52 results on '"K. K. Gandhi"'
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2. Acrosome damage and enzyme leakage of goat spermatozoa during dilution, cooling and freezing
- Author
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M. S. Chauhan, S. R. Anand, K. K. Gandhi, and Rajeev Kapila
- Subjects
Male ,food.ingredient ,Urology ,Acid Phosphatase ,Semen ,Biology ,Giemsa stain ,Cryopreservation ,Andrology ,fluids and secretions ,Endocrinology ,food ,Yolk ,Animals ,Aspartate Aminotransferases ,Acrosome ,4-Nitrophenylphosphatase ,urogenital system ,Goats ,Acid phosphatase ,Alanine Transaminase ,General Medicine ,Alkaline Phosphatase ,Spermatozoa ,Sperm ,Microscopy, Electron, Scanning ,biology.protein ,Alkaline phosphatase ,Semen Preservation - Abstract
Semen of Jamunapari goat bucks was frozen in three diluents egg yolk-tris, egg yolk/citrate/glucose, and skim milk/egg yolk. In fresh ejaculated semen over 90% of the spermatozoa had normal head and acrosome morphology. Quantification of goat sperm structure with Giemsa stain revealed significant (P < 0.01) damage to acrosome on freezing which varied between 38 to 43% in three diluents. Scanning electron microscopy defined and revealed greater damage during freezing with 50% sperm heads having normal acrosome structure in three diluents. The ultrastructural changes detected in frozen goat sperm was protrusion at the anterior cap, broken tail, swelling of acrosome, and loss of acrosomal contents. The leakage of five enzymes GOT, GPT, hyaluronoglucosaminidase, acid phosphatase, and alkaline phosphatase measured simultaneously revealed a positive correlation between enzyme release and acrosomal damage.
- Published
- 2009
3. Isolation and partial characterisation of the plasma and outer acrosomal membranes of goat spermatozoa
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P.R. Somanath and K. K. Gandhi
- Subjects
Membrane ,Food Animals ,Biochemistry ,Capacitation ,Vesicle ,Organelle ,Acrosome reaction ,Animal Science and Zoology ,Biology ,Acrosome ,Acrosin ,Sperm - Abstract
In order to achieve successful fertilization, the essential steps include maturation, species-specific binding and fusion of gametes followed by activation of the ovum. Implicit in this are a variety of molecular events, the most important among them being the receptor–ligand interaction. A protocol is described to isolate highly enriched fractions of goat sperm plasma and the outer acrosomal membranes and present data on the ultrastructure and enzyme assays of these membrane domains. The sperm, washed with 1.3 M sucrose sedimentation, was sonicated and subjected to discontinuous sucrose density gradient centrifugation, which allowed the separation of isolated plasma and the outer acrosomal membranes in a single step. While the isolated plasma membranes formed vesicles, the cap shaped acrosomal segments retained its characteristic morphology, as was seen in the ultrastructure. The plasma membrane fraction was relatively pure and free of any contamination of other cell organelles. The matrix associated with the isolated acrosomal membranes gave it a relatively higher density and a crescent shape. Enzyme assays showed high alkaline phosphatase activity in the plasma membrane fraction, with low activity of the acrosome bound enzymes. The acrosomal fraction had a higher specific activity of acrosin and hyaluronidase and a low alkaline phosphatase activity. Suggesting that both the membranes were pure. Membranes, thus purified could be used as initial material for elucidating the lipid as well as the antigenic composition and in understanding the mechanism involved in capacitation, gametic interaction and acrosome reaction, which eventually lead to fertilization.
- Published
- 2004
4. Role of Calcium and Calcium Channels in Progesterone Induced Acrosome Reaction in Caprine Spermatozoa
- Author
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K. K. Gandhi and P. R. Somanath
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medicine.medical_specialty ,Voltage-gated ion channel ,Fura-2 ,Nigericin ,Voltage-dependent calcium channel ,Acrosome reaction ,Sperm ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Capacitation ,Internal medicine ,medicine ,Biophysics ,Animal Science and Zoology ,Intracellular ,Food Science - Abstract
There are several physiological and pharmacological evidences indicating that opening of voltage dependent Ca 2+ channels play a critical role in induction of acrosome reaction in mammalian sperm. We determined the intracellular free Ca 2+ concentration in ejaculated goat sperm using a fluorescent, Ca 2+ -specific probe, Fura2/AM, after the suspension of sperm in KRB medium, capable of sustaining capacitation and the acrosome reaction. We used nifedipine, D-600 and diltiazem, the Ca 2+ channel antagonists belonging to the classes of dihydropyridines, phenylalkylamines and benzothiazepines, to investigate the possibility that L-type voltage gated Ca 2+ channels play a role in the progesterone-stimulated exocytotic response. Progesterone promoted a rise in intracellular Ca 2+ in goat sperm and addition of nifedipine (100 nM) just prior to progesterone induction, significantly inhibited both intracellular Ca 2+ rise and exocytosis suggesting that Ca 2+ channels are involved in the process. However, the intracellular Ca 2+ increase during the process of capacitation was not affected with the addition of nifedipine suggesting a role of focal channel for Ca 2+ during capacitation. Studies using monensin and nigericin, two monovalent cation ionophores showed that an influx of Na + also may play a role in the opening of Ca 2+ channels. These results strongly suggests that the entry of Ca 2+ channels with characteristics similar to those of L-type, voltage-sensitive Ca 2+ channels found in cardiac and skeletal muscle, is a crucial step in the sequence of events leading to progesterone induced acrosome reaction in goat sperm. (Asian-Aust. J. Anim. Sci. 2002. Vol 15, No. 7 : 949-956)
- Published
- 2002
5. Role of Diacyl Glycerol (DAG) in Caprine Sperm Acrosomal Exocytosis Induced by Progesterone
- Author
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P. R. Somanath and K. K. Gandhi
- Subjects
Phospholipase C ,biology ,urogenital system ,Chemistry ,Acrosome reaction ,Phosphatidic acid ,Sperm ,Exocytosis ,chemistry.chemical_compound ,Gq alpha subunit ,Biochemistry ,biology.protein ,Glycerol ,lipids (amino acids, peptides, and proteins) ,Animal Science and Zoology ,Receptor ,Food Science - Abstract
Capacitated goat spermatozoa generated diacyl glycerol (DAG) when suspended in Krebs-Ringer bicarbonate medium and induced by progesterone or Ca 2+ ionophore A23187. We have added Sn-1-oleoyl-2-acetyl glycerol externally, to study the effect of DAG in goat sperm acrosomal exocytosis. Addition of neomycin abolished the DAG generating capacity of progesterone in a dose dependent manner, suggesting the involvement of a phosphoinositidase C activated phospholipase C system in the process. The level of increase in phosphatidic acid was considerably low and was produced well after the DAG generation thereby suggesting the involvement of a DAG kinase which phosphorylates DAG to produce PA. The inhibition of progesterone mediated effect by inhibitors of GABAA/Cl - channel and Ca 2+ channels further supports the evidence that the events of binding of agonist to the receptor(s), opening of Ca 2+ channels and the activation of phospholipase C are reconciled to perform the function of acrosome reaction in capacitated goat spermatozoa. (Asian-Aust. J. Anim. Sci. 2002. Vol 15, No. 8 : 1091-1097)
- Published
- 2002
6. Inhibition of goat sperm-zona binding by monoclonal antibodies to a glycoprotein family (ZP4) of porcine zona pellucida
- Author
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Gautam Kaul and K. K. Gandhi
- Subjects
Antiserum ,chemistry.chemical_classification ,endocrine system ,Porcine zona pellucida ,urogenital system ,medicine.drug_class ,Biology ,Monoclonal antibody ,medicine.disease_cause ,Cross-reactivity ,Molecular biology ,Staining ,medicine.anatomical_structure ,Food Animals ,Antigen ,chemistry ,embryonic structures ,medicine ,Animal Science and Zoology ,Zona pellucida ,Glycoprotein ,reproductive and urinary physiology - Abstract
The zona pellucida (ZP) in a majority of species consists of three antigenic families with wide inter species cross reactivity. The glocoproteins of heat solubilized goat zona pellucida (gZP) were isolated into three families by high performance liquid chromatography on a gel filtration column. Their molecular identities were 180, 95 and 75 kDa for gZP1, gZP2 and gZP3 respectively. However under reducing conditions, four zona pellucida fractions of 135, 95, 75 and 42 kDa were observed. The monoclonal antisera Mab-5H4 against porcine ZP4 (a 23 kDa glycoprotein) easily recognized the 180 and 42 kDa gZP fractions. It was also found that the 5H4 antisera strongly inhibited homologous goat sperm-zona binding. Finally, using immunofluorescent staining the goat occytes reacted positively with the 5H4 antisera. The fluorescence was uniform at 1 : 10 antisera dilution but tended to fade at higher dilution’s. Results suggest that the gZP has an antigen epitope correlative to the 5H4 antisera which is involved in sperm-zona interaction and could be a good candidate for the development of a contraceptive vaccine. # 2000 Elsevier Science B.V. All rights reserved.
- Published
- 2000
7. Characteristics and smoking cessation outcomes of patients returning for repeat tobacco dependence treatment
- Author
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E S, Han, J, Foulds, M B, Steinberg, K K, Gandhi, B, West, D L, Richardson, S, Zelenetz, and J, Dasika
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Adult ,Counseling ,Male ,Tobacco Use Disorder ,Middle Aged ,Cohort Studies ,Psychotherapy ,Treatment Outcome ,Recurrence ,Retreatment ,Humans ,Female ,Smoking Cessation ,Aged ,Retrospective Studies - Abstract
Previous studies of tobacco dependence treatment have reported very low cessation rates among smokers who relapse and return to make a subsequent formal attempt to quit. This retrospective cohort study examined 1745 patients who attended a tobacco dependence clinic between 2001 and 2005, and the characteristics and outcomes of those who relapsed and returned for repeat treatment. Patients who returned for repeat treatment showed higher markers of nicotine dependence and were more likely to have a history of treatment for mental health problems than patients who attended the clinic for only one treatment episode. Among patients who relapsed and returned for repeat treatment, the 26-week abstinence rates were similar for each consecutive quit attempt (23%, 22% and 20%). Clinicians should encourage smokers who relapse after an initial treatment episode to return for treatment, and repeat treatment should focus on addressing high nicotine dependence and potentially co-occurring mental health problems in order to improve cessation outcomes.
- Published
- 2006
8. Antigens of goat spermatozoa that recognize homologous zona pellucida
- Author
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Gaurav Sharma, B. Singh, K. K. Gandhi, and Gautam Kaul
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Male ,endocrine system ,Size-exclusion chromatography ,Endocrinology ,Antigen ,medicine ,Animals ,Antigens ,Zona pellucida ,reproductive and urinary physiology ,Chromatography, High Pressure Liquid ,Zona Pellucida ,Antiserum ,biology ,urogenital system ,Vesicle ,Acrosome Reaction ,Goats ,Fast protein liquid chromatography ,Molecular biology ,Sperm ,Spermatozoa ,medicine.anatomical_structure ,biology.protein ,Animal Science and Zoology ,Female ,Antibody ,Biotechnology ,Protein Binding - Abstract
Contents Goat sperm surface proteins obtained from purified plasma membrane (PPM) vesicles (purity of membrane checked by marker enzymes and transmission electron microscopy) were size fractionated on an fast protein liquid chromatography (FPLC) gel filtration column. All the seven surface proteins (129, 100, 46, 28, 27, 18 and 10 kDa) obtained were further fractionated and purified on high-efficiency gel filtration (GFC-HPLC) as well as ion exchange (DEAE-HPLC) columns. Antibodies were generated against the PPM and the protein fractions. Such resolved and purified surface antigens were tested by Dot Blot Immunoassay and homologous in vitro sperm–zona binding assays. It was revealed that the binding of goat spermatozoa to homologous zona pellucida was inhibited by antisera raised against the five lower molecular weight surface antigens. Further, the components of FPLC-AIII (46 kDa; A represents antigenic protein) and IV (28 kDa) were most promising as the antibodies against these fractions inhibited sperm binding to zona pellucida even at a dilution of 1 : 1000 as tested by the sperm–zona binding assays.
- Published
- 2005
9. Expression of membrane associated non-genomic progesterone receptor(s) in caprine spermatozoa
- Author
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P.R Somanath and K. K. Gandhi
- Subjects
Male ,medicine.medical_specialty ,Acrosome reaction ,Population ,Biology ,Binding, Competitive ,Endocrinology ,Food Animals ,Capacitation ,Cell surface receptor ,Internal medicine ,Progesterone receptor ,medicine ,Animals ,Receptor ,education ,Acrosome ,Egtazic Acid ,Progesterone ,gamma-Aminobutyric Acid ,Chelating Agents ,education.field_of_study ,urogenital system ,Acrosome Reaction ,Goats ,Cell Membrane ,General Medicine ,Flow Cytometry ,Sperm ,Spermatozoa ,Cell biology ,Animal Science and Zoology ,Receptors, Progesterone ,Sperm Capacitation - Abstract
Mammalian spermatozoa have been used recently to model the study of rapid, non-genomic effects of progesterone on cell. Our study used progesterone–BSA–fluorescein isothiocyanate conjugate to indicate the presence of a progesterone receptor on the surface of >90% of a goat sperm population. The sperm possessed the receptor at 0 h and capacitation had no modulating effect on the number of sperm responsive to P–BSA–FITC. Although a decrease in receptor bearing cells was observed during the course of capacitation, the effect may have been due to the induction of acrosome reaction (AR) by the conjugate. This decrease was blocked by the pre-treatment of the spermatozoa with EGTA. Binding of conjugate occurred at the apical portion of the acrosome and at the post-acrosomal region in all the sperm, possibly mediating sperm functions other than the acrosome reaction. The P–BSA–FITC treated cells showed a single peak in a flow cytometer suggesting that the sperm population was homogeneous. Competition studies with free progesterone and GABA with P–BSA–FITC confirmed that the binding was specific and that progesterone mediated its action via a GABA A /Cl − channel complex akin to the one present in neuronal cells.
- Published
- 2002
10. Capacitation and acrosome reaction in buffalo bull spermatozoa assessed by chlortetracycline and Pisum sativum agglutinin fluorescence assay
- Author
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Gautam Kaul, K. K. Gandhi, B. Singh, and Gaurav Sharma
- Subjects
Male ,Buffaloes ,Acrosome reaction ,chemistry.chemical_element ,Calcium ,Biology ,Giemsa stain ,Andrology ,chemistry.chemical_compound ,Agglutinin ,Food Animals ,Capacitation ,Animals ,Small Animals ,Acrosome ,Egtazic Acid ,Calcimycin ,Chelating Agents ,Fluorescent Dyes ,Ionophores ,Equine ,Acrosome Reaction ,Peas ,Sperm ,Spermatozoa ,EGTA ,Kinetics ,Microscopy, Electron ,chemistry ,Microscopy, Fluorescence ,Immunology ,Animal Science and Zoology ,Sperm Capacitation ,Fluorescein-5-isothiocyanate ,Chlortetracycline - Abstract
Studies on buffalo sperm capacitation have been limited because of the non-availability of a direct assay system. We describe two methods for detecting the acrosomal status of buffalo spermatozoa, namely chlortetracycline (CTC) fluorescence assay and Pisum sativum agglutinin (FITC-PSA) stain. We also test them under various treatment regimens and simultaneously standardize and calibrate them with transmission electron microscopy. An initial comparison of three physiological media, such as Krebs-Ringer bicarbonate buffer, Tyrode solution and Brackett & Oliphant medium (having different calcium concentrations and osmolality) used for studying the capacitation of buffalo spermatozoa and assessed by CTC, FITC-PSA, Giemsa stain and TEM, revealed Brackett & Oliphant medium to be marginally better than the other two media. When stained with chlortetracycline, three distinct fluorescent patterns were visible in buffalo spermatozoa under capacitating conditions. These were 'F' with fluorescence in the post acrosomal region characteristic of uncapacitated acrosome-intact cells; 'B' with fluorescence on the anterior portion of the sperm head and a dark band in the post-acrosomal region, characteristic of capacitated, acrosome intact cells and 'AR' with a fluorescent band on the posterior portion of the head, characteristic of acrosome-reacted cells. The FITC-PSA intensely labels the acrosomal region of acrosome intact buffalo sperm. Acrosome reacted sperms had diminished acrosomal labelling by both the probes used. Buffalo spermatozoa was not capacitated when calcium was either omitted from the medium or chelated with EGTA. In the presence of Ca2+ ionophore, A23187, 68% at 4 h and 85% at 8 h completed the acrosome reaction. Time course studies revealed a 4 h incubation period at 1.71 mM Ca2+ concentration to be necessary before transformation of 'F' to 'B' cells could take place. Spontaneous acrosome reaction induced at 6 and 8 h incubation of buffalo spermatozoa in KRB medium resulted in conversion of 'B' cells to 'AR' cells while 'F' cells remained unchanged. A simultaneous evaluation of acrosome intact and acrosome-reacted cells using FITC-PSA, Giemsa and TEM gave results similar to examination by CTC stain. Both the assays are rapid, reproducible, reliable and they detect an increase or decrease in physiological acrosome reactions. They thus can be used to study effects of calcium and prove to be good monitoring systems to identify buffalo sperm capacitation and acrosome reaction in individual buffalo bulls for fertility studies.
- Published
- 2001
11. Surface protein changes in goat spermatozoa during capacitation
- Author
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G, Kaul, M, Kumar, K K, Gandhi, and S R, Anand
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Male ,Sperm-Ovum Interactions ,Acrosome Reaction ,Goats ,Blotting, Western ,Membrane Proteins ,Immunohistochemistry ,Spermatozoa ,Molecular Weight ,Animals ,Electrophoresis, Polyacrylamide Gel ,Female ,Sperm Capacitation ,Zona Pellucida - Abstract
Polypeptides of goat sperm surface before and after capacitation were examined by radiolabelling and immunologically using polyclonal antisera. Radioiodination revealed five protein bands having mol wt of 14.8, 72.4, 81, 100 and 128 kDa in uncapacitated ejaculated spermatozoa and only three bands of 23.4, 27 and 72.4 KDa in capacitated spermatozoa. The protein band with mol wt 72.4 kDa was only feebly iodinated in uncapacitated sperm surface but in capacitated spermatozoa it was heavily labelled. Western blot analysis of detergent-extracted proteins using gamma-globulin fraction of antisera raised against purified goat sperm plasma membrane revealed six antigens (17.8, 29.1, 33.4, 45.6, 85.1, 123.2 kDa) in uncapacitated spermatozoa, four (26, 32.1, 40.1, 45.6 kDa) in capacitated spermatozoa and only one (45.6 kDa) in acrosome-reacted spermatozoa. High mol wt proteins were more numerous on the surface of uncapacitated spermatozoa while the capacitated spermatozoa had relatively low mol wt proteins. An apparent effect of capacitation is the metabolism and reorganisation of proteins on goat sperm surface. Polypeptides on capacitated sperm surface revealed through radiolabelling and polyclonal antisera may have a likely receptor(s) role in the recognition and binding to homologous zona pellucida during fertilization.
- Published
- 2001
12. Caprine sperm acrosome reaction: promotion by progesterone and homologous zona pellucida
- Author
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K. K. Gandhi, P.R. Somanath, and K. Suraj
- Subjects
endocrine system ,medicine.medical_specialty ,urogenital system ,G protein ,Acrosome reaction ,chemistry.chemical_element ,Biology ,Calcium ,Sperm ,Exocytosis ,Andrology ,EGTA ,chemistry.chemical_compound ,Endocrinology ,medicine.anatomical_structure ,Food Animals ,chemistry ,Capacitation ,Internal medicine ,medicine ,Animal Science and Zoology ,Zona pellucida ,reproductive and urinary physiology - Abstract
Experiments were designed to characterize the effect of progesterone and the zona pellucida (ZP) on the goat sperm acrosome reaction (AR) through a comparative study. Goat spermatozoa were incubated for 4h in Krebs-Ringer bicarbonate media (KRB) for capacitation. Progesterone and ZP stimulated exocytosis of capacitated spermatozoa in a dose-dependent manner. EGTA and La(3+), added 10min before the addition of the agonists, completely abolished the stimulatory effects. Ca(2+) influx was observed to occur through a calcium phosphate transporter. Picrotoxin and bicuculline, two GABA(A)/Cl(-) channel antagonists, also inhibited progesterone-induced AR when added 10min before steroid addition. ZP-induced AR was unaffected by these antagonists. Studies using pertussis toxin (PTX) showed that, unlike ZP, progesterone acts without the involvement of a G-protein. Progesterone-3-(O-carboxymethyl) oxime: BSA conjugate (P-BSA) also induced AR in capacitated sperm suspension. Results suggest that progesterone and ZP induce AR via specific membrane receptors through different mechanisms, both requiring an influx of Ca(2+). It is assumed that both the mechanisms reconcile at some stages of the cascade and elicits a similar physiological response.
- Published
- 2000
13. Fuel Quality Requirements for Reduction of Diesel Emissions
- Author
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M K. Runda, I P. Singh, D C. Pandey, S K. Singal, P B. Semwal, and K K. Gandhi
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Reduction (complexity) ,Diesel exhaust ,Waste management ,Fuel quality ,Winter diesel fuel ,Environmental science - Published
- 1999
14. Projections on Automotive Fuel Quality in India for Meeting Future Vehicle Emission Norms
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K. K. Gandhi and A. K. Jain
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Engineering ,business.industry ,media_common.quotation_subject ,Quality (business) ,business ,Automotive engineering ,Manufacturing engineering ,Automotive fuel ,media_common - Published
- 1999
15. Diesel Fuel Quality and Particulate Emissions
- Author
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K. K. Gandhi and S. K. Singal
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Diesel fuel ,Diesel exhaust ,Diesel particulate filter ,Waste management ,Winter diesel fuel ,Environmental science ,Particulates - Published
- 1996
16. Hepatitis B virus infection and its transmission in preschool children
- Author
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G P, Mathur, K K, Gandhi, S, Mathur, V, Gupta, M, Bhalla, J N, Bhalla, and M, Irshad
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Male ,Cross-Sectional Studies ,Hepatitis B Surface Antigens ,Pregnancy ,Child, Preschool ,Humans ,Female ,Pregnancy Complications, Infectious ,Hepatitis B - Abstract
In the present study, 2.5% of 367 preschool children has HBsAg positivity. Of 11 mothers who were HBsAg positive during the third trimester of pregnancy, 4 had babies (36.4%) who developed HBsAg positivity by 2.5-3 months of age (vertical transmission). Two babies born of HBsAg negative mothers, with history of jaundice during first trimester, were HBsAg negative. All the relatives of HBsAg positive cases screened were negative for HBsAg.
- Published
- 1991
17. Lactobacillus therapy
- Author
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G P, Mathur, K K, Gandhi, S, Mathur, and G C, Upadhyay
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Lactobacillus ,Lactose Intolerance ,Advertising ,Humans ,Food Supply - Published
- 1991
18. Regulation of glycolysis/fructolysis in buffalo spermatozoa
- Author
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K. K. Gandhi and S. R. Anand
- Subjects
Male ,Embryology ,Buffaloes ,Phosphofructokinase-1 ,Pasteur effect ,Dehydrogenase ,Fructose ,chemistry.chemical_compound ,Endocrinology ,Allosteric Regulation ,Hexokinase ,Animals ,Glycolysis ,Phosphoglycerate kinase ,Glyceraldehyde-3-Phosphate Dehydrogenases ,Obstetrics and Gynecology ,Cell Biology ,Spermatozoa ,Reproductive Medicine ,Biochemistry ,chemistry ,Fructolysis ,Pyruvate kinase ,Phosphofructokinase - Abstract
Assay of maximal activities of 11 glycolytic enzymes in cell-free buffalo sperm extracts showed that hexokinase, phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase had the lowest activities, suggesting regulation of fructolysis at steps catalysed by these enzymes. The ratios of glyceraldehyde-3-phosphate dehydrogenase/phosphofructokinase (0.67) and phosphoglycerate kinase/phosphofructokinase (4.60) are typical of cells exhibiting high Pasteur effect (50% for ejaculated buffalo spermatozoa). The regulatory nature of phosphofructokinase was shown through its modulation by ATP, AMP and inorganic phosphate. The determination of fructolytic intermediates and cofactors and calculation of mass action ratios for each enzymic step revealed that hexokinase, phosphofructokinase, fructose-biphosphate aldolase, glyceraldehyde-3-phosphate dehydrogenase and pyruvate kinase catalysed reactions far removed from the equilibrium. A regulatory role by glyceraldehyde-3-phosphate dehydrogenase appeared to be most likely because triosephosphates and inorganic phosphate accumulated more under anaerobic than under aerobic conditions.
- Published
- 1982
19. Fructolysis and respiration of buffalo spermatozoa
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S. R. Anand and K. K. Gandhi
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Male ,Embryology ,Buffaloes ,Obstetrics and Gynecology ,Cell Biology ,Fructose ,Biology ,Spermatozoa ,Endocrinology ,Oxygen Consumption ,Reproductive Medicine ,Biochemistry ,Fructolysis ,Respiration ,Animals - Published
- 1975
20. The cellulase system of buffalo rumen microorganisms--carboxymethyl cellulase: isolation, assaykinetics of its action
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S R, Anand and K K, Gandhi
- Subjects
Rumen ,Bacteria ,Buffaloes ,Glycoside Hydrolases ,Animals ,Methylcellulose - Published
- 1971
21. Non-inferiority randomized controlled trial comparing CricOid pressure and para-laryngeal pressure in parturients undergoing cesarean delivery: NiCOP trial.
- Author
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Gupta M, Jain D, Jain K, Gandhi K, and Arora A
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- Adult, Female, Humans, Pregnancy, Anesthesia, General methods, Anesthesia, Obstetrical methods, Intubation, Intratracheal methods, Larynx, Prospective Studies, Cesarean Section methods, Cricoid Cartilage, Pressure
- Abstract
Background: Cricoid pressure has been surrounded with controversies regarding its effectiveness. Application of ultrasound-guided para-laryngeal (PL) force has been shown to occlude the esophagus effectively compared with cricoid pressure (CP) in awake patients. We hypothesized that there would be no meaningful difference in the change in antero-posterior esophageal diameter from with application of cricoid or para-laryngeal pressure in parturients undergoing cesarean delivery under general anesthesia., Methods: In this prospective, randomized, non-inferiority trial, 40 parturients scheduled for elective cesarean delivery under general anesthesia were randomized to receive rapid sequence induction with either cricoid pressure (n = 20) or para-laryngeal pressure (n = 20). The antero-posterior diameter of the esophagus, measured by sonography, was the primary outcome. Visualization of the esophagus, its position in relation to the glottic aperture, esophageal occlusion, percentage of glottic opening (POGO), time to intubation, first pass success rate, overall success rate and adverse events like desaturation or bronchospasm were secondary outcomes., Results: The mean change in anterior-posterior diameter in the CP group was 0.17 ±0.1 cm vs. 0.28 ±0.1 cm in the PL group. The mean difference (CP-para-laryngeal pressure) between the groups was -0.11 (95% CI -0.17 to -0.1) cm. As the upper limit of the 95% CI was lower than the prespecified non-inferiority margin (δ = -0.2), non-inferiority was established (P <0.001]. There was no significant difference in the POGO score (P = 0.818), time to intubation (P =0.55), or intubation attempts (P = 0.99)., Conclusions: Para-laryngeal pressure was non-inferior to CP in occluding the esophagus in parturients undergoing cesarean delivery under general anesthesia and furthermore, no significant deterioration in intubation parameters was seen., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
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22. Trans-arterial therapy for Fibrolamellar carcinoma: A case report and literature review.
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Bernon MM, Gandhi K, Allam H, Singh S, Kloppers J, and Jonas E
- Abstract
Introduction: Fibrolamellar carcinoma (FLC) is a rare pathologically distinct primary liver cancer. Surgical resection is the only treatment associated with prolonged survival. Trans-arterial embolization (TAE), which is a recognised treatment for hepatocellular carcinoma has been used to treat FLC. We present a case and performed a literature review of patients with FLC treated with TAE., Case Presentation: We present a 19-year old female with a large potentially resectable FLC which was initially treated with trans-arterial chemo-embolization (TACE) with drug eluting beads. The TACE was followed by surgical resection. Histology confirmed tumour necrosis related to the previous TACE., Discussion & Literature Review: We identified seven case reports and one case series of TAE for FLC. TAE was either used as a neo-adjuvant therapy to facilitate subsequent tumour resection or as a palliative treatment modality. We propose an algorithm for the treatment of FLC that includes TAE., Conclusion: The rarity of FLC and the paucity of data precludes establishing clear evidence-based standards of care. We propose an algorithm for the treatment of FLC. The establishment of an international registry may facilitate the collection of better quality evidence., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
23. Cardiac tamponade following post-pericardiotomy syndrome.
- Author
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Gandhi K, Reinders JSK, and Navsaria PH
- Subjects
- Humans, Pericardial Window Techniques, Pericardiectomy, Cardiac Tamponade diagnosis, Cardiac Tamponade etiology, Cardiac Tamponade surgery, Heart Injuries, Wounds, Penetrating
- Abstract
Summary: Subxyphoid pericardial window (SPW) is performed as both a diagnostic and therapeutic intervention in patients presenting with a penetrating cardiac injury (PCI). Post-pericardiotomy syndrome (PPS) with cardiac tamponade has been reported after penetrating cardiac trauma and after transdiaphragmatic pericardial window. We describe the first PPS with acute tamponade, weeks after diagnostic SPW for a PCI., (Copyright© Authors.)
- Published
- 2021
24. Predictive model of variables associated with health-related quality of life in patients with advanced chronic kidney disease receiving hemodialysis.
- Author
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García-Martínez P, Temprado-Albalat MD, Ballester-Arnal R, Gandhi-Morar K, Castro-Calvo J, and Collado-Boira E
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- Aged, Cross-Sectional Studies, Female, Humans, Male, Renal Insufficiency, Chronic psychology, Research Design, Quality of Life psychology, Renal Dialysis methods, Renal Insufficiency, Chronic therapy
- Abstract
Purpose: Chronic kidney disease (CKD) affects over 10% of the global population. Health-related quality of life (HRQoL) has been identified as a reliable indicator for assessing the effectiveness of treatment in chronic patients, and resilience as a predictor of low levels of stress and higher QoL. The aim of this research is to identify the relationship between HRQoL, resilience, perceived stress, and the different sociodemographic and clinical routine variables of advanced chronic kidney disease (ACKD)., Methods: Multicenter, cross-sectional, and correlational study with 155 ACKD patients in the Valencian Community (Spain). The measures for the study included the Kidney Disease Quality of Life 36 (KDQOL-36), the Perceived Stress Scale 10 (PSS10), and the Connors-Davidson Resilience Scale (CD-RISC). To identify the variables with predictive power over the scales and subscales of the KDQOL-36, multiple regression analyses were performed., Results: Average participants' age was 67.39, 68.4% were male, 29% diabetic, and 83.2% had undergone arteriovenous vascular access placement with a Charlson Comorbidity Index of 6 (SD = 2.09). The regression models identified that age and resilience explained up to 26.8% of the variance of the KDQOL-36 total score. As for the physical component of QoL, comorbidity with other clinical conditions, resilience, and the presence of diabetes explained 32.1% of its variance., Conclusions: Resilience was identified as one of the most important predictors of HRQoL. Thus, the development of interventions aiming to improve the level of resilience may have a positive impact over the quality of life of patients with CKD.
- Published
- 2020
- Full Text
- View/download PDF
25. Unmet needs in ankylosing spondylitis patients receiving tumour necrosis factor inhibitor therapy; results from a large multinational real-world study.
- Author
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Deodhar A, Strand V, Conaghan PG, Sullivan E, Blackburn S, Tian H, Gandhi K, Jugl SM, and Alten R
- Abstract
Background: Symptoms and comorbidities of ankylosing spondylitis (AS) considerably reduce health-related quality of life (HRQoL) and ability to work. This real-world study assessed rates of tumour necrosis factor inhibitor (TNFi) use and switching, treatment failure, and associations between failing TNFi and HRQoL, work productivity and activity impairment (WPAI)., Methods: AS patients and their treating physicians completed questionnaires capturing patient demographics, clinical status, TNFi treatment history, reasons for switching TNFi, HRQoL and WPAI. Current TNFi was determined as "failing" if, after ≥3 months, physician-rated disease severity had worsened, remained severe, was "unstable/deteriorating", physicians were dissatisfied with disease control and/or did not consider treatment a "success"., Results: The analysis included 2866 AS patients from 18 countries. Of 2795 patients with complete treatment data, 916 (32.8%) patients had never received TNFi therapy, 1623 (58.1%) patients were receiving their 1st TNFi and 200 (7.2%) patients had ever received ≥2 TNFi (treatment switch). Primary or secondary lack of efficacy were the commonest reasons for switching, and the mean delay in switching after primary lack of efficacy was 11.1 months. 232 (15.4%) patients on TNFi were currently "failing" who, compared to those with treatment success, reported poorer HRQoL: 5-dimension EuroQoL (EQ-5D-3 L): 0.63 vs. 0.78; Medical Outcomes Study Short-Form Health Survey version 2 (SF-36v2) mental component summary (MCS): 41.8 vs. 46.3; physical component summary (PCS): 40.2 vs. 45.1; impaired work productivity: 46.4% vs. 25.0%; and activity: 44.5% vs. 29.6%; all P < 0.001., Conclusions: Among AS patients, switching TNFi is uncommon and delayed by nearly 1 year despite primary lack of efficacy. Patients currently failing TNFi experience worse physical function, HRQoL and work productivity., Competing Interests: Competing interestsAD has received grants or research support from AbbVie, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer and UCB Pharma, and consulting fees from Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. VS has received grants and/or consulting fees from AbbVie, Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Celltrion, Corrona LLC, Crescendo Bioscience, EMD Serono, F. Hoffmann-La Roche Ltd./Genentech, Inc., GSK, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi and UCB, and has served on advisory boards for AbbVie, Amgen, AstraZeneca, BMS, Celltrion, Crescendo/Myriad Genetics, EMDSerono, Genentech/Roche, GSK, Janssen, Lilly, Novartis, Pfizer, Regeneron, Sandoz, Sanofi and UCB. PGC has received speakers’ bureau or consulting fees from Bristol- Myers Squibb, Pfizer and Novartis. RA has received grants or research support from Bristol-Myers Squibb, consulting fees from Bristol-Myers Squibb, Novartis, Pfizer Roche and Eli Lilly. ES & SB are employees of Adelphi Real World; HT and KG are shareholders and employees of Novartis; SJ is a shareholder and employee of Novartis Pharma AG., (© The Author(s) 2020.)
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- 2020
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26. Clinical, humanistic, and economic burden of osteoarthritis among noninstitutionalized adults in the United States.
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Zhao X, Shah D, Gandhi K, Wei W, Dwibedi N, Webster L, and Sambamoorthi U
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- Adolescent, Adult, Aged, Female, Humans, Male, Middle Aged, Morbidity trends, Osteoarthritis diagnosis, Osteoarthritis physiopathology, Severity of Illness Index, United States epidemiology, Young Adult, Cost of Illness, Health Care Costs, Osteoarthritis epidemiology, Quality of Life
- Abstract
Objective: To estimate the burden of osteoarthritis (OA) among noninstitutionalized adults (≥18 years of age) in the US., Design: Weighted nationally representative data from the 2015 Medical Expenditure Panel Survey were used to estimate OA prevalence in noninstitutionalized adults and compare adults with OA to those without OA for clinical (pain interference with activities [PIA], functional limitations), humanistic (health-related quality-of-life [HRQoL]) and economic outcomes (healthcare costs, wage loss). Productivity/wage loss was estimated among employed working-age adults (18-64 years). Multivariable regression analyses examined the associations between OA and outcomes., Results: In 2015, 10.5% (25.6 million) of noninstitutionalized US adults reported having any OA. Regression analyses indicated that adults with OA were significantly more likely than those without OA to report moderate (adjusted odds ratios [AOR] 1.99; 95% confidence interval [CI] 1.65-2.40] or severe PIA (AOR 2.59; 95% CI 2.21-3.04), any functional limitation (AOR 2.51; 95% CI 2.21-2.85), and poorer HRQoL on the SF-12 version 2 Physical Component Summary score (adjusted beta [standard error] -3.88 [0.357]; P < 0.001). Adjusted incremental annual total healthcare costs and lost wages among adults with OA relative to those without OA were $1778 and $189 per person, respectively, resulting in estimated national excess costs of $45 billion and $1.7 billion, respectively., Conclusions: OA affects approximately 10% of noninstitutionalized adults in the US, resulting in substantial clinical, humanistic, and economic burdens., (Copyright © 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2019
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27. Unmet needs in psoriatic arthritis patients receiving immunomodulatory therapy: results from a large multinational real-world study.
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Alten R, Conaghan PG, Strand V, Sullivan E, Blackburn S, Tian H, Gandhi K, Jugl SM, and Deodhar A
- Subjects
- Adult, Disease Management, Female, Humans, Immunologic Factors therapeutic use, Internationality, Linear Models, Male, Middle Aged, Quality of Life, Retrospective Studies, Severity of Illness Index, Treatment Failure, Arthritis, Psoriatic therapy, Biological Products therapeutic use, Drug Substitution, Immunomodulation, Patient Reported Outcome Measures
- Abstract
Objective: There are limited data on therapy selection and switching in psoriatic arthritis (PsA). This 18 country, real-world study assessed use and switching of immunomodulatory therapy (biologic/apremilast), the extent of treatment failure and its association with reduced physical functioning, health-related quality of life (HRQoL), and work productivity and activity impairment (WPAI)., Methods: PsA patients under routine care and their treating physicians provided demographics, current therapy, reasons for switching, duration of first therapy, HRQoL, HAQ-DI, and WPAI. Current immunomodulatory therapy was determined as "failing" if, after ≥ 3 months, physician-rated disease severity had worsened, remained severe, was "unstable/deteriorating," or they were dissatisfied with disease control and/or did not consider treatment a "success.", Results: Included were 3714 PsA patients; 1455 (40.6%) had never received immunomodulatory therapy; 1796 (50.1%) had ever received 1 immunomodulatory therapy and 331 (9.2%) ≥ 1. Lack of efficacy with first immunomodulatory therapy was the most common reason for switching; patients whose physicians indicated "primary lack of efficacy" as the reason, switched after a mean of 9.4 months. Patients currently failing immunomodulator therapies (n = 246) had poorer HRQoL compared with treatment success (n = 1472) measured by EQ-5D-3L (0.60 vs 0.77%; P < 0.0001); SF-36 PCS (40.8% vs 46.1%; P < 0.0001) MCS (41.1% vs 45.3%; P < 0.0001). Physical functioning, activity, and work productivity were also more impaired (HAQ-DI: 0.88 vs 0.56; activity impairment: 46.7% vs 29.7%; overall work impairment: 35.4% vs 26.1%; all P < 0.0001)., Conclusions: Poor treatment response in PsA is associated with substantial negative patient impact. In cases of primary treatment failure, timely switching is needed.
- Published
- 2019
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28. Transverse cardiac slicing and optical imaging for analysis of transmural gradients in membrane potential and Ca 2+ transients in murine heart.
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Wen Q, Gandhi K, Capel RA, Hao G, O'Shea C, Neagu G, Pearcey S, Pavlovic D, Terrar DA, Wu J, Faggian G, Camelliti P, and Lei M
- Subjects
- Animals, Endocardium diagnostic imaging, Heart Ventricles diagnostic imaging, Mice, Pericardium diagnostic imaging, Calcium Signaling, Endocardium metabolism, Heart physiology, Heart Ventricles metabolism, Membrane Potentials, Optical Imaging methods, Pericardium metabolism
- Abstract
Key Points: A robust cardiac slicing approach was developed for optical mapping of transmural gradients in transmembrane potential (V
m ) and intracellular Ca2+ transient (CaT) of murine heart. Significant transmural gradients in Vm and CaT were observed in the left ventricle. Frequency-dependent action potentials and CaT alternans were observed in all ventricular regions with rapid pacing, with significantly greater incidence in the endocardium than epicardium. The observations demonstrate the feasibility of our new approach to cardiac slicing for systematic analysis of intrinsic transmural and regional gradients in Vm and CaT., Abstract: Transmural and regional gradients in membrane potential and Ca2+ transient in the murine heart are largely unexplored. Here, we developed and validated a robust approach which combines transverse ultra-thin cardiac slices and high resolution optical mapping to enable systematic analysis of transmural and regional gradients in transmembrane potential (Vm ) and intracellular Ca2+ transient (CaT) across the entire murine ventricles. The voltage dye RH237 or Ca2+ dye Rhod-2 AM were loaded through the coronary circulation using a Langendorff perfusion system. Short-axis slices (300 μm thick) were prepared from the entire ventricles (from the apex to the base) by using a high-precision vibratome. Action potentials (APs) and CaTs were recorded with optical mapping during steady-state baseline and rapid pacing. Significant transmural gradients in Vm and CaT were observed in the left ventricle, with longer AP duration (APD50 and APD75 ) and CaT duration (CaTD50 and CaTD75 ) in the endocardium compared with that in the epicardium. No significant regional gradients were observed along the apico-basal axis of the left ventricle. Interventricular gradients were detected with significantly shorter APD50 , APD75 and CaTD50 in the right ventricle compared with left ventricle and ventricular septum. During rapid pacing, AP and CaT alternans were observed in most ventricular regions, with significantly greater incidence in the endocardium in comparison with epicardium. In conclusion, these observations demonstrate the feasibility of our new approach to cardiac slicing for systematic analysis of intrinsic transmural and regional gradients in Vm and CaT in murine ventricular tissue., (© 2018 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)- Published
- 2018
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29. Comparison of stress and burnout among anesthesia and surgical residents in a tertiary care teaching hospital in North India.
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Gandhi K, Sahni N, Padhy SK, and Mathew PJ
- Subjects
- Adult, Anesthesiology education, Burnout, Professional psychology, Female, Hospitals, Teaching, Humans, India epidemiology, Male, Occupational Stress psychology, Surgeons education, Tertiary Care Centers, Workload psychology, Anesthesiologists psychology, Burnout, Professional epidemiology, Internship and Residency, Occupational Stress epidemiology, Students, Medical psychology, Surgeons psychology
- Abstract
Objective: The residents undergoing training at hospitals in our country face challenges in terms of infrastructure and high workload with undefined working hours. The aim of the study was to compare the stress and burnout levels in trainee doctors doing residency in surgical fields and anesthesia at a tertiary care academic center in North India., Materials and Methods: A comparative, observational study was conducted in a tertiary care teaching hospital in North India. After Ethics Committee approval, 200 residents (100 each from surgical branches and anesthesia) were required to fill a questionnaire with information about age, sex, year of residency, marital status, and the Perceived Stress Scale-10, and Burnout Clinical Subtype Questionnaire-12. Burnout and perceived stress were compared between residents of anesthesia and surgical specialties., Results: Residents of both surgical and anesthesia branches scored high in perceived stress, namely 21 and 18, respectively. The score was significantly higher in surgical residents (P = 0.03) and increased progressively with the year of residency. The majority of residents (90% surgical, 80% anesthesia) felt that they were being overloaded with work. However, only 20%-30% of respondents felt that there was lack of development of individual skills and still fewer (<10%) reported giving up in view of difficulties., Conclusion: There is high level of stress and overload dimension of burnout among the residents of anesthesia and surgical branches at our tertiary care academic institution and the surgical residents score marginally higher than anesthesia residents., Competing Interests: There are no conflicts of interest
- Published
- 2018
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30. Racial and ethnic differences among children with new-onset autoimmune Type 1 diabetes.
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Gandhi K, Tosur M, Schaub R, Haymond MW, and Redondo MJ
- Subjects
- Adolescent, Child, Child, Preschool, Cohort Studies, Cross-Sectional Studies, Female, Humans, Infant, Male, Overweight complications, Overweight ethnology, Pediatric Obesity complications, Pediatric Obesity ethnology, Diabetes Mellitus, Type 1 ethnology, Ethnicity statistics & numerical data, Racial Groups statistics & numerical data
- Abstract
Aim: To compare demographic and clinical characteristics among children from ethnic minorities and non-Hispanic white children with new-onset autoimmune Type 1 diabetes., Methods: We analysed a single-centre series of 712 children with new-onset autoimmune Type 1 diabetes between January 2008 and March 2011. The median (range) age was 9.7 (0.3-18.1) years, the mean (sd) BMI percentile was 69.7 (25.4) and 48.3% of the cohort were girls. The cohort comprised 57.3% non-Hispanic white, 20.5% Hispanic and 14.8% African-American children, and 7.4% were of other, mixed or unknown race., Results: The Hispanic subgroup, compared with non-Hispanic white subgroup, had a higher mean (sd) C-peptide level [0.82 (1.62) vs 0.55 (0.47) ng/ml; P=0.004), and a greater proportion of children with elevated BMI (overweight or obesity; 49.6% vs 32.5%; P<0.001) and diabetic ketoacidosis (51.8% vs 38.2%; P=0.006). The African-American group had a higher mean (sd) glucose level [24.4 (12.8) vs 21.4 (10.7) mmol/l; P=0.017], a greater proportion of children with ketoacidosis (56.7% vs 38.2%; P=0.001), a greater proportion with elevated BMI (52.9% vs 32.5%; P<0.001), and a lower proportion of children at pre-pubertal stage (49.0% vs 61.6%; P=0.01), and tended to have higher C-peptide levels [0.65 (0.59) vs 0.55 [0.47] ng/ml; P=0.079) compared with the non-Hispanic white children. The differences in C-peptide levels compared with non-Hispanic white children persisted for Hispanic (P=0.01) but not African-American children (P=0.29) after adjustment for age, sex, BMI, ketoacidosis, glucose, Tanner stage and autoantibody number., Conclusion: At the onset of paediatric autoimmune Type 1 diabetes, Hispanic, but not African-American children had higher C-peptide levels, after adjustment for potential confounders, compared with non-Hispanic white children. These findings suggest that ethnicity may contribute to the heterogeneity of Type 1 diabetes pathogenesis, with possible implications for intervention., (© 2017 Diabetes UK.)
- Published
- 2017
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31. Bilateral renal cortical necrosis in a patient undergoing in vitro fertilization.
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Raveendran N, Gandhi K, Dsouza A, Prasad D, Malhotra V, Agrawal D, and Beniwal P
- Published
- 2016
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32. Periodic Peritoneal Dialysis in End Stage Renal Disease: Is it Still Relevant? A Single Center Study from India.
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Gandhi K, Prasad D, Malhotra V, Agrawal D, Beniwal P, and Mathur M
- Abstract
Background: High cost of maintenance hemodialysis (HD) and continuous ambulatory peritoneal dialysis (PD) in India has made renal replacement therapy out of reach of many patients with end stage renal disease (ESRD). Repeated puncture PD although inferior to HD biochemically, is easily and freely available across Rajasthan, India, and is simple to perform, and does not require sophisticated machines, thus making it an attractive option for dialysis for ESRD., Aim: To analyze the outcomes of periodic PD in patients with ESRD requiring dialysis support., Subjects and Methods: A prospective study analyzing the data of patients who underwent PD between August 2010 and January 2013 in Sawai Man Singh Hospital, Jaipur, India was conducted. Patients were divided into three groups based on the time period between first and second session of PD. Detailed demographic and clinical data during the study period were collected along with PD related complications. The main outcome studied was technique survival 1 year post initiation of PD., Results: 234 patients received an initial session of PD, of which 174 had a good response and were included in the study. 19 patients received the second PD within 7 days of first (Group 1), 45 patients within 8-14 days (Group 2) and 110 patients within 15-21 days (Group 3). The overall 1 year technique survival was 68.4% (91/133), with a rate of 50% (5/10), 56.8% (21/37), and 75.6% (65/86) for Group 1, Group 2, and Group 3, respectively. The time duration between first and second PD proved to be reliable indicator of the subsequent response, with a technique survival rate significantly lower in Group 1 patients compared to Groups 2 and 3 (P = 0.04). Median dialysis free days were 11, 16 and 21 days in Group 1, Group 2, and Group 3, respectively. Peritonitis rate observed was 2.1% (49/2261) during the study period., Conclusion: Periodic PD is a simple, safe and cheap procedure, which can be considered as used as a palliative measure in terminal uremia in underprivileged areas.
- Published
- 2015
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33. Glomerulonephritis with monoclonal IgG deposits.
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Gandhi K, Prasad D, Malhotra V, and Beniwal P
- Published
- 2015
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34. The WIP1 oncogene promotes progression and invasion of aggressive medulloblastoma variants.
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Buss MC, Remke M, Lee J, Gandhi K, Schniederjan MJ, Kool M, Northcott PA, Pfister SM, Taylor MD, and Castellino RC
- Subjects
- Adolescent, Animals, Cell Line, Tumor, Cerebellar Neoplasms genetics, Child, Child, Preschool, Female, G-Protein-Coupled Receptor Kinase 5 genetics, Humans, Infant, Male, Medulloblastoma genetics, Mice, Mice, SCID, Neoplasm Invasiveness, Neoplasm Transplantation, Phosphoprotein Phosphatases metabolism, Protein Phosphatase 2C, Receptors, CXCR4 metabolism, Signal Transduction, Young Adult, Cerebellar Neoplasms pathology, Chemokine CXCL2 metabolism, G-Protein-Coupled Receptor Kinase 5 metabolism, Medulloblastoma pathology, Phosphoprotein Phosphatases genetics, Receptors, CXCR4 genetics
- Abstract
Recent studies suggest that medulloblastoma, the most common malignant brain tumor of childhood, is comprised of four disease variants. The WIP1 oncogene is overexpressed in Group 3 and 4 tumors, which contain medulloblastomas with the most aggressive clinical behavior. Our data demonstrate increased WIP1 expression in metastatic medulloblastomas, and inferior progression-free and overall survival of patients with WIP1 high-expressing medulloblastoma. Microarray analysis identified upregulation of genes involved in tumor metastasis, including the G protein-coupled receptor CXCR4, in medulloblastoma cells with high WIP1 expression. Stimulation with the CXCR4 ligand SDF1α activated PI-3 kinase signaling, and promoted growth and invasion of WIP1 high-expressing medulloblastoma cells in a p53-dependent manner. When xenografted into the cerebellum of immunodeficient mice, medulloblastoma cells with stable or endogenous high WIP1 expression exhibited strong expression of CXCR4 and activated AKT in primary and invasive tumor cells. WIP1 or CXCR4 knockdown inhibited medulloblastoma growth and invasion. WIP1 knockdown also improved the survival of mice xenografted with WIP1 high-expressing medulloblastoma cells. WIP1 knockdown inhibited cell surface localization of CXCR4 by suppressing expression of the G protein receptor kinase 5, GRK5. Restoration of wild-type GRK5 promoted Ser339 phosphorylation of CXCR4 and inhibited the growth of WIP1-stable medulloblastoma cells. Conversely, GRK5 knockdown inhibited Ser339 phosphorylation of CXCR4, increased cell surface localization of CXCR4 and promoted the growth of medulloblastoma cells with low WIP1 expression. These results demonstrate crosstalk among WIP1, CXCR4 and GRK5, which may be important for the aggressive phenotype of a subclass of medulloblastomas in children.
- Published
- 2015
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35. Low CHD5 expression activates the DNA damage response and predicts poor outcome in patients undergoing adjuvant therapy for resected pancreatic cancer.
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Hall WA, Petrova AV, Colbert LE, Hardy CW, Fisher SB, Saka B, Shelton JW, Warren MD, Pantazides BG, Gandhi K, Kowalski J, Kooby DA, El-Rayes BF, Staley CA 3rd, Volkan Adsay N, Curran WJ, Landry JC, Maithel SK, and Yu DS
- Subjects
- Adenocarcinoma mortality, Adenocarcinoma surgery, Adenocarcinoma therapy, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor metabolism, Chemotherapy, Adjuvant, DNA Damage drug effects, DNA Helicases genetics, Deoxycytidine analogs & derivatives, Deoxycytidine therapeutic use, Disease-Free Survival, Female, Gene Expression Regulation, Neoplastic drug effects, Genes, Tumor Suppressor drug effects, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Nerve Tissue Proteins genetics, Pancreatic Neoplasms mortality, Pancreatic Neoplasms surgery, Pancreatic Neoplasms therapy, Prognosis, Treatment Outcome, Tumor Cells, Cultured, Gemcitabine, Adenocarcinoma metabolism, DNA Helicases metabolism, Nerve Tissue Proteins metabolism, Pancreatic Neoplasms metabolism
- Abstract
The DNA damage response (DDR) promotes genome integrity and serves as a cancer barrier in precancerous lesions but paradoxically may promote cancer survival. Genes that activate the DDR when dysregulated could function as useful biomarkers for outcome in cancer patients. Using a siRNA screen in human pancreatic cancer cells, we identified the CHD5 tumor suppressor as a gene, which, when silenced, activates the DDR. We evaluated the relationship of CHD5 expression with DDR activation in human pancreatic cancer cells and the association of CHD5 expression in 80 patients with resected pancreatic adenocarcinoma (PAC) by immunohistochemical analysis with clinical outcome. CHD5 depletion and low CHD5 expression in human pancreatic cancer cells lead to increased H2AX-Ser139 and CHK2-Thr68 phosphorylation and accumulation into nuclear foci. On Kaplan-Meier log-rank survival analysis, patients with low CHD5 expression had a median recurrence-free survival (RFS) of 5.3 vs 15.4 months for patients with high CHD5 expression (P=0.03). In 59 patients receiving adjuvant chemotherapy, low CHD5 expression was associated with decreased RFS (4.5 vs 16.3 months; P=0.001) and overall survival (OS) (7.2 vs 21.6 months; P=0.003). On multivariate Cox regression analysis, low CHD5 expression remained associated with worse OS (HR: 3.187 (95% CI: 1.49-6.81); P=0.003) in patients undergoing adjuvant chemotherapy. Thus, low CHD5 expression activates the DDR and predicts for worse OS in patients with resected PAC receiving adjuvant chemotherapy. Our findings support a model in which dysregulated expression of tumor suppressor genes that induce DDR activation can be utilized as biomarkers for poor outcome.
- Published
- 2014
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36. Half-and-half nails.
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Gandhi K, Prasad D, Malhotra V, and Agrawal D
- Published
- 2014
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37. Comparing sugammadex and neostigmine reversal of neuromuscular blockade in laparoscopic surgery.
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Jain D and Gandhi K
- Subjects
- Female, Humans, Male, Cholinesterase Inhibitors therapeutic use, Laparoscopy methods, Neostigmine therapeutic use, Neuromuscular Blockade methods, gamma-Cyclodextrins therapeutic use
- Published
- 2013
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38. British HIV Association guidelines for the management of HIV infection in pregnant women 2012.
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Taylor GP, Clayden P, Dhar J, Gandhi K, Gilleece Y, Harding K, Hay P, Kennedy J, Low-Beer N, Lyall H, Palfreeman A, Tookey P, Welch S, Wilkins E, and de Ruiter A
- Subjects
- Adult, Antiretroviral Therapy, Highly Active, Delivery, Obstetric methods, Female, HIV-1, Humans, Pregnancy, Societies, Medical, United Kingdom, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, Infectious Disease Transmission, Vertical prevention & control
- Abstract
The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of human immunodeficiency virus (HIV)-positive pregnant women in the UK. The scope includes guidance on the use of antiretroviral therapy (ART) both to prevent HIV mother-to-child transmission (MTCT) and for the welfare of the mother herself, guidance on mode of delivery and recommendations in specific patient populations where other factors need to be taken into consideration,such as coinfection with other agents. The guidelines are aimed at clinical professionals directly involved with, and responsible for, the care of pregnant women with HIV infection.
- Published
- 2012
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39. Effect of enamel preparations on fracture resistance of composite resin buildup of fractures involving dentine in anterior bovine teeth: an in vitro study.
- Author
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Gandhi K and Nandlal B
- Subjects
- Animals, Bisphenol A-Glycidyl Methacrylate chemistry, Cattle, Dental Bonding, Dental Enamel pathology, Dental Restoration Failure, Dental Stress Analysis instrumentation, Dentin pathology, Organophosphates chemistry, Random Allocation, Stress, Mechanical, Temperature, Time Factors, Tooth Fractures pathology, Water chemistry, Composite Resins chemistry, Dental Enamel injuries, Dental Restoration, Permanent methods, Dentin injuries, Tooth Fractures therapy, Tooth Preparation methods
- Abstract
Sixty bovine teeth with simulated mesio-incisal angle fracture were randomly and equally divided in one untreated (control) group and three experimental groups (Bevel, Chamfer and newly introduced Stair-step Chamfer preparation group) to evaluate the effect of enamel preparations on the fracture resistance of composite resin. Post restoration, fracture mechanics approach was used to quantify the failure of composite resins in testing the samples in Instron testing machine. Mean peak failure load (Newton) of composite amongst experimental groups was observed in the order; Chamfer (326.09 +/- 72.73), Stair-step chamfer (315.21 +/- 81.77) and Bevel (253.83 +/- 67.38). Results of the One-Way ANOVA revealed significant difference in the mean peak failure load values of the four different groups. (P<0.001) Scheffe's Post-Hoc comparison test (Subset for alpha = 0.05) revealed that there was no significant difference in the mean peak failure load values of the bevel, stair-step chamfer and chamfer preparation when considered together, but the mean peak values of control group (605.22 +/- 48.96) were observed significantly higher. Failure mode evaluation revealed, majority of failures occurred as cohesive and mixed type for all the experimental groups. Adhesive type failure was observed maximum (33%) in the bevel group. Stair-step chamfer preparation showed greatest potential for application and use as it no only demonstrated comparable values to Chamfer preparation ['t' value (0.39) (P > 0.05)] but also involved sacrificing less amount of tooth structure adjacent to fractured edge.
- Published
- 2006
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40. Addressing semen loss concerns: towards culturally appropriate HIV/AIDS interventions in Gujarat, India.
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Lakhani A, Gandhi K, and Collumbien M
- Subjects
- Adolescent, Adult, HIV Infections ethnology, Health Promotion methods, Humans, India, Male, Masturbation psychology, Persuasive Communication, Risk-Taking, Sex Work, Social Support, Attitude to Health ethnology, Cultural Characteristics, HIV Infections prevention & control, Health Promotion organization & administration, Masturbation ethnology, Semen
- Abstract
A situation analysis of sexual networking and sexual health in an industrial area of Gujarat, India, identified anxiety about masturbation and other semen loss concerns as major preoccupations among young men. This paper describes how the Deepak Charitable Trust addressed these concerns in their HIV prevention programme for young men aged 15 to 30. Flowcharts were used as participatory learning tools and to obtain data on the perceived consequences of masturbation, both before and after intervention activities. Research was also done on the relation between semen-related anxieties and sexual risk behaviour by DCT and two other NGOs among young men engaging in unsafe sexual behaviour. DCT advocates addressing masturbation and other semen loss concerns in all sexual health campaigns in South Asia, based on the magnitude of these concerns, their potential to confound syndromic management of STIs and their significance as an idiom of psychosocial distress. Masturbation and associated anxieties about sexual performance are seen as health issues and discussed as such by the programme. There is immediate identification among young men, whether or not they are already sexually active, and it provides an excellent entry point for sexual health and safer sex education. The community response to these efforts has been entirely positive.
- Published
- 2001
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41. Autoantibodies to type VII collagen have heterogeneous subclass and light chain compositions and their complement-activating capacities do not correlate with the inflammatory clinical phenotype.
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Gandhi K, Chen M, Aasi S, Lapiere JC, Woodley DT, and Chan LS
- Subjects
- Collagen genetics, Epithelium immunology, Epitopes immunology, Humans, Immunoglobulin G chemistry, Immunoglobulin Light Chains chemistry, Phenotype, Protein Structure, Tertiary, Recombinant Proteins immunology, Autoantibodies chemistry, Collagen immunology, Complement Pathway, Classical, Epidermolysis Bullosa Acquisita immunology, Lupus Erythematosus, Systemic immunology
- Abstract
Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus are blistering skin diseases characterized by IgG autoantibodies that predominantly target the noncollagenous domain 1 of type VII collagen, a skin basement membrane component. The basic immunologic events leading to the blistering processes in these diseases remains unclear. We defined the subclass and light chain compositions of the IgG autoantibodies in 15 patients, in order to gain insight into the blistering mechanism. Immunofluorescence correlated the patients' in vivo-bound and circulating antibasement membrane autoantibodies. Four eukaryotic recombinant proteins, including one full-length and three truncated noncollagenous domain 1 proteins generated by sequential deletion of C-terminal amino acids, were used to perform enzyme-linked immunosorbent assay to detect the patients' anti-type VII collagen autoantibodies. The majority of patients' autoantibodies contained both complement-activating and non-complement-activating IgG subclasses. The presence or absence of complement-activating IgG autoantibody subclasses did not correlate with the inflammatory or noninflammatory clinical phenotype. The majority of tested sera contained both kappa and lambda light chain autoantibodies. All sera that reacted to the full-length noncollagenous domain 1 also reacted to the smallest truncated protein containing the cartilage matrix protein and the first three fibronectinlike repeats. The patients' anti-type VII collagen autoantibodies, likely to be polyclonal in nature, may contribute to the pathogenesis of the blistering process by both complement-dependent inflammatory injury and complement-independent mechanical disruption of the anchoring function of type VII collagen. The N-terminal region of the noncollagenous domain 1 may contain an important antigenic epitope targeted by the IgG autoantibodies.
- Published
- 2000
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42. Diagnosis and treatment for children who cannot control urination.
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Maizels M, Gandhi K, Keating B, and Rosenbaum D
- Subjects
- Child, Child, Preschool, Diagnosis, Differential, Humans, Infant, Toilet Training, Enuresis diagnosis, Enuresis etiology, Enuresis therapy, Urinary Incontinence diagnosis, Urinary Incontinence etiology, Urinary Incontinence therapy
- Abstract
Primary NE is probably a condition rooted in biologic problems. There is a strong hereditary component. Altered nervous system function may lead to disorganization of how bladder function is controlled and how vasopressin is released. In extreme cases, this disorganization may also be reflected in psychologic issues, such as attention-deficit disorder. Primary NE should not be viewed as laziness of the child, but as an obstacle the child needs professional help to hurdle. The practitioner should collaborate with a pediatrician, urologist, and psychologist in managing children who wet. Routine office evaluation should exclude incontinence as a cause of wetting. When a screening ultrasonogram is normal, this helps the practitioner determine that striking birth defects are unlikely. Follow-up of management by interview with interested staff is necessary. Wetting is reliably correctable and probably best addressed by combination treatment structured as an ETP. Specific treatments vary according to personal preferences. The treatment with strongest scientific research, desmopressin, may be the least effective for cure. The most effective treatment for cure, alarm with behavior reinforcement, is the least often prescribed. A miscellany of adjunctive treatments should be suggested when there are abnormalities in functional bladder capacity, defecation, urethritis, vulvitis, diet sensitivity, upper-airway obstruction, and other areas.
- Published
- 1993
- Full Text
- View/download PDF
43. Management of the undescended testis.
- Author
-
Gandhi K and Maizels M
- Subjects
- Humans, Infant, Newborn, Infertility, Male epidemiology, Male, Palpation, Risk Factors, Testicular Neoplasms epidemiology, Testis embryology, Cryptorchidism diagnosis, Cryptorchidism surgery
- Published
- 1993
44. Instantaneous topical anesthesia.
- Author
-
OPPENHEIMER P, KAPLAN J, GANDHI K, and PEARLMAN S
- Subjects
- Humans, Anesthesia, Local, Anesthetics, Anesthetics, Local
- Published
- 1960
45. Emergency interin treatment of upper airway obstruction.
- Author
-
KAPLAN J and GANDHI K
- Subjects
- Humans, Airway Obstruction, Disease, Respiration Disorders, Respiratory System, Respiratory Tract Diseases
- Published
- 1961
46. Bilateral parotid enlargement due to iodides. A case report.
- Author
-
OPPENHEIMER P, NELSON K, and GANDHI K
- Subjects
- Humans, Hypertrophy, Iodides toxicity, Parotid Diseases, Parotitis etiology
- Published
- 1960
47. Emergency carotid ligation.
- Author
-
GANDHI K and OPPENHEIMER P
- Subjects
- Humans, Ligation, Arteries, Cardiovascular System, Carotid Arteries surgery
- Published
- 1962
- Full Text
- View/download PDF
48. Repair of traumatic myringorupture.
- Author
-
OPPENHEIMER P, KAPLAN J, HARRISON W, and GANDHI K
- Subjects
- Humans, Tympanic Membrane injuries, Wound Healing
- Published
- 1961
- Full Text
- View/download PDF
49. Glass fiber mats to reduce effluents from industrial processes.
- Author
-
Goldfield J, Greco V, and Gandhi K
- Subjects
- Economics, Environmental Exposure, Glass, Methods, Odorants, Photometry, Air Pollution prevention & control, Filtration, Industrial Waste
- Published
- 1970
- Full Text
- View/download PDF
50. Nasoalveolar cyst.
- Author
-
OPPENHEIMER P, FRIEDMAN E, and GANDHI K
- Subjects
- Humans, Cysts, Jaw Cysts, Nose Diseases
- Published
- 1961
- Full Text
- View/download PDF
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