Published papers

SS-A/Ro52 (Ro52) protein is one of the targets of autoantibodies in Sjogren's syndrome and systemic lupus erythematosus. Ro52 structurally belongs to the RING-B-box/coiled-coil family, which appears to carry out diverse functions, but the physiological function of Ro52 remains largely unknown. Here, the authors demonstrate that hydrogen peroxide but not other oxidative stressors induced translocation of Ro52 protein from the cytoplasm to the nucleus and this phenomenon was attenuated by inhibition of MAP kinases, ERK in particular. These findings raise the possibility that SS-A/Ro52 may function as a hydrogen peroxide-selective, oxidative stress-sensitive signaling molecule that is activated via the MAP kinase pathway.

Creatinine clearance (Ccr) is generally used as a halmark of glomerular filtration rate (GFR) in clinical medicine. Recently, it has been suggested that serum cystatin C measurement in serum reflects GFR. We compared serum cystatin C, serum creatinine, and serum beta2-microgrobrin in 70 patients with renal diseases in reference to creatinine clearance. The correlation between Ccr and 1/cystatin C was higher (r = 0.830) than that between Ccr and 1/serum creatinine (r = 0.789) or 1/serum beta2-microgroburin (r = 0.732). The levels of serum cystatin C in patients with Ccr ranging from 51 to 70 ml/min were significantly higher than those in patients with Ccr ranging more than 91 ml/min. Receiver-operated characteristic (ROC) analysis revealed that serum cystatin C showed the highest area under the curve among the three when Ccr = 90 ml/min was used as the cutoff point. We conclude that serum cystatin C is more useful than serum creatinine to detect early renal dysfunction.

Background. The aim of this study was to confirm the change in haemoglobin A1c consequent to pre-operative donation of autologous blood for elective surgery in patients with diabetes mellitus. Material and methods. For enrolment in this prospective study, patients had to be scheduled for multiple autologous blood donations at different times and have a haemoglobin A1c level more than 5.8% at the first donation. The values of four factors, haemoglobin, haemoglobin A1c, glycated albumin, and glycated albumin/haemoglobin A1c ratio were determined. Changes in the values of these four factors between before and after the blood donations were calculated. Results. In all 24 patients studied, haemoglobin and haemoglobin A1c decreased as a result of the autologous blood donations. The group with a reduced glycated albumin/haemoglobin A1c ratio had short intervals between blood donations. Correlations were observed between donation interval and change in haemoglobin A1c (r=0.63, P=0.003), and between donation interval and change in the glycated albumin/haemoglobin A1c ratio (r=0.489, P=0.045). Discussion. Haemoglobin A1c levels are likely to be underestimated after autologous blood donation by patients with diabetes mellitus, so glycated albumin may be a better indicator of these patients' glycaemic control.

Background. Variability in colon cancer recurrence after laparoscopic colectomy (LAC) remains poorly understood. The aim of our study was to quantify the influence of LAC on colon cancer recurrence patterns. Methods. We included 986 patients undergoing curative colectomy at our institution between 1992 and 2008. Kaplan-Meier, multivariable Cox regression, propensity score adjustment, and competing risks modeling were used to evaluate the influence of laparoscopic surgery on the site of colon cancer recurrence, including the following: liver metastasis, lung metastasis, local recurrence, peritoneal dissemination, other, and multiple sites. We estimated the risk factors for each recurrence site. Results. Laparoscopic surgery was used in 419 (42.5 %) of 986 patients, with an overall median follow-up time of 5.0 years (interquartile range 3.5). The overall 5-year disease-free survival rate was 86.1 % (open surgery 81.8 % vs. laparoscopic surgery 92.0 %; p < 0.001). However, after covariates and propensity score adjustment, laparoscopic surgery was not a significant risk factor for each type of recurrence: liver hazard ratio (HR) 0.93 (95 % CI 0.45-1.89), p = 0.84; lung HR 0.67 (95 % CI 0.26-1.70), p = 0.39; local HR 0.56 (95 % CI 0.12-2.63), p = 0.46; peritoneal HR 2.49 (95 % CI 0.75-8.27), p = 0.14; others HR 0.47 (95 % CI 0.04-5.13), p = 0.53; multiple HR 0.88 (95 % CI 0.25-3.14), p = 0.84. The risk factors for each type of recurrence were variable and characterized by specific clinicopathological features. Conclusion. Our study reveals that LAC and open colectomy demonstrate comparable overall colon cancer recurrence rates and recurrence sites. Specific clinicopathological characteristics may have a stronger influence on colon cancer recurrence site compared with the surgical technique.

Background Conducting randomized controlled trial (RCT) for each of the risk factors associated with prophylactic pancreatic duct stent (PPDS) for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is difficult owing to the volume of cases and ethical considerations. In this study, we tried to reveal the degree of preventive effects of PPDS for each individual risk factor within the high-risk group of PEP using the propensity score analysis. Methods The clinical data of 1131 ERCP practices performed at Kobe University Hospital from April 2006 to February 2009 were collected prospectively. We investigated their clinical characteristics including the risk factors of PEP, the use of PPDS and complications of ERCP. We conducted the stratification analysis using the propensity score matching analysis. Results In 210 propensity score-matched ERCPs, PPDS proved to be effective in preventing PEP in patients with a history of pancreatitis (odds ratio 0.11, 95% CI 0.01-0.76, P = 0.01) and cases of difficult cannulation (requiring more than 30 min) (odds ratio 0.13, 95% CI 0.01-1.14, P = 0.08). Conclusions Patients with a history of pancreatitis and cases of difficult cannulation are strongly recommended for PPDS placement. The propensity score analysis can be adapted to the ERCP-related analysis with many procedure-related factors with using retrospective data, and may be adapted to investigate the matters that are unsuitable for RCT by volume and ethical issue.

In the Japanese workplace, employers are required to provide annual health checkups for workers in accordance with the "Industrial Safety and Health Law," which also mandates that an occupational physician be assigned to companies employing at least 50 workers. The annual medical examination includes testing for the early detection of cardiovascular risk factors such as hypertension, dyslipidemia, diabetes, and the metabolic syndrome. This approach has successfully contributed to the extremely low incidence of coronary artery disease among Japanese workers. However, problems such as poor health and the low rate of participation in health checkups among small-scale companies still persist. Furthermore, although most wellness delivery systems in Japan employ strategies targeting high-risk individuals, instituting a strategy addressing the broader population irrespective of screening may be effective in reducing disease risk in the overall population. As a future direction, we should therefore develop practical methods for implementing a population strategy.

Internal vascular shunts for haemodialysis can cause different complications. One of the most serious complications is steal syndrome, which can result in disturbed peripheral circulation causing finger necrosis and lead to amputation. Thus, prevention of these complications is important. Measurement of skin perfusion pressure (SPP) has been used in various clinical settings, including wound-healing management, and its usefulness has been increasingly unveiled. The present study was undertaken to evaluate changes in haemodynamics after internal shunt creation by measuring SPP of the thumb and the little finger before and after surgery in five patients undergoing shunt surgery using the radial artery and the cephalic vein. The study revealed average changes of-22.8 mmHg in thumb SPP. The change in the thumb was statistically significant (p <0.05). If the effect of surgery and the threshold for wound healing are taken into account, the present results indicate the necessity to pay extra attention to fingers with extremely low preoperative SPP values. For the prevention of serious disturbances of peripheral circulation (e.g. steal syndrome), routine preoperative SPP measurement seems effective for screening of high-risk patients.

Purpose Obesity contributes to the technical difficulty of rectal surgery and is considered to be a risk factor for postoperative complications. The impact of obesity on the long-term outcomes of rectal cancer surgery remains unclear. Methods A total of 263 consecutive rectal cancer patients who underwent surgery were categorized into two groups according to the body mass index (BMI) based on the Asian BMI classification: non-obese (BMI <25 kg/m2) and obese (BMI ≥25 kg/m2). The postoperative survival and recurrence rates and oncological surgical quality indicators were compared between groups using the univariate and multivariate analyses. The differences in recurrence patterns were assessed by a competing risk regression analysis. Results 64 (24 %) patients were included in the obese group. The number of retrieved lymph nodes was significantly greater in the non-obese group than in the obese group (22.4 vs. 16.0, P < 0.01). The 5-year disease-free survival (DFS) rates were 86.5 and 68.8 % in the obese and non-obese groups, respectively (P = 0.01). The multivariate analysis demonstrated that obesity significantly decreased the postoperative recurrence rate (P = 0.04). Moreover, the BMI was significantly associated with distant metastasis (P = 0.04). Conclusions Obese rectal cancer patients have high DFS rates and a decreased incidence of distant metastases compared to non-obese patients. The BMI may be a key factor for predicting the postoperative prognosis and determination of an appropriate strategy for the treatment of rectal cancer patients.

Objective: To clarify the incidence and predictive risk factors of cervical spine instabilities which may induce compression myelopathy in patients with rheumatoid arthritis (RA). Methods: Three types of cervical spine instability were radiographically categorized into "moderate" and "severe" based on atlantoaxial subluxation (AAS: atlantodental interval >3 mm versus ≥10 mm), vertical subluxation (VS: Ranawat value, 13 mm versus ≤10 mm), and subaxial subluxation (SAS: irreducible translation ≥2 mm versus ≥4 mm or at multiple). 228 "definite" or "classical" RA patients (140 without instability and 88 with "moderate" instability) were prospectively followed for >5 years. The endpoint incidence of "severe" instabilities and predictors for "severe" instability were determined. Results: Patients with baseline "moderate" instability, including all sub-groups (AAS+ [VS- SAS-], VS+ [SAS- AAS ±], and SAS+ [AAS± VS ±]), developed "severe" instabilities more frequently (33.3% with AAS+, 75.0% with VS+, and 42.9% with SAS+) than those initially without instability (12.9%; p<0.003, p<0.003, and p = 0.061, respectively). The incidence of cervical canal stenosis and/or basilar invagination was also higher in patients with initial instability (17.5% with AAS+, 37.5% with VS+, and 14.3% with SAS+) than in those without instability (7.1%; p = 0.028, p<0.003, and p = 0.427, respectively). Multivariable logistic regression analysis identified corticosteroid administration, Steinbrocker stage III or IV at baseline, mutilating changes at baseline, and the development of mutilans during the follow-up period correlated with the progression to "severe" instability (p<0.05). Conclusions: This prospective cohort study demonstrates accelerated development of cervical spine involvement in RA patients with pre-existing instability - especially VS. Advanced peripheral erosiveness and concomitant corticosteroid treatment are indicators for poor prognosis of the cervical spine in RA. © 2014 Yurube et al.

The aim of this study was to compare the diagnostic and analytical performances of nine anti-cyclic citrullinated peptide (CCP) antibody assays. Anti-CCP antibody titers were measured in sera from 89 patients with rheumatoid arthritis (RA), 121 with rheumatic diseases other than RA (non-RA), 47 with osteoarthritis (OA), 142 with chronic inflammatory diseases (CID) and 168 healthy subjects. Reproducibility, sensitivity, specificity, correlation and concordance rate of the nine assays were compared. Coeficients of variations of within-run and between-run reproducibility at two different concentrations for each assay ranged from 0.7 to 8.5% and from 0.6 to 8.3%, respectively. With our proposed optimal cut-oFF value for the third-generation assay, concordance rates were 96.8~99.6%. The range of sensitivity was 75.3~78.7% and the ranges of specificity for non-RA, OA, CID, and healthy subjects were 93.4~97.5%, 97.9%, 96.5~98.6% and 98.8~100%, respectively. However, several discrepant samples were detected and their titer levels were about 3 times higher than the normal upper limit in the 2010 RA classification criteria. Good positive correlations were observed for parts of the second-generation assay. Our study showed that each of the nine assays has good reproducibility and high diagnostic accuracy, and is thus equally useful for the diagnosis of RA.

Aortohepatic conduits provide a vital alternative for graft arterialization during liver transplantation. Conflicting results exist with respect to the rates of comorbidities, and long-term survival data on primary grafts are lacking. To identify the complications associated with aortohepatic conduits in primary liver transplantation and their impact on survival, we conducted a single-center, retrospective cohort analysis of all consecutive adult (n = 1379) and pediatric primary liver transplants (n = 188) from 1998 to 2009. The outcomes of aortohepatic conduits were compared to those of standard arterial revascularization. Adults with a conduit (n = 267) demonstrated, in comparison with adults with standard arterialization (n = 1112), an increased incidence of late (>1 month after transplantation) hepatic artery thrombosis (HAT; 4.1% versus 0.7%, P < 0.001) and ischemic cholangiopathy (7.5% versus 2.7%, P < 0.001) and a lower 5-year graft survival rate (61% versus 70%, P = 0.01). The adjusted hazard ratio (HR) for graft loss in the conduit group was 1.38 [95% confidence interval (CI) = 1.03-1.85, P = 0.03]. Notably, the use of conduits (HR = 4.91, 95% CI = 1.92-12.58) and a warm ischemia time > 60 minutes (HR = 11.12, 95% CI = 3.06-40.45) were independent risk factors for late HAT. Among children, the complication profiles were similar for the conduit group (n = 81) and the standard group (n = 107). In the pediatric cohort, although the 5-year graft survival rate for the conduit group (69%) was significantly impaired in comparison with the rate for the standard group (81%, P = 0.03), the use of aortohepatic conduits did not emerge as an independent predictor of diminished graft survival via a multivariate analysis. In conclusion, in adult primary liver transplantation, the placement of an aortohepatic conduit should be strictly limited because of the greater complication rates (notably late HAT) and impaired graft survival; for children, its judicious use may be acceptable. © 2013 American Association for the Study of Liver Diseases.

Objective To examine cancer incidence in patients with systemic sclerosis (SSc) through a meta-analysis of population-based cohort studies. Methods Five different databases (Medline, Scopus, CINAHL [Cumulative Index to Nursing and Allied Health Literature], Web of Science, and Cochrane Collaboration) were searched for articles published between January 1966 and May 2012; review articles and the reference lists from the articles that resulted from the search were also evaluated. Population-based cohort studies with data relevant to the determination of cancer risk in patients with SSc were included. All articles that met strict inclusion criteria were analyzed for data on population size, time of followup, and observed-to-expected cancer ratios, also known as standardized incidence ratios (SIRs). Results Six articles met criteria and were included in the meta-analysis. The pooled SIR for the incidence of cancer overall was 1.41 (95% confidence interval [95% CI] 1.18-1.68), and significant heterogeneity was observed as a consequence of variability in the participants, outcome, study design, and risk of bias among the studies. Men had a significantly higher pooled SIR (1.85 [95% CI 1.49-2.31]) than women (SIR 1.33 [95% CI 1.18-1.49]) (P < 0.01), and stratification for sex eliminated heterogeneity, which indicates that variability among the studies greatly contributed to differences between the sexes. There were no differences between limited cutaneous SSc and diffuse cutaneous SSc (P = 0.77). Significant increases were observed in the risk of cancer of the lung, liver, hematologic system, and bladder, as well as of non-Hodgkin's lymphoma and leukemia. Conclusion SSc is associated with an increased risk of cancer, particularly lung, liver, hematologic, and bladder cancers, although absolute risk is relatively low. Men with SSc have a higher risk of developing cancer than women. Copyright © 2013 by the American College of Rheumatology.

Objectives: Recent studies have shown that mycophenolate mofetil (MMF) is similar to intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis (LN), but that treatment response may vary according to location and race/ethnicity. Moreover, no studies have been conducted to compare the efficacy of MMF with that of IVC for a Japanese population. We therefore conducted a retrospective study to clarify the efficacy and safety of MMF compared with that of IVC for induction therapy for active LN, classes III and IV, in a Japanese population of 21 patients, 11 of whom received MMF and 10 IVC. Methods: The primary endpoint was expressed as the percentage of responders, who in turn were defined as the patients who met complete or partial response criteria according to the European consensus statement. The secondary endpoints comprised the renal activity component and serological activity. Results: The primary endpoint was achieved in nine (81.8 %) patients receiving MMF and in four (40.0 %) receiving IVC, with no significant difference between the two groups (p = 0.081), while there was also no significant difference between them in terms of secondary endpoints. However, the MMF group suffered significantly fewer hematologic toxic effects than the IVC group. Conclusions: MMF may be used as an alternative to IVC for inducing renal remission of LN in Japanese patients. © 2012 Japan College of Rheumatology.

Objective While much attention is given to the fifth vital sign, the utility of the 4 classic vital signs (blood pressure, respiratory rate, body temperature, and heart rate) has been neglected. The aim of this study was to assess a possible association between vital signs and the Sequential Organ Failure Assessment (SOFA) score in patients with sepsis. Methods We performed a prospective, observational study of 206 patients with sepsis. Blood pressure, respiratory rate, body temperature, and heart rate were measured on arrival at the hospital. The SOFA score was also determined on the day of admission. Results Bivariate correlation analysis showed that all of the vital signs were correlated with the SOFA score. Multiple regression analysis indicated that decreased values of systolic blood pressure (multivariate regression coefficient [Coef] = -0.030, 95% confidence interval [CI] = -0.046 to -0.013) and diastolic blood pressure (Coef = -0.045, 95% CI = -0.070 to -0.019), increased respiratory rate (Coef = 0.176, 95% CI = 0.112 to 0.240), and increased shock index (Coef = 4.232, 95% CI = 2.401 to 6.062) significantly influenced the SOFA score. Conclusion Increased respiratory rate and shock index were significantly correlated with disease severity in patients with sepsis. Evaluation of these signs may therefore improve early identification of severely ill patients at triage, allowing more aggressive and timely interventions to improve the prognosis of these patients. © 2012 The Japanese Society of Internal Medicine.

Aim: High-sensitivity C-reactive protein (hs-CRP) identifies individuals at risk for cardiovascular disease (CVD) without an increased level of low-density lipoprotein cholesterol (LDL-C). The present study was performed to compare hs-CRP and LDL-C in association with the cardio-ankle vascular index (CAVI) in Japanese community dwellers considered to be at low risk for atherosclerosis from their level of traditional CVD risk factors. Methods: A community-based study involving 386 healthy Japanese (261 men and 125 women) without a history of CVD and medications for hypertension, diabetes, and dyslipidemia was performed. Multiple adjustments were performed with linear regression models to estimate the association between CAVI and hs-CRP or LDL-C levels. The participants were divided into four groups on the basis of whether they were above or below the median hs-CRP and LDL-C values, and CAVI was compared among the four groups by analysis of covariance after adjusting for confounders. Results: In multiple linear regression models, hs-CRP showed a significant positive association with CAVI; however, no clear association was observed between CAVI and LDL-C. These results were similar in the analyses among the participants with LDL-C <140 mg/dL or hs-CRP <1.0 mg/L. CAVI was higher in the groups with high hs-CRP than in those with low hs-CRP, irrespective of LDL-C; however, CAVI was highest in the group with high LDL-C and high hs-CRP. Conclusions: The present study suggests that hs-CRP could be a better risk factor assessor for atherosclerosis than LDL-C in individuals considered to be at low risk for atherosclerosis assessed by their traditional CVD risk factors.

We propose the "CAT concept", a new theory for surgical reconstruction after oncological segmental mandibulectomy. The essence of the theory is to reconstruct three reference points on the mandible - "C" (condylar head) "A" (mandibular angle) and "T" - necessary and sufficient for its surgical reconstruction. An anthropometric analysis of the mandible of ten preserved human cadavers showed that the mandibular contour can be made merely 3 to 7 mm smaller than the original when the CAT concept is adopted, suggesting that the concept sufficiently satisfies the condition for surgical reconstruction of the mandible. A review of our 45 clinical cases of mandibular reconstruction after oncological ablation demonstrated a positive trend between the number of reconstructed or non-resected reference points of the CAT concept and the esthetic outcome of each patient (Fisher's exact test, p<0.01), suggesting that the concept satisfies the necessary condition. Given these results, we concluded that the CAT concept is a highly practical theory for the surgical reconstruction of segmental mandibular defects.

Background: Hypertriglyceridemia and postprandial hyperlipidemia is thought to play an important role in atherosclerosis, but to select patients at high-risk for cardiovascular diseases is difficult with triglycerides (TG) alone in these patients. Methods. To predict postprandial hyperlipidemia without inconvenient test meal loading, we examined lipid concentrations before and after test meal loading and fasting adiponectin, and investigated which of these other than TG were significant during the fasting period in 45 healthy individuals (men: women, 26:19). Results: TG, remnant-like particle-cholesterol and -triglyceride (RemL-C, RLP-C, and RLP-TG), and TG/apolipoprotein(apo)B were significantly elevated after loading and fasting values significantly and positively correlated with incremental area under the curve (iAUC) (r=0.80, r=0.79, r=0.63, r=0.58, r=0.54; p<0.0001). Fasting adiponectin positively correlated with fasting high-density lipoprotein-cholesterol (r=0.43, p<0.005) and apoA-I (r=0.34, p<0.05), and negatively correlated with iAUC of TG, RemL-C, RLP-C, RLP-TG, and TG/apoB (r=-0.37, r=-0.41, r=-0.37, r=-0.36, r=-0.37; p<0.05). We constructed the model of multivariable linear regression analysis without fasting TG. In the sex-, BMI-, age-, and waist circumference-adjusted analysis of postprandial TG elevation 2 h after test meal loading in all participants, RemL-C, RLP-C, RLP-TG, and TG/apoB were significant factors, but adiponectin was not. Conclusion: Fasting triglyceride-rich lipoprotein-related values, especially RemL-C, RLP-C, RLP-TG, and TG/apoB are useful predictors of postprandial hyperlipidemia in young healthy individuals. Although fasting adiponectin concentration correlated with the iAUCs for TG, RemL-C, RLP-C, RLP-TG, and TG/apoB, it was not a significant predictor of postprandial hyperlipidemia in multivariable linear regression analysis. © 2012 Nagata et al.; licensee BioMed Central Ltd.

STUDY DESIGN. A prospective minimum 5-year follow-up study of the cervical spine in patients with rheumatoid arthritis (RA) initially without cervical involvement. OBJECTIVE. To clarify the incidence and aggravation of cervical spine instabilities and their predictive risk factors in patients with RA. SUMMARY OF BACKGROUND DATA. Many reports have shown the progression of cervical spine involvement in RA. However, few articles have described comprehensive evaluation of its prognostic factors. METHODS. A total of 140 patients with "definite" or "classical" RA initially without cervical involvement were prospectively followed for more than 5 years. Radiographical cervical findings were classified into 3 instabilities: atlantoaxial subluxation (AAS: atlantodental interval >3 mm), vertical subluxation (VS: Ranawat value <13 mm), and subaxial subluxation (SAS: irreducible translation ≥2 mm). "Severe" extents were defined as AAS with atlantodental interval 10 mm or more, VS with Ranawat value 10 mm or less, and SAS with translation 4 mm or more or at multiple levels. Incidence of these developments and predictors for "severe" instabilities were investigated. RESULTS. During 6.0 ± 0.5 years, 43.6% of 140 patients developed cervical instabilities: AAS in 32.1%, VS in 11.4%, and SAS in 16.4% with some combinations. "Severe" instabilities were exhibited in 12.9% of patients: AAS in 3.6%, VS in 6.4%, and SAS in 5.0%. Furthermore, 4.3% presented canal stenosis, with 13 mm or less space available for the spinal cord (SAC) due to "severe" AAS or "severe" VS in 2.9% and 12 mm or less SAC due to "severe" SAS in 2.1%. Multivariable logistic regression analysis identified corticosteroid administration, mutilating changes at baseline, and the development of nonmutilating into mutilating changes during the follow-up period correlated with "severe" instabilities (P < 0.05). CONCLUSION. A minimum 5-year follow-up reveals the occurrence of cervical instabilities in 43.6%, "severe" aggravation in 12.9%, and decreased SAC in 4.3% of patients with RA. Characteristics of severe disease activity - established mutilating changes, progressive development into mutilating changes, and potentially concomitant corticosteroid treatment - are indicators for poor prognosis of the cervical spine in RA. © 2012, Lippincott Williams & Wilkins.

Prevention of the atrophy of denervated muscles is essential for a good outcome in facial contouring and oral reconstruction. In this study, we compared the effectiveness of end-to-end and end-to-side neurorrhaphy of the motor nerve, and end-to-end neurorrhaphy of the sensory nerve, all of which are frequently used in such reconstruction for the prevention of muscle atrophy. Wistar rats were divided into four groups: group 1, motor nerve division of semi-membranosus without repair; group 2, motor nerve division and end-to-end coaptation to the saphenous nerve; group 3, motor nerve division and end-to-side coaptation to the sciatic nerve; and group 4, motor nerve division and end-to-end repair. Measurement of semi-membranosus volume, histological evaluation and staining of neuromuscular junctions that were carried out 3 months postoperatively revealed that muscle volume preservation was larger in groups 3 and 4 than in the other two groups (p < 0.05), but slightly superior in group 4 (p < 0.05). There was no statistical difference between groups 2 and 1; histologically, muscle architecture was better preserved in group 2 than in group 1; reactivation of the neuromuscular junctions was observed in all except group 1. End-to-side repair of motor nerves is one of the better options for the preservation of muscle volume when end-to-end nerve repair is not indicated. Sensory protection may also provide some advantages in the preservation of muscle volume. © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.