COPD exacerbation rates are higher in non-smoker patients in India.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is common among non-smokers exposed to solid fuel combustion at home. Different clinical characteristics in these patients may have significant therapeutic and prognostic implications.METHODS: We used medical record review and a questionnaire among COPD patients at 15 centres across India to capture data on demographic details, different types of exposures and clinical characteristics. Chest radiography and pulmonary function testing were performed in all 1984 cases; C-reactive protein and exhaled breath nitric oxide were measured wherever available.RESULTS: There were 1388 current or ex-smokers and 596 (30.0%) non-smokers who included 259 (43.5%) male and 337 (56.5%) female patients. Sputum production was significantly more common in smokers with COPD (P < 0.05). The frequency of acute symptomatic worsening, emergency visits and hospitalisation were significantly higher (P < 0.05) in non-smokers with COPD; however, intensive care unit admissions were similar in the two groups. There was no significant difference with respect to the use of bronchodilators, inhalational steroids or home nebulisation among smoker and non-smoker patients. The mean predicted forced expiratory volume in 1 sec in smokers (43.1%) was significantly lower than in non-smokers (46.5%).CONCLUSION: Non-smoker COPD, more commonly observed in women exposed to biomass fuels, was characterised by higher rate of exacerbations and higher healthcare resource utilisation.

Scrub typhus causing neonatal hepatitis with acute liver failure-A case series.

Neonatal hepatitis with acute liver failure due to varied etiology including various infections is reported in the past. Scrub typhus as a cause of neonatal hepatitis has rarely been reported in literature. A high index of clinical suspicion is required for early diagnosis and timely treatment. Severity and prognosis of the disease varies widely because several different strains of Orientia tsutsugamushi exist with different virulence. Delayed diagnosis can result in complication and significant morbidity and mortality. Here, we report three cases of neonatal hepatitis with acute liver failure caused by scrub typhus to increase awareness.

Distribution and Trends of Human Parainfluenza Viruses in Hospitalised Children.

OBJECTIVE: To study the distribution of Human Parainfluenza viruses (HPIV) 1-4 and their trends in children ≤5 y of age, hospitalised at a tertiary care centre, Jaipur and co-infection with other respiratory viruses. METHODS: Nasopharyngeal aspirate and throat swabs were collected and processed for extraction of nucleic acid using automated extraction system and real time RT-PCR was performed using primers and probes specific to HPIV 1-4 and other respiratory viruses on 743 samples. RESULTS: Total positivity for Parainfluenza viruses 1-4 was found to be 69/743 (9.28 %), of which 50/533 (9.38 %) were boys and 19/210 (9.05 %) girls. Predominance of HPIV- 3 was observed [41/743 (5.52%)] followed by HPIV-1 in 13/743 (1.75%), HPIV-4 in 10/743 (1.34%) and HPIV-2 in 5/743 (0.67%) patients. Maximum positivity was observed in age group 25-36 mo (12.98%) followed by 13-24 mo group (11.96%). HPIVs were found to be circulating round the year and each year. Co-infections with other respiratory viruses were observed in 22/69 (31.88%) of HPIV positive patients. CONCLUSIONS: All the four types of HPIV were found to be circulating in the index population during all the three years, predominantly during post monsoon and winter seasons. HPIV vaccination should be targeted for all types.

Viruses causing severe acute respiratory infections (SARI) in children ≤5 years of age at a tertiary care hospital in Rajasthan, India.

BACKGROUND & OBJECTIVES: Severe acute respiratory infection (SARI) is one of the leading causes of death among children worldwide. As different respiratory viruses exhibit similar symptoms, simultaneous detection of these viruses in a single reaction mixture can save time and cost. The present study was done in a tertiary care children's hospital for rapid identification of viruses causing SARI among children less than or equal to five years of age using multiplex real-time reverse transcription polymerase chain reaction (RT-PCR) kit. METHODS: A total of 155 throat swabs were collected from equal number of children suspected to have SARI and processed for extraction of nucleic acids using automated extraction system. Multiplex real-time RT-PCR was done to identify the viruses in the samples. RESULTS: The overall positivity for viruses in the study was found to be 72.9 per cent with a co-infection rate of 19.5 per cent. Human metapneumovirus (HMPV) was the predominant virus detected in 25.7 per cent children followed by influenza A (H1N1)pdm09, human rhinovirus (HRV) and human adenovirus (HAdV) in 19.9, 11.0 and 8.8 per cent children, respectively. The HMPV was at its peak in February 2013, HAdV showed two peaks in March-April, 2012 and November 2012-March 2013 while HRV was detected throughout the year. INTERPRETATION & CONCLUSIONS: Multiplex real-time PCR helped in rapid identification of viruses. Seventeen viruses were detected in SARI cases with overall positivity of 72.9 per cent. HMPV was the most predominant virus. However, for better clinico-virological correlation, studies are required with complete work up of all the aetiological agents, clinical profile of patients and treatment outcome.

The combination of the active principles of Podophyllum hexandrum supports early recovery of the gastrointestinal system via activation of Nrf2-HO-1 signaling and the hematopoietic system, leading to effective whole-body survival in lethally irradiated mice.

This study is aimed at the development of a safe radioprotective formulation to minimize human sufferings during accidental nuclear exposures. In the current study, a combination of three active principles, namely podophyllotoxin, podophyllotoxin beta-D-glucoside, and rutin (G-002M), isolated from Podophyllum hexandrum rhizomes, has been evaluated for its radioprotective potential and mode of action. Total body protection studies have demonstrated that a single prophylactic dose of G-002M delivered more than 85% survival in mice exposed to a lethal (9 Gy) dose of gamma radiation, and significantly protected the radiosensitive hematopoietic and gastrointestinal organs. Studies have also revealed a reduction in free radical generation, lipid peroxidation, protein carbonylation, and cell death in mouse intestine after G-002M treatment, while GSH was observed to be enhanced in the same tissue. Redox-sensitive transcription factor (Nrf2) activation and subsequent upregulation of heme oxygenase-1 (HO-1) and SOD-1 revealed the cytoprotective role of G-002M. A histological examination of the jejunum pretreated with the formulation also demonstrated less damage to the villi, crypts, and the mucosal layers. These observations reiterated that the reduction in the ROS levels, protection of cellular macromolecules, and activation of the antioxidant signaling pathway may have been the principle factors involved in G-002M- mediated protection against radiation-induced tissue impairment. The potentially safe and effective radioprotective characteristics of this new combination are encouraging for further studies for human application.

Blood biomarkers in metal scrap workers accidentally exposed to ionizing radiation: a case study.

The detrimental effect of nuclear accidents due to localized or whole body radiation exposure results in severe cellular damage. The current study was carried out to evaluate radiation-mediated variability in blood components of metal scrap workers exposed accidently to cobalt-60 source. Blood samples collected initially from five hospitalized patients, coded P1-P5, were processed for total leukocyte counts (TLC), platelet (PLT) counts, haemoglobin, estimation of DNA double strand breaks by measuring phosphorylated form of H2AX (γ-H2AX) and chromosomal aberrations (dicentrics). Blood cells count (TLC), in all the patients except P2, was found decreased. Dicentrics increased in all the five patients. γ-H2AX was found significantly elevated in patients P2 and P4. After 3 days, 21 subjects working in close vicinity of accident site were evaluated for the above-mentioned markers to confirm their possibility of radiation exposure; however, all the parameters in these subjects were found within normal limits. Blood from patients P1-P5 was collected again after 11 days. Studies revealed exorbitant increase in γ-H2AX in lymphocytes and monocytes of patients P1, P4 and P5. TLC and PLT count in these patients had fallen further. Dicentrics declined with time in all the five patients. Based on the studied blood biomarkers, we conclude that the five subjects showed signs of radiation exposure. Measurement on radiation dose could not be performed in the current study; however, the generated data particularly on dicentrics provide ample evidence of radiation exposure.

Bioavailability, antioxidant and non toxic properties of a radioprotective formulation prepared from isolated compounds of Podophyllum hexandrum: a study in mouse model.

The current study was aimed to determine the stability, serum protein binding ability, biodistribution, antioxidant potential and tissue toxicity status of a novel radioprotective formulation (G-002M) from Podophyllum hexandrum. G-002M is the combination of a flavonoid, a lignan and its glucoside isolated from P. hexandrum rhizome that exhibit high radioprotective potential. Stability of G-002M tagged with 99mTc was observed in vitro and with mice serum till 24 hr of incubation. The formulation was investigated for its antioxidant status and its bioavailability and toxicity in different organs of mice. Biodistribution study of 99mTc-G-002M revealed its uptake by all the vital organs of mice. Higher absorbed dose was observed in lungs, liver, jejunum and kidney. Maximum retention of G-002M in kidney revealed that G-002M was excreted predominantly through renal route. G-002M was also observed to have high free radical scavenging and total reducing properties. Histopathological observations showed no significant alterations in tissue morphology of lungs, liver, jejunum and kidney by G-002M administration. The data conclusively demonstrate that high stability, multi organ availability, longer retention and non-toxic behavior of G-002M might help in exhibiting strong protective potential against lethal radiation.

Inhibition in radiation mediated cellular toxicity by minimizing free radical flux: one of the possible mechanisms of biological protection against lethal ionizing radiation by a sub- fraction of Podophyllum hexandrum.

The study has focused on exploring the mechanism of action of Podophyllum hexandrum sub-fraction (G-001M) exhibiting >90% protection in lethally irradiated mice. Currently, G-001M was assessed for antioxidant characteristics by evaluating DPPH, superoxide and hydrogen peroxide radical formation, anti-lipid per oxidation, metal chelation and total flavonoid content. To affirm cytoprotective efficacy of G-001M, plasmid DNA protection, blood WBC counts, marker for lipid peroxidation (MDA) and antioxidant status (GSH) in mice splenocytes and thymocytes were studied. G-001M, having high amount of total phenolic contents (200±10mg, w/w), exhibited dose dependent inhibition in DPPH and superoxide radical formation. Hydrogen peroxide radical scavenging was higher than standards. With pre-treatment of G-001M, plasmid DNA was also maximally restored to supercoiled form. Radiation modulated MDA and GSH values in splenocytes and thymocytes of mice altered significantly after 24 hrs and at later intervals, values were close to the controls. Radiation mediated losses in WBC counts were significantly regained (p<0.001) in G-001M pre-treated irradiated mice. The above findings explicitly conveyed that G-001M has successfully minimized radiation inflicted free radicals generation and their multiplication. This activity of G-001M could be undoubtedly among one of the major modes of action in extending whole body survival in lethally irradiated mice.

Modulation of gamma radiation-inflicted damage in Swiss albino mice by an alcoholic fraction of Podophyllum hexandrum rhizome.

A partially characterized extract of Podophyllum hexandrum rhizomes was studied for its radioprotective potential in mice. A major portion of the podophyllotoxin was obtained from the extract by further fractionation. Acute toxicity and maximum tolerated dose (MTD) of a single intraperitoneal dose of the extract were studied in mice to evaluate the toxicity of the extract, if any. Radioprotective efficacy was determined in terms of survival against 10 Gy whole-body irradiation (WBI), protection against 1 Gy-induced chromosomal aberration (CA), and estimation of dose reduction factor (DRF) in irradiated and extract pretreated mice. The MTD was observed to be 60 mg/kg of body weight, whereas a dose of 90 mg/kg of body weight yielded 50% death in mice within 72 hours of intraperitoneal administration of the extract. A dose range of 15-20 mg/kg of body weight administered 2 hours before 10 Gy WBI of mice yielded 66% survival, while administration of 10-15 mg/kg of body weight of the extract 1 hour before WBI yielded more than 90% survival. A DRF of 1.625 was estimated for 10 and 15 mg/kg of body weight of the extract administered 1 hour before WBI. Further studies on modulation of 1 Gy-induced CA revealed significant radioprotective efficacy of the extract in mouse bone marrow cells. Partial removal of podophyllotoxin was useful in reducing toxicity of the extract without altering its radioprotective efficacy.

Radiomodulatory and free-radical scavenging activity of the fractionated aquo-alcoholic extract of the adaptogenic nutraceutical (Rhodiola imbricata)--a comparative in vitro assessment with ascorbate.

OBJECTIVE: Immense interest has been generated in recent years for the development of drugs of herbal origin for the mitigation of deleterious effects of environmental pollutants like ionizing radiation, mainly to protect against radiation leakages resulting from mishaps in nuclear reactors, deliberate use of dirty bombs, etc. METHOD: The radio modifying effects of a fractionated extract of the high-altitude Himalayan plant species Rhodiola imbricata, along with its electron-donation potential, super-oxide ion scavenging (IC50 ≤ 0.025 mg/ml), nitric oxide (NO) scavenging potential (IC(50) = 0.5 mg/ml), and antihemolytic activity were evaluated in the present study. Reducing power, superoxide ion (O(2)(•-)), and nitric oxide scavenging ability of the fractionated extract increased in a dose-dependent manner. Rhodiola imbricata also exhibited antihemolytic potential preventing radiation-induced membrane degeneration of human erythrocytes. CONCLUSION: Thus, it can be stated that Rhodiola imbricata provides protection against gamma radiation via multifarious mechanisms that act in a synergistic manner. Rhodiola imbricata is widely used as a nutraceutical supplement in the trans-Himalayan region nations, and the current study shows that Rhodiola has immense potential for alleviation of biological damage in a radiation environment.

Protective efficacy of semi purified fraction of high altitude podophyllum hexandrum rhizomes in lethally irradiated Swiss albino mice.

A fraction of high altitude Podophyllum hexandrum rhizome, REC-2006, was evaluated for its radioprotective efficacy against lethal gamma-irradiation (10 Gy, whole body) in Swiss albino mice. The maximum tolerated dose (MTD) and LD50 of this fraction were found to be 45 mg/kg b.w. and 74 mg/kg b.w. respectively. Pre-irradiation (- 2 h, ) administration (i.p.) of 6 or 8 mg/kg b.w. of REC-2006 rendered > 90% survival in lethally irradiated mice. The dose reduction factor was calculated to be 1.62 considering survival as the end point. REC-2006 treatment marked in significant increase in endogenous spleen colony forming units. In REC-2006 treated group, super oxide dismutase activity was increased significantly compared to the radiation control group (Liver, p = 0.00, Jejunum p = 0.00). The extract also inhibited radiation induced lipid peroxidation in liver (p = 0.00) at 24 h. REC-2006 administration (100-200 microg/ml) significantly reduced the halo diameter in mice thymocytes. Nearly 10 fold difference between the effective dose (6 mg/kg b.w.) and LD50 and the high degree of whole body survival (> 90% against 10 Gy irradiation) indicates REC-2006 to be safe and highly promising to achieve significant radioprotection against lethal radiation. Further purification and identification of active molecules and their efficacy studies in higher animals therefore demand attention.

An insight into the grain auger injury problem in Queensland, Australia.

Grain auger-related injuries were studied by examining the injury data obtained from the Queensland worker's compensation database. Close to 60% of 52 claimants were male employees in the 20 to 34 age group. Fingers, hands, and arms were affected in 65% of all cases, and the auger flighting was involved in 60% of claims. The severity of auger-related injuries is reflected in the high average cost of claims and number of working days lost, which were more than double the all-industries values. Injuries involving the auger flighting are three times more costly (in time and money) than the all-industries values. More claims were made during winter and towards the end of summer, with the majority of injuries occurring in the animal industries. Most incidents occurred in the early or middle periods of a working shift. In addition, two focus group meetings were held to gain a broader perspective of the grain auger injury picture in Queensland, Australia. Focus group participants suggested that the operator's state of mind and attitude to safety are important, while the auger's age, type, and shielding were cited as important risk factors. They suggested that older augers are less likely to be adequately shielded, and mobile augers are most likely to be involved in injury events. The information gained from this study is being used to develop strategies to help farmers minimize injuries associated with the use of grain augers.

A case of human thelaziasis from Himachal Pradesh.

Small, chalky-white, threadlike, motile worms were isolated from the conjunctival sac of a 32 year-old woman residing in the Himalaya mountains. They were identified as both male and female worms of Thelazia callipaeda. To the best of our knowledge, this is the second case report of human thelaziasis from India.

Amoebic renal cyst: a case report.

Entamoeba histolytica can infect any organ of the body, but only one case of renal involvement has been reported till now in the literature. We report a rare case of amoebic renal cyst in a 78-year showing favorable outcome with metronidazole treatment and therapeutic drainage.

Investigation of an outbreak of scrub typhus in the himalayan region of India.

In Indira Gandhi Medical College, Himachal Pradesh, India, during autumn of 2003 (September-November), more than 100 cases of fever of unknown origin (FUO) were reported with 15 ensuing deaths. In addition to all routine investigations and cultures, the Weil-Felix test was incorporated for the investigation of these cases. Antigen was procured from the Central Research Institute, Kasauli. Forty-six percent (45/96) of the cases demonstrated a > or =1:80 titer of agglutinins against OXK antigen. A team from the National Institute of Communicable Diseases, New Delhi, confirmed the antibodies for scrub typhus in some of the serum samples tested for leptospirosis, dengue fever, and rickettsial infections. Twelve blood samples positive for OXK antigen were sent to the Defense Research Development Establishment, Gwalior, for polymerase chain reaction studies, but none of the samples were positive, as all of the patients were already on broad-spectrum antibiotics and had reported to our hospital after 7-10 days of fever. At our institute, the Weil-Felix test has now been rountinely introduced for the investigation of cases of FUO, and the results until April 2004 (150 cases) revealed the presence of other rickettsial infections prevalent in the region. To evaluate the epidemiology and magnitude of the problem, further prospective studies are required.

Amoebic renal cyst: a case report

Entamoeba histolytica can infect any organ of the body, but only one case of renal involvement has been reported till now in the literature. We report a rare case of amoebic renal cyst in a 78-yearshowing favorable outcome with metronidazole treatment and therapeutic drainage.

Cutaneous sporotrichosis in Himachal Pradesh, India.

During the period 1990-2002 in Himachal Pradesh, India, 103 new patients with cutaneous sporotrichosis were detected. Lymphocutaneous and fixed cutaneous varieties were the most common and seen in 49% and 43% respectively. Chronic non-specific inflammation without granuloma formation was seen in 46% skin biopsy specimens, 29% showed acute or chronic inflammation and tuberculoid granuloma formation was seen in 25%. In 32% of cases Sporothrix schenckii growth was seen on Sabouraud glucose agar. A saturated solution of potassium iodide was used as first-line treatment and in 93% patients healing of lesions occurred in 4-32 weeks (average 8.7 weeks) without significant side-effects. Itraconazole, used in 12 patients, was highly effective in recommended doses. Rapid healing was seen with higher than previously used doses of fluconazole in one patient who also had unusual exacerbation of lesional inflammation with saturated solution of potassium iodide.

Hemodynamic effects of arteriovenous fistula in end-stage renal failure.

Hemodynamic parameters using Swan Ganz catheter were studied in 17 patients with end stage renal disease. The acute effects of radiocephalic AV fistula on the hemodynamic parameters were studied at 24 hours of surgery. The chronic effects were studied in 8 of these patients at 6 weeks of arteriovenous (AV) fistula. The AV fistula matured in 3 to 4 weeks time and blood flow was sufficient for hemodialysis (400 mL/min). Patients with chronic renal failure had normal or high normal hemodynamic parameters. Six weeks after the AV fistula, the cardiac index and the stroke volume index slightly increased along with a significant increase in systolic and mean systemic arterial pressure. None of the patients had significant increase in cardiac filling pressures. Although there was some fall in systemic vascular resistance index and rise in cardiac index and stroke volume index, these changes were physically small and unlikely to put any extra hemodynamic load. Thus, AV fistula in dialysis patients is not an appreciable cause of circulatory or pulmonary congestion.

Intergeneric hybridization between Erucastrum cardaminoides and two diploid crop Brassica species.

Two intergeneric hybrids involving wild species Erucastrum cardaminoides (2 n=18, E(cd) E(cd)) and two crop brassica species, Brassica rapa (2 n=20, AA) and B. nigra (2 n=16, BB), were synthesized through in vitro sequential ovary culture. Morphological, molecular and cytological studies were conducted to establish their hybridity. Both hybrids, though morphologically distinct, were intermediate phenotypically between their respective parents. Cytological analysis of the E. cardaminoides x B. rapa hybrid (2 n=19), revealed the occurrence of 17 I+1 II at diakinesis/metaphase in the majority (28%) of the pollen mother cells (PMCs), whereas in E. cardaminoides x B. nigra hybrid (2 n=17), 13 I+2 II was the predominant (32%) meiotic configuration. A maximum of 5 II was recorded in both hybrids, indicating homoeologous pairing in the respective combined genomes. Chromosome doubling by colchicine application gave rise to two new amphiploids (AA E(cd)E(cd) and BB E(cd)E(cd)) having normal chromosome pairing and pollen fertility. The occasional occurrence of one quadrivalent in the amphiploids confirmed partial homoeology between the E(c) and A/B genomes. The E. cardaminoides x B. nigra hybrid and amphiploid appeared to be tolerant to alternaria blight under field conditions.