Medical and Dental Consultantsí Association of Nigeria
Home - About us - Editorial board - Search - Ahead of print - Current issue - Archives - Submit article - Instructions - Subscribe - Advertise - Contacts - Login 
  Users Online: 2163   Home Print this page Email this page Small font sizeDefault font sizeIncrease font size
 

  Table of Contents 
ORIGINAL ARTICLE
Year : 2017  |  Volume : 20  |  Issue : 2  |  Page : 188-193

Influence of Helicobacter pylori infection on the prevalence and patterns of upper gastrointestinal symptoms in Nigerians with diabetes mellitus


1 Gastroenterology Unit, ReMay Consultancy and Medical Services, Ikeja, Lagos, Nigeria
2 Gastroenterology Unit, Health Gates Consultancy and Medical Services, Maryland, Lagos, Nigeria
3 Division of Molecular Biology, Nigerian Institute of Medical Research, Lagos, Nigeria
4 Endocrinology Unit, College of Medicine, University of Lagos, Lagos, Nigeria

Date of Acceptance03-May-2016
Date of Web Publication13-Jan-2017

Correspondence Address:
Dr. A Oluyemi
ReMay Consultancy and Medical Services, Ikeja, Lagos
Nigeria
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1119-3077.183257

Rights and Permissions
   Abstract 

Background: Infection with Helicobacter pylori infection is widespread in our environment. However, whether this fact has any bearing on the prevalence and pattern of symptoms referable to the upper gastrointestinal (GI) system in our population of diabetes mellitus (DM) patients has not been much studied.
Aim: We embarked on this study to evaluate if H. pylori infection played any significant role in the prevalence and patterns of upper GI symptoms in type 2 DM patients in Lagos, Nigeria.
Materials and Methods: A case–control design was employed. One hundred consecutive, consenting, and ambulant type 2 DM patients were recruited from the Lagos University Teaching Hospital and 100 age- and sex-matched nondiabetic controls were drawn from medical outpatient clinics of the same hospital. All subjects were investigated for a marker of active infection with H. pylori via stool antigen testing, had anthropometric measurements taken, and completed a structured questionnaire administered to elicit for the presence of various upper GI symptoms over the preceding 3 months prior to the time of the study. The controls were further tested for DM. For analysis, the symptoms were divided into dyspepsia, gastroesophageal reflux (GER), and others.
Results: H. pylori infection status was neither significantly associated with dyspepsia in either cases or controls (χ2 [1] = 2.198, P = 0.138) nor significantly associated with the symptomatic suggestion of GER in either cases or controls (χ2 [1] = 3.742, P = 0.053). Moreover, the same held for the other upper GI symptoms in cases or controls (χ2 [1] = 0.157, P = 0.203). H. pylori infection was detected in 18% of DM patients and 13% of controls, but there was no statistical significance in this difference (χ2 [1] = 0.954, P = 0.329).
Conclusion: Infection with H. pylori does not appear, from the results of this study, to influence the prevalence and patterns of upper GI symptoms in patients with DM in Nigeria.

Keywords: Diabetes mellitus, gastrointestinal symptoms, Helicobacter pylori, Nigeria


How to cite this article:
Oluyemi A, Anomneze E, Smith S, Fasanmade O. Influence of Helicobacter pylori infection on the prevalence and patterns of upper gastrointestinal symptoms in Nigerians with diabetes mellitus. Niger J Clin Pract 2017;20:188-93

How to cite this URL:
Oluyemi A, Anomneze E, Smith S, Fasanmade O. Influence of Helicobacter pylori infection on the prevalence and patterns of upper gastrointestinal symptoms in Nigerians with diabetes mellitus. Niger J Clin Pract [serial online] 2017 [cited 2020 Apr 9];20:188-93. Available from: http://www.njcponline.com/text.asp?2017/20/2/188/183257


   Introduction Top


Some researchers consider that gastrointestinal (GI) symptoms are more prevalent in diabetes mellitus (DM) patients than in the general population.[1],[2],[3] Furthermore, others have noted that Helicobacter pylori infection might contribute significantly to this relationship. The latter notion has been put to the test by various researchers.

Gasbarrini et al.[4] reported a higher prevalence of several dyspeptic symptoms in type 1 DM patients with H. pylori infection as compared with the H. pylori-negative group. The study, however, did not correct for confounding factors such as age, gender, and socioeconomic factors with multivariate analyses. The same investigators also suggested that the upper GI symptoms observed previously were improved with H. pylori eradication.[5] The second report was also flawed in that there was no placebo control group. Their results were supported by similar earlier findings among type 2 diabetics.[6] In addition, a local study from Lagos showed a higher prevalence of GI symptoms in DM patients than in nondiabetics.[7]

On the other hand, later studies have strengthened arguments against the notion that H. pylori infection influences GI symptoms in DM. Xia et al.[8] found that H. pylori infection was not associated with any upper GI symptom, either before or after adjustments for potential risk factors. Similarly, findings were reported in a population of young people with type 1 DM.[9]

Again, other workers in the Iasi region of Romania reported that the prevalence of H. pylori infection was neither associated with the known duration of diabetes nor any significant difference in the upper GI symptoms score between H. pylori-positive and H. pylori-negative diabetic patients.[10] In fact, the endoscopic findings in patients with DM (whatever their H. pylori infection status) were in the same range with those found in dyspeptic subjects from the same region.

In 2008, a Turkish publication reported that even within a type 2 DM population, there was no significant increase in H. pylori prevalence between those who complained of dyspeptic symptoms and those who did not.[11] Such results were mirrored a study from Abakaliki where it was found that prevalence and patterns of dyspeptic symptoms were not significantly different between H. pylori seropositive diabetics and similarly, infected nondiabetic controls.[12]

Aim

The objective of this study was to investigate if H. pylori had any significant role to play in the pattern of upper GI symptoms in Nigerians with DM.


   Materials and Methods Top


Study location

Lagos University Teaching Hospital (LUTH), the location for this study, is situated in Idi-Araba, Surulere Local Government Area of Lagos State, Nigeria. The catchment area of the hospital referral base is statewide (and even beyond) and embraces a diverse array of patients with differing tribal, socioeconomic, and lineage backgrounds.

Study design

The study employed a case–control design. Here, measurement of cause and outcome variables among both cases and controls was carried out at the same point in time.

Subjects

The subjects for this study were drawn from adults with type 2 DM patients of LUTH. They were all ambulant patients attending the DM outpatient clinics.

The age of the patients was from 31 to 82 years, and they agreed to sign the consent forms as an indication of willingness to participate in the study.

Selection criteria for cases

Inclusion criteria for cases

(1) Patients with objective evidence of DM as demonstrated by the World Health Organization (WHO) criteria for diagnosis of diabetes,[13] i.e., fasting plasma glucose is ≥7.1 mmol/l (126 mg/dl) or a 2-h postprandial plasma glucose of ≥11.1 mmol/l (200 mg/dl) or those with classical symptoms and random blood glucose >11 mmol/l. Those who had been previously diagnosed with DM by this criterion but whose blood glucose had now been controlled with diet, drugs ± insulin were included in the study. (2) All recruited subjects agreed to sign the informed consent form for permission to be included in the study.

Exclusion criteria for cases

Presumed type 2 DM patients whose blood glucose estimations at diagnosis do not meet the minimum requirements as dictated by the WHO were excluded from this study along with those that declined the offer to sign the informed consent form.

As diarrheic stools are not appropriate for testing with the immunoassay-based Rapid Strip HpSA™ kit,[14] cases (and controls) whose submitted loose, watery stools were excluded.

Selection criteria for controls

Inclusion criteria for controls

Age- and sex-matched controls were drawn from the other patients attending the other nondiabetic medical outpatient clinics.

All were required to show consent to participate in the study by agreeing to sign the informed consent form in the presence of a witness before being enrolled in the study and before samples are taken for relevant tests.

Exclusion criteria for controls

Controls whose blood glucose estimations met the WHO criteria for diagnosis of DM were excluded from inclusion as controls. Prospective controls with diarrhea and those who declined the offer to sign the informed consent form were also excluded from the study.

The possibility of bias was excluded by ensuring that patients with dyspepsia complaints attending the gastroenterology clinics were excluded from the study. Further, all controls who had had eradication therapy for H. pylori in the past were excluded from the study.

Data collection

Questionnaire

After obtaining informed consent, 100 consecutive consenting patients and 100 consenting controls satisfying the inclusion criteria were recruited from among only ambulant outpatients of LUTH.

A well-structured pretested questionnaire was administered by a medical doctor to each participant. The first page of the questionnaire included biodata, anthropometry, socioeconomic variables such as occupation and level of education, and if the participant had prior knowledge of whether he or she was diabetic.

The already validated diabetes bowel symptom questionnaire was modified and administered to determine GI symptoms.[15] All questionnaires were administered by a medical doctor.

The patients were then required to submit stool samples which were tested for evidence of H. pylori infection with the immunoassay-based Rapid Strip HpSA™ (Meridian Bioscience, Europe- a division of Meridian Bioscience, Incorporated, Cincinnati, U.S.A) (sensitivity 96.1%, specificity 90.6%).[14]

Age- and gender-matched controls were then selected from the pool of nondiabetics attending the other outpatient clinics in LUTH. After signing informed consent forms, they had the questionnaires administered to them.

However, each one of the controls had blood drawn for fasting blood glucose and those who met the minimum WHO requirements were excluded from being controls in this study. They were also required to provide stool samples for H. pylori testing. However, they were encouraged to submit their own stool samples early on a working day morning as they would simultaneously have fasting blood glucose analysis.

Sample analysis

The two analyses run in this study were those of determining if all participants were positive or not for H. pylori stool antigen and if the controls had blood glucose ranges that were diabetic or not. A glucometer was used to determine the latter in the fasted state according to the WHO guidelines. The former parameter was determined as stated in the manual of the immunoassay-based Rapid Strip HpSA™.[14]

Ethical considerations

Ethical approval was obtained from the Ethics Committee of LUTH prior to the commencement of the study.

Statistical analysis

For analysis, the upper GI symptoms were divided into three groups:

  1. Dyspepsia (defined as pain or discomfort centered around the upper abdomen)
  2. Gastroesophageal reflux (GER; indicated in the questionnaire as persistent heartburn and/or regurgitation)
  3. Overall (defined as any of the above symptoms put together).


The body mass index (BMI) was used to determine obesity by the formula; weight/height 2 - a value of ≥30 kg/m 2 being the threshold for obesity.[15]

The data obtained were analyzed using the IBM SPSS Statistics for Windows, Version 20.0. IBM Corp. Released 2011. Armonk, NY: IBM Corp. Data were expressed as means ± standard deviation and frequencies.

Statistical analysis was done using Student's t-test for continuous variables and Chi-square for categorical data. Multivariate analysis was included in view of possible confounding factors.


   Results Top


Helicobacter pylori and dyspepsia

Of the 100 recruited type 2 DM patients, 30% (n = 30) had symptoms of pain and/or discomfort in the upper half of the abdomen (dyspepsia) over the preceding 3 months to time of questionnaire administration. A similar high percentage of controls, 40% (n = 40), also had these complaints [Figure 1]. Infection with H. pylori was not significantly associated with the difference in the prevalence of dyspepsia across the two groups (χ2 [1] = 2.198, P = 0.138).
Figure 1: Proportion of participants with dyspepsia

Click here to view


Helicobacter pylori and gastroesophageal reflux-suggestive symptoms

The predominant complaints in GER are typically heartburn and acid regurgitation [16] – these two symptoms were itemized in the administered questionnaire.

Results show that a high proportion of respondents (20% of diabetics and 32% of controls) had, within a 3-month period, symptoms suggestive of GER. There was no significant relationship between groups (χ2 [1] =3.742, P = 0.053) [Figure 2].
Figure 2: Prevalence of gastroesophageal reflux symptoms among study participants

Click here to view


Again, H. pylori infection status was not significantly associated with the symptomatic suggestion of GER in either cases or controls (χ2 [1] = 3.742, P = 0.053). The association between sex and likelihood of having GER symptoms was not statistically significant in either set-controls (χ2 [1] = 2.804 P = 0.094) and diabetics (χ2 [1] = 0.500, P = 0.480).

A noteworthy fact from the data in this study is that it did not reveal significant relationship between BMI and the presence of symptoms suggestive of GER (case: [χ2 [1] = 1.667 P = 0.435]; control: [χ2 [1] = 3.236 P = 0.357]). Further, smoking appeared not to be significantly associated with GER symptoms both in cases (χ2 [1] = 0.336 P = 0.845) and in controls (χ2 [1] = 0.064 P = 0.969).

Helicobacter pylori and other upper gastrointestinal symptoms

[Table 1] summarizes the pattern of upper GI symptoms among respondents.
Table 1: Prevalence of Helicobacter pylori infection and gastrointestinal symptoms in diabetics and nondiabetic controls

Click here to view


Among control subjects, a high percentage (56%) had experienced one or more upper GI symptoms within 3 months of symptoms questionnaire administration – the list of symptoms is presented in [Figure 3]. In the nondiabetic controls, the prevalence of individual symptoms ranged from 40% (for abdominal pain or discomfort) to 2% (for dysphagia).
Figure 3: Prevalence of upper gastrointestinal symptoms in cases (n = 100) and controls (n = 100)

Click here to view


The overall prevalence of upper GI symptoms was 51% in men and 61% in women which was not significantly different across the sexes for controls (χ2 [1] = 2.029, P = 0.154). Age was similar in those with or without symptoms (means 53.8 ± 10.85 vs. 55.8 ± 9.86 years), t (198) = −1.364, P > 0.05.

Overall, symptoms were not associated with H. pylori status in controls 53.9% in H. pylori-negative subjects and 55.2% in H. pylori-positive subjects, (χ2 [1] = 0.020, P = 0.887) neither BMI (χ2 [1] = 1.376, P = 0.241) nor smoking history (χ2 [1] = 0.064, P = 0.469).

A similar high proportion of type 2 DM cases (47%) had experienced one or more upper GI symptoms. On comparison with controls, upper GI symptoms were not significantly associated with the presence or otherwise of type 2 diabetes among the study population (χ2 [1] = 3.742, P = 0.053).

However, analysis of relationship between DM status and dyspepsia in obese participants revealed that female sex in this subgroup was significantly associated with this particular symptom (χ2 [1] = 5.000, P = 0.025, odds ratio = 0.143, 95% confidence interval = 0.023–0.877). The same did not hold true for male sex in this subgroup (χ2 [1] = 0.117, P = 0.733).

H. pylori infection as detected by the presence of the stool antigen marker was positive in 18% of DM patients and 13% of controls; however, there was no statistical significance in this difference (χ2 [1] = 0.954, P = 0.329) [Figure 4].
Figure 4: Prevalence of Helicobacter pylori infection among study participants

Click here to view



   Discussion Top


The objective of this study was to assess whether H. pylori infection is associated with prevalence and patterns of upper GI symptoms in the study population. From the findings in this study, H. pylori infection does not appear to significantly influence the prevalence in both cases and controls or pattern of GI symptomatology. The results are in keeping with findings in a local study where it was found that H. pylori infection prevalence did not have any relationship with dyspeptic symptoms between diabetics and nondiabetics.[12] Although another study reported a higher prevalence of GI symptoms in Lagos DM patients versus nondiabetics, the difference failed to reach statistical significance.[7]

There are also various reports that support this finding.[8],[11] While the former [8] was a report from a community-based, seroprevalence study, the latter [11] is a 2008 Turkish study on histology findings from the gastric mucosa of dyspeptic diabetics and controls.

An Italian study reported a higher prevalence of several upper GI symptoms in H. pylori-positive compared with H. pylori-negative patients with type 1 DM.[4] The need for correction for potential confounding variables such as age and socioeconomic factors by multivariate analysis has been noted above. Unfortunately, it seems that this was not done by the Italian team before reaching conclusions about the differences observed.[8]

Female sex in the subgroup of obese DM patients was shown to be significantly associated with dyspeptic symptoms. This might have not been previous documented in our locality, but it is not a novel concept. Previous studies had identified female gender as an independent risk factor for upper GI symptoms.[8],[17],[18],[19] Xia et al.[8] summarized the proposed underlying mechanisms that are speculated to account for this association:

  • Estrogen and progesterone secretion may modulate GI motility [20],[21]
  • Psychological factors play a significant role in this difference as Talley et al.[22] had reported that emotional and psychological distress was independently associated with upper GI symptoms in diabetes while Wredling et al.[23] have reported that women with DM experienced more anxiety and depression than men.


In addition, obesity has been established to have a significant association with several key GI symptoms.[24] Increasing BMI has long been significantly related to increases in prevalence and differences in pattern of GI symptoms.[24],[25],[26]

The sample size was small, and thus, the study is rather underpowered to decisively answer the scientific question of whether H. pylori has any influence at all on the prevalence and pattern of upper GI symptomatology in DM patients. However, it represents an initial step to this. Another possible confounding factor could be control of diabetes in the study subjects. Hence, the interpretation of the results of this study will be limited as this was not accounted for. All in all the study results, however, still merit consideration as a springboard for further discuss inquiries and larger more empowered studies on the subject matter.


   Conclusion Top


Colonization of the GI tract with H. pylori did not have a significant association with the prevalence and patterns of upper GI symptoms in patients with DM in Lagos, Nigeria. The study shows that female sex in the subgroup of obese DM patients was significantly associated with symptoms of dyspepsia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Ricci JA, Siddique R, Stewart WF, Sandler RS, Sloan S, Farup CE. Upper gastrointestinal symptoms in a U.S. national sample of adults with diabetes. Scand J Gastroenterol 2000;35:152-9.  Back to cited text no. 1
    
2.
Ko GT, Chan WB, Chan JC, Tsang LW, Cockram CS. Gastrointestinal symptoms in Chinese patients with Type 2 diabetes mellitus. Diabet Med 1999;16:670-4.  Back to cited text no. 2
    
3.
Enck P, Rathmann W, Spiekermann M, Czerner D, Tschöpe D, Ziegler D, et al. Prevalence of gastrointestinal symptoms in diabetic patients and non-diabetic subjects. Z Gastroenterol 1994;32:637-41.  Back to cited text no. 3
    
4.
Gasbarrini A, Ojetti V, Pitocco D, De Luca A, Franceschi F, Candelli M, et al. Helicobacter pylori infection in patients affected by insulin-dependent diabetes mellitus. Eur J Gastroenterol Hepatol 1998;10:469-72.  Back to cited text no. 4
    
5.
Gasbarrini A, Ojetti V, Pitocco D, Armuzzi A, Silveri NG, Pola P, et al. Efficacy of different Helicobacter pylori eradication regimens in patients affected by insulin-dependent diabetes mellitus. Scand J Gastroenterol 2000;35:260-3.  Back to cited text no. 5
    
6.
Gentile S, Turco S, Oliviero B, Torella R. The role of autonomic neuropathy as a risk factor of Helicobacter pylori infection in dyspeptic patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 1998;42:41-8.  Back to cited text no. 6
    
7.
Onyekwere C, Ogbera A. Prevalence of gastrointestinal symptoms in diabetics in an urban Hospital in Nigeria. Internet J Endocrinol 2006;4:1039-46.  Back to cited text no. 7
    
8.
Xia HH, Talley NJ, Kam EP, Young LJ, Hammer J, Horowitz M. Helicobacter pylori infection is not associated with diabetes mellitus, nor with upper gastrointestinal symptoms in diabetes mellitus. Am J Gastroenterol 2001;96:1039-46.  Back to cited text no. 8
    
9.
Candelli M, Rigante D, Marietti G, Nista EC, Crea F, Bartolozzi F, et al. Helicobacter pylori, gastrointestinal symptoms, and metabolic control in young type 1 diabetes mellitus patients. Pediatrics 2003;111(4 Pt 1):800-3.  Back to cited text no. 9
    
10.
Stanciu OG, Trifan A, Sfarti C, Cojocariu C, Stanciu C. Helicobacter pylori infection in patients with diabetes mellitus. Rev Med Chir Soc Med Nat Iasi 2003;107:59-65.  Back to cited text no. 10
    
11.
Demir M, Gokturk HS, Ozturk NA, Kulaksizoglu M, Serin E, Yilmaz U. Helicobacter pylori prevalence in diabetes mellitus patients with dyspeptic symptoms and its relationship to glycemic control and late complications. Dig Dis Sci 2008;53:2646-9.  Back to cited text no. 11
    
12.
Ugwu N, Ugwuja E, Ejikeme B, Obeka N. Helicobacter pylori Seropositivity in Nigerians with Type 2 Diabetes Mellitus. Internet J Trop Med 2007;4(2).  Back to cited text no. 12
    
13.
Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycemia. Report of a WHO/IDF Consultation; 2006.  Back to cited text no. 13
    
14.
Rapid Strip HpSA™ Information Pamphlet from Meridian Bioscience, Europe- a division of Meridian Bioscience, Incorporated, Cincinnati, USA.  Back to cited text no. 14
    
15.
World Health Organization. Obesity: Preventing and Managing the Global Epidemic. Report of a WHO Consultation. WHO Technical Report Series 894. Geneva: World Health Organization; 2000.  Back to cited text no. 15
    
16.
Quan C, Talley NJ, Cross S, Jones M, Hammer J, Giles N, et al. Development and validation of the diabetes bowel symptom questionnaire. Aliment Pharmacol Ther 2003;17:1179-87.  Back to cited text no. 16
    
17.
Talley NJ, Axon A, Bytzer P, Holtmann G, Lam SK, Van Zanten S. Management of uninvestigated and functional dyspepsia: A working party report for the World Congresses of gastroenterology 1998. Aliment Pharmacol Ther 1999;13:1135-48.  Back to cited text no. 17
    
18.
Schvarcz E, Palmér M, Ingberg CM, Aman J, Berne C. Increased prevalence of upper gastrointestinal symptoms in long-term type 1 diabetes mellitus. Diabet Med 1996;13:478-81.  Back to cited text no. 18
    
19.
Spångéus A, El-Salhy M, Suhr O, Eriksson J, Lithner F. Prevalence of gastrointestinal symptoms in young and middle-aged diabetic patients. Scand J Gastroenterol 1999;34:1196-202.  Back to cited text no. 19
    
20.
Malaty HM, Graham DY. Importance of childhood socioeconomic status on the current prevalence of Helicobacter pylori infection. Gut 1994;35:742-5.  Back to cited text no. 20
    
21.
Patel P, Mendall MA, Khulusi S, Northfield TC, Strachan DP. Helicobacter pylori infection in childhood: Risk factors and effect on growth. BMJ 1994;309:1119-23.  Back to cited text no. 21
    
22.
Talley SJ, Bytzer P, Hammer J, Young L, Jones M, Horowitz M. Psychological distress is linked to gastrointestinal symptoms in diabetes mellitus. Am J Gastroenterol 2001;96:1033-8.  Back to cited text no. 22
    
23.
Wredling R, Stålhammar J, Adamson U, Berne C, Larsson Y, Ostman J. Well-being and treatment satisfaction in adults with diabetes: A Swedish population-based study. Qual Life Res 1995;4:515-22.  Back to cited text no. 23
    
24.
Eslick GD. Gastrointestinal symptoms and obesity: A meta-analysis. Obes Rev 2012;13:469-79.  Back to cited text no. 24
    
25.
Delgado-Aros S, Locke GR 3rd, Camilleri M, Talley NJ, Fett S, Zinsmeister AR, et al. Obesity is associated with increased risk of gastrointestinal symptoms: A population-based study. Am J Gastroenterol 2004;99:1801-6.  Back to cited text no. 25
    
26.
Chirila I, Drug VL, Petrariu FD, Gavat V. Overweight and gastrointestinal symptoms among adults of working age in Iasi City, Romania. Rev Med Chir Soc Med Nat Iasi 2012;116:268-73.  Back to cited text no. 26
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1]


This article has been cited by
1 Prevalence of Helicobacter pylori infection among dyspeptic patients with and without type 2 diabetes mellitus in Nigeria
Stella I. Smith,Tolulope Jolaiya,Charles Onyekwere,Muinah Fowora,Rose Ugiagbe,Ifeanyi Agbo,Cara Cookey,Olufunmilayo Lesi,Dennis Ndububa,Olusegun Adekanle,Pia Palamides,Isaac Adeleye,Henry Njom,Ayodeji Idowu,Anna Clarke,Rinaldo Pellicano
Minerva Gastroenterologica e Dietologica. 2019; 65(1)
[Pubmed] | [DOI]



 

Top
  
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
   Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed3188    
    Printed82    
    Emailed0    
    PDF Downloaded289    
    Comments [Add]    
    Cited by others 1    

Recommend this journal