Biomechanical effects of cranial closing wedge osteotomy on joint stability in normal canine stifles: an ex vivo study.

BACKGROUND: Cranial closing wedge osteotomy (CCWO) is a functional stabilisation technique for cranial cruciate ligament (CrCL) ruptures. This biomechanical study aimed to evaluate the influence of CCWO on the stability of the stifle joint. Eighteen Beagle stifle joints were divided into two groups: control and CCWO. The stifle joints were analyzed using a six-degree-of-freedom robotic joint biomechanical testing system. The joints were subjected to 30 N in the craniocaudal (CrCd) drawer and proximal compression tests and 1 Nm in the internal-external (IE) rotation test. Each test was performed with an extension position, 135°, and 120° of joint angle. RESULTS: The stifle joints were tested while the CrCLs were intact and then transected. In the drawer test, the CCWO procedure, CrCL transection, and stifle joint flexion increased CrCd displacement. The CCWO procedure and CrCL transection showed an interaction effect. In the compression test, the CCWO procedure decreased and CrCL transection and stifle joint flexion increased displacement. In the IE rotation test, CCWO, CrCL transection, and stifle joint flexion increased the range of motion. CONCLUSIONS: CCWO was expected to provide stability against compressive force but does not contribute to stability in the drawer or rotational tests. In the CCWO-treated stifle joint, instability during the drawer test worsened with CrCL transection. In other words, performing the CCWO procedure when the CrCL function is present is desirable for stabilizing the stifle joint.

Effect of the Material Properties and Knee Position to the Bone Bruise Pattern in Skeletally Mature and Immature Subjects.

A bone bruise is generated by a bony collision that could occur when the anterior cruciate ligament (ACL) is injured, and its pattern reflects the injury mechanism and skeletal maturity. Thus, the bone bruise pattern is useful to predict a subject-specific injury mechanism, although the sensitivity and/or effect of the material property and the knee position at injury is still unclear. The objective of the present study was to determine the effect of the material property and knee position on the bone bruise pattern in skeletally mature and immature subjects using finite element analysis. Finite element models were created from a magnetic resonance (MR) image in the sagittal plane of a skeletally mature (25 y. o.) and immature (9 y. o.) male subject. The femur and tibia were collided at 2 m/s to simulate the impact trauma and determine the maximum principal stress. The analysis was performed at 15, 30, and 45 deg of knee flexion, and neutral, 10 mm anterior and posterior translated position at each knee flexion angle. Although high stress was distributed toward the metaphysis area in the mature model, the stress did not cross the growth plate in the immature model. The size of the stress area was larger in the mature model than those in the immature model. The location of the stress area changed depending on the joint position. Young's modulus of cartilage and trabecular bone also affected the location of the stress area. The Young's modulus for the cartilage affected peak stress during impact, while the size of the stress area had almost no change. These results indicate that the bone bruise pattern is strongly associated with subject-specific parameters. In addition, the bone bruise pattern was affected not only by knee position but also by tissue qualities. In conclusion, although the bone bruise distribution was generally called footprint of the injury, the combined evaluation of the quality of the structure and the bone bruise distribution is necessary for properly diagnosing tissue injury based on the MR imaging.

High tibial osteotomy alone does not decrease medial meniscus extrusion in the setting of medial meniscus posterior root tear: A cadaveric study.

PURPOSE: This study investigated whether inducing valgus alignment and shifting the load laterally through high tibial osteotomy (HTO) alone decreases the extent of medial meniscus extrusion (MME) in the setting of medial meniscus posterior root tear(MMPRT) using ultrasound evaluation. METHODS: Eight fresh-frozen human cadaveric knee specimens were tested using a six-degree-of-freedom robotic testing system and ultrasound. Each specimen was tested in five conditions: (1) intact, (2) MMPRT, (3) medial meniscus repair (MMR), (4) combined medial open-wedge HTO + MMR, and (5) HTO + MMPRT. Measurements were obtained over the medial collateral ligament (MCL, central image) and posterior to the MCL (posterior image) with a 250 N axial load at 0°, 30°, and 90° of knee flexion. Statistical analysis was performed using a two-factor repeated-measures ANOVA. RESULTS: MME was significantly greater in HTO + MMPRT(0°: 2.44 ± 0.41mm, 30°: 2.47 ± 0.37mm, 90°: 2.41 ± 0.28mm) than HTO + MMR in central images (mean difference +0.83 mm, p < .001). No significant difference was found between HTO + MMPRT and MMPRT in MME . MMR had significantly less MME than MMPRT (mean difference -0.58mm, p < .001, posterior image at 0°and central image at 90°, p=.002). HTO + MMR showed significantly less MME than MMR alone at 30° and 90° knee flexion in central image (30°: -0.38 ± 0.05mm, 90°: -0.45 ± 0.06mm, p < .001) and 90° knee flexion in posterior image (-0.38 ± 0.08mm, p = .004). CONCLUSION: HTO alone did not decrease MME in the setting of MMPRT, while MMR alone decrease MME after MMPRT. Additionally, HTO + MMR decreases MME aftrer MMPRT compared to MMR alone, although the clinical significance was uncertain. CLINICAL RELEVANCE: The findings of this study provide clinicians with valuable insights for improving MME. HTO alone does not decrease MME in cases of MMPRT.

Basic fibroblast growth factor promotes meniscus regeneration through the cultivation of synovial mesenchymal stem cells via the CXCL6-CXCR2 pathway.

OBJECTIVE: To investigate the efficacy of basic fibroblast growth factor (bFGF) in promoting meniscus regeneration by cultivating synovial mesenchymal stem cells (SMSCs) and to validate the underlying mechanisms. METHODS: Human SMSCs were collected from patients with osteoarthritis. Eight-week-old nude rats underwent hemi-meniscectomy, and SMSCs in pellet form, either with or without bFGF (1.0 × 106 cells per pellet), were implanted at the site of meniscus defects. Rats were divided into the control (no transplantation), FGF (-) (pellet without bFGF), and FGF (+) (pellet with bFGF) groups. Different examinations, including assessment of the regenerated meniscus area, histological scoring of the regenerated meniscus and cartilage, meniscus indentation test, and immunohistochemistry analysis, were performed at 4 and 8 weeks after surgery. RESULTS: Transplanted SMSCs adhered to the regenerative meniscus. Compared with the control group, the FGF (+) group had larger regenerated meniscus areas, superior histological scores of the meniscus and cartilage, and better meniscus mechanical properties. RNA sequencing of SMSCs revealed that the gene expression of chemokines that bind to CXCR2 was upregulated by bFGF. Furthermore, conditioned medium derived from SMSCs cultivated with bFGF exhibited enhanced cell migration, proliferation, and chondrogenic differentiation, which were specifically inhibited by CXCR2 or CXCL6 inhibitors. CONCLUSION: SMSCs cultured with bFGF promoted the expression of CXCL6. This mechanism may enhance cell migration, proliferation, and chondrogenic differentiation, thereby resulting in superior meniscus regeneration and cartilage preservation.

The Effect of Elbow Flexion On Valgus Carrying Angle.

PURPOSE: This study aimed to examine the effect of flexion on valgus carrying angle in the human elbow using a dynamic elbow testing apparatus. METHODS: Active elbow motion was simulated in seven cadaveric upper extremities. Six electromechanical actuators simulated muscle action, while 6 degrees-of-freedom joint motion was measured with an optical tracking system to quantify the kinematics of the ulna with respect to the humerus as the elbow was flexed at the side position. Repeatability of the testing apparatus was assessed in a single elbow over five flexion-extension cycles. The varus angle change of each elbow was compared at different flexion angles with the arm at 0° of humerothoracic abduction or dependent arm position. RESULTS: The testing apparatus achieved excellent kinematic repeatability (intraclass correlation coefficient, >0.95) throughout flexion and extension. All elbows decreased their valgus carrying angle during flexion from 0° to 90° when the arm was maintained at 0° of humerothoracic abduction. Elbows underwent significant total varus angle change from full extension of 3.9° ± 3.4° (P = .007), 7.3° ± 5.2° (P = .01), and 8.9° ± 7.1° (P = .02) at 60°, 90°, and 120° of flexion, respectively. No significant varus angle change was observed between 0° and 30° of flexion (P = .66), 60° and 120° of flexion (P = .06), and 90° and 120° of flexion (P = .19). CONCLUSIONS: The dynamic elbow testing apparatus characterized a decrease of valgus carrying angle during elbow flexion and found that most varus angle changes occurred between 30° and 90° of flexion. All specimens underwent varus angle change until at least 90° of flexion. CLINICAL RELEVANCE: Our model establishes the anatomic decrease in valgus angle by flexion angle in vitro and can serve as a baseline for testing motion profiles of arthroplasty designs and ligamentous reconstruction in the dependent arm position. Future investigations should focus on characterizing motion profile change as the arm is abducted away from the body.

An improved quantitative ultrasonographic technique could assess anterior translation of the glenohumeral joint accurately and reliably.

PURPOSE: Since poor repeatability of the load and shift test using a grading scale has been reported, an objective and quantitative method to assess anterior translation should be established to assess glenohumeral joint function. The purpose of this study was to assess the accuracy and repeatability of the ultrasonographic techniques to quantify anterior translation of the glenohumeral joint. METHODS: Eight fresh-frozen cadaveric shoulders were used. For the standard technique, the ultrasound transducer was positioned on the anterolateral aspect of the shoulder viewing the coracoid process, glenoid, and humeral head. For the revised technique, the transducer was positioned on the anterior aspect of the shoulder, perpendicular to the scapular plane, viewing the conjoint tendon, glenoid, and humeral head. During the load and shift test, the distance between anterior edges of the glenoid and the humeral head was measured. The difference between distances before and after applying an anterior load was calculated as an anterior translation and compared with the anterior translation assessed using a motion tracking system. The repeatability and accuracy of both techniques were analyzed statistically. RESULTS: Intra- and inter-observer repeatability was good-excellent for both ultrasonographic techniques (ICC, 0.889-0.998). The revised technique achieved a stronger correlation to the anterior translations obtained using the motion tracking system (R = 0.810-0.913, p < 0.001) than the standard technique (R = 0.619-0.806, p < 0.001). CONCLUSION: Better accuracy and repeatability was found in the revised technique than the standard technique. The revised technique will be useful to determine the individual laxity and modify the treatment plan and return-to-sports protocol. LEVEL OF EVIDENCE: III.

Elbow Biomechanics: Bony and Dynamic Stabilizers.

The elbow positions the hand in a stable manner relative to the trunk while allowing flexion and extension as well as forearm rotation at varying shoulder positions. Its ability to perform this task without joint subluxation is accomplished through a combination of bony congruency, ligamentous restraint, and dynamic stabilization. This article reviews the bony and dynamic contributors to elbow stability and kinematics. Bony stability is conferred through the morphology of the humeroulnar, humeroradial, and radioulnar joints. Depending on the arm position relative to the trunk and the degree of elbow flexion, the bony contribution will vary. Dynamic elbow stabilizers confer stability through the activation of various muscles that cross the elbow. These forces help resist valgus and varus forces and may also increase bony stability by generating compressive forces. The goal of this article is to review the literature surrounding the biomechanics of bony and dynamic stabilizers of the elbow while drawing clinically relevant biomechanical observations.

A Biomechanical Comparison of Single-, Double-, and Triple-Bundle Anterior Cruciate Ligament Reconstructions Using a Hamstring Tendon Graft.

PURPOSE: The first objective of our cadaveric study was to perform a biomechanical comparison of single-bundle (SB), double-bundle (DB), and triple-bundle (TB) anterior cruciate ligament (ACL) reconstructions using a hamstring tendon graft to determine the laxity match pre-tension (LMP) value, which is the tension within the graft required to re-create the same anterior laxity as the ACL-intact knee. The second objective was to determine the anterior laxity and force distribution during the application of both an anterior force and a simulated pivot-shift test. METHODS: Eleven fresh-frozen cadaveric knees were tested using a robotic/universal force-moment sensor system in the intact state, TB-reconstructed knee, DB-reconstructed knee, and SB-reconstructed knee. The LMP in each reconstruction was recorded. Each reconstructed knee was tested with an external load of 100-N anterior drawer and combined rotatory loads of 10-Nm valgus moment and 5-Nm internal rotation. The anterior tibial translation and tensile forces of each graft bundle were measured. RESULTS: The LMP values for the TB reconstruction were 1.7 N for the anteromedial-medial graft, 1.7 N for the anteromedial-lateral graft, and 3.4 N for the posterolateral graft (PLG). The LMP value was 5.6 N for the anteromedial graft and PLG in the DB reconstruction. The LMP value was 26.3 N for the whole graft in the SB reconstruction. No statistically significant difference in stability was found between TB and DB reconstructions during the anterior load and the combined rotatory load test. For force distribution, the PLG tension in the TB reconstruction was statistically lower than that in the DB reconstruction. CONCLUSIONS: Anatomic TB ACL reconstruction with the lowest initial tension on the graft stabilized the knee equally to DB or SB reconstruction, which required greater initial tension. CLINICAL RELEVANCE: Although SB, DB, and TB ACL reconstructions through the anatomic tunnel position could equally restore stability, the initial tension on the graft required to restore stability was less in the latter 2 multi-tunnel reconstructions.

Effectiveness and nephrotoxicity of a 2-year medium dose of cyclosporine in pediatric patients with steroid-dependent nephrotic syndrome: determination of the need for follow-up kidney biopsy.

BACKGROUND: High dose of cyclosporine (CyA) for ≥2 years in children with steroid-dependent nephrotic syndrome (SDNS) increases the risk for nephropathy. Considering this, risk can be lowered with lower doses of CyA; we evaluated the effects of a medium dose of CyA, with target serum level, C2, of 450 ng/ml, over a 2-year period of observation, to determine the need for follow-up kidney biopsy. METHODS: We retrospectively evaluated C2 levels in 38 patients (17 males, 5.2 ± 2.9 years old) with SDNS at treatment initiation, at 6, 12 and 18 months during treatment, and at the time of kidney biopsy, 2-year after treatment initiation. Fifteen patients were also treated with mizoribine or mycophenolate mofetil. A number of relapses-per-patient-per-year, relative to SDNS onset and initiation of CyA treatment, were evaluated. Serum levels of total protein, albumin and total cholesterol, blood urea nitrogen level, and the estimated glomerular filtration rate were measured at treatment initiation and at 1- and 2-year post-treatment initiation. RESULTS: Only one very mild case of CyA-associated nephrotoxicity was identified based on biopsy results at 2-year post-treatment initiation. C2 concentrations were maintained at 422.2 ± 133.5 ng/ml and the number of relapses decreased from 3.0 relapses-per-patient-per-year prior to CyA treatment to 0.47 relapses-per-patient-per-year after CyA treatment. No effects of the treatment on the estimated glomerular filtration rate were noted. CONCLUSION: A 2-year treatment with a medium dose of cyclosporine A with or without other immunosuppressive agents is relatively safe with regard to the development of cyclosporine A nephrotoxicity.

Down syndrome and mild kidney dysfunction.

Few studies have evaluated kidney function in children with Down syndrome (DS) in detail. This study investigated kidney function in pediatric DS patients without complications that affect kidney function. Creatinine (Cr)- and cystatin C (cysC)-based estimated glomerular filtration rate (eGFR) were measured in a cohort of Japanese DS patients. The kidney function in these children with DS was approximately 80% that of the healthy Japanese children, suggesting that children with DS have smaller kidneys or a lower number of glomeruli than children without DS.

Carboxylated phytosterol derivative-introduced liposomes for skin environment-responsive transdermal drug delivery system.

Transdermal drug delivery systems are a key technology for skin-related diseases and for cosmetics development. The delivery of active ingredients to an appropriate site or target cells can greatly improve the efficacy of medical and cosmetic agents. For this study, liposome-based transdermal delivery systems were developed using pH-responsive phytosterol derivatives as liposome components. Succinylated phytosterol (Suc-PS) and 2-carboxy-cyclohexane-1-carboxylated phytosterol (CHex-PS) were synthesized by esterification of hydroxy groups of phytosterol. Modification of phytosterol derivatives on 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes was confirmed by negatively zeta potentials at alkaline pH and the change of zeta potentials with decreasing pH. In response to acidic pH and temperatures higher than body temperature, Suc-PS-containing and CHex-PS-containing liposomes exhibited content release at intracellular acidic compartments of the melanocytes at the basement membrane of the skin. Phytosterol-derivative-containing liposomes were taken up by murine melanoma-derived B16-F10 cells. These liposomes delivered their contents into endosomes and cytosol of B16-F10 cells. Furthermore, phytosterol-derivative-containing liposomes penetrated the 3 D skin models and reached the basement membrane. Results show that pH-responsive phytosterol-derivative-containing DMPC liposomes are promising for use in transdermal medical or cosmetic agent delivery to melanocytes.

Pharmacokinetics of mycophenolic acid in children with clinically stable idiopathic nephrotic syndrome receiving cyclosporine.

BACKGROUND: The suitable dosage regime of mycophenolate mofetil (MMF) based on the pharmacokinetics of mycophenoric acid (MPA) for pediatric patients with idiopathic nephrotic syndrome (INS) is controversial. The pharmacokinetics of MPA is influenced by renal function, serum albumin concentration, and concomitant medications, especially calcineurin inhibitors. This study analyzed the pharmacokinetics of MPA in clinically stable children with INS receiving cyclosporine (CyA). METHODS: This retrospective study enrolled children with INS receiving MMF (Cellcept®) (30-40 mg/kg/day in two divided doses) combined with CyA (Neoral®) without relapse and renal dysfunction. Pharmacokinetic parameters, including the area under the concentration-time curve (AUC) calculated by the trapezoid method, were calculated from seven serial blood samples. RESULTS: Thirty-two patients (22 males) of median age 11.0 years were included; 32 pharmacokinetic studies were performed. The median MMF dose was 16.2 mg/kg/time or 470.4 mg/m2/time. The median AUC0-12 was 44.3 ng h/mL. AUC0-12 of all patients showed excellent correlations with C2 (r 2  = 0.6405, P < 0.0001), resulting in a regression formula of AUC0-12 = 21.971 + 2.6059 C2. Comparisons of dose/body weight-normalized AUC0-12 values among age groups showed a lower value in the youngest group (≤5 years). CONCLUSION: In children with clinically stable INS receiving CyA, C2 monitoring was the most useful single parameter for estimating MPA pharmacokinetics. Younger children required higher MMF doses.

Use of Robotic Manipulators to Study Diarthrodial Joint Function.

Diarthrodial joint function is mediated by a complex interaction between bones, ligaments, capsules, articular cartilage, and muscles. To gain a better understanding of injury mechanisms and to improve surgical procedures, an improved understanding of the structure and function of diarthrodial joints needs to be obtained. Thus, robotic testing systems have been developed to measure the resulting kinematics of diarthrodial joints as well as the in situ forces in ligaments and their replacement grafts in response to external loading conditions. These six degrees-of-freedom (DOF) testing systems can be controlled in either position or force modes to simulate physiological loading conditions or clinical exams. Recent advances allow kinematic, in situ force, and strain data to be measured continuously throughout the range of joint motion using velocity-impedance control, and in vivo kinematic data to be reproduced on cadaveric specimens to determine in situ forces during physiologic motions. The principle of superposition can also be used to determine the in situ forces carried by capsular tissue in the longitudinal direction after separation from the rest of the capsule as well as the interaction forces with the surrounding tissue. Finally, robotic testing systems can be used to simulate soft tissue injury mechanisms, and computational models can be validated using the kinematic and force data to help predict in vivo stresses and strains present in these tissues. The goal of these analyses is to help improve surgical repair procedures and postoperative rehabilitation protocols. In the future, more information is needed regarding the complex in vivo loads applied to diarthrodial joints during clinical exams and activities of daily living to serve as input to the robotic testing systems. Improving the capability to accurately reproduce in vivo kinematics with robotic testing systems should also be examined.

Pitfalls of diagnosing urinary tract infection in infants and young children.

BACKGROUND: The aim of this study was to examine the sensitivity and specificity of pyuria-based diagnosis of urinary tract infection (UTI) in urine collected by transurethral catheterization, and the reliability of diagnosis of pyuria in urine collected in a perineal bag. The gold standard for UTI diagnosis is significant colony counts of a single organism in urine obtained in a sterile manner. METHODS: We enrolled 301 patients who underwent medical examination at the present hospital for possible UTI between January 2005 and December 2009. We collected 438 urine samples by transurethral catheterization. We investigated the accuracy of pyuria-based diagnosis of UTI using transurethral catheterization urine specimens, and the reliability of diagnosis of pyuria using bag-collected urine specimens. RESULTS: The false-negative rate of UTI diagnosis based on pyuria in transurethral catheterization urine sediments was 9.0%; there was no significant difference in the false-negative rate of UTI diagnosis between boys and girls. Approximately 28% of pyuria-positive bag-collected urine specimens were pyuria negative on transurethral catheterization; this rate was significantly higher in girls than in boys (56.7% vs. 8.9%, P < 0.0001). CONCLUSIONS: The absence of pyuria in transurethral catheterization urine sediments does not rule out UTI. Pyuria in bag-collected urine specimens frequently consists of urine leukocytes from external genitalia as well as from the urinary tract.

Assessment of kidney function in children by enzymatic determination of 2- or 24-h creatinine clearance: comparison with inulin clearance.

BACKGROUND: Although renal inulin clearance (Cin) is the gold standard for evaluation of kidney function, it cannot be measured easily. Therefore, creatinine clearance (Ccr) is often used clinically to evaluate kidney function. Enzymatically measured Ccr was recently found to be much higher than Cin because of the tubular secretion of creatinine (Cr). This study compared three measures of renal clearance, inulin, 2-h Ccr, and 24-h Ccr, in children. METHODS: Kidney function was evaluated in 76 children (51 males and 25 females) aged 1 month to 18 years with chronic kidney disease (CKD) by three renal clearance methods at almost the same time. RESULTS: Correlations between each pair of three renal clearance measurements were determined. Approximate glomerular filtration rate (GFR) was equal to 62 % of 2-h Ccr or 76 % of 24-h Ccr. CONCLUSION: Cr secretion by renal tubules was approximately 50 % of the GFR. In this study, we indicate that the measurements of 2-h Ccr or 24-h Ccr do not show true GFR but we could infer approximate GFR from the values. The use of 2- or 24-h Ccr might contribute to the treatment of pediatric CKD patients.

Stenosing ureteritis in Henoch-Schönlein purpura: report of two cases.

Stenosing ureteritis (SU), a rare complication of Henoch-Schönlein purpura (HSP), typically presents with severe symptoms. We report the cases of two HSP patients presenting with gross hematuria, blood clotting, and colicky flank pain, followed by purpura on the lower extremities. Early-stage ultrasonography indicated hydronephrosis, thickened renal pelvic mucous membrane, and ureteral dilatation (UD), suggesting HSP complicated with SU. After early SU treatment with prednisolone, kidney function, thickened renal pelvic mucous membrane, and UD progressively normalized and the pain gradually disappeared. Regular ultrasonography of HSP patients from the onset of gross hematuria can be useful to detect early SU and facilitate conservative therapy with prednisolone. Diagnosis of SU can be easily missed by assuming HSP nephritis, particularly owing to the non-specific symptoms. Common characteristics as well as treatment methods and prognosis of SU are given in the literature review.

The ratios of urinary ß2-microglobulin and NAG to creatinine vary with age in children.

BACKGROUND: Although urinary biochemical markers can be assessed by their ratio to urinary creatinine (U-Cr) concentration, reference values in adults may not be applicable to children because the amount of Cr excreted varies by body size. We therefore measured the relationship between age and the ratios of urinary ß-2-microglobulin (U-ß2MG), N-acetyl-ß-d-glucosaminidase (U-NAG), calcium (U-Ca) and protein (U-Pr) concentration to those of U-Cr in children. METHODS: Fifty-seven patients aged >1 year with benign familial hematuria (median age, 6.3 years) were divided into three age groups: 1-4, 5-9, and ≥10 years. Urinary biomarkers were assayed using actual values; ratios to actual U-Cr values; and our standardized metric, namely 100-fold the ratio of serum Cr to U-Cr concentration; and the relationship of each of these to age was determined. RESULTS: The ratios of U-ß2MG, U-NAG and U-Ca to Cr varied significantly by age, being higher in younger than in older children, but the actual and standardized values of each did not vary by age, nor did any measurement of U-Pr. CONCLUSIONS: The ratios of urinary markers of tubular function, including U-ß2MG, U-NAG and U-Ca, to Cr vary by age, being higher in younger children. In contrast, the ratios of urinary markers of glomerular filtration (such as U-Pr)to Cr do not vary by age, making them suitable for corrections relative to Cr.

Three year outcome of childhood idiopathic nephrotic syndrome under a unified immunosuppressive protocol.

BACKGROUND: This retrospective study was performed to assess the 3 year outcome of a unified protocol for childhood idiopathic nephrotic syndrome. METHODS: Cyclosporine A (CsA) or CsA plus mycophenolate mofetil (MMF) were used in patients without remission on high-dose steroid therapy. CsA was maintained at an area under the whole blood concentration-time curve up to 4 h after dose (AUC0-4 ) of 1500 and 2000 ng·h/mL in steroid-dependent nephrotic syndrome (SDNS) and steroid-resistant nephrotic syndrome (SRNS), respectively. Ninety-one children were enrolled in the study (SDNS, n = 64; SRNS, n = 18). Patients were divided into minimal change (MC) and focal segmental glomerulosclerosis (FSGS) groups. Three year outcome was evaluated using clinical severity defined as degree of dependence on immunosuppressive therapy for maintenance of remission. RESULTS: In the SDNS group, the numbers of MC and no biopsy were 51 and 13, respectively. No patient had FSGS. Twelve SRNS patients had FSGS and six had MC. In SDNS, 15/64 patients (23%) received no medication. CsA was effective as steroid-sparing agent in 31/38 patients (82%). MMF was effective in all eight patients for whom CsA was unsuccessful. Remission rate in the SRNS group was 14/18 (78%; eight with CsA, and six with a combination of CsA + MMF). Five of the 14 SRNS remission patients received methylprednisolone pulse therapy. Four were resistant to therapy, and had impaired renal function. The clinical severity of MC and FSGS overlapped. CONCLUSIONS: Treatment with CsA and combination of CsA plus MMF was useful for SDNS and for remission induction in SRNS.

A complement factor B mutation in a large kindred with atypical hemolytic uremic syndrome.

PURPOSE: Gain-of-function mutations in complement factor B (CFB) were recently identified in patients with atypical hemolytic uremic syndrome (aHUS), but are extremely rare. Our purpose is to describe a large kindred with aHUS associated with a CFB mutation and to further understand CFB-mutated aHUS patients. METHODS AND RESULTS: We report a large kindred in which 3 members had aHUS. This kindred revealed that 9 of 12 members, including 2 affected patients, had persistent activation of the alternative pathway with low complement component 3 and that those 9 members showed a CFB mutation (c.1050G > C, p.Lys350Asn) in exon 8. This missense mutation was heterozygous in 8 of them and homozygous in only one. From structural studies, this mutation is shown to be located in close proximity to the Mg2-binding site within a von Willebrand factor type A domain of CFB, resulting in a gain-of-function effect of CFB and predisposition to aHUS. At present, 2 of the 3 members with aHUS have maintained normal renal function for a long-term period. CONCLUSIONS: This kindred illustrates that a CFB mutation (c.1050G > C, p.Lys350Asn) can result in aHUS. In the future, phenotype-genotype correlations and outcome in CFB-mutated aHUS patients need to be further investigated by accumulation of a number of cases.

Mechanical Evaluation of Bone-Patellar Tendon-Bone Graft Fixation to the Tibia in ACL Reconstruction: Bone Plug Tensioning and Fixation System versus Interference Screw.

This study aimed to evaluate the mechanical properties of bone plug fixation to the tibia with a novel device, the Bone plug Tensioning and Fixation (BTF) system.Forty bone-tendon-bone grafts consisting of the whole patella-patellar tendon-tibial bone plug of 10-mm width and tibiae from the porcine were prepared. After creating a 10-mm tibial tunnel, the tibial bone plug was fixed to the tibia with the BTF system or the interference screw (IFS) to prepare a test specimen of the patella-patellar tendon-tibial bone plug fixed to the tibia. For the graft tension controllability study, a predetermined initial tension of 9.8 or 19.6 N was applied and maintained for 5 minutes. Then the bone plug was fixed to the tibia with the BTF system or IFS in 10 specimens, monitoring the residual tension for an additional 5 minutes. Then, a cyclic loading test and a tension-to-failure test were performed.The mean difference between the residual tension and the predetermined tension was significantly smaller in BTF fixation (9.8 N → 10.6 ± 2.2 N; 19.6 N → 18.9 ± 2.1 N) than in IFS fixation (9.8 N → 23.4 ± 7.4 N; 19.6 N → 28.9 ± 11.5 N). The mean displacement of the bone plug after cyclic loading was significantly less in the BTF group (1.2 ± 0.6 mm) than in the IFS group (2.2 ± 1.0 mm; p < 0.01). Stiffness was significantly greater in the BTF group (504.6 ± 148.8 N/mm) than in the IFS group (294.7 ± 96.7 N/mm; p < 0.01), whereas the maximum failure loads in the two groups did not differ significantly (724.2 ± 180.3 N in the BTF and 634.8 ± 159.4 N in the IFS groups).BTF system better performed in graft tension controllability than IFS did. BTF fixation was superior to IFS fixation in the displacement of the bone plug during the cyclic loading test and in stiffness in the tension-to-failure test.