Skip Navigation


NDT Advance Access originally published online on September 27, 2006
Nephrology Dialysis Transplantation 2006 21(12):3545-3549; doi:10.1093/ndt/gfl407
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
21/12/3545    most recent
gfl407v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Shukla, A.
Right arrow Articles by Bargman, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shukla, A.
Right arrow Articles by Bargman, J. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Streptococcal PD peritonitis—a 10-year review of one centre's experience

Ashutosh Shukla, Zita Abreu and Joanne M. Bargman

University Health Network and University of Toronto, Toronto, Ontario, Canada

Correspondence and offprint requests to: Joanne M. Bargman, MD, FRCPC, 200 Elizabeth Street 8N-840, Toronto, Ontario M5G 2C4, Canada. Email: joanne.bargman{at}uhn.on.ca



   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Acknowledgements
 References
 
Background. Detailed descriptive studies focusing on streptococcal peritonitis in patients on peritoneal dialysis are lacking. Most of the current information is available through isolated case reports.

Methods. We conducted a retrospective analysis of our peritoneal dialysis (PD) peritonitis database over the last decade to study the clinical profile and treatment outcomes of streptococcal peritonitis.

Results. A total of 68 patients (age: 57.12 ± 16.6 years; male: 58.7%) with 104 episodes of streptococcal peritonitis (11.7% of total peritonitis) were identified. Of the patients, 18 (26.4%) were considered immunocompromised [failed renal transplant, systemic lupus erythematosus (SLE)] and 28 (41.1%) had diabetes.

Streptococcus viridans accounted for the majority (94 episodes: 90.3%) of the streptococcal peritonitis. One patient developed S. viridans peritonitis after dental cleaning without antibiotic prophylaxis. Two (1.9%) infections with S. agalactiae and S. bovis each and seven (6.7%) with non-haemolytic Streptococcus were noted. Three patients had hospital-acquired infection. Twenty-six (25%) episodes needed 8 ± 5.9 days of hospitalization.

Concurrent infection with two organisms accounted for 17 (16.3%) episodes. Cefazolin (71) and vancomycin (29) were the primary antibiotics used for the treatment. Five episodes needed two antibiotics and one patient required antifungal treatment.

A third of the patients (33.3%) had peritonitis that resolved slowly, although the majority of those (94%) did ultimately resolve with antibiotics alone. Five (4.8%) episodes required removal of the PD catheter. Three of them were associated with dual infections (one each with yeast, Stenotrophomonas and Enterococcus). Relapse occurred in eight (7.6%) episodes, and 11 (10.5%) recurred over the period from 4 weeks to 6 months after treatment.

Conclusions. Streptococci remain a significant cause of PD peritonitis. Viridans strep is the primary subtype responsible. Isolated infections with these organisms are associated with slower response, good outcome and higher rates of recurrence.

Keywords: PD peritonitis; peritoneal dialysis; streptococcal peritonitis



   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Acknowledgements
 References
 
Peritoneal dialysis (PD)-associated peritonitis is most commonly caused by the Gram-positive cocci with predominance of staphylococcal subgroup [1–3]. Approximately 20% of all PD peritonitis is caused by Gram-negative, anaerobes, fungal or mixed infections [2,3]. Clinical characteristics and outcomes of these infections and associated risk factors have been well described in the literature. Around 10–15% of peritonitis is caused by the streptococcal subgroup of organisms [1,2]. Systemic studies of this subcategory of Gram-positive infections are lacking. Furthermore, the classification of Streptococci has evolved over the last three decades [4]. Hence, pure Streptococcus-induced PD peritonitis has mainly been reported as isolated cases. Inclusion of infections caused by Enterococcus, which now has been recognized as a separate genus of Gram-positive cocci, is another source of confusion and may cause disparity in reporting over the last years [5]. Hence, we conducted a retrospective study of our PD peritonitis database to study the clinical profile and treatment response of streptococcal peritonitis to identify the factors associated with outcome in order to facilitate an evidence-based management approach.



   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Acknowledgements
 References
 
This retrospective study was carried out at the Home Peritoneal Dialysis Unit of the University Health Network, Toronto, Canada. We included all episodes of peritonitis occurring between 1 April 1995 and 31 March 2005. Culture-negative peritonitis was excluded from the analysis. We obtained our data by reviewing case records of all patients with bacterial peritonitis. Diagnosis of bacterial peritonitis was made based on the presence of a positive bacterial culture of the PD effluent if it was associated with an effluent white cell count of >100/µl, with >50% polymorphonuclear leucocytes or signs of peritoneal inflammation. We considered an episode of peritonitis that recurred within 4 weeks after the treatment of a previous episode to be a relapse. Repeat peritonitis was considered as infection by the same organism after 4 weeks of treatment. The data recorded included age at the time of peritonitis, age at the start of PD, sex, presence of diabetes mellitus (DM), cause of end stage renal disease (ESRD) and the duration of PD before the onset of the peritonitis episode. A patient receiving corticosteroids at the time of peritonitis, or having previous renal transplantation or with evidence of malignancy was considered immunocompromised.

For each episode of peritonitis, data were collected on the symptoms of peritonitis, the condition of the exit site, the initial PD effluent cell count, the initial effluent neutrophil count, the systemic white blood cell (WBC) count, the species of micro-organism causing peritonitis, and the type and duration of antibiotic treatment. Changes in the microbiological reporting terminology were noted during the data collection and these were clarified by discussion with the primary laboratory microbiologist. A record was made of the number of days the PD fluid cell count was >100/µl. We also recorded the ‘peritonitis count’ (i.e. the number of episodes of peritonitis before the current one). Peritonitis that was slow to resolve, or refractory peritonitis, was defined as the presence of PD fluid cell count >100/µl after 5 days of antibiotic therapy [6]. Serum albumin prior to each episode of peritonitis was recorded as a measure of patients’ nutritional and inflammatory status. Also, we recorded the date of catheter removal, death or transfer to haemodialysis. ‘Non-resolution’ was defined as either death of the patient due to peritonitis, catheter removal, or temporary or permanent transfer to hemodialysis (HD) secondary to unresolved peritonitis. Hospitalization was decided by the treating physician. All patients were treated initially with two rapid exchanges for peritoneal lavage prior to adding an antibiotic to the exchanges. During our study period, we used three different empirical antibiotic regimens following International Society of Peritoneal Dialysis (ISPD) recommendations: cefazolin with tobramycin, vancomycin with tobramycin and cefazolin with ceftazidime. Vancomycin was used as an alternative to cefazolin therapy in some cases during the early study period and used only in cases of cefazolin allergy or resistance in the latter part of the study period. Antibiotics were changed according to the culture and sensitivity results of the PD effluent.



   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Acknowledgements
 References
 
A total of 68 patients with 104 episodes of streptococcal peritonitis were identified. They comprised 11.7% of the total peritonitis cohort. However, we found that the incidence of the strep peritonitis was 6% in 1995–96 and subsequently increased to 12–16% from 1997 onwards. Demographic characteristics of the patient population are shown in Table 1. The current episode of the peritonitis occurred after a median of two (range: 1–12) previous episodes of peritonitis. Of all patients, 18 (26.4%) were considered immunocompromised, and 28 (41.1%) diabetic. These values are similar to the percentage of immunocompromised and diabetic patients in our previously published review of all peritonitis episodes in our centre [2]. Abdominal pain was the most common symptom of peritonitis present in 85 (81.7%) episodes. We did not have data on the severity of the abdominal pain to compare with other forms of peritonitis. Nausea and vomiting were present in 31 (29.8%), fever in 20 (19.2%) and diarrhoea in 12 (11.5%) episodes. Cloudy PD effluent was present in all but two episodes, which occurred in the hospital-acquired infections. PD fluid cell count was not available in two episodes at presentation and were found to be <100 in three (2.9%) of the remaining episodes. These patients were diagnosed based on two out of the three cardinal symptoms of peritonitis. PD fluid cell count varied from <100 to 22 000 (median: 3175). Elevated blood leucocyte count was present in just 11 (10.5%) episodes. Twenty-six episodes (25%) needed 8 ± 5.9 days of hospitalization.


View this table:
[in this window]
[in a new window]

  		Table 1. Demographic characteristics

 
Exit site discharge was found in just eight (7.6%) episodes, of which only one had culture-positive infection with coagulase-negative Staphylococci (CNS). Peritoneal leak and co-existent intestinal obstruction were found in one patient each. Interestingly, one patient developed Streptococcus viridans peritonitis after undergoing dental cleaning without antibiotic prophylaxis. Three episodes were acquired in the hospital, with PD being performed by the trained nursing staff. No definite precipitating cause could be found in the remaining patients.

S. viridans (94 episodes; 90.3%) accounted for the majority of the streptococcal peritonitis. The subtype of the viridans streptococcus group was identified in only three of the episodes. They were oralis, milleri and mutans. S. bovis and S. agalactiae were isolated in two (1.9%) episodes each. Seven (6.7%) patients had infections with non-haemolytic Streptococci. These were not classified further. One patient with unresponsive peritonitis had non-typable streptococcal infection. Of all the episodes, 87 were isolated streptococcal peritonitis. Concurrent infection with two or more organisms accounted for 17 (16.3%) episodes. Of these episodes, 16 were in association with S. viridans peritonitis. In addition to the Streptococci, CNS [5], Enterococcus [2], Neisseriae [2], Haemophilus [1], Pseudomonas [1], Stenotrophomonas [1] and yeast [1] comprised the spectrum of co-existent infections (Table 2).


View this table:
[in this window]
[in a new window]

  		Table 2. Microbiological spectrum of the infectious organisms

 
After the initial empirical antibiotics, 71 episodes (68.2%) were treated with cefazolin, 29 (27.4%) with vancomycin, two episodes (1.9%) each with ampicillin and clindamycin and one patient with S. bovis infection responded to treatment with penicillin after failing intraperitoneal vancomycin. All patients treated with cefazolin demonstrated in vitro sensitivity to penicillin and cephalosporins. Vancomycin was used in five patients allergic to penicillin, in 10 episodes with partial/complete resistance to penicillin or cephalosporins, and in nine episodes empirically (even though the organisms were sensitive to penicillin and cephalosporins). Five episodes needed two antibiotics and one patient needed antifungal treatment for associated fungal peritonitis. Duration of antibiotic therapy was 21 (range: 14–43) days.

Rapidity of the response was assessed by the number of days taken to achieve a PD fluid cell count of <100/µl. Median time taken to achieve the normalization was 4 (range: 2–17) days. Three patients had no follow-up data of the cell count available to comment on the rapidity of the response, but had clinical resolution of peritonitis. Similarly, the rapidity of the response could not be commented upon in two patients who had a normal PD fluid cell count at the time of the diagnosis of the peritonitis. Refractory peritonitis, as defined by non-resolution of PD fluid cell count after 5 days of treatment was seen in 33 (33.3%) of the remaining episodes. However, the majority of these (94%) ultimately responded to treatment, with only two needing PD catheter removal. In all, only five (4.8%) episodes required removal of the PD catheter. Of these five, two (2.2%) of the isolated streptococcal peritonitis (one with viridans and the second with non-typable Streptococci) were non-responsive to therapy and needed catheter removal. The other three non-responsive episodes were associated with dual infection (one each with yeast, Stenotrophomonas and Enterococcus). One patient with associated pseudomonas infection cleared the infection after adjustment of the antibiotics. Eight (7.6%) episodes relapsed within the first 4 weeks of the treatment. Eleven (10.5%) other episodes had repeat peritonitis over the period from 4 weeks to 6 months after the treatment. Over the entire study period, 22 patients (accounting for a total of 57 episodes) had more than one episode of streptococcal peritonitis. Of these 22 patients, 17 had just one recurrent episode, a median of 334 days after the initial peritonitis. All these episodes were resolved. Strep peritonitis occurred at more frequent intervals in the patients with multiple recurrences. There were no deaths related to the peritonitis in the entire study population.



   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Acknowledgements
 References
 
Gram-positive cocci are the most common (60–80%) pathogens associated with PD peritonitis [1,2,7,8]. Predominant among these are the Staphylococcus bacteria, including coagulase-negative Staphylococci and Staphylococcus aureus. Streptococcal sp. causes roughly 6–16% of the cases of PD peritonitis [1,2,7,9–11]. However, it is noteworthy that apart from the one report describing the outcome of a small group of streptococcal peritonitis, these organisms have attracted little attention in the PD literature [5]. Most of the publications are comprised of case reports or isolated case series. This has led to a concept of the streptococcal peritonitis and patterns of its behaviour based on little outcome data. In this report, we present our experience with 104 cases of streptococcal PD peritonitis in 68 patients over a 10-year period. To our knowledge, this is the largest case series describing the characteristics of streptococcal peritonitis.

Enterococcal infections have also been included in the previously available study on streptococcal peritonitis [5]. However, inclusion of Enterococcus sp. in the description of the streptococcal peritonitis generates two major problems. First, Enterococcus, previously described as a non-haemolytic Streptococcus, has now been recognized as a separate genus of bacteria [4]. Secondly, Enterococcus sp. is more virulent compared with Streptococcus sp. and is associated with a much worse outcome. Both these factors lead to improper understanding of the streptococcal peritonitis. In our study, we have excluded the peritonitis caused by Enterococcus sp.

The rate of streptococcal peritonitis in our study was 11.7% of the total peritonitis. This is in congruence with the available literature over the past 10–20 years [1,2,8,11]. The increase in proportion of streptococcal peritonitis from 6 to 12–16% was also the time of two of the major protocol changes in our PD programme; namely introduction of the Y-set system and the use of mupirocin for routine exit site care. Together, these changes resulted in a significant fall in the peritonitis rate from 1 every 21.4 patient-months in 1995–96 to 1 every 35.9 patient-months in the year 2000–01. The change in the spectrum of organisms caused by a decline of the staphylococcal infections [12], resulting in apparently a higher proportion of non-staphylococcal peritonitis seems the likely explanation for this finding (Figure 1). Similar observations have been made in the past regarding the non-staphylococcal peritonitis in general [10,11,13,14] and streptococcal peritonitis in particular [10].


Figure 1
View larger version (9K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1. Incidence of peritonitis (total and streptococcal) over the time in our unit.

 
A higher incidence of streptococcal peritonitis in females has been observed [5]. However, this observation may have been influenced by a higher incidence of enterococcal peritonitis in females hypothesized on the basis of its presence in the female genital tract and perineal skin. Our study is unable to substantiate this finding in the absence of enterococcal sp.

Reports have suggested the use of penicillin as the drug of first choice in streptococcal peritonitis [5,15]. However, in our data, the majority of the episodes (68.2%) responded to cefazolin. Vancomycin (27.8%), the second most common antimicrobial, was used in patients based on the culture and sensitivity report or as the first-line antimicrobial in patients as a more practical option for administration purposes in the early part of the study, and in patients with allergy to cephalosporins in the latter part of the study. The need for the alternative agents was restricted to <5% of the population with one of the patients (S. bovis) needing penicillin after failing therapy with vancomycin. It may be reasonable to state that the penicillin group drugs are important for some of the uncommon forms of strep peritonitis (e.g. S. bovis, S. agalactiae, etc.) [15]. In our study, we have demonstrated that a third of the patients had recurrent streptococcal peritonitis and were responsible for roughly 60% of all the episodes (Figure 2). Individual factors in these patients may have caused the high rate of recurrence rather than the PD technique. Haematological dissemination of viridans Streptococci with oral and dental procedures, including cleaning the teeth, has been well recognized as a cause of infective endocarditis and now of PD peritonitis [16]. Al-wali et al. [17] reported a case of viridans strep peritonitis in association with gastro intestial (GI) intraluminal infection. One of our patients had co-existent intestinal obstruction with isolated S. oralis (from the viridans family) peritonitis. The presence of other organisms also suggests an alternative GI origin of the infection in some cases. However, in a retrospective study like ours, it is difficult to establish precipitating factors. Attention to oral health in general and timely intervention may be of benefit.


Figure 2
View larger version (20K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2. Outcome of streptococcal peritonitis.

 
Multiple case reports of streptococcal peritonitis are available in the literature [15,18–22]. Woo et al. [20] compiled the available case reports of PD peritonitis with group B streptococcus (agalactiae) suggesting an unfavourable outcome compared with viridans infections. The first reported case of S. bovis was in 2003 [23]. Two patients with S. bovis peritonitis (1998 and 2005) found in our database were treated with vancomycin. However, one of them needed therapy with penicillin after failing vancomycin. Non-enterococcal, non-haemolytic streptococcal infections were seen in seven of our patients with four of them being dual infections. All of them recovered completely with either cefazolin (five patients) or vancomycin (two patients).

In summary, our retrospective study over the last 10 years suggests that streptococcal sp. is an important cause of PD peritonitis, comprising roughly 12% of the cases. The percentage incidence increased over the years reflecting the declining rates of PD peritonitis in general, and staphylococcal peritonitis in particular, coincident with improvement in connection techniques and exit site care. These organisms cause relatively benign peritonitis if treated properly, with the treatment failure rate of just 1–2%. They have a higher rate of relapse. Current ISPD guidelines suggesting use of cefazolin or vancomycin for treatment seem adequate for most of these cases, with <5% needing penicillin derivatives. The most common form of streptococcal peritonitis is caused by viridans Streptococci. Non-viridans streptococcal infection is uncommon, and is not associated with a significantly different outcome.



   Acknowledgements
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Acknowledgements
References
 
The authors thank Dr Michael Gardam for helpful discussions, and Lisa Harley and Andrea Heywood for their assistance with data collection.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Acknowledgements
 References
 

  1. Vas SI. (1994) Treatment of peritonitis. Perit Dial Int 14:Suppl 3, S49–55.[Medline]
  2. Krishnan M, Thodis E, Ikonomopoulos D, et al. (2002) Predictors of outcome following bacterial peritonitis in peritoneal dialysis. Perit Dial Int 22:573–581.[Abstract/Free Full Text]
  3. Kavanagh D, Prescott GJ, Mactier RA. (2004) Peritoneal dialysis-associated peritonitis in Scotland (1999–2002). Nephrol Dial Transplant 19:2584–2591.[Abstract/Free Full Text]
  4. Mandell GL, Bennett JE, Dolin R. (2005) Principles and Practice of Infectious Diseases 6th edn Churchill Livingstone, an imprint of Elsevier pp. 2360.
  5. Munoz de Bustillo E, Aguilera A, Jimenez C, Bajo MA, Sanchez C, Selgas R. (1997) Streptococcal versus Staphylococcus epidermidis peritonitis in CAPD. A comparative study. Perit Dial Int 17:392–395.[Free Full Text]
  6. Piraino B, Bailie GR, Bernardini J, et al. (2005) ISPD Ad Hoc Advisory Committee. Peritoneal dialysis-related infections recommendations: 2005 update. Perit Dial Int 25:107–131.[Free Full Text]
  7. Rubin J, Rogers WA, Taylor HM, et al. (1980) Peritonitis during continuous ambulatory peritoneal dialysis. Ann Intern Med 92:7–13.[Abstract/Free Full Text]
  8. Pérez Fontán M, Rodríguez-Carmona A, García-Naveiro R, Rosales M, Villaverde P, Valdés F. (2005) Peritonitis-related mortality in patients undergoing chronic peritoneal dialysis. Perit Dial Int 25:274–284.[Abstract/Free Full Text]
  9. Fenton S, Wu G, Cattran D, Wadgymar A, Allen AF. (1981) Clinical aspects of peritonitis in patients on CAPD. Perit Dial Bull 1:94–96.
  10. Nakamoto H, Hashikita Y, Itabashi A, Kobayashi T, Suzuki H. (2004) Changes in the organisms of resistant peritonitis in patients on continuous ambulatory peritoneal dialysis. Adv Perit Dial 20:52–57.[Medline]
  11. Kim DK, Yoo TH, Ryu DR, et al. (2004) Changes in causative organisms and their antimicrobial susceptibilities in CAPD peritonitis: a single center's experience over one decade. Perit Dial Int 24:424–432.[Abstract/Free Full Text]
  12. Daly CD, Campbell MK, MacLeod AM, et al. (2001) Do the Y-set and double-bag systems reduce the incidence of CAPD peritonitis? A systematic review of randomized controlled trials. Nephrol Dial Transplant 16:341–347.[Abstract/Free Full Text]
  13. Szeto CC, Chow KM, Leung CB, et al. (2001) Clinical course of peritonitis due to Pseudomonas species complicating peritoneal dialysis: a review of 104 cases. Kidney Int 59:2309–2315.[Web of Science][Medline]
  14. Troidle L, Gorban-Brennan N, Kliger A, Finkelstein FO. (2003) Continuous peritoneal dialysis-associated peritonitis: a review and current concepts. Semin Dial 16:428–437 Review.[CrossRef][Web of Science][Medline]
  15. Scanziani R, Dozio B, Baragetti I, et al. (1999) Vaginal colonization with group B Streptococcus (Streptococcus agalactiae) and peritonitis in a woman on CAPD. Nephrol Dial Transplant 14:2222–2224.[Free Full Text]
  16. Kiddy K, Brown PP, Michael J, Adu D. (1985) Peritonitis due to Streptococcus viridans in patients receiving continuous ambulatory peritoneal dialysis. Br Med J (Clin Res Ed) 290:969–970.
  17. Al-Wali W, Baillod R, Hamilton-Miller JM, Brumfitt W. (1990) Detective work in continuous ambulatory peritoneal dialysis. J Infect 20:151–154.[CrossRef][Web of Science][Medline]
  18. Koruk ST, Hatipoglu CA, Oral B, Yucel M, Demiroz AP. (2005) Streptococcus oralis: a rare cause of CAPD-related peritonitis. Perit Dial Int 25:290–291.[Free Full Text]
  19. Liakopoulos V, Petinaki E, Bouchlariotou S, Mertens PR, Trakala M, Kourti P. (2004) Group B streptococcus (Streptococcus agalactiae) peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). Clin Nephrol 62:391–396.[Web of Science][Medline]
  20. Woo PC, Wong SS, Lau SK, Yuen KY. (2004) Continuous ambulatory peritoneal dialysis-related peritonitis associated with Lancefield group G beta-hemolytic Streptococcus: report of two cases requiring Tenckhoff catheter removal. J Clin Microbiol 42:4399–4402.[Abstract/Free Full Text]
  21. Tuncer M, Ozcan S, Vural T, Sarikaya M, Suleymanlar G, Yakupoglu G. (1998) Streptococcus equinus peritonitis in a CAPD patient. Perit Dial Int 18:654.[Free Full Text]
  22. Abraham G. (1995) Streptococcus pyogenes peritonitis associated with genital swelling and gastroenteritis caused by Cryptosporidium and Salmonella paratyphi B in an HIV infected patient on CAPD. Nephrol Dial Transplant 10:140–141.[Web of Science][Medline]
  23. Wong SS, Woo PC, Ho PL, Wang TK. (2003) Continuous ambulatory peritoneal dialysis-related peritonitis caused by Streptococcus bovis. Eur J Clin Microbiol Infect Dis 22:424–426.[CrossRef][Web of Science][Medline]
Received for publication: 10. 2.06
Accepted in revised form: 13. 6.06


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
21/12/3545    most recent
gfl407v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Shukla, A.
Right arrow Articles by Bargman, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shukla, A.
Right arrow Articles by Bargman, J. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?