Diagnoses and management of adult cough: An Indian Environmental Medical Association (EMA) position paper.

BACKGROUND: Cough is a common yet distressing symptom that results in significant health care costs from outpatient visits and related consultations. OBJECTIVE: The understanding of the pathobiology of cough in recent times has undergone an evolution with Cough hypersensitivity syndrome (CHS) being suggested in most cases of dry cough. However, in the case of productive cough, ancillary mechanisms including impaired Mucociliary clearance, in addition to hypermucosecretory bronchospastic conditions of Smoker's cough, asthma-COPD overlap, bronchiectasis, and allergic bronchopulmonary aspergillosis, need to be critically addressed while optimizing patient care with symptomatic therapy in outpatient settings of India. METHODS: In this review, evidence-based graded recommendations on use of antitussives - & protussives as a Position Paper were developed based on the Level and Quality of Scientific evidence as per Agency for Health Care and Quality (AHRQ) criteria listing and Expert opinions offered by a multidisciplinary EMA panel in India. RESULTS: Management of acute or chronic cough involves addressing common issues of environmental exposures and patient concerns before instituting supportive therapy with antitussives or bronchodilatory cough formulations containing mucoactives, anti-inflammatory, or short-acting beta-2 agonist agents. CONCLUSION: The analyses provides a real world approach to the management of acute or chronic cough in various clinical conditions with pro- or antitussive agents while avoiding their misuse in empirical settings.

Prevalence & pattern of respiratory diseases including Tuberculosis in elderly in Ghaziabad - Delhi - NCR.

Elderly population is continuously increasing all over the world including India. Old age is associated with significant prevalence of chronic illnesses. Population based study to find prevalence & pattern of respiratory diseases in elderly in India is difficult to find. Present study was done in an urban locality of Ghaziabad inhabited mainly by low socio - economic status population. Two part questionnaire was used as main tool. Through part one 1522 elderly were screened for respiratory disease. Respiratory disease was confirmed & diagnosed by part two of questionnaire, physical examination & necessary investigations. Prevalence of respiratory diseases was 18.8% in this study. Prevalence of respiratory diseases was almost double in elderly males as compared to females. COPD was most prevalent respiratory disease followed by Bronchial asthma.

Autologous stem cell transplantation for multiple myeloma: Long-term results.

BACKGROUND: Survival of myeloma patients has improved considerably in the past decade. However, limited data are available on their long-term outcome. We analysed the data of 225 consecutive patients who underwent autologous stem cell transplantation (ASCT) at our centre. METHODS: Between April 1990 and December 2013, a total of 225 patients with multiple myeloma (median age 53 years, range 27-67 years, 69.3% men) underwent ASCT. High-dose melphalan 200 mg/m2 was used for conditioning. Before transplant, the patients received induction therapy with novel agents (thalidomide and dexamethasone, or lenalidomide and dexamethasone, or bortezomib and dexamethasone); or vincristine, doxorubicin, dexamethasone; or alkylating agents (vincristine, melphalan, cyclophosphamide and prednisolone; or melphalan and prednisolone). The response to transplant was evaluated using the European Bone Marrow Transplant criteria, and an intention-to-treat analysis was done. RESULTS: Four-fifths (79.6%) of our patients had Durie Salmon Stage (DSS) IIIA and nearly a quarter (24%) of them had International Stage III disease. Before the transplant, 80.4% of patients had chemosensitive disease. The median interval from diagnosis to transplant was 10 months (range 2-128 months). Following ASCT, 197 (87.5%) patients responded. Complete response was obtained in 54.7%, very good partial response in 19% and partial response in 13.8%. At a median follow-up of 90 months (range 18-266 months), the median progression-free survival (PFS) and overall survival (OS) were 32 and 85.5 months, respectively. The estimated PFS and OS at 10 years were 29.7% and 43.6%, respectively. On multivariate analysis, the presence of extramedullary disease (HR 3.05, p < 0.001), and ISS III (HR 0.50, p < 0.02) predicted inferior OS. Extramedullary disease at diagnosis (HR 1.585, p < 0.03), and more than one regimen pre- transplant (HR 0.53, p < 0.02) predicted an inferior PFS. Complete response was a predictor of superior OS and PFS (p < 0.001). CONCLUSION: Complete response following ASCT is associated with good long-term outcome. Alternative treatment strategies are needed to improve results in patients who fail to achieve CR post-transplant and in those with high-risk disease.

Ethno-botanical study of medicinal plants of Paddar Valley of Jammu and Kashmir, India.

The Paddar Valley, historically known as Sapphire Valley situated in Kishtwar district, is a prime landmark in the Jammu region of J&K state and is known for its rich cultural and plant diversity because of diverse habitats such as rivers, streams, meadows and steep mountain slopes. The area is located in the dry temperate region comprising typical vegetation which disappears completely on the eastern slopes, dominated by a variety of economical species which play an important role in the rural life. The inhabitants are dependent on plant resources for food, fuel, timber, shelter, fodder/forage, household articles and traditional medicines in treating diseases like malaria, cancer, gastro-intestinal ailments, etc. This paper deals with the observations on traditional therapeutic application by the inhabitants of Paddar Valley. The ethno-botanical information on medicinal plants would not only be useful in conservation of traditional cultures and biodiversity but also community health care and drug development. Exploration survey in Paddar Valley has revealed that people collect and sell these medicinal species through local intermediaries / contractors to earn their livelihood. But the scientific cultivation and appropriate post-harvest management would improve employment opportunity and income of local farmers in the region.

Influence of phenolic compounds of Kangra tea [Camellia sinensis (L) O Kuntze] on bacterial pathogens and indigenous bacterial probiotics of Western Himalayas

Phenolic compounds of nutraceutical importance viz., catechins (C), (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG) were estimated in fresh green tea shoots of Camellia sinensis (L) O Kuntze cultivar. The total polyphenols and total catechins were in the range of 219.90 to 317.81 and 140.83 to 271.39 g/kg, respectively in monthly samples of tea. The values of C, EC, EGC, EGCG and ECG in tea powders as analyzed through high performance liquid chromatography (HPLC) were in the range of 1.560 to 3.661, 13.338 to 27.766, 26.515 to 39.597, 62.903 to 102.168 and 18.969 to 39.469 mg/g, respectively. Effect of tea extracts and standard flavanols against five pathogenic bacteria viz., Listeria monocytogenes (MTCC-839), Pseudomonas aeruginosa (MTCC-741), Bacillus cereus (MTCC-1272), Staphylococcus aureus (MTCC-96) and Escherichia coli (MTCC-443), and eleven indigenous potential bacterial probiotics belonging to genera Enterococcus, Bacillus and Lactobacillus spp. obtained from fermented foods of Western Himalayas, was investigated. EGCG, ECG and EGC exhibited antibacterial activity but, C and EC did not show this activity. Tea extracts having high concentrations of EGCG and ECG were more potent in antibacterial action against bacterial pathogens. Tea extracts and standard flavan-3-ols augmented viability of potential probiotics in an order of EGCG > EGC > ECG > EC > C. Tea extracts and standard flavanols had no antibacterial activity against Escherichia coli (MTCC-443) but, in combination with probiotic culture supernatants, this activity was seen. The Kangra tea thus, exerts antibacterial effect on bacterial pathogens through EGCG, ECG and EGC constituents while stimulatory effect on growth of indigenous potential probiotics.

Imaging depiction of retrograde jejunogastric intussusception.

Retrograde jejunogastric intussusception is an unusual long term complication of gastro-jejunostomy or Billroth-II reconstruction. Acute and chronic forms have been well recognised with the acute form being fatal without timely surgical intervention. The imaging findings are diagnostic, and an established emergency imaging protocol would be very useful for clinical decision making, as the clinical features are usually ambiguous. We present the systematic imaging description in a case of retrograde (type II) jejunogastric intussusception with strangulation following gastric bypass procedure.

Influence of phenolic compounds of Kangra tea [Camellia sinensis (L) O Kuntze] on bacterial pathogens and indigenous bacterial probiotics of Western Himalayas.

Phenolic compounds of nutraceutical importance viz., catechins (C), (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG) were estimated in fresh green tea shoots of Camellia sinensis (L) O Kuntze cultivar. The total polyphenols and total catechins were in the range of 219.90 to 317.81 and 140.83 to 271.39 g/kg, respectively in monthly samples of tea. The values of C, EC, EGC, EGCG and ECG in tea powders as analyzed through high performance liquid chromatography (HPLC) were in the range of 1.560 to 3.661, 13.338 to 27.766, 26.515 to 39.597, 62.903 to 102.168 and 18.969 to 39.469 mg/g, respectively. Effect of tea extracts and standard flavanols against five pathogenic bacteria viz., Listeria monocytogenes (MTCC-839), Pseudomonas aeruginosa (MTCC-741), Bacillus cereus (MTCC-1272), Staphylococcus aureus (MTCC-96) and Escherichia coli (MTCC-443), and eleven indigenous potential bacterial probiotics belonging to genera Enterococcus, Bacillus and Lactobacillus spp. obtained from fermented foods of Western Himalayas, was investigated. EGCG, ECG and EGC exhibited antibacterial activity but, C and EC did not show this activity. Tea extracts having high concentrations of EGCG and ECG were more potent in antibacterial action against bacterial pathogens. Tea extracts and standard flavan-3-ols augmented viability of potential probiotics in an order of EGCG > EGC > ECG > EC > C. Tea extracts and standard flavanols had no antibacterial activity against Escherichia coli (MTCC-443) but, in combination with probiotic culture supernatants, this activity was seen. The Kangra tea thus, exerts antibacterial effect on bacterial pathogens through EGCG, ECG and EGC constituents while stimulatory effect on growth of indigenous potential probiotics.

The high prevalence of chronic kidney disease-mineral bone disorders: A hospital-based cross-sectional study.

Mineral bone disorder (MBD) is an important complication of chronic kidney disease (CKD). However, there are limited data on the pattern of MBD in Indian CKD population. The aim of this study was to describe spectrum of MBD in patients with CKD in our center. This was a hospital-based cross-sectional observational study. Patients with stage 4 and 5 CKD were included in this study. Those receiving calcium supplement, vitamin D or its analogues, and calcimimetic were excluded. Serum/plasma levels of creatinine, albumin, calcium, phosphate, total alkaline phosphatase (TAP), intact parathormone (iPTH), and 25-OH vitaminD (25-vitD) were measured. Radiological survey of bones was carried out in all cases, and echocardiography done in selected patients. Statistical analysis was done using Sigmaplot 10.0 software. A total of 150 patients (114 males, 36 females) were included in this study. Mean age was 45.67±16.96 years. CKD stage 4 and 5D were found in 26% (n=39) and 74% (n=111) of study population, respectively. The most common underlying native kidney diseases in patients of CKD 4 and 5D were diabetic nephropathy (41.03%) and CGN (41.44%), respectively. Median (first quartile, third quartile) values for serum levels of corrected calcium (cCa), phosphate, cCaXPO4 product, TAP, plasma iPTH, and 25-vitD in stage 4 CKD were 8.36 (7.79, 8.91) mg/dL, 4.9 (3.92, 6.4) mg/dL, 41.11 (34.01, 53.81) mg(2)/dL(2), 97 (76.5, 184.25) IU/L, 231 (124.5, 430.75) pg/mL, and 12 (6.98, 23.55) ng/mL, respectively; and in stage 5D CKD were 8.36 (7.66, 8.95) mg/dL, 5.7 (4.23, 6.95) mg/dL, 46.5 (37.16, 54.47) mg(2)/dL(2), 180 (114.5, 276.25) IU/L, 288 (169.75, 625.0) pg/mL, and 18.4 (10.0, 26.4) ng/mL, respectively. Prevalence of hypocalcemia (56.41% vs. 54.95%), hyperphosphatemia (64.10% vs. 70.27%), and hyperparathyroidism (84.62% vs. 88.29%) was not different between patients with CKD 4 and 5D. However, iPTH level outside the target range and increased TAP level were significantly (P<0.001) more common in CKD stage 5D. Multiple logistic regression analysis for hyperparathyroidism revealed significant inverse correlation with cCa in CKD 5D. There were no significant differences in vitamin D status and prevalence of valvular calcification between CKD stage 4 and 5D. X-ray revealed renal osteodystrophy in 8 (5.33%) patients, while it was normal in 118 (78.67%) patients. Secondary hyperparathyroidism, hyperphosphatemia, hypocalcemia, increased TAP, and 25-OH vitamin D deficiency and insufficiency were quite common in CKD 4 and 5 patients. The commonest type of MBD in CKD 4 and 5D was secondary hyperparathyroidism.

Membrane proteins in four acts: function precedes structure determination.

Studies on four membrane protein systems, which combine information derived from crystal structures and biophysical studies have emphasized, as a precursor to crystallization, demonstration of functional activity. These assays have relied on sensitive spectrophotometric, electrophysiological, and microbiological assays of activity to select purification procedures that lead to functional complexes and with greater likelihood to successful crystallization: (I), Hetero-oligomeric proteins involved in electron transport/proton translocation. (1) Crystal structures of the eight subunit hetero-oligomeric trans-membrane dimeric cytochrome b(6)f complex were obtained from cyanobacteria using a protocol that allowed an analysis of the structure and function of internal lipids at specific intra-membrane, intra-protein sites. Proteolysis and monomerization that inactivated the complex and prevented crystallization was minimized through the use of filamentous cyanobacterial strains that seem to have a different set of membrane-active proteases. (2) An NADPH-quinone oxido-reductase isolated from cyanobacteria contains an expanded set of 17 monotopic and polytopic hetero-subunits. (II) ß-Barrel outer membrane proteins (OMPs). High resolution structures of the vitamin B(12) binding protein, BtuB, solved in meso and in surfo, provide the best example of the differences in such structures that were anticipated in the first application of the lipid cubic phase to membrane proteins [1]. A structure of the complex of BtuB with the colicin E3 and E2 receptor binding domain established a "fishing pole" model for outer membrane receptor function in cellular import of nuclease colicins. (III) A modified faster purification procedure contributed to significantly improved resolution (1.83Å) of the universal porin, OmpF, the first membrane protein for which meaningful 3D crystals have been obtained [2]. A crystal structure of the N-terminal translocation domain of colicin E3 complexed to OmpF established the role of OmpF as an import channel for colicin nuclease cytotoxins. (IV) α-Synuclein, associated with the etiology of Parkinson's Disease, is an example of a protein, which is soluble and disordered in solution, but which can assume an ordered predominantly α-helical conformation upon binding to membranes. When subjected in its membrane-bound form to a trans-membrane electrical potential, α-synuclein can form voltage-gated ion channels. Summary of methods to assay functions/activities: (i) sensitive spectrophotometric assay to measure electron transfer activities; (ii) hydrophobic chromatography to deplete lipids, allowing reconstitution with specific lipids for studies on lipid-protein interactions; (iii) microbiological screen to assay high affinity binding of colicin receptor domains to Escherichia coli outer membrane receptors; (iv) electrophysiology/channel analysis (a) to select channel-occluding ligands for co-crystallization with ion channels of OmpF, and (b) to provide a unique description of voltage-gated ion channels of α-synuclein.

Analysis of 3'-Terminal Region of Bean common mosaic virus Strains Infecting Common Bean in India.

Four strains (NL-1, NL-1n, NL-7 and NL-7n) of Bean common mosaic virus (BCMV) prevalent on common bean (Phaseolus vulgaris) in Himachal Pradesh, a north-western Himalayan state of India were compared at the 3' terminal region of the viral genome to elucidate variation and relationship among these strains. 3' terminal region comprising of partial nuclear inclusion b (NIb) (171-233 bp), complete coat protein (CP) (860 bp) and 3' untranslated region (UTR) (208-244 bp) shared 96-98% nucleotide and 96-99% amino acids identity among various strains of BCMV. Multiple alignment as well as cluster dendrograms of the 3' terminal region placed the test isolates in BCMV species of genus Potyvirus. Phylogenetic analysis of complete CP as well as 3' UTR also showed Indian strains to be distinct strains. Sequence homology, multiple alignment and evolutionary divergence of 3' terminal region could not differentiate the pathogenic strain groups, thereby establishing least role of this region in strain characterization of the virus. Comparisons of CP and 3' UTR region of BCMV strains and other members of genus Potyvirus clearly indicated the little utility of 3' terminal region in distinction of virus strains. Implications of coat protein region in viral strain distinction are also discussed.

First Report on Association of Colletotrichum coccodes with Chili Anthracnose in India.

Chili (Capsicum annuum L.) is an important condiment and cash crop grown throughout India, including Andhra Pradesh, Karnataka, Maharashtra, Punjab, Tamilnadu, and Himachal Pradesh. In Himachal Pradesh (HP), a northwestern Himalayan state of India, chilies including sweet pepper occupy an area of 2,447 ha with total production of approximately 31,810 t and productivity of 13.00 t per hectare. In 2007 and 2008, chili- and sweet pepper-growing areas of HP were surveyed for the prevalence of fruit rot/anthracnose disease caused by a complex of Colletotrichum species. Fields infested with disease were randomly sampled and four samples from each location were collected. Disease incidence ranged from 12.5 to 45.0% based on total plants assessed in the field. Symptoms of disease in the field included light brown, sunken lesions containing salmon-colored masses of conidia and microsclerotia on the fruit. Microscopic examination of the diseased samples revealed a variation in morphology of spores from two isolates (Cc 70 and Cc 74) collected from two locations in HP, the Kotkhai area of district Shimla and Shamsher (Ani) locality of district Kullu. Five fruits and ten leaves from five plants of a susceptible local variety were inoculated with a suspension of 5 × 105 conidia/ml of isolates Cc70 and Cc74 using a pin prick method as described by Montri et al. (2). The inoculated fruits and leaves were kept in humid chambers at 25 ± 1°C with 12 h of light. After 48 h, the fruits and leaves were observed daily for the appearance of disease symptoms. Disease symptoms were similar to those of natural infections but with darker lesions. The fungus was recovered from infected fruit on Mathur's medium (glucose 2.80 g, peptone 2.00 g, magnesium sulfate hydrated 1.72 g, potassium dihydrogen orthophosphate 1.23 g, and agar 1.50 g/liter) and initially produced white-to-gray mycelia that became dark brown with age. Setae were present along with production of microsclerotia by the tenth day of culturing. A daily average growth of 8.1 mm was recorded on potato dextrose agar at 25 ± 1°C. Conidia were hyaline, unicellular, aseptate, and fusiform abruptly tapering to each end, and 15.5 to 19.6 µm long and 4.2 to 5.3 µm wide. The fungus was identified as Colletotrichum coccodes based on morphological and cultural traits as per the descriptions of Junior et al. (1). The identity of the isolates was confirmed by amplifying the internal transcribed spacer (ITS) region using primer pair ITS1 and ITS4 (3). The sequences (550 bp) were subjected to a BLAST search with the isolates showing the highest identity to GenBank Accession Nos. GU935878 and EF017205. The sequences have been submitted to GenBank (Accession Nos. HQ264175 and HQ264176). Very few reports exist about the natural occurrence of C. coccodes on Capsicum spp. around the world. To our knowledge, this current report constitutes the first record of this pathogen on Capsicum spp. from the Indian subcontinent. References: (1). H. J. T. Junior et al. Summa Phytopathol. Botucatu 33:418, 2007. (2). P Montri et al. Plant Dis. 93:17, 2009. (3) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, 1990.

Fahr's syndrome: report of two cases.

Two cases (one female and one male) of Fahr's syndrome are reported here. Both of them had neuropsychiatric disturbances and intracranial calcifications in bilateral basal ganglia and cerebral hemispheres. CT scan helped in establishing the diagnosis. Both of them were treated with antipsychotic drugs and responded to some extent.

Sarcoidosis: a rare cause of Kleine-Levine-Critchley syndrome.

Hypothalamic sarcoidosis is a rare entity that can alter the hypothalamic-pituitary axis and induce various combinations of endocrine changes. We present a case of neurosarcoidosis with uncommon features of hypersomnolense and hyperphagia. Current strategies to increase awareness and prevention of the harmful effects of obesity require clinicians to be cognizant of potential disorders that produce these features The mechanism, differential diagnosis and therapeutic options of this organic etiology are reviewed.

A historical sketch; life and time of Jonathan Hutchinson (1828-1913), the first sarcoidologist.

In the years preceding and following the turn of the 19th century several publications appeared independently that drew attention to what is now regarded as sarcoidosis. The first recorded and illustrated example is attributed to Jonathan Hutchinson of London. It appeared in Illustrations of Clinical Surgery (1877).