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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524188EnglishN2016April20HealthcareCORRELATION OF COAGULATION PROFILE IN LIVER DISEASE PATIENTS IN A TERTIARY CARE HOSPITAL
English0103G. K. TripathiEnglish Ankita A. KataraEnglish Shweta V. AwasthiEnglish Shashank V. SrivastavaEnglishObjective: To determine the coagulation abnormalities among liver disease patients admitted in a tertiary care hospital of Hind Institute of Medical Sciences, Barabanki, Uttar Pradesh (India) for a period of 1 year (January 2015 to December 2015). Methods: Patients were labeled as liver disease patients on the basis of Liver Function Tests (LFT) done in the hospital at the time of admission. Patients blood were collected in sodium citrate and plain vaccutainer for coagulation tests [prothrombin time (PT), activated partial thromboplastin time (aPTT)] and liver function tests respectively. The prothrombin time ratio was calculated and then used to calculate the international normalized ratio. Following parameters were included in Liver Function Test, serum bilirubin, SGOT, SGPT, ALP, Total Protein and serum albumin. Results: Total number of cases studied in a period of 1 year (January 2015 to December 2015) were 311. In 284(91.3%) cases both LFT and coagulation profile were done. In 261 (83.9%) cases (out of total 311 cases) coagulation tests were normal and in 50 (16.1%) cases coagulation tests were found to be deranged. Out of these 50 cases, PT was raised in 44(100%) cases, APTT was raised in 21(95.4%) cases and both PT and APTT were raised in 15(93.75%) cases. Conclusion: Coagulation abnormalities were profound patients with chronic liver diseases. In case of acute liver disease ,usually PT( Prothrombin Time) is increased, but aPTT (activated partial thromboplastin time)is found to be normal. aPTT (activated partial thromboplastin time)is usually increased in chronic liver diseases, but the PT(Prothrombin Time) prolongation is usually not seen in initial stages of chronic liver disease until the stage of liver fibrosis and cirrhosis is reached. Nevertheless, these parameters (PT and aPTT) were still widely used as prognostic markers in liver disease patients..
EnglishCoagulation abnormalities, Chronic liver disease, PT, aPTTINTRODUCTION Liver plays a major role in hemostasis, as most of the coagulation factors, anticoagulant proteins and components of the fibrinolytic system are synthesized here. Additionally, it acts as a reticuloendothelial system and regulates coagulation and fibrinolysis by removing these coagulation factors from the circulation. As the liver is a highly vascularized organ liver diseases can alter the abdominal blood flow and predispose patients to significant bleeding problems. Impaired haemostasis resulting from abnormal liver function has multifactorial etiology like impaired coagulation factor synthesis, synthesis of coagulation factors with altered function, increased consumption of coagulation factors and altered clearance of coagulation factors . Coagulation disorders in liver disease are usually measured by the prolongation of global screening tests such as the prothrombin time (PT) and the activated partial thromboplastin time (aPTT)8 . PT determines the time needed for the platelet-poor plasma to clot after the addition of tissue factor (thromboplastin) and calcium chloride. Whereas aPTT determines the time needed for the platelet-poor plasma to clot when mixed with a particulate or soluble activator of the contact coagulation factors (factor XII, pre-kallikrein and high-molecular-weight kininogen) and negatively charged phospholipids such as platelet substitutes9 . PT determines vitamin K dependent extrinsic factors VII, X, II, V and fibrinogen. The aPTT measures the activities of intrinsic and common pathways of coagulation cascade most sensitive to factor VIII, IX, XI, XII and those of the contact system10.
MATERIALS AND METHODS Patients were labeled as liver disease patients on the basis of Liver Function Tests( LFT) done in the hospital at the time of admission. Patients blood were collected in sodium citrate and plain vaccutainer for coagulation tests[prothrombin time (PT), activated partial thromboplastin time (aPTT)] and liver function tests respectively. The prothrombin time ratio was calculated and then used to calculate the international normalized ratio. Following parameters were included in Liver Function Test, serum bilirubin, SGOT, SGPT, ALP ,Total Protein and serum albumin.
RESULTS Total number of cases studied in a period of 1 year ( January 2015 to December 2015) were 311. In 284(91.3%) cases both LFT and coagulation profile were done (Table 1). Out of these 284 cases LFT was deranged in 83(29.2%) cases and 201(70.7%) cases LFT was found to be normal (Table 2). In 261 (83.9%) cases (out of total 311 cases) coagulation tests were normal and in 50 (16.1%) cases coagulation tests were found to be deranged (Table 3). Our study was mainly focused on these 50 (16.1%) cases of deranged coagulation tests. We did LFT in these 50 cases of deranged coagulation tests and found that out of these 50 cases LFT was found to be deranged in 44(88%) cases only. 6(12%)cases in which LFT was found normal were of anticoagulant medication.
Out of these 50 cases only PT was done in 28 (56%) cases, only APTT was done in 6 (12%) cases and in 16(32%) cases both PT and APTT was done (Table 4). Total number of cases in which PT was done were 44 and total number of cases in which APTT was done were 22 (Table 5). PT was raised in 44(100%)cases, APTT was raised in 21(95.4%) cases and both PT and APTT were raised in 15(93.75%) cases (Table 6).
DISCUSSION Liver plays a major role in hemostasis , as it is the primary site for synthesis of most of the coagulation factors and various proteins involved in fibrinolytic pathway. These include vitamin K dependent coagulation factors( factor II, VII, IX, X, Protein C and Protein S ), factor V, XIII, fibrinogen, antithrombin and plasminogen. All the Vitamin K dependent factors have glutamic residues at their amino terminal. These glutamic residues must be converted to gamma-carboxyglutamic acid residues, which then bind to calcium and lead to formation of activation complexes1 . Most of the patients with liver disease have coagulopathies1 , resulting in imbalanced hemostasis.
These changes lead to increase risk of bleeding as well as thrombosis. Coagulation tests are especially important in patients who are at bleeding and thrombotic risks such as gastrointestinal varices and vascular stasis. PT is a measure of synthetic function of liver and is involved in most of the liver disease .It is used all over the world as a major therapeutic indicator regarding liver transplantation in acute liver failure and cirrhosis, or regarding steroid therapy in alcoholic hepatitis234. Various hepatic disorders, vitamin K deficiency, warfarin toxicity, and fibrinolysis may be associated with prolongation of PT 5 . In acute liver diseases, usually PT is increased, but the aPTT is normal and, but in chronic liver disease, prolongation of PT is not seen initially until the stage of cirrhosis and the liver fibrosis reaches6 .
As the disease progresses both PT and aPTT levels are prolonged, but in compensated cirrhosis, high level of factor VIII may blunt the prolongation of aPTT7 . This finding matches with our study, as in our study PT(44)was increased in more number of patients in comparision to aPTT(21) [TABLE-5].In addition, in advanced liver disease there is a strict balance of the procoagulant.
CONCLUSION Coagulation abnormalities were profound patients with chronic liver diseases.. . In acute liver diseases, usually PT is increased,but the aPTT is normal and, but in chronic liver disease , prolongation of PT is not seen initially until the stage of cirrhosis and the liver fibrosis. Nevertheless, these parameters (PT and aPTT) were still widely used as prognostic markers in liver disease patients.
Englishhttp://ijcrr.com/abstract.php?article_id=288http://ijcrr.com/article_html.php?did=2881. Borowski M, Furie BC, Bauminger S et al. (1986) Prothrombin requires two sequential metal dependent conformational transitions to bind phospholipid. Conformation- specific antibodies directed against the phospholipid-binding site on prothrombin.JBiol Chem261 (32),14969-14975.
2. Caraceni P, Van Thiel DH. Acute liver failure.Lancet 1995;345:163-169.
3. Dickson ER, Grambsch PM, Fleming TR, Fischear LD, Langworthy A. Progformer. Hepatology1989;10:1-7.
4. Carithers RL, Herlong HF, Diehl AM, Shaw EW, Combes B, Fallon HJ, Maddrey WC. Methyl prednisolone therapy in patients with severe alcoholic hepatitis. Ann Intern Med 1989;110:685- 690.
5. Michal J, Carey , George M. Rodgers . Disseminated Intravascular Coagulation: Clinical and Laboratory Aspects, American Journal of hematology1998; 73: 65-73.
6. Xavier Forns ,SergiAmpurdanès, Josep M. Llovet, and et al. Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology 2003; 36 : 986 – 992.
7. TTOCO2.4 Synthetic Function. 2.4.2 The liver and coagulation, page 255-263.
8. Rverter JC. Abnormal hemostasis tests and bleeding in chronic liver disease: are they related? Yes. J Thrombheamost 2006; 4: 717-20.
9. Tripodi A. Tests of coagulation in liver disease. Clin Liver Dis 2009; 13: 55-61.
10. Thachil J. Relevance of clotting tests in liver disease. Postgrad Med J 2008; 84: 177-81.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524188EnglishN2016April20HealthcareDETERMINATION OF BACTERIOCIDAL ACTIVITY OF BACTERIOCIN PRODUCED BY A CLINICAL ISOLATE OF E.COLI AGAINST HUMAN PATHOGENS
English0407Joseph Pushpa Innocent D.English Margaret Theresa J.English Premkumar D.EnglishAim: The aim of this study is to estimate the bactericidal activity of bacteriocin against the common human pathogens. A total of 62 specimens were collected from patients attending the department of surgery, Karpaga Vinayaga Institute of Medical sciences and Research Centre, during a period of six months. Methodology: Specimens collected were superficial pus swab from the wound, deep tissue biopsy and scraping from the base of the ulcers. Samples were cultured on Blood agar (BA) and MacConkey agar (MA). The plates were incubated at 37C over night. The aerobic organisms were identified by standard microbiological procedures as described in Bailey and scott’s Daignostic Microbiology. (Finegold et al.1986).(1) The E coli which was isolated and identified was used in the preparation of crude bacteriocin.( 2) It was purified by Ammonium sulphate precipitation(3)and concentrated by centrifugation. Desalting of protein was done by dialysis method.(4) The protein concentrations of these purified bacteriocin was determined by Lowry’s method.(5) Bacteriocin prepared from E coli was subjected for its bactericidal activity against some human pathogens by minimum inhibitory concentration method. Optical density (OD) of the culture was measured at 660 nm using spectrophotometer. Bactericidal activity of bacteriocin against human pathogens was estimated. Results: The results were analyzed, most of the pathogens need a very low concentration of the bacteriocin for the minimum inhibitory concentration (MIC).We observed that there is a slight variation in MIC among the different bacterial pathogens. Conclusion: In General when the concentration of the bacteriocin increased then the OD values of the culture tubes were decreased. In conclusion Bacteriocin not only have the bacteriocidal activity but also dose dependent in different bacteria.
EnglishBacteriocin, Bactericidal activity, Microbial virulenceINTRODUCTION Pathogenic microbes produce disease in man is due to certain enzymes and toxic substances released by bacteria called virulence factors. Some chemicals released by the bacteria may cause self destruction are known as autolytic enzymes. Similarly some other biologically active compounds, produced by the bacteria may active against strains of other species or closely related species. This type of bactericidal agents produced by Gram negative bacteria are called bacteriocins.(6) Bacteriocins are ribosomally synthesized antimicrobial peptides.(7) Classification of bacteriocins based on molecular size, producer organisms, chemical structure and the mode of action. Various names are given to these agents such as colicin, pyocin and or marcescins etc. Bacteriocin affect the essential function of livings cells such as transcription, replication and cell wall biosynthesis.(8) They also act by forming membrane channels or pores that destroy the energy potential of sensitive cells.(9) However bacteriocin producing strains are resistant to their own product. It has been evaluated for intended use as mouth wash since it kills the bacteria which cause dental plaque. Hence it is safe to use as a natural alternative to antibiotics and chemical germicides. Keeping this in mind, it was planned to study the bactericidal activity of bacteriocin on some of the human pathogens. Informed consent was obtained from those who underwent the test procedure in this study. Ethics committee of Dr. MGR University approved this study.
MATERIALS AND METHODS A total of 62 specimens were collected from gulutial, thigh, knee, leg, foot, breast and umbilical areas which included the wound swabs, pus, tissue biopsy and scraping from ulcers. Samples were collected aseptically from patients attended the surgery department of Karpaga Vinayaga Institute of Medical science and Research Centre, Chinnakolambakkam. Samples collected were inoculated on to culture media and the organisms grown after incubation were identified by standard microbiological methods. Among the organisms isolated, the E. coli was the most commonly observed (10) The clinically isolated E.coli was used in the preparation of crude bacteriocin, because it is the common source of bacteriocin.(11) E. coli isolates had been grown on nutrient broth with 5% inoculums by batch fermentation at a pH of 6.2. The broth culture was incubated at 37c for 12 hours. For the separation of bacteriocin the culture was centrifuged at 8000 rpm for 20 minutes. Cell free supernatant was subjected to solid ammonium sulphate at pH 4 with gradual increase of 20 to 90% saturation and held for 3hours at 4c. The mixtures were centrifuged at 12000 rpm for 20 minutes. The precipitate was recovered and it was then suspended in 5ml of 50m.mol of sodium phosphate buffer at pH 7 followed by desalting of the protein by dialysis. Protein concentration was determined by lowry’s method and compared with the standard bovine serum albumin. Estimation of bactriocin activity The purified bacteriocin compound from E.coli was subjected for its bacteriocidal activity against commom human pathogens. Organisms used for the assay were Klebsiella spp, Salmonella typhi, staphylococcus aureus and corynebacterium. Estimation of MIC for the above culture of organisms, 0.5 ml of each log phase cultures were transferred in to test tubes contain nutrient broth of appropriate concentration of bacteriocin. 100µl/mL to 500µl/ml were prepared and added to 8ml of broth culture and were inoculated at 37c for 24hours. Minimum inhibitory concentration was estimated by measuring the optical density of the culture tubes at 660nm using spectrophotometer.
RESULTS Antibacterial sensitivity of bacteriocin against human pathogens were estimated and the results were tabulated .Table: 1 showed the turbidity measurements of klebsiella spp
DISSCUSSION Bacteriocins are the subject of increasing attention as a major replacement for the conventional antibiotics and as natural food preservatives.(12) There are multiple bacteriocins present in the population of E.coli (13) and (14). Colicin production and the effect of growth inhibition was tested by solid methods.(15) In the present study turbidometry was used to assay the growth inhibition. In medicine the bacteriocins are important as they are produced by some non pathogenic bacteria act as commmonsal and loss of these bacteria following the use of antibiotics may cause the invasion of opportunistic pathogens. Hence it is decided to demonstrate the effect of bacteriocin on human pathogens. Further most of the mechanisms of bacteriocin in killing the bacteria are similar to that of antibiotics.(16)(17) Therefore it may replace the use of the antibiotics in the treatment. Hence this study was conducted as a step to determine the effect of bacteriocin on human pathogens.
CONCLUSION Though MIC studies of bacteriocin on human pathogens may not showed any consolidated report, but the results were encouraging. Present study results revealed that some strains of bacteria were sensitive to bacteriocin and are showed a response to its concentration. Each of the pathogen responded differently. Further studies are essential with still highly purified form of bacteriocin and the pathogens to be studied with wide range of bacteriocin concentration.
ACKNOWLEDGEMENT Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors/ editors/ publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
Englishhttp://ijcrr.com/abstract.php?article_id=289http://ijcrr.com/article_html.php?did=2891. Finegold, S.M., Baron E.J. 1986. In. Bailey and Scott’s Diagnostic Microbiology. VII. Edn. Masby Company. St Louis. P. 106-125.
2. Yildirim. Z and Johnson M.G; ( 1998) Detection and characterization of a bacteriocin produced by Lactococcus lactis subsp. cremoris R isolated from radish,Latters in Applied Microbiology,26, 297-304.
3. Klaenhammer,T.R;(1998) Biochim, 70, 337-349.
4. Rajaram. G,Manivasagan.P,Thilagavathy .B, Saravanakumar .A.(2010) Purification and charactrization of a bacteriocin producied by Lactobacillus lactis isolated from marine environment. Advan J. food scie, and technology 2 (2) 138 – 144.
5. Lowry, O.H, Rosebrough .N.J, Farr A.L and Randall.R.J. (1951) Protein measurement with the folin –phenol reagent. J. Biol. chem.,193:265-275.
6. Gillis, R.R.,(1957) Colicin production as on epidemiological marker of Shigella sonnei,J.Hyg , 62, 1-9
7. Klienkauf ,H.V on Dohren, H.,(1990) Non ribosomal biosynthesis of peptide antibiotic, Eur ,J. bio chem. 192, 1-15.
8. Lakey,J.H. Gonzalezmanas,J.M.et al ., (1992) The membrane insertion of colicins, FEDS Lett, 307, 26-29.
9. Riley,M.A.,(1993) Positive secretion for colicin diversity in bacteria, Mol; Boil vol
10, 1048-1058. 10. Saleem M;Joseph Pushpa Innocent D.(2014) Comparison of microbial flora by deep tissue biopsy and superficial swab culture of specimen collected from various anatomical sites in early wound infections Int J Cur Res Rev, Vol 6.Issue 18, 24-28.
11. Shih-Chun yang, Chih- Hung Lin, Calvin T. Sung, and Jia-You Fang (20140) Antibacterial activities of bacteriocins: application in foods and pharmaceuticals Front Microbiol vol 5;241
12. Gillor O, Kirkup BC, Riley MA (2004) Colicins and Microcins the next generation antimicrobials. In Laskin BennettJW, M. Gadd G.Adv Appl. Microbiol Academic Press P 129-146
13. Margaret A. Riley, John E, Wertz (2002) Bacteriocin diversity: ecological and evolutionary prespecitves Biochimic 84-357- 364.
14. Maria Papagianni, Nicholaos Avramidis, George Filioussis, Despina Dasiou and loannis Ambrosiadis (2006) Determination of bacteriocin activity with bioassays carried out on solid and liquid substractes assessing the factor indicator Microorganism Microbial cell Factories 5: 30
15. David Smajs, Lenka Mioenkova, Jan Smarda, MartinVrba a(2010) Alena Sevcikova Zuzana valisova and Commensal Escherichia coli: colicin E1is a potential virulence factor BMC. Microbiology 10: 288.
16. Renee’ Pieterse; Svetoslav D.;Todorov (2010) Bacteriocins-exploring alternatives to antibiotics in mastitis treatment Braz J. Microbiol. Vol 41 no 3 Sao Paulo Oct 2010.
17. Cotter, P.D; Hill, C; Ross, R.P. (2005) Bacteriocins: Developing innate immunity for food. Nature Rev. Microbiology; 3;777- 788.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524188EnglishN2016April20HealthcareBIOAVAILABILITY AND BIOEQUIVALENCE EVALUATION OF SOME GENERIC PRODUCTS OF ARTEMETHER-LUMEFANTRINE DOUBLE STRENGTH TABLETS MARKETED IN NIGERIA
English0814Awofisayo Sunday O.English Okhamafe Augustine O.English Arhewoh Matthew I.EnglishThe study was aimed at evaluating the bioavailability and bioequivalence of generic products of artemether-lumefantrine (AL) antimalarial double strength oral tablet formulation. A non-randomized open label single dose study in eighteen healthy African male subjects was designed. The volunteers were administered one tablet of a product with a fatty meal and 0.5 L of water, after overnight fast. Venous blood sampling was taken at 0, 1, 2, 4, 6 and 8 h post-dose and plasma samples analyzed for artemether and lumefantrine exposure simultaneously using a validated high performance liquid chromatographic system with Chromosil C18 column, flow rate and UV detection at 1.0 mL/min and 216 nm, respectively. Acetonitrile: potassium dihydrogen phosphate (70: 30%, v/v) and nevirapine were employed as mobile phase and internal standard, respectively. The primary endpoints were area under the plasma concentration time curve (AUC) from zero to 8 h and maximum plasma concentration (Cmax). The 90% confidence interval for the ratio of the geometric means of AUC0-8 was compared with the established bioequivalence limit. All enrolled subjects with mean age 28.5 ± 4.5 years completed the study. The Cmax for artemether and lumefantrine for the products ranged from 0.225 - 0.558 µg/mL and 0.319 – 0.517 µg/mL, respectively. Drug products AL1 and AL2 met the bioequivalence criteria. The other products failed the pharmacopoeia test specification for chemical content with respect to either or both API and their pharmacokinetic profiles varied with statistical significant differences (P>0.05). Only two of the generic products studied were bioequivalent and could be switched.
EnglishBioavailability, Bioequivalence, Pharmacokinetics, Artemether, LumefantrineINTRODUCTION Oral administration of drugs is convenient and this route forms the largest means of drug administration (Martinez and Amidon, 2001). To produce a clinical response, drugs are required to achieve an effective concentration at the site of action and this maintained for an adequate length of time (Abdou, 1989). Orally administered drugs required for systemic agents, involves the transfer of the drugs from the gut to the systemic circulation. Bioavailability describes the fraction of the drug dose that reaches the systemic circulation unchanged. As many drugs are made and marketed by more than one pharmaceutical company, the application of biopharmaceutics gives substantial evidence on the effect of the method of manufacture (i.e., procedures and materials) on bioavailability of the drug (Chow and Liu, 1992).
The plethora of drug products containing the same active ingredients and possibly different excipients may require that all concerned (i.e., physician, pharmacists and end-users) select products that produce equivalent therapeutic effects. Most bioavailability studies, either for new or generic product, require qualitative tests to assess the performance of orally administered formulations (Pabst and Jaeger, 1990]. Some useful guidelines and methods have been developed by the U.S. Food and Drug Administration for determining drug bioavailability (Ribeiro et al., 2000). Bioavailability studies are therefore important in defining the safety and efficacy of drug products in terms of its effect on drug pharmacokinetics while bioequivalence studies compares the bioavailability of a drug from various drug products (USP, 2001)
In cases where there is approval of multisource marketing of any particular product, generic substitution and dispensing of different brands or unbranded products in place of the prescribed products may prevail without sufficient evidence of pharmaceutical equivalence or assurance of therapeutic performance (Committee for Proprietary Medicinal Products, 1992). Artemether-lumefantrine is the most widely employed fixeddose artemisinin combination therapy (ACT) employed for the treatment of uncomplicated malaria (FDA-CDER, 2002; WHO, 2013). In Nigeria, the National Guidelines on Malaria Treatment, Prevention and Control recommends, and in principles, supports the multisource availability of AL products (Dondorp et al., 2005). The national drug regulatory agency in Nigeria has similarly approved for marketing, in recent times, DS formulations but speculations as to the bioavailability and bioequivalence indices of the several marketed products has been raised. In previous studies on bioavailability of AL generic tablet formulation conducted in Tanzania, it was concluded that the bioequivalence was not demonstrated due to non-compliance with FDA 90% confidence interval criteria (Federal Republic of Nigeria, 2005). This study was aimed at assessing the bioavailability and bioequivalence of some AL DS tablet formulation marketed in Nigeria.
MATERIALS AND METHODS Chemicals HPLC grade acetonitrile and potassium dihydrogen phosphate (Sigma-Aldrich, Germany) were used for the LC analysis. Nevirapine powder, artemether and lumefantrine reference standards were donated by Central Medical Laboratory of University of Lagos (CMUL). Deionized water was used throughout and obtained from a Milli-Q system (Millipore, MA, USA). The generic products of artemether-lumefantrine were purchased in a licensed pharmacy outfit in Uyo, Nigeria. Details of the generic products are presented in Table 1.
All other reagents were of analytical grade. Chromatographic system Simultaneous determination of artemether and lumefantrine was done using HPLC (HPLC Peak 7000 System (Rheodyne manual sample injector, analytical Chromosil column C18, 250x4.6 mm column, Germany) with wavelength of UV detection at 216 nm and nevirapine as internal standard. The mobile phase was a mixture of acetonitrile and 25 mM potassium dihydrogen phosphate (70:30%, v/v). The total run time was 8 min. The method of analysis was developed by the CMUL and modified from an earlier reported method by Cesar and co-workers (International Conference on Harmonization, 1995). Study design The study had an open label randomized one-period and single-dose design. Eighteen healthy volunteers were randomly assigned to one of six AL DS generic products.
The study was conducted in accordance with the Declaration of Helsinki 2013 and Good Clinical Practices Guidelines set up by the International Conference on Harmonization and local applicable laws and regulations (Minzi et al., 2013). Subject Recruitment and Management Volunteers were eligible for the study if they had a negative result for malaria parasite test (using microscopic detection of parasites in blood smear after Giemsa stain) and had not taken any antimalarial in the past 2 months from the commencement of the study. Other eligibility criteria included Haemoglobin level >9.0 g/dL (5.5 mmol/L, serum bilirubin ≤ 2 mg/dL (34 µmol/L) and adequate renal function defined as serum creatinine clearance ≥ 60 mL/min. Volunteers were excluded if they had gross ascites or an evidence of active peptic ulcer disease or other documented gastrointestinal (GI) diseases that might influence GI motility (Cesar et al., 2008).
They were certified healthy by a physician based on their medical history, clinical examination, haematological and biochemical screening. The study protocol was approved by the Institutional Health Research Committee of University of Uyo Teaching Hospital (approval certificate number UUTH/AD/S/96/VOL.XVI/67). All volunteers gave written informed consent. The study was done according to the Guidelines of Helsinki Declaration, 2013 (World Medical Association, 2013).
Drug products and administration Volunteers received a single dose of the drug after an overnight fast, administered with 500 mL of water within 15 min of finishing breakfast (a standard measure of oily rice). Food and water intake was restricted for 4 h after ingestion of AL tablet. Blood sample collection Blood samples (5 mL each), taken from an indwelling intravenous cannula placed in the arm were collected in heparinized tubes at 0, 1, 2, 4, 6 and 8 h post dose. The samples were centrifuged at 3000 rev/min for 5 min and the clear supernatant transferred to a polypropylene tube and immediately stored at -60o C until analysis.
Pharmacokinetic analysis The maximum drug concentration (Cmax), time to achieve the maximum concentration (Tmax) and area under the curve (AUC0-8) were determined by imputing the experimental data for each subject in each group into GraphPad Prism pharmacokinetic software (Prism for Windows version 6.05, USA). The pharmacokinetic parameters (AUC0-8, Cmax, Tmax) for the AL tablet formulations were compared with that of the established product. Statistical analysis Minitab for Windows Statistical Package (Minitab Inc., USA), was used for statistical analysis. The statistical analysis employed single factor one way analysis of variance (ANOVA).
The parameters C max and AUC (0-8) were computed for individuals and the mean for each group was tested. The null hypothesis of no difference amongst the means of parameters for the generic products was tested at a 5% level of significance. Classical 90% confidence Intervals (CI) were calculated for the parameters based on the currently accepted criteria for assessing bioequivalence (Cesar et al., 2008). To test for differences amongst the generic products, post hoc multiple comparison was performed using Duncan Multiple Range (DMR) and Student Neuman Keul (SNK).
Pharmacokinetic analysis The maximum drug concentration (Cmax), time to achieve the maximum concentration (Tmax) and area under the curve (AUC0-8) were determined by imputing the experimental data for each subject in each group into GraphPad Prism pharmacokinetic software (Prism for Windows version 6.05, USA). The pharmacokinetic parameters (AUC0-8, Cmax, Tmax) for the AL tablet formulations were compared with that of the established product. Statistical analysis Minitab for Windows Statistical Package (Minitab Inc., USA), was used for statistical analysis.
The statistical analysis employed single factor one way analysis of variance (ANOVA). The parameters C max and AUC (0-8) were computed for individuals and the mean for each group was tested. The null hypothesis of no difference amongst the means of parameters for the generic products was tested at a 5% level of significance. Classical 90% confidence Intervals (CI) were calculated for the parameters based on the currently accepted criteria for assessing bioequivalence (Cesar et al., 2008). To test for differences amongst the generic products, post hoc multiple comparison was performed using Duncan Multiple Range (DMR) and Student Neuman Keul (SNK).
RESULTS AND DISCUSSION Malaria is a common parasitic disease known across the globe with all attention geared at combating the menace. The multisource proliferation of the generic products of antimalarial agents will therefore require establishing their comparable drug release and bioequivalence. Analysis of drug samples The result of the chemical content of the drug samples is presented in Table 2. Samples AL1 and AL2 had satisfactory drug contents with respect to the active ingredients. Samples AL3, AL4, AL5 and AL6 failed the Pharmacopoeia specification for chemical content with values less than 90% content for lumefantrine (USP, 1990). Volunteers and treatment Eighteen healthy male volunteers were enrolled for the study. The median age was 28 (and range, 26-34) years, mean body weight and mean body mass index (BMI) of 76.5 Kg and 27.5 Kg/m2 , respectively. Overall, the drug was well-tolerated. Figures 2 and 3 presented the plasma concentration versus time curves for the drug products with respect to artemether and lumefantrine, respectively. The resulting pharmacokinetic parameters for the various sampled drugs are presented in Table 3. The study was conducted in accordance with the Declaration of Helsinki 2002 (Henderson et al., 1992; International Conference on Harmonization, 1995), Good Clinical Practices Guidelines set up by the International Conference on Harmonization and local applicable laws and regulations. The study here provides a simultaneous determination of the active pharmaceutical ingredients (i.e., artemether and lumefantrine) components of the drug. Previous work by Souppart et al., evaluated the plasma levels of artemether using HPLC-MS (Souppart et al., 2002) and another work involving LC-MS/MS method for the determination of lumefantrine and its metabolite desbutyl lumefantrine in plasma from patients infected with Plasmodium falciparum malaria (Sethi et al., 2011).
This present work evaluates the selected products based on the simultaneous determination of the unchanged drugs (i.e., artemether and lumefantrine components) in the dosage form and in plasma. Following up on the bioequivalence of artemether-lumefantrine drug products through artemether exposure has presented some difficulties because on the instability of this drug component. The use of high performance liquid chromatographic system involving nevirapine as internal standard, as employed in this study, was able to resolve the variability issues associated with artemether instabilities/analytical handling complexities. Previous work employed halofantrine for the single drug component analysis of lumefantrine (Huang et al., 2012). The wavelength of UV detection in the work by Huang et al. was 335 nm while in this study involving nevirapine as internal standard, UV detection was at 216.
Nevirapine gave signals with shorter resolution time distinct from those of the analytes of interest. Periodically interfering peaks have been reported with the analytes when halofantrine is used as internal standard (Huang et al., 2012). As at the time of this study, the patent right owners of AL markets only the 20/120 tablet formulation hence AL1 being the established and most widely prescribed generic, was referred to as the reference product. AL1 also gave a satisfactory chemical content that met the pharmacopoeia standard. The comparative bioavailability of the AL DS generics revealed that only product AL2 met the bioequivalence criteria by possessYing a relative bioavailability of 0.85. The calibration curve for artemether and lumefantrine determination in plasma gave a correlation coefficient of 0.98 and 0.94 respectively.
The values were considered satisfactory for drug absorption kinetics involving plasma samples, so much more with the use of an internal standard in the analysis. The chemical content of the AL generic products Table 2 revealed that only products AL1 and AL2 were pharmaceuti- cal equivalents with respect to both component drugs. The other products failed the chemical content test with respect to lumefantrine whereas AL6 failed with respect to both drug components. Bioequivalence was therefore not considered for these products regardless of their relative bioavailability values. Several antimalarial products that are artemisinin-based have been reported with lower than required concentration of active ingredients (Kaur et al., 2008; Nayyar et al., 2012). It is however required that products considered for bioequivalence meet pharmacopoeia standards before being evaluated for bioequivalence with reference product (Ribiero et al, 2000). Products AL3, AL4, AL5 and AL6 are thus not meet for bioequivalence considerations.
CONCLUSION Many antimalarial agents in use have been reported to fall below the regulatory standards due to deliberate counterfeiting, poor quality control during manufacture or decomposition due to improper handling or storage. The wide difference in the chemical content and gross relative bioavailability of the selected products serve as a pointer to the causes of the nagging issue of drug resistance and failure in malaria treatment.
ACKNOWLEDGEMENT The authors are grateful to Mr. P. Ojobor for his technical assistance. AUTHOR’S STATEMENT The authors have no conflict of interest to disclose.
Englishhttp://ijcrr.com/abstract.php?article_id=290http://ijcrr.com/article_html.php?did=2901. Abdou H.M. 1989. Dissolution, bioavailability and Bioequivalence. Easton: MACK Publishing Company.
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18. Sethi P., Dua V.K., Jain R. 2011. A LC-MS/MS method for the determination of lumefantrine and its metabolite desbutyl lumefantrine in plasma from patients infected with Plasmodium falciparum malaria. J Liq Chromatr and Related Tech 34:25-35.
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524188EnglishN2016April20HealthcarePERIODONTAL TISSUE HEALTH IN ENDEMIC FLUOROSIS AREAS: A CASE STUDY
English1522V. B. Jayantha PadmanabhanEnglish R. M. Therraddi MuthuEnglish C. SumathiEnglishAim: The objective of the study was to determine if there is any reduction in periodontal disease in people living in areas where the drinking water contains fluoride in more than optimum level- as compared to its definite proven anti caries activity. Methodology: A survey with 320 patients in two groups of 160 each in Sengattur [4.4ppm] Salem District, Tamil Nadu and Nalgonda [3.5ppm], in Andhra Pradesh, with a control of 200 patients from Mamandur in Chengalpet District Tamil Nadu with fluoride in a level of less than optimum, by using the OHI(S) Greene and Vermillion index for oral hygiene, PI., Periodontal Index Of Russell DMF index for caries, and Deans index for assessing Fluorosis of the teeth. The sample was divided into four groups of age as A (10-15 years), B (16-30 years), C (31-45 years), D (46-60 years). The socioeconomic status and oral hygiene habits were held constant and the following indices were used to assess the oral health condition. The accumulated data were statistically analyzed using the ‘Z test’ and student ‘t test’. Results: The results showed a lesser severity of periodontal disease with a slight reduction in OH1(S) scores also. There was a definite decrease in DMF and a direct positive correlation between DMF and PI. Conclusion: The study clearly indicates that DMF and periodontal scores are less in populations with excess fluoride in their drinking water; than in people drinking water, with fluoride in less than optimum level.
EnglishEndemic fluorosis, Fluoride, Gingival diseases, Gingivitis, PeriodontitisINTRODUCTION The prevalence of the periodontal diseases dominates among all the oral and dental diseases. The prevention, cure and control of them have been attempted by various methods. In the case of caries its lesser incidence was noted in certain geographical areas wherein there existed natural presence of fluorides in the drinking water . This fluoride by incorporation into the enamel and increasing the re-mineralization apart from enzymatically inhibiting the bacteria had reduced the susceptibility of the teeth to caries. With this knowledge of the effects of fluorides on bacteria that cause caries many studies have been conducted using both local and systemic forms of fluorides to study and recognize their similar effect, if any, on the bacteria that cause the periodontal diseases.
This opened the eyes of some authors and lead them to further investigate, whether there is any reduction in periodontal’ disease in people living in areas where the drinking water contains fluoride in more than optimum level. Consequent to such an idea a few studies were conducted in which the periodontal health and the oral hygiene status of people in endemically high fluoride containing areas were assessed and also compared with those living in areas where the fluoride content in drinking water is less. Some of these studies even included the analysis of intraoral radiographsto detect the effects on the alveolar bone. But all these studies did not reveal many differences between the two groups. Hence the aim of the present study is to assess the periodontal health and the oral hygiene status of people residing in endemic fluorosis areas; to compare these data with those from a population living in an area with negligible fluoride in water; and also to recognize and correlate the periodontal health with that of caries incidence and its relation to fluoride level in the drinking water, so that it will throw more light on the periodontal health in fluoride variant areas.
These studies were followed by studies on the effects of local application of different forms of fluorides. Bjarne svatun 1978 studied the influence of stannous fluoride on pH changes on dental plaque in vivo after use of mouth rinses or a toothpaste. 0.2% solution of stannous fluoride reduced the fall in the pH markedly for at least 7 hours, measured using gold , glass electrodes. The stannous fluoride adsorbed to the bacterial cell wall disturbed membrane transport mechanisms and also inhibited the enzyme systems from forming of the sugar for energy production. Previous researchers reported that sucrose rinses lead to higher acid production in residents of low fluoride area thereby implying inhibition of bacterial metabolism by fluoride on an altered plaque ecology as a result of fluoride ingestion . This finding was also recorded by Houte et al., where he said that was found to be less in plaque and subsequent plaque formation and maturation, because of presence of fluorides . An important property of fluoride ion is its ability to inhibit enzyme action and so exert a direct effect on plaque bacteria .
Bibby 1940, Wright and Jenkins 1954 have shown that small amounts of fluoride ions (1-10 ppm) will decrease acid production by pure cultures or by saliva-glucose mixture . Higher levels of ionic fluoride above 32 ppm are required to reduce acid production by plaque. Such higher levels were not observed in oral cavity but later Dawes etal(1965) found that fluoride was concentrated within the plaque, which fluoride originated from the oral fluid than the Enamel. Only 2-5% of the fluoride is ionic and the rest is bound at neutral pH. The bound fluoride is a fluoride reservoir, since it can dissociate when more acid is produced by plaque organisms. The concentration of fluoride above 2 ppm in solution progressively decreases transport or uptake of glucose or its analogues into cells of oral Streptococci. When plaque has been depleted of its exogenous sugar supply, Fluoride inhibits the metabolism of the iodophilic polysaccharides by the micro-organisms present in plaque and also by the salivary bacteria, thus indirectly interfering with acid production .
Masanobu mizohata et al., 1988 in their study of rats fed on different dosages orally for three weeks found that the fluoride in small dosage had no significant effect on Dentin, Cementum, Periodontal Ligament and Alveolar bone. Higher doses of 35 mg./kg body weight lead to more formation of Dentin and less volume of Cementum and decrease in the density of the alveolar bone with not much changes in the periodontal ligament. Aim of the present study is to identify the changes after administration of fluoride in the formation of tooth and Enamel, Dentin, Cementum and Alveolar bone and also in their mineralisation.
MATERIALS AND METHODS The subjects for this study were selected randomly in populations living in endemic areas for fluorosis in Salem District, Sengattur (4.4 ppm) of Tamil Nadu and Nalgonda District, Nalgonda (3.5ppm) of Andhra Pradesh as experimental groups I and II. The control groups were also randomly selected from a non-fluoridated area, Mamandur in Chengleput district, Tamil nadu. Both the experimental and the control groups were subdivided into four subgroups of age as, group A 10-15 years, group B 16-30 years, group C 31-45 years and group D 46-60 years. Case selection: In the experimental groups it was confirmed that the subjects were residents in the locality from birth continuously without a break for more than 5 years at a stretch. People with not less than 10 teeth were only considered In both the experimental and control groups the socioeconomic status of the subjects was controlled to be the same and also the oral hygiene habits were noted to be the same .
Those with known systemic diseases were not considered for the study . The field equipment used was a mouth, mirror and an explorer. Adequate light was ensured either artificial or natural. With these parameters the following criteria were observed and indices recorded in the proforma. Oral cleanliness was estimated according to OHI (S) index of Greene and Vermillion . Relative prevalence and severity of periodontal diseases were determined by means of the Periodontal Index Of Russell. The grade of dental fluorosis was estimated with the help of Dean’s index . The DMF Index was also utilized to record the caries incidence. A mouth mirror and an explorer with the aid of adequate light was always ensured for recording the findings using a proforma for the same Statistical Methods on accumulation of data for the above said indices were tabulated and analyzed using the following statistical methods.
The mean value for each index was subjected to comparison between the two experimental groups with that of the control group. Hence the Mean values were tabulated for these three divisions separately. For each index a separate table was drawn. In each table the variation of the index values along with age were tabulated in order to study the element of progressiveness, if it existed along with age. Detailed discussions of the index values for the different age groups were recorded under each table separately along with their statistical significance. This was further analyzed by using the test of significance between the two means, by using larger sample methods. In view of the fact that the sample size is more than thirty the following formula was adopted for the calculations.
RESULTS The results showed a lesser severity of periodontal disease with a slight reduction in OH1(S) scores also. There was a definite decrease in DMF and a direct positive correlation between DMF and PI. The behaviours pattern of the PI differs from that of the OHI(S). PI declines in both the sampling units in the earlier and older age groups. Though there exists a decline there is no statistical significance at two points. But anyhow the levels of PI decline in the units when compared with that of the control. The reduction in the value of PI is appreciably large in the experimental group II when compared to the group I. This important finding indirectly connotes the presence of large amount of fluoride content in the drinking water of the II experimental area. With regards to the DMF the reduction is uniformly highly significant age groups. Hence we can safely expect a due amount of reduction in DMF (table3) with 99% certainly irrespective of the age groups in the sampling units.
The most interesting factor is the amount of reduction found to be equally likely in the two units for the four different age groups. This shows that the particular parameter behaves distinctly, without the influence of any other associated extraneous factor. In other words, the behaviour of the DMF is unique in all respects and this factor is not influenced either by OHI (S) or by PI. There exists a distinct and clear positive correlation between PI and DMF in both the experimental groups. This correlation is seen to be statistically significant in almost all the groups. The existence of a positive correlation implies that when there is an-increase in DMF there is a corresponding increase in the PI in both the experimental groups. This means that the value of DMF index is directly dependent on the values of PI irrespective of the area of sampling. This area factor seems to be an additional factor along with the influence of PI as far as DMF is concerned.
DISCUSSION The existing studiesthat have been conducted were done in countries where there is good dental care available for people from all walks of life. In contrast to those this study in India, has utilized the subjects for whom there is no such easy availability of dental care. Added to this is the fact that the socioeconomic status is also less here, which has a definite role to play in the periodontal health of the people . As in the study of Englander and Kesel this study did not attempt to quantify calculus. The chance of examiner variability was also nullified by the fact that there was only one examiner for the entire study . From the observations of the study it seems that fluoride in a concentration higher than the optimum is not directly detrimental to the tissues of the Periodontium. This study was subdivided into four subgroups (W.H.O. Report 1978, on oral health surveys). An objective evaluation of oral hygiene paralleled the periodontal survey in order to detect any effect of the fluoride and also to determine if such differences in oral hygiene could account for any differences, if any, in the prevalence and severity of periodontal involvement. As stated by Russell the factors of socio-economic status, oral hygiene habits, dietary and nutritional habits within each group were controlled to coincide, to eliminate variations .
Dental caries experience was also estimated as one aspect of the study so as to observe if it can possibly influence the periodontal disease. The inverse relationship between the caries and water fluoride was also brought to light again. The study did not make use of radiographs due to the distant and remote locations of the field study in various places The need for the radiographs is obviated with reference to Russell’s point on field studies; where he opines that radiographs are not essential for comparisons between populations because their use merely raises the average scores to similar degree and does not affect differences in scores used for comparison. He also emphasizes the need of radiographs in individual patient treatment, and says that such deviations are tolerable in the epidemiological studies, as long as they are random i.e., as apt to occur in one group as in another and adds that, “about the same findings will be returned whether radiograph is used, or whether the estimate is based upon the field examination only”. The table1 gives an idea about the patterns of the OH1(S) scores.
The scores in the experimental groups I and II are lesser than that of the control and also statistically significant except in the age groups A and D of the experimental group I.’ In the experimental group II all the age groups show significantly less scores meaning that the oral hygiene in experimental group II is better. As seen in the study of Englander the level of dental care was similar in both the groups, ruling out the assumption that dental care would have influenced the difference in the scores. So we may assume that there, may be a favourable effect of fluoride in drinking water on plaque and calculus inhibition as revealed by earlier investigatorswho consider the property of the fluoride ion to exert a direct effect on plaque bacteria, and deter the plaque bacteria. This can also be considered as an explanation for the reduction of the OHI(S) score.
This is also in concurrence with the study of Ericsson et al (1967) who found that fluoride in enamel surface, by substituting the OH— ion alters the surface energy and thereby alters the depositions of the pellicle and subsequent plaque formation. These studies may be considered to explain the low scores only partially because the scores though less are not dramatically so. The table 1 of periodontal indices for the experimental groups also shows lesser scores in age groups studied. The lowest scores in the age group D in experimental group II may be because of the loss of already terminally diseased teeth that might have left behind the less affected teeth with less scores, the experimental group II shows consistently lesser scores that the experimental group I which actually has more fluoride in water (4.4 ppm) than the group II (3.5). This may be due to the geographical and a consequential climatic variation which will influence the amount of water consumption daily and thereby may have different effect, on the experimental groups.
The difference between the values though not very drastic but significant enough indicates the basic truth that periodontal disease is equally prevalent in all the communities, held as control and experimental. For the reason that the periodontal index (PI) reflects the incidence and the severity of the periodontal disease; and since we see that the prevalence is equal in all the groups it is only true that the lesser scores in the experimental groups go to prove that the severity of the periodontal disease is less in the experimental groups than in the group held as a control. As an explanation to this less severity the following findings may be cited. Previous researchersfound that fluoride had a retarding effect on the resorption of the alveolar crestal bone. Many factors contribute to the destructive periodontal disease and it may well be that fluoride can, “increase the crystallinity of the bone and by that reduce the surface area per unit mass of bone; thus apatite may be less reactive in the presence of inflammation or other catabolic factors”, as. noted by Zipkin et al maintain that there is osteosclerosis and peri-osteal bone deposition, respectively due to fluorine in excess of the optimum level.
This might have reduced the severity of the bone loss also. But Ramseyer and Kristofferson proved on the contrary that such excess fluoride in the drinking water increased the periodontal disease . Furthermore, the studies that fluorides in high doses increases the bone density was also confirmed by Jowsey, Schenk and Reutter and well add to the support of the theory and account for the reduction in the severity and the scores of the Periodontal Index, in the experimental groups. But the study of Masanobu Mizohata et al with animals reports that the alveolar bone density decreased with increased fluoride ingestion and adequate maintenance of Vit. D and Calcium such decrease in density is not observed; instead such a measure of fluoride as a therapeutic agent increases new bone formation in patients with Osteoporosis and in patients with Multiple Myelomatosis. With all these views we may safely assume that fluoride in drinking water in endemic areas may act favourably in reducing the periodontal disease.
It can also be said that the lower dental caries experience as denoted by the lesser DMF values in the experimental groups with periodontal disease . Inflammation is often found in gingivae adjacent to carious lesions, and more gingivitis would be expected in groups having more open carious lesions. Russellfound that PI tended to be higher around carious than non- carious teeth due to loss of contact and food impaction etc. This might be the reason for the lesser PI scores in the experimental groups compared with that of the control where it is high. The last two tables go to prove this theory by having significant and highly significant positive correlation between the PI and the DMF; meaning that, the periodontal disease is severe when there are many diseased or carious teeth. The PI and DMF are found to have positive relation. The table on the DMF values reveals that the DMF scores for all the age groups are less, highly significantly in both the experimental groups as compared to that of the control group. This aspect does not need any explanation in specific, since it has been doubtlessly proved that water fluoridation does reduce the caries experience from 50% 35%. The differences in the scores within the experimental group and other such incongruity can be due to the distant geographical locations, climatic alterations, cultural habits which have a definite effect on the epidemiology of diseases.
The fact that these effects have been found in populations that have been resident in the specific locations from birth and so were consuming the fluoridated water continuously, it has to be studied whether addition of fluoride in certain amounts only when periodontal disease is detected and in people who are living in endemic fluorosis areas will have any beneficial effects in contrast to the subjects of this study who had the influence of the fluoride even in the formative stages of the dental tissues in their development.
These studies can further be augmented by involving twins of similar physiology and habits in areas with and without fluoride and studying the effects of fluorides in them. It is also important that studies to specify, the effects on soft tissues and hard tissues of the oral cavity have to be conducted. With many people in the endemic areas being normal and many in the areas also being severely affected by periodontal disease, it is imperative that the mechanism of host response with respect to each individual has also to be seriously considered. Previous investigators proposed that frequent use of fluoride induces dramatical decline in past three decades is thought to be main reason for the marked caries reduction in many countries. Fluoride provides significant declines in edentulism among adults and site-specific protective effect in the lumbar vertebrae .
CONCLUSION It is evident that DMF and periodontal scores are less in populations with excess fluoride in their drinking water; than in people drinking water, with fluoride in less than optimum level. The study also reveals the need for advanced methods of bone and soft tissue analyses to specifically corroborate such properties of fluoride.
ACKNOWLEDGEMENT Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
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35. Carranza FA. Glickman’s clinical Periodontology.V Edtn, W.B.Saunders
36. KristofersonT. Lack of effects of high doses of fluoride on prevention of alveolar bone resorption in rats. J Periodontal Res 1970; 5(2): 127–134.
37. Jowsey, Riggs, Kelly. Effects of combined therapy with NaF Vitamin D and Calcium in osteoporosis. Am J Med. 1972;53(1):43- 9.
38. Rolla G, Ekstrand J. Fluoride in Oral Fluids and Dental Plaque. Fluoride in Dentistry, 2Edn. Munksgaard, Denmark. 1996; 215.
39. Cheng KK. Adding fluoride to water supplies. Brit. Med. J 2007 335(7622): 699-702.
40. Aoba T, Fejerskov O. Dental fluorosis: chemistry and biology. Crit Rev Oral Biol Med 2002;13: 155-70.
41. Neurath C. Tooth decay trends for 12 year olds in nonfluoridated and fluoridated countries. Fluoride 2005; 38: 324-325.
42. Millar WJ, Locker D. “Edentulism and denture use,” Health Reports 2005; 17(1): 55-58.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524188EnglishN2016April20HealthcareESTIMATION OF SERUM LIPID LEVELS IN CHRONIC PERIODONTITIS PATIENTS: A CASE-CONTROL STUDY
English2326Deepu Mathews PanickalEnglish Prashanth EvuruEnglish Jeethu John JerryEnglish Little MahendraEnglish Sandhya CherukuriEnglish Jaideep MahendraEnglishAims and Objectives: Hyperlipidemia refers to abnormally elevated levels of lipids and/or lipoproteins in the blood. Elevated serum cholesterol is a modifiable risk factor that is associated with a cardiovascular disease (CVD) with an estimated 4.4 million deaths each year. A positive association between serum triglyceride concentration and risk of coronary heart disease has been observed in many case-control studies. Infection such as periodontitis causes bacteremia and/or endotoxemia producing a cytokine cascade that leads to increased levels of serum pro-inflammatory cytokines. These molecules promote enhanced lipogenesis, increased lipolysis, and reduced lipid clearance resulting in hyperlipidemia. Hence the aim of the study is to estimate the serum lipid levels in chronic periodontitis patients. Materials and Methods: 100 subjects were screened for the study and were grouped as experimental (50 subjects with chronic periodontitis) and control (50 systemically healthy subjects). To assess the periodontal condition all the subjects underwent the estimation of Clinical Attachment Loss (CAL). Blood samples were obtained and analyzed for serum lipid levels of Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), Triglyceride (TG) and Total Cholesterol (CHOL). Results: The mean values of LDL, HDL, TG and CHOL were significantly higher in chronic periodontitis subjects than healthy controls. Conclusion: The study concludes that patients with chronic periodontitis exhibited higher serum lipid levels. Hence these patients may be at a higher risk for further coronary events.
EnglishChronic Periodontitis, Low Density Lipoprotein, High Density Lipoprotein, Triglyceride, Total CholesterolINTRODUCTION Periodontitis is a chronic inflammatory disease primarily caused by gram – negative anaerobic microorganisms that lead to destruction of periodontal tissues and alveolar bone. [1] These microorganisms, particularly Porphyromonas gingivalis produce endotoxins in the form of lipopolysaccharides (LPS) that are instrumental in generating a host-mediated immune response. [2] Hyperlipidemia refers to increased levels of any or all lipids and/or lipoproteins in the blood.
It is well known that a causal relationship exists between serum lipid levels and systemic health, particularly cardiovascular disease, diabetes, tissue repair capacity, immune cell function, and serum levels of pro-inflammatory cytokines. It is hypothesized that periodontitis causes bacteremia and/or endotoxemia producing a cytokine cascade that leads to increased levels of proinflammatory cytokines. These molecules promote enhanced lipogenesis, increased lipolysis and reduced lipid clearance. [3] Though various studies have shown association with periodontitis and hyperlipidemia, however the results are still conflicting. Hence the present study was aimed at estimating the serum lipid levels of LDL, HDL, TG and CHOL in chronic periodontitis patients and compared with the healthy subjects.
MATERIALS AND METHODS One hundred and fifty subjects were recruited from the outpatient pool of Department of Periodontology, Vinayaka Dental College, with approval from ethical review board [VMSDC/IEC/019], following the Declarations of Helsinki for the study. [4] Twenty-five subjects did not meet the inclusion criteria and twenty-five subjects declined to participate. Finally, hundred subjects met the eligibility criteria and were selected for the present investigation. The selected subjects were informed about the study, and informed consent was obtained from them. Periodontal status was assessed by measuring the CAL.
They were then categorized as the experimental and control group with 50 subjects in each group based on the following inclusion and exclusion criteria. (Figure-1) Inclusion criteria of the experimental group included subjects between 25 to 70 years of age with generalized chronic periodontitis having ≥ 10 natural teeth. [5] Subjects with history of systemic diseases that affect lipid metabolism, history of drug treatment for hyperlipidemia, previous periodontal treatment and pregnancy were excluded from the study. Control group included subjects with systemically healthy and intact periodontium. Age and Body Mass Index (BMI) was calculated as body weight (kg) divided by height (m2 ).
MEASUREMENT OF CLINICAL ATTACHMENT LOSS It is the distance between base of the pocket and a fixed point on the crown, such as cemento-enamel junction. In this study, Clinical attachment loss (CAL) is measured with a periodontal probe from the cemento-enamel junction to the base of the pocket (mm).
SAMPLE COLLECTION COLLECTION OF BLOOD After clinical examination approximately 3cc of blood was drawn from the antecubital vein of each subject and analyzed for serum lipid levels of Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), Triglyceride (TG) and Total Cholesterol (CHOL) using Lipid panel test. Lipid panel test is a panel of blood tests that serves as an initial broad medical screening tool fort for quantitative determination of High-Density Lipoprotein, Low- Density Lipoprotein, Total Cholesterol and Triglycerides. Measuring a Lipid Panel/Cholesterol is recommended by NCEP (National Cholesterol Education Program) every five years in healthy adults and every year in high risk patients. [6] STATISTICAL ANALYSIS Data was analyzed using IBM SPSS 16 statistical software. Statistical comparisons were performed using student’s t-test for lipid levels between the groups. p value of Englishhttp://ijcrr.com/abstract.php?article_id=292http://ijcrr.com/article_html.php?did=2921. Socransky SS, Haffajee AD. The bacterial etiology and progression of destructive periodontal disease: current concepts. J Periodontol 1992; 63: 322-31.
2. Offenbacher S. Periodontal diseases: pathogenesis. Ann Periodontol 1996; 1: 821-78.
3. Cutler CW, Shinedeling EA, Nunn M. Association between periodontitis and hyperlipidemia: Cause or effect? J Periodontol 1999; 70: 1429–34.
4. World Medical Association Declaration of Helsinky. Ethical Principles for Medical Research Involving Human Subjects. 18th WMA General Assembly, Helsinky; 1964.
5. Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol 1999; 4: 1-6.
6. Rick Daniels. Delmar’s guide to laboratory and diagnostic tests. 3rd ed. Cengage Publishers. p. 495-500.
7. Lowe GD. pathogenesis of cardiovascular disease. Ann Periodontol 1998; 3(2): 12–5.
8. Sridhar R, Byakod G, Pudakalkatti P, Patil R. A study to evaluate the relationship between periodontitis, cardiovascular disease and serum lipid levels. Int J Dent Hyg 2009; 7(2): 144–50.
9. Hamissi J, Shahsavarani MT, Hamissi H. A Comparison of Serum Lipid Profile between Periodontitis Patients and Healthy Individuals. Iran Red Crescent Med J 2011; 13(4): 283-4.
10. Lösche W, Karapetow F, Pohl A, Pohl C, Kocher T. Plasma lipid and blood glucose levels in patients with destructive periodontal disease. J Clin Periodontol 2000; 27(8): 537-41.
11. Katz J, Chaushu G, Sharabi Y. On the association between hypercholesterolemia, cardiovascular disease and severe periodontal disease. J Clin Periodontol 2001; 28(9): 865-8.
12. Zhou SY, Xiao WM, Ouyang XY. Lipoprotein-associated phospholipase A2 and serum lipid levels in subjects with chronic periodontitis and hyperlipidemia. Chin J Dent Res 2012; 15(1): 25-9.
13. Alvares C, Ramos A. Lipids, Lipoproteins and apoproteins in serum during infection. Clin Chem 1986; 32: 142-5.
14. Beck JD, Offenbacher S, Williams R, Gibbs P, Garcia R. Periodontitis: a risk factor for coronary heart disease? Ann Periodontol 1998; 3: 127-41.
15. Valtonen VV. Infection as a risk factor for infarction and atherosclerosis. Ann Med 1991; 23 (5): 539-43.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524188EnglishN2016April20HealthcareTO STUDY THE PREVALENCE OF ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD) AMONGST ADOLESCENT CHILDREN REFERRED FOR BEHAVIOURAL PROBLEMS TO TERTIARY CARE RURAL MEDICAL INSTITUTE IN CENTRAL INDIA
English2731Vaidya A.English Dua H.English Mujawar N.English Edbor A.EnglishAttention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, disorganization, and/or hyperactivity/impulsivity. Aims and Objectives: To study the prevalence of ADHD in adolescents referred for behavioral problems to rural tertiary health care center, to identify the gender difference andco-morbid factors associated with ADHD. Materials and Methods: Present study was a hospital based cross sectional study done at rural tertiary health care centre in central India. Multi Health Systems (MHS) CONNERS-3 questionnaire was used for assessment. Adolescent boys/girls referred by school or brought by their parents for behavioral problems at Child Guidance Clinic, Department of Pediatrics, were included in the study. Results: Amongst 148 study subjects, 21 subjects (14.18%) were diagnosed with ADHD, 73 (49.32%) were diagnosed with inattention, 58 (39.18%) with impulsivity/hyperactivity, 112 (75.67%) with learning problems, 62 (41.89%) with aggression, and 103 (69.58%) with family relation problems. There was statistically significant gender difference in the prevalence of ADHD, with male preponderant; male: female ratio was 3.2:1. Conclusion: The present study revealed that prevalence of ADHD is high amongst adolescents in rural health care setting. It is needed to formulate policies in rural India for effective combating ADHD at early age.
EnglishADHD, Hyperactivity, Impulsivity, MHS Conner’s -3 questionnaireINTRODUCTION
Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, disorganization, and/or hyperactivity/impulsivity.[1] Inattention and disorganization entail inability to stay on task, seeming not to listen, and losing materials, at levels that are inconsistent with age or developmental level. Hyperactivity/impulsivity involves over activity, fidgeting, inability to stay seated, intruding into other people’s activities, and inability to wait, symptoms that are excessive for age or developmental level. [2] In childhood, ADHD frequently overlaps with disorders that are often considered to be “externalizing disorders,” such as oppositional defiant disorder and conduct disorder.[3]
ADHD often persists into adulthood, with resultant impairments of social, academic and occupational functioning.First reliable description of ADHD, came from England in early 20th century. Population surveys suggest that ADHD occurs in most cultures in about 5% of children and about 2.5% of adults.[4]Around 60% of ADHD children will carry some of their behavior into adulthood. According to Diagnostic and Statistical Manual for diagnosis of mental disorders (DSMV), ADHD symptoms includes: difficulty staying focused and paying attention, difficulty controlling behavior ,very high levels of activity.[5] WHO identifies adolescence as the period in human growth and development that occurs after childhood and before adulthood, from ages 10 to19 years.[6] It is high time we reach out to 99% of the child population that is being unattended by any agency,114 million children have no facilities even in the urban areas.
There is only a limited source of information regarding the prevalence Of ADHD in the Indian context. The effect of ADHD/behaviour problem occurs at home, school, workplace, relations, physical and educational aspects of life. Currently, early diagnosis of ADHD has gained importance in pursuit of treating them at the earliest, so as to avoid/reduce its complications in various aspects of life.[4]After exhaustive literature search, we could not find any study on prevalence of ADHD in rural health care setting in India. So, the present study is first of its kind to find prevalence of ADHD in rural health care setting in central India.
AIMS AND OBJECTIVES
(i) To study the prevalence of ADHD in adolescents referred for behavioral Problems to rural tertiary health care center. (ii) To identify the gender difference, if any, in the prevalence of ADHD.
(iii) To identify the presence of any co-morbid factors associated with ADHD.
MATERIALS AND METHODS
• Study Design: Cross sectional study (hospital based)
• Place of Study : This study was conducted at NKP Salve Institute of Medical Sciences and Research Centre and Lata Mangeshkar Hospital, Nagpur, (M.S.)
• Period of Study : January 2014 to October 2014 (10months )
• Sample size: A total of 148 participants were enrolled into the present study.
• Study population: Adolescents boys/girls, referred by school or brought by their parents for behavioral problems at Child Guidance Clinic, Department of Pediatrics, NKPSIMS and LMH, Nagpur were included in the study.
• Ethical clearance: Taken prior to start of study from Institutional Ethics Committee (IEC).
• Inclusion Criteria: All school going adolescent boys and girls (age group of 11-16 years) referred by school or brought by parents for behavioral problems.
Exclusion Criteria:
(i) Adolescent whose parents were not willing to sign consent form,
(ii) Adolescents having behavioral issues less than 6 months duration.
DATA COLLECTION:
The informed written consent was taken from the parents/guardian of the adolescent subjects. All subjects were assessed with validated
CONNERS Questionnaire by Multi Health Systems (MHS) and socio-economic status was assessed with modified Kuppuswami scale. A questionnaire developed by MHS- CONNERS-3 was used, which included41 Questions related to following areas: a. Inattention b. Hyperactivity/ Impulsivity c. Learning Problems d. Defiance/ Aggression e. Family Relations • Statistical Analysis and Results: All the data was entered in Microsoft Excel 2013and further Statistical Analysis was done with the help of SPSS statistical software (version 17).
RESULTS
Out of total 148 study participants, 80 were boys and 68 were girls. Amongst study population, 21 participants (14.18%) were diagnosed with ADHD, 73 (49.32%) were diagnosed with inattention, 58 (39.18%) with impulsivity/hyperactivity, 112 (75.67%) with learning problems, 62 (41.89%) with aggression, and 103 (69.58%) with family relation problems. There was significant gender difference in occurrence of ADHD; 16 boys and 5 girls had ADHD, 53 boys and 20 girls had inattention, 43 boys and 15 girls had hyperkinetic/ impulsivity, 67 boys and 45 girls had learning problems, 47 boys and 15 girls had aggression, 52 boys and 51 girls had family relation problems (Figure 1). Amongst MHSConner’s score, mean score in ADHD group was 42.14 for boys and 46.79 for girls, 50.34 for boys and 42.49 for girls in inattention group, 49.44 for boys and 47.56 for girls in learning problem group, 53.35 for boys and 46.53 for girls in defiance/aggression group, 52.23 for boys and 57.69 for girls in family problem group (Table 1).
Sex-wise difference in responses were statistically significant in inattention, hyperkinetic/impulsivity, learning difficulty groups (pEnglishhttp://ijcrr.com/abstract.php?article_id=293http://ijcrr.com/article_html.php?did=2931. Identifying and treating Attention Deficit Hyperkinetic Disorder: A resource for learning for school and home, ED Pubs, Washington DC., 2006.
2. Teaching children with Attention Deficit Hyperkinetic Disorder: Instructional strategies and practices, ED Pubs, Washington DC., 2008.
3. National Institute of Mental Health: Attention Deficit Hyperkinetic Disorder. Bethesda (MD), US Department of Health and Human Services, 2004. Available from http://www.nimh.nih. gov/publicat/index.cfm. [Last assessed on Dec. 28, 2015].
4. Attention Deficit Hyperkinetic Disorder in children and adolescents. Available from http://www.effectivehealthcare.ahrq.gov/ ehc/products/191/1149/adhd_clin_fin_to_post.pdf. [Last assessed on Jan 4, 2016].
5. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-V). Washington DC, American Psychiatric Association, 2013.
6. Attention Deficit Hyperkinetic Disorderin adolescents. Available from http://www.who.int/maternal_child_adolescent/topics/ adolescence/dev/en [last assessed on Dec 29 2015].
7. Heidi Aase and Terje Sagvolden.Moment-to-moment dynamics of ADHD behaviour, Behavioral and Brain Functions 2005, 1:12 doi: 10.1186/1744-9081-1-12, Published: 1 August 2005, Available from http://www.behavioralandbrainfunctions.com/content/1/1/12/abstract
8. Barkley RA, Murphy KR. Attention Deficit Hyperkinetic Disorder: A clinical workbook. 2006, 3rd ed Guilford Publications, New York, 1-10.
9. Visser SN, Zablotsky B, Holbrook JR, et al. Diagnostic experiences of children with attention-deficit/hyperactivity disorder. National health statistics reports; no 81. Hyattsville, MD: National Center for Health Statistics. 2015.
10. Hinshaw SP, Arnold LE. Attention-deficit hyperactivity disorder, multimodal treatment, and longitudinal outcome: evidence, paradox, and challenge. WIREs Cogn Sci 2015, 6:39–52.
11. Skogan AH, Zeiner P. Parent ratings of executive function in young preschool children with symptoms of attentiondeficit/-hyperactivity disorder, Behavioral and Brain Functions 2015, 11:16 doi:10.1186/s12993-015-0060- 1.Available from http://www.behavioralandbrainfunctions.com/ content/11/1/16.
12. Hoover DW, Milich R. Effects of sugar ingestion expectancies on mother-child interaction. Journal of Abnormal Child Psychology, 1994; 22; 501-515.
13. Consensus Development Panel. Defined Diets and Childhood Hyperactivity. National Institutes of Health Consensus Development Conference Summary, Volume 4, Number 3, 1982.
14. Faraone SV, Biederman J. Neurobiology of Attention- Deficit Hyperactivity Disorder. Biological Psychiatry, 1998; 44: 951- 958.
15. DSM-IV-TR workgroup. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524188EnglishN2016April20HealthcareSTUDY OF PAEDIATRIC CNS TUMORS IN TERTIARY CARE CENTER
English3236Grishma P. JobanputraEnglishObjective: To elaborate pattern and frequency of CNS Tumors in a tertiary care center. Primary Neoplasm of the Central Nervous system are the most common solid tumors of childhood, making up 20% of all paediatric oncologic conditions,1,7 surpassed only by leukemia and lymphoma in frequency2 . They have tendency to occur along the central neural axis and posterior fossa and CNS metastasis from extra-cerebral tumors are uncommon in childhood. Material Andmethod: In the present study, A two year retrospective review of CNS tumors in paediatric age group (EnglishIntracranial, Infratentorial, MedulloblastomaINTRODUCTION
Primary Neoplasm of the Central Nervous system (CNS) are the most common solid tumors of childhood, making up 20% of all paediatric oncologic conditions1,7 and are surpassed only by leukemia and lymphoma in frequency2 . They have included many histological subtypes, which vary in their site of origin and degree of malignancy. Seventy percent of childhood CNS tumours arise in the posterior fossa; a comparable number of tumours in adults arise within the cerebral hemispheres above the tentorium.7 Thus overall, infratentorial tumors occurs more in frequency then supratentorial tumors. Supratentorial tumors are more common in Englishhttp://ijcrr.com/abstract.php?article_id=294http://ijcrr.com/article_html.php?did=2941. Atlas of paediatric Oncology: D.Sinniah; giulio J. D’Angio; Jane Chatten; Mahboubi; Henrietta Rosenberg.
2. Young JR, Dohrmann GJ, Flannery Jt. Intracranial Neoplasm in infants.
3. Hassari Kadri, Alkhakam A. Mawla, Lina Murad Incidence of childhood brain tumours in Syria,(1993-2002).
4. Farwell Jr ; Dohrman GJ and Flannery Jt. Medulloblastoma in childhood; an epidemiologic study journal of neurosurgery.
5. Jacqueline R. Farwell, MD , George J. Dohrmann, MD, George J. Dohrmann, MD, PH.D and John T. Flannery , BS : Central Nervous System in children.
6. Heiskanen O:Intracranial tumours of children.
7. Rosai and Ackerman’s Surgical Pathology, 10th edition, Vol. 2
8. Robbins SL; Cartan RS ; and Kumar V. Robbin’s Pathological Basis of Disease. 8th edition.
9. Brain and other central nervous tumours- UK incidence statistics, Cancer Research UK.
10. Wilne S, Koller K,Collier J , et al; The diagnosis of brain tumours in children: a guideline to assist healthcare Arch Dis Child. 2010 Jul;95(7):534-9. Epub 2010 Apr 6. [abstract]
11. Childhood cancer incidence statistics, Cancer Research UK, Oct 2005.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524188EnglishN-0001November30HealthcareMAGNITUDE OF PULMONARY DISEASES - INCIDENTALLY DIAGNOSED ON AUTOPSY - AT LARGEST HOSPITAL AND MEDICAL COLLEGE OF RAJASTHAN
English3743Kalpana MangalEnglish Praveen DhakarEnglish Ajay YadavEnglish Karuna GuptaEnglish Sapna GandhiEnglishObjective: A wide histopathological spectrum of preventable diseases can affect lungs. Many times radiological and clinical findings in pulmonary diseases are non specific hence pathology investigations can play important role in prompt diagnosis. In our 4 years cross-sectional study period (January2012- December2015), we have examined lungs of 1715 medico-legal autopsy cases. Objectives: 1. To know the histopathological spectrum of Lung diseases. 2. To know the frequency of pulmonary lesions in respect to age and sex. Materials and Methods: Representative sections from pulmonary lesions were taken and studied with the help of H and E and special stains wherever necessary. Results: The various pulmonary lesions were edema and congestion in 1325 (77.2%) cases, non tubercular pneumonia 137 (7.99%) cases, bronchopneumonia 15 (0.87%) cases, interstitial pneumonia 6 (0.35%) cases. Cases of tubercular pneumonia were 70 (4.08%) and pulmonary malignancies were 7 (0.41%) cases out of total pulmonary lesions. Pneumonias were occupying a large number, next to edema and congestion. Conclusion: The present study reveals the load and spectrum of lung disease in the largest Hospital and Medical College of Rajasthan, where infectious lesions (non-tubercular and tubercular pneumonias) are still the most common preventable causes of morbidity and mortality; hence autopsy study can be of great value in improving the vision and diagnostic setups for better clinical assessment, timely diagnosis and therapy.
EnglishEdema and Congestion, Pneumonia, Autopsy, ARDS, EmphysemaINTRODUCTION The lungs are ingeniously constructed to carry out their cardinal function: the exchange of gases between inspired air and blood.1 During their functional course, lungs can become vulnerable for a wide range of inflammatory, neoplastic and other lesions, and almost always involved secondarily by terminal events of cardiovascular causes.2 Millions of people all over the world suffer by various chronic respiratory diseases, which can be prevented, if diagnosed timely.3 Most of the time clinical and radiological findings in pulmonary diseases are non specific hence prompt pathology investigations and diagnosis are essential to improve patient’s survival and to reduce further morbidity and mortality.4 Autopsy is an important and most useful way to find out the condition of internal organs, for this a systematic examination of organs was undertaken according to standardised research protocol, to evaluate diseases or injury that may be present and to determine cause and manner of death.5In present study, status of lungs was examined grossly and microscopically. On gross examination we observed various findings like consolidation, nodule, scarring, fibrosis, collapse, or hyper inflated lungs as well as congestion. Pulmonary diseases are the significant cause of death worldwide affecting mostly 20-59 years age group. We performed this retrospective study to describe spectrum of various histopathologically proven pulmonary lesions and their incidences in respect to age and sex over a 4 year period that is January 2012 to December 2015.
MATERIAL AND METHODS Study was conducted in the department of pathology, SMS medical college Jaipur on 1715 specimens of lung from deceased of 0 - >70 years of age. We examined all lungs grossly as well as microscopically. The medical and clinical histories were traced. Gross examination of lungs included colour, volume (collapsed or inflated), and consistency, presence of any consolidation, nodule, bullae, scarring, fibrosis, infarction and congestion. All specimens were adequately fixed in 10% formalin, weighed, and dimensions measured. Sections from representative areas were taken and paraffin blocks were made following standard protocol. Four micron sections were cut and stained with haematoxylin and eosin according to standard procedures.6 Special stains were used wherever required. All the cases were analysed by descriptive statistics.
RESULTS In this study, we have observed that 1305 (76.09%) cases were from male deceased while 410 (23.91%) were of female, out of total 1715 cases. The male to female ratio was 3.18:1. Distribution of various pulmonary lesions out of 1715 autopsy cases was done (Table-1). After histopathological examinations, various pathological lesions were noted in 1549 (90.32%) cases while 166 (09.68%) cases were within normal limits. Out of these 1549 cases edema and congestion were the most common findings seen in 1325 (77.26%) cases, 1009 (76.15%) were males and 316 (23.85%) were females with male to female ratio (3.19:1). Most common age group affected was 20-59 years i.e.1106 cases (83.47%) and predominant age group in congestion and edema was 20-39 years with 621 cases (46.87%). Non tubercular pneumonia was the second most common finding noted in 137 cases (7.99%), 106 (77.37%) were males, females were 31 (22.63%) and male to female ratio 3.42:1. Most common age group affected was 20-59 years i.e. 108 (78.83%) cases. Tubercular pneumonia was the next common finding i.e. 70 cases (4.08%), 59 (84.29%) were males while 11 (15.11%) were female with male to female ratio 5.36:1. Most common age group affected was 20-59 years i.e. 59 (84.29%) cases. Next in order were malignant pulmonary lesions (including primary and secondary) 7 (0.41%) cases. All the cases found were males, most common age group affected was 40-59 years i.e. 4 (57.14%) cases, lung abscess and acute respiratory distress syndrome were 3 (0.17%) each with male to female ratio 1:2 in both the cases, as well as most common age group affected was 20-39 years in both the cases, as shown in table -2. Other findings were aspirational lung diseases 2 (0.12%), emphysema 2 (0.12%). Causes of death were taken out (Table-3). These were, due to unknown reason 812 (47.34%), sudden death 399 (23.27%), alcoholism 209 (12.17%), long illness 139 (8.11%), heart attack 122 (7.11%), poisoning 18 (1.08%), hanging 11 (0.63%) and drowning 5 (0.29%).
DISCUSSION The role and value of autopsy remains a vital component for the study and evaluation of the disease process, inspite of advances in diagnostic technology. There are large no. of cases of preventable respiratory diseases, still leads to morbidity and mortality.7, 8 and 9 In the present study age and sex wise distribution of pulmonary cases shows that the incidences were higher in 20-59 years age group. It is comparable to study done by V. Selvam et al where they found maximum incidences of pulmonary diseases in 3rd to 4th decades of life, men were more prone to death by diseases as compare to women 410 (23.91%)10 , while in study conducted by Chauhan et al, most common age group was 50->60 years.7 The reason may be that as men usually were bread earners and women usually indulged in household works. This makes the men more vulnerable for exposure of risk factors on their respective occupations as well as more addiction for smoking and alcoholism makes them prone for various diseases. Other studies were also showing comparable results with higher disease incidences in males as compare to females .11 In present study, we observed congestion and edema in 1325 (76.26%) cases while Chauhan et al found 182 (54.32%) and V. Selvam observed 32 (29.6%) cases. Non tubercular pneumonias were 137 (7.99%) in present study, while Chauhan et al and V. Selvam found.
Magnitude of Pulmonary diseases 14.62% and 10.2% respectively. Tubercular pneumonias in our study were 70 (4.08%) while these were 6.26% and 2.80% respectively in Chauhan et al and V. Selvam et al studies. Cases of emphysema were quite high in study conducted by V. Selvam et al i.e. 50% and Chauhan et al 7.06% while in present study they were only 0.12%. we found 0.17% each in lung abscess and ARDS cases, 0.12% cases of aspirational lung diseases. These cases were not found in studies conducted by Chauhan et al and V. Selvam et al. Malignant pulmonary lesions were found 0.41% in our study while it was 2.08% in study by Chauhan et al. No specific pathology was observed in 166 (9.68%) cases. [Table-4 ] The reason of difference amongst studies may be due to difference in sample size and pattern of studies.12 ,13 and 14
CONCLUSION The present study provides a comprehensive data about spectrum and frequency of Lung lesions, and up to our knowledge no such study has been done in our region. Autopsy studies can be of great value in improving the vision and diagnostic setup for better clinical assessment and timely diagnosis, to reduce further morbidity and mortality.
ACKNOWLEDGMENT
Authors wish to express and convey their sincere thanks and gratitude to all those who helped for completion of this research article. Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to author’s /editors/ publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
Authors acknowledge that we did not get any grants for this study; required funds were generated by ourselves. The Authors declare and acknowledges that we have no conflict of interest.
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2. Manjit S Bal, P S Sethi, Anil K Suri, Vijay K Bodal, G Kaur. Histopathological pattern in lung autopsies, Journal of Punjab Academy of Forensic Medicine and Toxicology 2008; 8(2):29- 31.
3. John E Hall. Guyton and Hall Textbook of Medical Physiology, 13th Edition, Elsevier: Saunders, 2015.
4. Kasper, Fauci, Hauser, Longo, Jameson, Loscalzo. Harrison’s principles of internal medicine, 19th ed. Vol 2, Mc Graw Hill; Indian edition:2015.
5. KS Narayan Reddy, OP Murty. The essentials of Forensic Medicine and Toxicology, 33rd edition. JayPee Brothers:2014.
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7. Chauhan, Madhuri Agrawal, Nirali Thakkar: Histopathological lesions in lung autopsy Journal of research in medical and dental science/vol.3/ issue 2/april-june.
8. Manjit et al: Journal of Punjab Academy of Forensic Medicine and Toxicology 2008.
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524188EnglishN2016April20HealthcareINTRAOPERATIVE AND POSTOPERATIVE COMPLICATIONS, ACCIDENTS AND FAILURES RELATED WITH DENTAL IMPLANT APPLICATIONS
English4449Damla TorulEnglish Mehmet Cihan BereketEnglish Ismail SenerEnglish Ali Ilker BastanEnglishWith revolutions in biotechnology, implant surgery has become a routine therapy in the last three decades for the rehabilitation of completely or partially edentulous patients. Despite implant surgery increasing popularity and high success rates of, complications due to implant therapy are still unavoidable. Complications can occur either intra-operative or post-operative period of the surgery. Intra-operative complications such as hematoma and ingestion or inhalation of mechanical components or instruments can be serious as life-threatening. Other complications that occur during implant placements are usually associated with local damages such as nerve injury, adjacent teeth damage and perforations of the nasal cavity or maxillary sinus. Also mandible fractures, sinusitis, peri-implant mucositis, peri-implantitis and periapical implant lesions are the complications that frequently encountered after surgery. Therefore implant therapy is a complicated procedure and the management of the complications associated with this therapy requires a special training and experience. This review categorized complications associated with dental implant applications and discusses management options of these complications.
EnglishDental implant, Displacement, Hemorrhage, Life-threating, Nerve injuryINTRODUCTION Dental implants are appliances placed in the jawbones for the management of tooth loss to maintain adequate function and aesthetic [1].Since dental implants have been first introduced in 1970s, they are used in various areas of the mouth with an increasing success rate and popularity[2,3].In 2003, Ardekian et al. [4] reported the 5-year success rate of implants range between 93 % and 97 %.However, complications in implant surgery are frequently encountered and management of these complications are become an important issue [5-7]. Until recently, these implant-related complications have increased by the increase in the number of implants placed and dentists, not only specialist, placing implants [2]. This article examined implant complications in two parts. The first section focuses on intraoperative complications and the second segment addresses the post-operative complications of the implant therapy.
INTRAOPERATIVE COMPLICATIONS Intraoperative complications occur during surgeries and could either be life threatening or local damage triggering. Hemorrhage Hemorrhages can occur during any kind of surgery and they can be taken care of by simple local measures. However, excessive and long lasting hemorrhage is generally considered to be a complication, while it is rarely as serious as life threatening [4,8]. Severe hemorrhages can be associated with the incision of arteries, sinus-lift procedures and preparation of the implant hole [5].The facial and maxillary arteries and their branches are mainly provided the blood supply of the mandible [6].During surgery these arteries may be injured because of the perforation of cortical plates and may leads hemorrhagic accidents [6].Bleeding can be result with a “pseudo-Ludwig phenomenon” which is characterized by elevation of the tongue, elevation of the floor of the mouth and airway obstruction[9]. In maxilla the posterior superior alveolar, infraorbital, descending palatinal and posterior palatin arteries can be damaged during placement of implant or sinus lift procedures [5,6]. Bleeding which arise from the branch of the maxillary artery has been described previously [10,11]. In the presence of hemorrhage, treatment techniques include bone wax, compression, electrocoagulation, bone grafts and in severe cases ligation of the damaged vessels [5,7,8].
It is not recommended to aspirate the area because of its limiting effect on the tamponading effect of the blood clot. In the cases which have restricted visibility external carotid angiography and endovascular management may be necessary [9]. In severe cases airway control can be provided by nasotracheal intubationand cricothyroidotomyor tracheostomy [11]. To prevent this kind of complication, detailed preoperative evaluation and rigorous surgery should be provided. Also, preoperative CT scans and usage of short implants in the risk areas decreases the prevalence of this complication(Figure 1) [4,7,12].
Involuntary Ingestion or Inhalation of Mechanical Components or Instruments During intraoperative period of surgery, a slippery area shows up due to blood and saliva. Hence, the instruments or implant components can slip and fall into the mouth accidentally from the operator’s hand [8].In these accidents, instruments can aspirated or ingested in 13 % and 87 % of the cases respectively [13].Also, sharpness of the instruments may cause vital structure injuries[13]. Therefore, a life threatening complication may occur when these materials are ingested or inhaled by the patient [7,8]. When the instrument is in the gastrointestinal tract the first management options are radiographic examination and a fiber-rich diet [13]. If, a foreign object is aspirated, airway embarrassment can occur and this is a potentially life-threatening condition. Thus, the patient airway must provide immediately and the foreign object should remove as quick as possible [5,14]. Also, bronchoscopy or gastroscopy are useful to reduce the morbidity [13].
To prevent this complication, gauze throat screens and silk ligatures can be used during surgery[5,14]. Nerve injury Neurosensory disturbances are unpleasant experiences that occur as a result of poor flap design, direct mechanical damage to nerve, compression of intra-alveolar edema or hematoma, excessive preparation during implant placement, nerve repositioning and implant placement in atrophic mandible [4,5,7,8]. These disturbances are classified in increasing severity as neuropraxia, axonotmesis and neurotmesis, respectively. Generally these injuries are temporary and continue as 4 weeks to 10 months [7]. Within this period, patients with such injuries may have difficulties performing common activities due to paresthesia, anesthesia dysesthesia or hyperesthesia [7,15]. Commonly inferior alveolar nerve, the mental nerve, the incisor branch of the mandibular nerve, the lingual nerve, and the nasopalatine nerve are likely to be exposed to iatrogenic injury during implant placement procedures [8]. To prevent the nerve injury the preoperative evaluation and exact localization of anatomic structures in the implantation area are mandatory. CBCT and CT scans are the techniques of choice for locate the anatomic structures [6,7,16].
When nerve injury occur as a result of pressure originate from an implant, management options include the removal of the implant or placement of a short implant. In the cases of minor injuries spontaneous healing can observed within days or months. However, prolonged pressure and neuritis may result with permanent degeneration of the nerve [17]. The primary treatment of nerve injuries include neuronal anti-inflammatory drugs or vitamin B-complex, but if a persistent anesthesia or dysesthesia is present more specialized procedures such as microsurgery may be required [5,17]. Damage to Adjacent Teeth Adjacent tooth damage is a rare complication of implant surgery and generally occurs with single implant placements [4,8].Tooth damage can be associated with inadequate distance between the implant and adjacent tooth, wrong angulation of the implant or occurrence of excessive heat during surgery [18].
As a result of above mentioned factors total or partial vitality loss can be seen in the adjacent tooth. Patients are generally asymptomatic but pain or sensitivity may occur occasionally [8]. To prevent the damage of adjacent tooth, a minimum distance of 1,5 to 2mm should be provided between adjacent tooth and the implant [6,7].Also, pre-surgical computed tomography may help ensure accurate diagnosis [18].In the presence of this complication, root-canal treatment, apicectomy and extraction are among the available treatment options(Figure 2) [6]. Perforations of Nasal Cavity or Maxillary Sinus Placement of implants in maxilla close to the nasal cavity or maxillary sinus may result with the perforation of the maxillary sinus or the nasal floor [5-8,19]. Management of perforations of the sinus membrane is commonly provided with the placement of biomaterials [6,19]. Other methods for treating perforation are folding the membrane up against itself, using sutures and fibrin glue[19].However, in the presence of large perforations surgery must postpone during the healing process [7,8]. Several investigators mentioned that these complications are generally well-tolerated and didn’t affect the implant survival [4,5,7].
Displacement of the Implant Inside the Sinus or Nasal Cavity Insertion of implant several millimeters into the sinus or nasal cavity is well tolerated [7]. However, displacement of the implant inside the sinus or nasal cavity is a serious complication [8]. This may be caused by inadequate primer stability, suction effect and improper distribution of occlusal forces [6]. Also, thin maxillary bone, inadequate planning and lack of experience are contribute the movement of the implants in the maxillary sinuses and nasal cavities [20]. In the case of a dislocated implant, it must remove surgically by intraoral or transnasal approach to prevent further complications [6,8]. To prevent these complications knowledge of anatomy, correct pre-surgical planning and adequate post-surgical follow up is mandatory(Figure 3) [6].
EARLY POSTOPERATIVE COMPLICATIONS Mandible Fractures The most important risk factor for the mandible fractures is the placement of an implant in the severely atrophic mandible. Also, lateralization of inferior alveolar nerve increases the risk of the fracture [4,6,7]. The compression stress during these surgical procedures and the prepared osteotomy sites weakens bones and leads to pathologic fractures [4]. The reported prevalence of this complication is 0,2% in the edentulous mandible [21]. Fractures of the mandible associated with implant placement can occur either immediately or in the post-operative period of the surgery [22]. To avoid such complications, Parkand Wang [17] mentioned that atrophic mandible must have a minimum of 7 mm height and 6 mm width. The management of this complication is related with severity of the fracture, volume of the mandibular bone and the location of the implant [5,7].
Open reduction or conservative approaches with bone grafts can used for the fixation of the fractured mandible [22]. Flap Dehiscence Dehiscence can be defined as the surgical wound opening that result with the exposure of the dental implant [8].Coverscrew loosening, mechanical irritation and flap tension are among the contributing factors of this complication [17]. The reported incidence of this complication vary between 2% and 13% [6].In the presence of small dehiscence, granulation tissue can compensate the opening but if the dehiscence is large re-suturing of the area should be performed [8].
Emphysema Emphysema is a complication which is caused by the high intraoral pressure and it is rarely encountered [7,8]. Air originate from the surgical devices or materials can be forced into the surgical area and the emphysema will occur [7]. Clinically it presents with swelling of half of the face and patients complained of pain similar to the tension sensation [23]. A characteristic crackling sound is evinced upon palpation [8,23]. Massage and compression are the therapeutical measures to manage emphysema by accelerating resorbtion of the air trapped in the tissues [8].
LATE POSTOPERATIVE COMPLICATIONS Failed Osseointegration Impaired healing, occlusal loading during osseointegration, failure to follow the planned protocol, technical errors during surgery, infections and especially bone overheating during implant site preparation leads failures in osteointegration. Lack of osseointegration is results in loss of the implant [8,24].Failure of endosseous implants can occur before or after occlusal loading with a prosthetic superstructure. The reported failure rate is from 0,7% to 3,8% [25]. Infections Maxillary Sinusitis Posterior maxilla is a complicated area for implant placement, so sinus lifting and grafting procedures are usually used to overcome the limitations of this area. However, complications include sinusitis and infection can unavoidably occur as a result of these procedures [26]. Symptoms of sinusitis may include fever, facial pain, and yellow to green purulent discharge from the nose, which may drain posteriorly causing a cough and malaise [7]. Management of implant associated sinusitis is surgical and maintaining the drainage and ventilation are the purposes of this procedure [20].
Peri-Implant Mucositis Peri-implant mucositis is defined as the reversible inflammation of the mucosa adjacent to the implant and may be caused by inadequate prosthetic restorations, poor oral hygiene and improper abutments or healing caps [4,27,28]. Generally no signs of bone losses are observed in this situation [4]. Reddish color of the inflamed mucosa adjacent to implant, swelling and bleeding are the clinical features of the periimplant mucositis[28]. Mechanical, antiseptic and antibiotic treatments are possible procedures of choice for controlling an ongoing infection (Figure 4)[28].
Peri-Implantitis Peri-implantitis is an inflammatuar process around tissues of an implant and it results with the loose of the bone around the implant [29,30]. It is an important cause of implant failures and accounts for 10% to 50% of all failures observed one year after the implantation [1]. Early implant exposure, poor oral hygiene are the risk factors contributing peri-implantitis [4]. Diagnosis of peri-implantitis is based on degree of supporting boneloss, clinically detectable pocket depths, purulent discharge and implant mobility [28]. Management of peri-implantitis depend on the severity of the cases and include debridement, antimicrobial treatment or regenerative procedures [1,30].
Periapical Implant Lesions The symptoms of apical peri-implantitis is pain, swelling, tenderness and occasionally the presence of a fistula [31]. Possible causes of this complication are excessive heating, contamination, vascular ischemia and pre-existing bone pathology [4,31,32]. Removal of granulation tissue, curettage of the bony walls and if the primary stability is absent scarification of the implant are the treatment options [32]. Implant Fractures Implant fracture is a biomechanical complication with the reported incidence of 0,2 % in totally edentulous and 1,5 % in the partially edentulous jaws. The lack of periodontal ligament is an important risk factor for this complication and hinder the compensation against the forces that occur at the time of chewing [33].
Also bone loss, manufacturing defects, excessive occlusal load and patients-related habits are the other possible causes of the implant fractures [30]. To overcome these shortcomings, periodic occlusal evaluation and proper preoperative planning by considering biomechanical principles are essential. Removal of the implant, modification of the existing prosthesis or modification of the fractured implant are the options for management of this condition (Figure 5) [34].
CONCLUSION Nowadays, there is no doubt that implant therapy has become the most predictable treatment option for rehabilitation of tooth loss. However, complications related with implant therapy are inevitable events that effect the success of the entire therapy. To reduce the incidence of these complications knowledge of surgical anatomy, careful clinical and radiographic examination, proper treatment planning, usage of appropriate instruments and rigorous surgery are important prerequisites. If all of these factors are carefully followed, the complications are effectively avoided. But, adequate training and experience are required when these complications occur.
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