Annals of Surgical Oncology Cite Track
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
10.1245/s10434-006-9261-z
Annals of Surgical Oncology 14:744-749 (2007)
© 2007 Society of Surgical Oncology
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Black, M. J.
Right arrow Articles by Chen, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Black, M. J.
Right arrow Articles by Chen, H.

Original Article

Local/Cervical Block Anesthesia versus General Anesthesia for Minimally Invasive Parathyroidectomy: What are the Advantages?

Michael J. Black, MD1, Ann E. Ruscher, MD2, Julie Lederman, NP1 and Herbert Chen, MD, FACS1

1 Section of Endocrine Surgery, Department of Surgery, University of Wisconsin, Madison, WI, USA
2 Department of Anesthesiology, University of Wisconsin, Madison, WI, USA

Correspondence: Address correspondence and reprint requests to: Herbert Chen, MD, FACS; E-mail: chen{at}surgery.wisc.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Minimally invasive parathyroidectomy (MIP) under local/cervical block anesthesia (LA) is safe and effective for patients with primary hyperparathyroidism (HPT). Advantages of LA versus general anesthesia (GA) for these focused procedures have not been clearly demonstrated.

Methods: Between 3/01 and 6/04, 177 consecutive patients with primary HPT and positive localization studies underwent MIP. Seventy-three (41%) had surgery under LA while 104 (59%) had GA. Primary endpoints were IV narcotic use, anti-emetic use, nausea, vomiting, and post-operative pain.

Results: Patients who had parathyroidectomy under LA were older (64 ± 2 vs. 57 ± 2 years, P = 0.001). Cure and complication rates were identical between the two groups. Patients who had parathyroidectomy under LA required less IV narcotic pain mediation (mean morphine equivalents 11.4 ± 1.3 mg vs. 22.5 ± 1.1 mg; P < 0.001) compared to GA patients. The LA patients had better pain control as shown by lower post-operative peak pain scores (2.9 ± 0.3 vs. 5.0 ± 0.4; P < 0.001) and lower overall pain scores (mean 1.9 ± 0.2 vs. 3.1 ± 0.2; P < 0.001). The LA group required fewer anti-emetic medications compared to the GA patients (mean 0.4 ± 0.1 vs. 1.7 ± 0.1 doses; P < 0.001). Fewer LA patients experienced post-operative nausea (16% vs. 49%; P < 0.001), and vomiting (7% vs. 24%; P = 0.002). Length of stay was similar between the groups (0.4 ± 0 vs. 0.3 ± 0; P = 0.22).

Conclusions: In this study the choice of anesthesia did not affect surgical cure rate, morbidity, or length of stay. LA was associated with significantly lower post-operative pain, nausea, and vomiting. LA appears to offer specific advantages more than GA for patients undergoing MIP.

Key Words: Parathyroidectomy • Hyperparathyroidism • Minimally invasive parathyroidectomy • Local anesthesia • MIRP • Radioguided


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Multiple surgical approaches are available to surgeons to treat hyperparathyroidism (HPT). Bilateral neck exploration, minimally invasive parathyroidectomy (MIP), and video-assisted MIP are all utilized by experienced endocrine surgeons to achieve high cure rates in primary HPT. Controversy remains as to which technique is the best for patients with primary HPT.

However, bilateral neck exploration remains the "gold standard" for treatment of primary HPT with a 95% cure rate.1,2 Recently MIP has been used in conjunction with localizing studies and intra-operative parathyroid assay with good results.3,4 Reported benefits of the minimally invasive technique include less post-operative pain and better cosmetic results.

Minimally invasive parathyroidectomy under cervical/local block has been shown to be safe and effective previously.3,4,5,6,22,23,24 However, the benefits of cervical/local block anesthesia compared to general anesthesia in MIP still have to be fully realized.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
From March 2001 to September 2004, 273 consecutive patients with HPT underwent parathyroidectomy by one surgeon (HC) at the University of Wisconsin. Of these patients, 177 had primary HPT and a positive localization study. Therefore, all were eligible for MIP.

All 177 patients who were candidates for an MIP were offered local/cervical block anesthesia (LA) or general anesthesia (GA) for their cases. Patients chose their anesthetic technique based on personal preference; 73 chose LA while 104 chose GA. LA was administered pre-operatively using a superficial block technique4 supplemented intra-operatively with 1% lidocaine local anesthesia injections in conjunction with propofol infusion for sedation. LA block was performed via injection of 1% lidocaine along the sternocleidomastoid muscle both anteriorly and posteriorly to the muscle mass. Injection depth was 1 cm and a total of 20 ml of 1% lidocaine generally used. This technique reliably blocks the great auricular nerve, the anterior cervical nerve, and the supraclavicular nerve.

Patients undergoing MIP are cared for by any one of the 12 faculty anesthesiologists who regularly work in the outpatient surgery center. While no formal standardized protocol exists for these patients, this group of anesthesiologists use similar techniques, including propofol infusion for patients undergoing both GA and LA, as well as appropriate benzodiazapenes and narcotics. Patients who have GA receive desflurane as the inhalation agent and nitrous oxide is avoided. Patients are given 12.5 mg of dolasetron as a prophylactic antiemetic.

We routinely use radioguided techniques for patients undergoing surgery for primary, secondary, and tertiary HPT.7,8,9 All patients in this series underwent radioguided surgery with an 11-mm collimated gamma probe. We have previously described our technique for radioguided parathyroidectomy.7,10 Briefly, patients are injected with 10 mCi of Tc-99m-sestamibi 1–2 h before surgery on average. In the operating room, background counts are obtained by placing an 11-mm collimated gamma probe (Neoprobe 2000; Ethicon Endo-Surgery Breast-Care, Cincinnati, OH, USA) on the thyroid isthmus through the skin. After incision, intra-operative scanning is performed looking for radionuclide counts more than background to localize abnormal parathyroid glands. After excision of the enlarged parathyroid, the tissue is placed on top of the gamma probe (directed away from the patient) to determine "ex vivo" counts. Ex vivo counts are expressed as a percentage of background counts and ex vivo parathyroid count >20% of background is definitive for parathyroid tissue.

All 177 patients in this study had intra-operative PTH testing. We have previously described our protocol for intra-operative PTH testing and interpretation at the University of Wisconsin.11,12 All PTH levels were analyzed on the Elecsys 2010 machine. For each patient, a PTH level is drawn before surgical incision and serves as the "baseline" level. After resection of the enlarged parathyroid gland, PTH levels are drawn after 5, 10, and 15 min. Our criteria for a curative resection is a >50% drop in intra-operative PTH levels compared with baseline at 5, 10, or 15 min. If a >50% drop occurs, then the operation is terminated. If the PTH level fails to fall, the neck is explored for a second adenoma or for additional hyperplastic glands. If exploration of the contralateral neck is required in a patient undergoing LA (failure of PTH to normalize after adenoma excision), most of the time conversion to GA occurs. After resection of the second adenoma and/or other enlarged parathyroids, the PTH level is checked again after an additional 5 and 10 min.

Patients post-operative pain rating, IV pain medication usage, nausea, vomiting, and anti-emetic usage, were recorded prospectively in the post-anesthesia care unit and on the hospital wards. Postoperative pain was quantitated and recorded by the nursing staff using a visual analog scale (1 = no pain to 10 = severe pain). Assessment occurs when the patient becomes oriented in the post-operative recovery area, when the patient complains of pain, and periodically through the recovery period. Data on pain rating, IV pain medication usage, nausea, vomiting, and anti-emetic usage were collected from hospital charts retrospectively. All pain ratings during the hospitalization were recorded and each patient’s peak pain rating and average pain rating was calculated. Patients IV pain medication usage postoperatively was tabulated and converted to morphine equivalents. Episodes of post-operative nausea and vomiting were recorded by the nursing staff in the recovery unit and on the wards using standard nursing flow sheets. Post-operative nausea and vomiting was recorded in a qualitative fashion (yes/no) and quantifying the number of events. Anti-emetic dosages required throughout the hospitalization were recorded. Patients were given a variety of anti-emetics as no conversion to a recognized standard is available. The number of anti-emetic doses required was recorded from a combination of the nursing flow sheets and medication administration records.

Surgical cure was defined as a serum calcium level <10.5 mg/dL at least 6 months after surgery. Recurrence was defined as a serum calcium level exceeding 10.5 mg/dL in consecutive samples 6 months after surgery. Persistent disease was defined as a serum calcium level greater than 10.5 mg/dL within 6 months of surgery. Data were recorded as mean ± standard error of mean. Statistical analysis was performed with SPSS software (SPSS Inc.) Statistical significance was defined as P < 0.05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Patient Data
Patients undergoing MIP under LA were older on average than patients undergoing GA, 64 ± 2 versus 57 ± 2 years, respectively (P = 0.001; Table 1Go). There was no statistical difference in patient gender when comparing those choosing LA (male 13, female 69) versus GA (male 29, female 75). Patients choosing GA were statistically heavier then those in the LA group 188 ± 6 vs 167 ± 5 pounds, respectively, P = 0.009. Pre-operative calcium levels were equivalent between the two groups LA 11.3 ± 0.09 mg/dL versus GA 11.4 ± 0.09 mg/dL. Pre-operative PTH levels were statistically higher in the GA group 157 ± 10 pg/mL when compared to LA 125 ± 8 pg/ mL, P = 0.03.


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

  		TABLE 1. Pre-operative patient demographics and secondary outcomes measured
 
Operative Data
The location of the resected parathyroid gland was recorded as superficial to the tracheo-esophageal groove versus at the level or deeper than the tracheo-esophageal groove. In the LA group 49% of the glands were found at or deeper than the tracheo-esophageal groove versus only 21% in the GA group (P = 0.001). Gland weight in the two groups was similar, LA 902 ± 152 mg versus GA 988 ± 137 mg. Post-operative PTH and calcium levels were the same for both groups: post-operative PTH, LA 50 ± 3 pg/mL versus GA 53 ± 4 pg/mL, and post-operative calcium LA 9.4 ± 0.06 mg/dL versus GA 9.3 ± 0.07 mg/dL. Cure rates in both groups were equivalent; 100% in LA group versus 99% in GA group. One patient in the GA group had persistent elevation of calcium and PTH levels within 6 months of operation. Two additional patients in the GA group had recurrent hyperparathyroidism diagnosed greater then 6 months following surgery. No patients in the LA group experienced persistent or recurrent hyperparathyroidism to date. These differences are not statistically significant. Complication rates between the two groups were equivalent. In each group two patients suffered from transient hypo-calcemia requiring oral supplementation which subsequently resolved. One patient in the LA group suffered from transient recurrent laryngeal nerve palsy, which has fully resolved. Length of stay was equivalent between the two groups, LA 0.4 ± 0 days versus GA 0.3 ± 0 days. (Table 1Go)

Pain, Nausea, Analgesic, and Anti-emetic
Patients who had parathyroidectomy under LA required less IV pain mediation (mean morphine equivalents 11.4 ± 1.3 mg vs. 22.5 ± 1.1 mg, P < 0.001) compared to GA patients. (Fig. 1Go) Despite receiving less pain medication, LA patients had better pain control as shown by lower post-operative peak pain scores (2.9 ± 0.3 vs. 5.0 ± 0.4; P < 0.001) (Fig. 2Go) as well as lower overall pain scores (mean 1.9 ± 0.2 vs. 3.1 ± 0.2; P < 0.001). (Fig. 3Go) Furthermore, patients in the LA group required fewer anti-emetic medications compared to GA patients (mean 0.4 ± 0.1 vs. 1.7 ± 0.1 doses; P < 0.001). (Fig. 4Go) Moreover, fewer LA patients experienced post-operative nausea (16% vs. 49%; P < 0.001), and vomiting (7% vs. 24%; P = 0.002). (Fig. 5Go).


Figure 1
View larger version (37K):
[in this window]
[in a new window]

  		FIG. 1. IV pain medication (morphine equivalents) required during hospitalization.

 

Figure 2
View larger version (23K):
[in this window]
[in a new window]

  		FIG. 2. Peak post-operative pain as recorded using a visual analog scale (1 = no pain, 10 = severe pain).

 

Figure 3
View larger version (21K):
[in this window]
[in a new window]

  		FIG. 3. Overall pain as recorded on a visual analog scale throughout hospitalization (1 = no pain, 10 = severe pain).

 

Figure 4
View larger version (30K):
[in this window]
[in a new window]

  		FIG. 4. Total anti-emetic doses required during hospitalization.

 

Figure 5
View larger version (26K):
[in this window]
[in a new window]

  		FIG. 5. Percentage of patients experiencing post-operative nausea and vomiting in each anesthetic group.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Parathyroidectomies may be accomplished by multiple surgical techniques. Recently many endocrine surgeons have begun to remove abnormal parathyroid tissue by minimally invasive techniques using local/regional anesthesia.22,23,24 These techniques have been shown to be as safe and efficacious as standard four-gland exploration. Some have suggested that using minimally invasive techniques for parathyroidectomy have specific advantages over open four-gland exploration including improved cosmesis and decreased transient hypo-calcemia.3,7

Little research has been performed to evaluate specific advantages of LA over GA techniques when performing MIPs. Intuitive benefits of LA exist; however, intuitive benefits are not always realized when rigorously investigated. With few studies focusing on the benefits of LA over GA in parathyroid operations we may look to other literature evaluating GA versus LA for a variety of operations to gain insight.

Fiorani’s retrospective review of carotid endarterectomy over 10 years demonstrated a 50% reduction in perioperative cardiac complications during LA as compared to GA.13 More recently Sbaigia et al. examined carotid endarterectomy in a prospective randomized fashion and noted that LA in patients with no previous history of cardiac disease resulted in 1/2 the rate of myocardial ischemic episodes when compared to GA.14

Inguinal hernia repair with LA is felt by many to have specific benefits over GA; however, a recently reported randomized prospective study by O’Dwyer et al., demonstrated the benefit of LA versus GA to be limited to pain with mobilization at 6 h postoperatively.15 Interestingly, at 1 year post-operatively patients whom had undergone inguinal hernia repair with LA were less likely to recommend the operation to a friend when compared to their GA counterparts. These findings are in contrast to multiple prospective non-randomized studies demonstrating better pain control with LA.16–20

The literature on LA versus GA in parathyroidectomy is incomplete and non-definitive. The cervical block/local anesthesia techniques in this and other studies have been shown to be safe, and allow for cure rates equivalent to GA.3,4,23,24 Bergenfelz et al. demonstrated that MIP under LA reduced operative time and post-operative hypo-calcemia when compared to bilateral neck exploration under GA.3 These findings are likely the result of operative technique rather than anesthesia. No trial exists specifically evaluating LA versus GA for MIP.

This study suggests that cervical block/local anesthesia may not just be equal to GA but may have specific advantages. Patients receiving LA in the current study experienced complications at a rate equivalent to those who underwent GA. Furthermore, cure rates in the two groups were equivalent. Beyond this equivalency, patients in the LA group reported less post-operative pain when looking at both peak post-operative pain reported and mean pain experienced. This difference may have been underestimated given patients in the LA group tended to have deeper glands at time of operation than those undergoing GA, and may have had undergone more operative dissection. As further evidence of improved pain control, patients in the LA group required less post-operative IV pain medication but reported less pain. Patients in the LA group further benefited from their anesthetic choice by experiencing less post-operative nausea and vomiting. They also required fewer doses of anti-emetic medications during their hospitalization. It is possible that a portion of the decreased nausea and vomiting maybe due to propofol infusions. Sonner et al. demonstrated in a randomized prospective study that maintenance of anesthesia with propofol infusion significantly decreased severe post-operative nausea/vomiting in women undergoing thyroid or parathyroid surgery.21 However, in our current study, propofol was used in patients in both GA and LA groups. In fact, more than 90% of all patients having outpatient surgery receive propofol during their operation. Thus, the reduction in nausea and vomiting in the LA is not likely due to propofol infusion.

We believe this study suggests specific advantages patients may receive by undergoing their minimally invasive parathyroidectiomies under cervical block/ local anesthesia. This study does have limitations. Although the data were recorded prospectively it was gathered retrospectively for analysis. All efforts were undertaken to ensure the data to be complete; however, errors are always a concern. Patients in this study chose their anesthetic for a multitude of undefined reasons; they were not randomly assigned to a treatment group. Our study design allows questions to remain. Did patients with an innately higher pain tolerance threshold choose LA more frequently than GA, thus affecting the results of the study? Patients who chose LA were older on average by 7 years compared to those who chose GA. Data were not collected on the patient’s co-morbid states or ASA class. It is imaginable that the older patients have more co-morbidities, yet they experience equivalent morbidity post-operatively. Is this secondary to a yet undefined benefit of LA over GA?

Some may suggest that the differences found in this study while statistically significant may not be clinically significant. With our study design it is hard to address this question; however, most patients given the option would chose even small improvements in post-operative pain, nausea, and vomiting. Why would we deny this improvement when complications and cure rates are equivalent? In conclusion the choice of anesthesia did not affect surgical cure rate, morbidity, or length of stay. LA was associated with significantly lower post-operative pain, nausea, and vomiting. LA appears to offer specific advantages over GA for patients undergoing MIP.


   FOOTNOTES
 
This study was presented at the 59th Annual Meeting of the Surgical Society of Oncology, San Diego, CA, USA, March 23–26 2006

Received for publication May 10, 2006. Accepted for publication October 5, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Van Heerden JA, Grant CS. Surgical treatment of primary hyperparathyroidism: an institutional perspective. World J Surg 1991; 15:688–92.[CrossRef][Medline]
  2. Chen H, Parkerson S, Udelsman R. Parathyroidectomy in the elderly: do the benefits outweight the risks?. World J Surg 1998; 22:531–6.[CrossRef][Medline]
  3. Bergenfelz A, Kanngiesser V, Zielke C, Nies C, Rothmund M. Conventional bilateral cervical exploration versus open minimally invasive parathyroidectomy under local anesthesia for primary hyperparathyroidism. Br J Surg 2005; 92:190–7.[CrossRef][Medline]
  4. Chen H, Sokoll L, Udelsman R. Outpatient minimally invasive parathyroidectomy: a combination of sestamibi-SPECT localization, cervical block anesthesia, and intraoperative PTH assay. Surgery 1999; 126:14–8.
  5. Chen H. Surgery for primary hyperparathyroidism: what is the best approach?. Ann Surg 2002; 236:552–3.[CrossRef][Medline]
  6. Miccoli P, Barellini L, Monchik JM, Rago R, Berti PF. Randomized clinical trial comparing regional and general anaesthesia in minimally invasive video-assisted parathyroidectomy. Br J Surg 2005; 92:814–8.[CrossRef][Medline]
  7. Chen H. Radioguided parathyroid surgery. Adv Surg 2004; 38:377–92.[Medline]
  8. Nichol PF, Mack E, Bianco J, Hayman J, Starling JR, Chen H. Radioguided parathyrioidectomy in patients with secondary and tertiary hyperparathyroidism. Surgery 2003; 134:713–7.[CrossRef][Medline]
  9. Sippel RS, Bianco J, Chen H. Radioguided parathyroidectomy for recurrent hyperparathyroidism caused by forearm graft hyperplasia. J Bone Miner Res 2003; 18:939–42.[CrossRef][Medline]
  10. Chen H, Mack E, Starling JR. Radioguided parathyroidectomy is equally effective for both adenomatous and hyperplastic glands. Ann Surg 2003; 238:332–7.[Medline]
  11. Chen H, Pruhs Z, Starling JR, Mack E. Intaoperative parathyroid hormone testing improves cure rates in patients undergoing minimally invasive parathyroidectomy. Surgery 2005; 138(4):583–7.[CrossRef][Medline]
  12. Chen H, Mack E, Starling JR. A comprehensive evaluation of peri-operative adjuncts during minimally invasive parathyroidectomy: which is most reliable?. Ann Surg 2005; 242:375–83.[Medline]
  13. Fiorani P, Sbarigia E, Speziale F, et al. General anaesthesia versus cervical block and perioperative complications in carotid artery surgery. Eur J Vasc Endovasc Surg 1997; 13:37–42.[CrossRef][Medline]
  14. Sbaigia E, DarioVizza C, Antonini M, et al. Locoregional versus general anesthesia in carotid surgery: is there an impact on peri-operative myocardial ischemia? Results of a prospective monocentric randomized trial. J Vasc Surg 1999; 30:131–8.[CrossRef][Medline]
  15. O’Dwyer P, Serpell M, Millar K, et al. Local or general anesthesia for open hernia repair: a randomized trial. Ann Surg 2003; 237:574–9.[CrossRef][Medline]
  16. Berhia R, Hashemi F, Stryker SJ, Wjiki G, Paticha S. A comparison of general versus local anesthesia during inguinal herniorrhaphy. Surg Gynecol Obstet 1992; 174:277–80.[Medline]
  17. Makuria T, Alexander-Williams J, Keighley M. Comparison between general and local anaesthesia for repair of groin hernias. Ann R Coll Surg Engl 1979; 61:291–4.
  18. Peiper C, Tons C, Schippers E, Busch F, Schumpelick V. Local versus general anesthesia for Shouldice repair of the inguinal hernia. World J Surg 1994; 18:912–6.[CrossRef][Medline]
  19. Teasdale C, Mccrum A, Williams NB, Horton R. A randomized controlled trial to compare local with general anaesthesia for short-stay inguinal hernia repair. Ann R Coll Surg Engl 1982; 64:238–242.
  20. Young DV. Comparison of local, spinal, and general anesthesia inguinal herniorraphy. Am J Surg 1987; 153: 560–3.[CrossRef][Medline]
  21. Sonner JM, Hynson JM, Clark O, Katz JA. Nausea and vomiting following thyroid and parathyroid surgery. J Clin Anesth 1997; 9:398–402.[CrossRef][Medline]
  22. Carling T, Donovan P, Rinder C, Udelsman R. Minimally invasive parathyroidectomy using cervical block. Arch Surg 2006; 141:401–4.[Abstract/Free Full Text]
  23. Cohen MS, Finkelstein SE, Brunt M, Haberfeld E, Kangrga I, Moley J, Lairmore TC. Outpatient minimally invasive parathyroidectomy using local/regional anesthesia: a safe and effective operative approach for selected patients. Surgery 2005; 138:681–9.[CrossRef][Medline]
  24. Inabnet WB, Fulla Y, Richard B, Bonnichon P, Icard P, Chapuis Y. Unilateral neck exploration under local anesthesia: the approach of choice for asymptomatic primary hyperparathyroidism. Surgery 1999; 126:1004–10.[CrossRef][Medline]



This article has been cited by other articles:


Home page
 Arch Otolaryngol Head Neck SurgHome page
M. L. Shindo and J. M. Rosenthal
Minimal Access Parathyroidectomy Using the Focused Lateral Approach: Technique, Indication, and Results
Arch Otolaryngol Head Neck Surg, December 1, 2007; 133(12): 1227 - 1234.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Black, M. J.
Right arrow Articles by Chen, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Black, M. J.
Right arrow Articles by Chen, H.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS