxicillin + clavulanic acid against 55 Gram-positive and 123 Gram-negative beta-lactamase positive clinical isolates. Micro-organisms isolated from different clinical specimens were tested for beta-lactamase/ESBL by using nitrocefin disc test and for metallo beta-lactamase by using double disc synergy test. A total of 299 (93 Gram-positive and 206 Gram-negative) clinical isolates were tested for beta-lactamase. Among 93 Gram-positive clinical isolates 25 (78.12%) out of 32 coagulase positive S. aureus, 23 (60.52%) out of 38 coagulase negative S aureus, 7 (63.63%) out of 11 enterococci and 0 (0%) out of 12 Strept pneumoniae were positive for beta-lactamase /ESBL. Notably Strept pneumoniae was found to be beta-lactamase/ESBL negative. Among 206 Gram-negative clinical isolates, 25 (69.44%) out of 36 acinetobacter spp, 20 (41.66%) out of 48 Branhamella catarrhalis, 24 (64.86%) out of 37 E. coli, 7 (46.66%) out of 15 H influenzae and 22 (62.85%) out of 35 proteus were positive for beta-lactamase/ ESBL/metallo beta-lactamase. Positive strains were tested for comparative sensitivity to amoxicillin+ clavulanic acid and cefpodoxime+clavulanic acid by Kirby Bauer disc diffusion method. As regards comparative sensitivity among beta-lactamase/ESBL positive Gram-positive strains, 84% and 92% strains of coagulase positive S aureus, 65.21% and 86.95% strains of coagulase negative S. aureus, 83.33% and 100% strains of Strept pneumoniae and 71.42% and 100% strains of enterococci were found sensitive to amoxicillin +clavulanic acid and cefpodoxime + clavulanic acid respectively. Sensitivity to amoxicillin+ clavulanic acid and cefpodoxime +clavulanic acid among beta lactamase/ESBL positive Gram-negative strains of acinetobacter spp, Branhamella catarrhalis, E. coli, H. influenzae and proteus spp were found to be 20% and 28%, 100% and 100%, 50% and 75%, 71.42% and 100%, 50% and 68.18% respectively. This study demonstrated that cefpodoxime +clavulanic acid combination has more potent in vitro activity in comparison to amoxicillin+ clavulanic acid combination against beta-lactamase producing strains of Gram-positive and Gram-negative bacteria. Given this broad spectrum of activity, cefpodoxime+clavulanic acid appears well suited for use in the treatment of a variety of healthcare-associated infections.

Efficacy and safety of oxum in treatment of the venous ulcer.

The present study was carried out to find out the efficacy and safety of oxum in the treatment of venous ulcers. The oxum (superoxidised water) is a pH neutral, non-irritating, aqueous solution that possesses a good antiseptic, antimicrobial activity and wound healing properties. The study was conducted in 30 patients of venous ulcers with a culture examination positive for pathogenic microbial flora. All patients received a gauze dressing impregnated with oxum followed by compression bandage for 28 days. The primary endpoint was the calculation of ulcer size using ulcer tracing. Assessment of periwound oedema, periwound erythema, wound fibrin and wound granulations were considered as secondary endpoints. There was a singificant reduction in ulcer size starting from day 7 of the treatment. Significant improvements in secondary endpoints were observed. This study has demonstrated that oxum improved the clinical status, reduced the signs of inflammation in venous ulcers in addition to its well confirmed anti-infective properties.

Itopride and pantoprazole outcomes in diabetic gastroparesis trial (IPOD trial).

The most common cause of gastroparesis is diabetes mellitus. The present study was carried out to asses the combination of itopride and pantoprazole in the treatment of diabetic gastroparesis. The study was an open label, multicentre, conducted in 743 patients with diabetic gastroparesis for a period of 3 weeks. The efficacy parameters included nausea, vomiting, early satiety, bloating, postprandial fullness, epigastric pain and regurgitation. The patients were evaluated based on the frequency and severity of symptoms and compared with the baseline scores. There were significant improvement in severity as well as the frequency of all the symptom parameters of the disease (p<0.001). The physicians' evaluation to the therapy was rated either excellent or good.

Distal arthrogryposis syndrome.

A 5-month-old male infant presented with weak cry, decreased body movements, tightness of whole body since birth, and one episode of generalized seizure on day 4 of life. He was born at term by elective caesarian section performed for breech presentation. The child had failure to thrive, contractures at elbow and knee joints, hypertonia, microcephaly, small mouth, retrognathia, and camptodactyly. There was global developmental delay. Abdominal examination revealed umbilical and bilateral inguinal hernia. Visual evoked response and brainstem evoked response audiometry were abnormal. Nerve conduction velocity was normal. Magnetic resonance imaging of brain revealed paucity of white matter in bilateral cerebral hemispheres with cerebellar and brain stem atrophy. The differential diagnoses considered in the index patient were distal arthrogryposis (DA) syndrome, cerebroculofacioskeletal syndrome, and Pena Shokier syndrome. The index patient most likely represents a variant of DA: Sheldon Hall syndrome.