Detection of bone marrow-derived fibrocytes in human dental pulp repair.

AIM: To explore the expression profile of CD45+/pro-collagen I+ fibrocytes in intact dental pulps as well as during wound healing in adult dental pulp tissue. METHODOLOGY: A total of 16 healthy permanent teeth were obtained from young patients (18 to 25 years) undergoing orthodontic treatment. Routine pulp capping with mineral trioxide aggregate (MTA) was performed under local anaesthesia to induce a mineralized barrier at the exposed surface. Teeth were extracted from patients after 7, 14 and 35 days. Sections of the extracted teeth were prepared and stained for various markers using indirect immunofluorescence. Fibrocytes were counted, and the data were statistically evaluated using the Dunnett test. RESULTS: In uninflammed pulp tissue, a pro-collagen I-positive reaction was detected in odontoblasts, as well as in perivascular cells. Most of the CD45-positive cells were negative for pro-collagen I in normal pulp tissue, whereas CD45+/pro-collagen I+ fibrocytes were detected 7 days after injury. At day 14, fibrocytes were recognized under the fibrous matrix in contact with MTA and had infiltrated into regions of new capillary formation, where the fibrocytes were positively stained for vascular endothelial growth factor. By 35 days, fibrocytes were few, coincident with the formation of dentine bridges. The number of fibrocytes peaked 7 days post-injury and decreased at 14 days. CONCLUSIONS: The presence of fibrocytes in human pulp wound healing was observed. The spatiotemporal distribution of fibrocytes suggests that fibrocytes are involved in the early stages of pulp wound healing, specifically by contributing to new blood vessel formation.

On Rhythms in Neuronal Networks with Recurrent Excitation.

We investigate rhythms in networks of neurons with recurrent excitation, that is, with excitatory cells exciting each other. Recurrent excitation can sustain activity even when the cells in the network are driven below threshold, too weak to fire on their own. This sort of "reverberating" activity is often thought to be the basis of working memory. Recurrent excitation can also lead to "runaway" transitions, sudden transitions to high-frequency firing; this may be related to epileptic seizures. Not all fundamental questions about these phenomena have been answered with clarity in the literature. We focus on three questions here: (1) How much recurrent excitation is needed to sustain reverberating activity? How does the answer depend on parameters? (2) Is there a positive minimum frequency of reverberating activity, a positive "onset frequency"? How does it depend on parameters? (3) When do runaway transitions occur? For reduced models, we give mathematical answers to these questions. We also examine computationally to which extent our findings are reflected in the behavior of biophysically more realistic model networks. Our main results can be summarized as follows. (1) Reverberating activity can be fueled by extremely weak slow recurrent excitation, but only by sufficiently strong fast recurrent excitation. (2) The onset of reverberating activity, as recurrent excitation is strengthened or external drive is raised, occurs at a positive frequency. It is faster when the external drive is weaker (and the recurrent excitation stronger). It is slower when the recurrent excitation has a longer decay time constant. (3) Runaway transitions occur only with fast, not with slow, recurrent excitation. We also demonstrate that the relation between reverberating activity fueled by recurrent excitation and runaway transitions can be visualized in an instructive way by a (generalized) cusp catastrophe surface.

Phenytoin-induced gingival overgrowth caused by death receptor pathway malfunction.

OBJECTIVE: In this study, we investigated the role of phenytoin (PHT) in death receptor-induced apoptosis of gingival fibroblasts to clarify the mechanism of PHT-induced gingival overgrowth. METHODS: Human gingival fibroblasts were cultured to semiconfluence and treated with PHT (0.025, 0.1, 0.25, and 1.0 µM) for 48 h, and then, the apoptotic cell numbers were relatively determined by absorptiometry. After 24 h of 0.25 µM PHT treatment, caspase activity was measured by absorptiometry, apoptotic and cell cycle phase distribution was analyzed by flow cytometry, expression levels of apoptotic genes were quantified by real-time qPCR, and expression of apoptotic proteins was detected by Western blot analysis. After 48 h of 0.25 µM PHT treatment, appearance of apoptotic cells was detected by TUNEL assay. RESULTS: PHT treatment decreased the proportion of apoptotic cells in gingival fibroblasts compared to a serum-free control culture in response to the protein changes as follows: PHT upregulated c-FLIP and, in turn, downregulated FADD, caspase-8, and caspase-3; PHT upregulated c-IAP2 and downregulated TRAF2; PHT downregulated caspase-9 and caspase-3 via decreased RIPK1 activity and increased Bcl-2 activity. CONCLUSION: PHT-induced gingival overgrowth may result from the above-mentioned mechanisms involving apoptosis inhibition in gingival fibroblasts.

Possible pharmacotherapy for nifedipine-induced gingival overgrowth: 18α-glycyrrhetinic acid inhibits human gingival fibroblast growth.

BACKGROUND AND PURPOSE: This investigation aimed to establish the basis of a pharmacotherapy for nifedipine-induced gingival overgrowth. Gingival overgrowth has been attributed to the enhanced growth of gingival fibroblasts. In this study, we investigated the effects of 18-α-glycyrrhetinic acid (18α-GA) on growth, the cell cycle, and apoptosis and on the regulators of these processes in gingival fibroblasts isolated from patients who presented with nifedipine-induced gingival overgrowth. EXPERIMENTAL APPROACH: Gingival fibroblasts were cultured in medium containing 1% FBS with/without 10 µM 18α-GA for 24 or 48 h, and the cell number, cell cycle phase distribution, relative DNA content, apoptotic cell number and morphological characteristics of the cells undergoing apoptosis were measured together with the levels of proteins that regulate these processes and the level of caspase activity. KEY RESULTS: 18α-GA significantly decreased cell numbers and significantly increased the percentage of cells in the sub-G1 and G0 /G1 phases of the cell cycle and the number of apoptotic cells. Nuclear condensation and fragmentation of cells into small apoptotic bodies appeared in the fibroblasts treated with 18α-GA. In addition, 18α-GA significantly decreased the protein levels of cyclins A and D1, CDKs 2 and 6, phosphorylated Rb (ser(780) and ser(807/811)), Bcl-xL and Bcl-2 and increased the protein levels of p27, cytosolic cytochrome c, pro-caspase-3, and cleaved caspase-3 and the activities of caspases 3 and 9. CONCLUSIONS AND IMPLICATIONS: 18α-GA inhibited gingival fibroblast growth by suppressing the G1 /S phase transition and inducing apoptosis. In conclusion, 18α-GA may be used as a pharmacotherapy for nifedipine-induced gingival overgrowth.

Pentax Airway Scope® vs Macintosh laryngoscope for tracheal intubation in adult patients: a systematic review and meta-analysis.

The Pentax Airway Scope(®) is a single-use optical videolaryngoscope designed to assist with difficult tracheal intubation. We systematically reviewed the efficacy of the Pentax Airway Scope with that of a conventional laryngoscope for tracheal intubation in adults with 'normal' and 'difficult' airways. We included 17 randomised controlled trials with a total of 1801 participants. We used the DerSimonian and Laird random-effects model to calculate pooled relative risk or weighted mean differences. The relative risk (95% CI) of a Cormack-Lehane grade-1 laryngeal view was 2.40 (1.76-2.49) with the Pentax Airway Scope compared with the Macintosh laryngoscope, p < 0.00001. We found no other differences between the two laryngoscopes. Despite a superior laryngeal view, the Pentax Airway Scope provides little clinical benefit over the conventional laryngoscope.

Self-assessed approach to improving school health in Niger.

INTRODUCTION: Award schemes and self-evaluation systems have been developed to implement the 'Health-Promoting School (HPS)' concept in European and Asian countries. While there have been many successes in these regions, the implementation of HPS in African countries has been minimal. This study evaluated the impact of a self-evaluation system on school health in Niger. METHODS: A school health activity guide was developed and distributed to 1999 primary schools in the Niger Tahoua region to raise awareness and solve problems related to school health and hygiene. The number of schools that planned or implemented health-related activities, and the budget and implementation status of their activities was compared over 3 years (before, soon after, and 1 year after distribution). Focus group discussions (FGDs) were also conducted targeting Conseillers Pédagogiques (CPs), who supervise primary schools and teachers, primary school principals and members of Comité de Gestion des Etablissement Scolaire (COGES), which is a type of school steering committee. RESULTS: The number of schools planning at least one health-related activity increased from 47% to 79% soon after distribution of the guide (p <0.001).The number of schools implementing activities increased from 44% to 65% one year after distribution (p <0.001). Health-related budget per school also increased after distribution (p <0.0001) and increases were maintained 1 year after the intervention (p=0.8414). Fulfilment or partial fulfilment rates for health-related activities were lower compared with other (non-health) activities in all three years (80%, 77% & 84% in health-related activities vs 88%, 90% & 91% in others; p <0.001, p <0.001, & p=0.004, respectively). Most FGD participants expressed a positive impression of the program and noted the usefulness of the guide. However, some respondents reported difficulties, especially in relation to budget. CONCLUSION: The introduction of a health activity guide for self-assessment was effective in increasing health-related activities in primary schools in Niger, where a simple monitoring system should be introduced to establish the HPS concept.

Navigated opening wedge high tibial osteotomy improves intraoperative correction angle compared with conventional method.

PURPOSE: The correction angle after high tibial osteotomy (HTO) depends on an accurate preoperative planning and an accurate intraoperative technique. We hypothesized that the use of a navigation system in opening wedge HTO would improve the intraoperative target angles in the coronal and sagittal planes. METHODS: Postoperative femoro-tibial angle (FTA) and tibial posterior slope (TPS) in 28 knees with navigated opening wedge HTO were compared to those in 31 knees with the conventional method. Intraoperative correction angle was determined by the predicted medial opening width in the conventional group, and by the change of hip-knee-ankle angle in the navigated group. We defined lateral unstable knee as the knees with lateral cortex breakage or lateral tibial plateau fracture. RESULTS: Mean postoperative FTA was higher in the conventional group than in the navigated group (P < 0.037). In the conventional group, 4 lateral unstable knees were corrected to 174.6°. In the navigated group, 5 lateral unstable knees were corrected to 170.3° and no knees showed FTA > 173°. Mean change in TPS was greater in the conventional group than in the navigated group (P = 0.001). CONCLUSION: The navigation system in opening wedge HTO might reduce undercorrection in the knees with lateral cortex breakage or lateral tibial plateau fracture, and provide the better intraoperative FTA and TPS. LEVEL OF EVIDENCE: III.

Cross-cultural adaptation and validation of the Oxford 12-item knee score in Japanese.

INTRODUCTION: With the high incidence of knee osteoarthritis (OA) in Japan, there is a strong need not only for surgical therapies, but also for validated outcome measures. For this study, we completed cross-cultural adaptation, testing and validation of the Oxford knee score (OKS) for prospective use in national and international clinical studies involving Japanese patients. MATERIALS AND METHODS: The Japanese version of the OKS was developed according to the standard cross-cultural adaptation guidelines. For validation, the OKS was tested on 54 patients diagnosed with OA, osteonecrosis, ligament or meniscus injury. Reliability was tested using the intraclass correlation coefficient (ICC). Internal consistency or homogeneity was assessed using Cronbach's alpha. The correlation between the Japanese OKS, WOMAC and SF-36 questionnaires was used to assess construct validity. RESULTS: No major difficulties were encountered with the translation and pre-testing stages. For reliability and validity, the Japanese OKS was completed without any missed responses by 53 (98.15%) and 52 (96.30%) patients at the first and second distribution, respectively. The total OKS showed good reliability with an ICC of 0.85. Internal consistency was strong (Cronbach's alpha = 0.90). Strong construct validity (ICC values of 0.51-0.84) was obtained against the WOMAC and SF-36 (physical functioning, role-physical, bodily pain, and social functioning subscales) scores. Notable "ceiling" effects of the OKS were reported for 11 of the 12 questionnaire items. CONCLUSION: The Japanese OKS has proven to be a reliable and valid instrument for the self-assessment of knee pain and function in Japanese speaking patients with knee OA and other knee complaints.

Rats with high left ventricular end-diastolic pressure can be identified by Doppler echocardiography one week after myocardial infarction

The severity of left ventricular (LV) dysfunction in rats with myocardial infarction (MI) varies widely. Because homogeneity in baseline parameters is essential for experimental investigations, a study was conducted to establish whether Doppler echocardiography (DE) could accurately identify animals with high LV end-diastolic pressure as a marker of LV dysfunction soon after MI. Direct measurements of LV end-diastolic pressure were made and DE was performed simultaneously 1 week after surgically induced MI (N = 16) or sham-operation (N = 17) in female Wistar rats (200 to 250 g). The ratio of peak early (E) to late (A) diastolic LV filling velocities and the ratio of E velocity to peak early (Em) diastolic myocardial velocity were the best predictors of high LV end-diastolic pressure (>12 mmHg) soon after MI. Cut-off values of 1.77 for the E/A ratio (P = 0.001) identified rats with elevated LV end-diastolic pressure with 90 percent sensitivity and 80 percent specificity. Cut-off values of 20.4 for the E/Em ratio (P = 0.0001) identified rats with elevated LV end-diastolic pressure with 81.8 percent sensitivity and 80 percent specificity. Moreover, E/A and E/Em ratios were the only echocardiographic parameters independently associated with LV end-diastolic pressure in multiple linear regression analysis. Therefore, DE identifies rats with high LV end-diastolic pressure soon after MI. These findings have implications for using serial DE in animal selection and in the assessment of their response to experimental therapies.

Rats with high left ventricular end-diastolic pressure can be identified by Doppler echocardiography one week after myocardial infarction.

The severity of left ventricular (LV) dysfunction in rats with myocardial infarction (MI) varies widely. Because homogeneity in baseline parameters is essential for experimental investigations, a study was conducted to establish whether Doppler echocardiography (DE) could accurately identify animals with high LV end-diastolic pressure as a marker of LV dysfunction soon after MI. Direct measurements of LV end-diastolic pressure were made and DE was performed simultaneously 1 week after surgically induced MI (N = 16) or sham-operation (N = 17) in female Wistar rats (200 to 250 g). The ratio of peak early (E) to late (A) diastolic LV filling velocities and the ratio of E velocity to peak early (Em) diastolic myocardial velocity were the best predictors of high LV end-diastolic pressure (>12 mmHg) soon after MI. Cut-off values of 1.77 for the E/A ratio (P = 0.001) identified rats with elevated LV end-diastolic pressure with 90% sensitivity and 80% specificity. Cut-off values of 20.4 for the E/Em ratio (P = 0.0001) identified rats with elevated LV end-diastolic pressure with 81.8% sensitivity and 80% specificity. Moreover, E/A and E/Em ratios were the only echocardiographic parameters independently associated with LV end-diastolic pressure in multiple linear regression analysis. Therefore, DE identifies rats with high LV end-diastolic pressure soon after MI. These findings have implications for using serial DE in animal selection and in the assessment of their response to experimental therapies.

[Usefulness of the thoracoscopic surgery under local anesthesia and irrigation for the patient with Bacillus cereus empyema; report of a case].

The case was 54-year-old male with some risks such as chronic heart failure, atrial fibrillation, and liver chirrhosis. He was admitted because of severe back pain and diagnosed as empyema by preoperative thoracentesis. By thoracoscopic procedures under local anesthesia, fibrinopurulent tissues were cleaned as much as possible and 3 of chest tubes were replaced. The final diagnosis was Bacillus cereus pyothorax by bacterial cultures of pleural effusion. Intrathoracic cavity was cleaned with physiological saline solution. The patient made favorable progress and recovered. Thoracoscopic surgery under local anesthesia with thoracic irrigation was so effective and safe methods to control the infection.

Unicompartmental knee arthroplasty for osteoarthritis of the knee: remaining postoperative flexion contracture affecting overall results.

The success rate of unicompartmental knee arthroplasty has been variable, and controversy still surrounds its use. Achieving good functional results from this surgery may require understanding surgical principles, precise operative techniques, and careful patient selection. This paper evaluates clinical results and factors influencing postoperative knee function after unicompartmental knee arthroplasty. The follow-up assessment of 109 knees that underwent unicompartmental knee arthroplasty showed that 90 of 109 knees were classified as excellent or good (82.6%) using the Hospital for Special Surgery knee scoring system. In the excellent group (54 knees), 52% of the postoperative, standing femorotibial angles converged on a range of 170 degrees to 175 degrees with a mean of 174 degrees +/- 4 degrees. The knees with residual flexion contracture after surgery showed poorer clinical results. Therefore, complete elimination of the flexion contracture during surgery is considered mandatory.

Significance of magnetic resonance imaging in the diagnosis of nodular regenerative hyperplasia of the liver complicated with systemic lupus erythematosus: a case report and review of the literature.

Nodular regenerative hyperplasia of the liver (NRH), characterized by multiple hepatic nodules in the absence of fibrosis, is a rare but important complication of systemic lupus erythematosus (SLE) associated with non-cirrhotic portal hypertension. The diagnosis of NRH is based on the pathological examination, and radiological findings of NRH are poorly documented. We report a case of a 40-year-old woman with SLE complicated with NRH. Sixteen years after diagnosis of SLE, esophageal varices were incidentally found and diagnosis of portal hypertension due to NRH was made by magnetic resonance imaging (MRI) and confirmed by needle liver biopsy. Although MRI showed the lesions as significant nodules, neither computed tomography nor ultrasonography could demonstrate the nodules. However, serial MRI showed significant enlargement of the nodules for 2 years Because NRH may lead to portal hypertension with life-threatening variceral haemorrhage in patients with SLE, MRI is a useful, non-invasive examination to screen the patients for its presence and follow-up. We reviewed the literature regarding NRH in SLE and discuss the management of the affected patients.

[Destructed knee in patient with systemic lupus erythematosus treated with total knee arthroplasty: a case report].

We reported a case of a 61-year-old female with arthritis of right knee associated with systemic lupus erythematosus (SLE). She suffered from SLE at age 31 and felt pain around her right knee at age 60. It gradually increased despite intraarticular injections of steroid and arthroscopic synovectomy. On admission, the range of motion of her right knee was 20 to 135 degrees and remarkable gait disturbance were noted due to the pain. Radiographs of the right knee showed joint space narrowing and bone erosion. YMCK total knee arthroplasty was performed. Operation findings showed smooth and thick synovium and cartilage defect. Histological examination revealed fibrin on surface, proliferad connective tissue and newly development of vasculature. Synovium eroded both cartilage and bone. In SLE, soft tissue contructure was reported to be a main cause of joint dislocation, but there were only a few report of progressive joint destruction due to SLE. In this case, the main cause of joint destruction may be invasion synovium into cartilage and bone.

Treatment of the unstable distal radius fracture with external fixation and a hydroxyapatite spacer.

A prospective study was performed on 25 patients (15 women, 10 men) with unstable fractures of the distal radius selectively treated with a dynamic type of external fixation combined with a hydroxyapatite spacer. The fractures ranged from type VI to type VIII according to Frykman's classification. The patients' mean age at surgery was 49 years (range, 19-75 years). The mean follow-up period was 2.5 years, and overall outcome was assessed using Gartland and Werley's demerit point system as modified by Sarmiento. Radial inclination was 26 degrees +/- 4 degrees at the time of reduction and 26 degrees +/- 5 degrees at follow-up, palmar tilt was 9 degrees +/- 2 degrees at reduction and 8 degrees +/- 3 degrees at follow-up, and ulnar variance was 1.4 +/- 0.6 mm at reduction and 2.1 +/- 0.9 mm at follow-up. The mean range of motion at follow-up was 80 degrees +/- 10 degrees in flexion, 80 degrees +/- 10 degrees in extension, 85 degrees +/- 10 degrees in supination, and 80 degrees +/- 5 degrees in pronation. The outcome in 24 of 25 patients was evaluated as excellent. In the surgical treatment of unstable fractures of the distal radius using external fixator, the fracture reduction should be supported with bone graft or a bone substitute, and a hydroxyapatite spacer was considered to be a useful substitute for a bone graft.

Iridium complex-catalyzed allylic amination of allylic esters.

Iridium complex-catalyzed allylic amination of allylic carbonates was studied. The solvent strongly affected the catalytic activity. The use of a polar solvent such as EtOH is essential for obtaining the products in high yield. The reaction of (E)-3-substituted-2-propenyl carbonate and 1-substituted-2-propenyl carbonate with pyrrolidine in the presence of a catalytic amount of [Ir(COD)Cl](2) and P(OPh)(3) (P/Ir = 2) gave a branch amine with up to 99% selectivity. Both secondary and primary amines could be used for this reaction. When a primary amine was used, selective monoallylation occurred. No diallylation product was obtained. The reaction of 1,1-disubstituted-2-propenyl acetate with amines exclusively gave an alpha,alpha-disubstituted allylic amine. This reaction provides an alternative route to the addition of an organometallic reagent to ketimines for the preparation of such amines. The reaction of (Z)-3-substituted-2-propenyl carbonate with amines gave (Z)-linear amines with up to 100% selectivity. In all cases, no (E)-linear amine was obtained. The selectivities described here have not been achieved in similar palladium complex-catalyzed reactions.

Effects of collagen gel mixed with hydroxyapatite powder on interface between newly formed bone and grafted achilles tendon in rabbit femoral bone tunnel.

The Achilles tendon was implanted into a bone tunnel made in the femoral condyle of 20 rabbits. In the left femur, collagen gel mixed with hydroxyapatite powder (C-HAp) was injected between the graft and the bone tunnel. On the other hand, as a control, simple saline was injected in the right femur. Five rabbits were sacrificed at 4, 8, 12, and 16 weeks after surgery. Histological findings showed that in the C-HAp group, the grafted tendon came in direct contact with new bone, and Sharpey-like collagen fibers arising from the grafted tendon were observed to penetrate new bone by 4 weeks after surgery. In the control group, however, fibrous tissue was observed between new bone and the grafted tendon, but no penetrating fibers from the grafted tendon into the new bone were observed until 16 weeks. The area of new bone in the C-HAp group was significantly greater than that in the control group 4, 8, and 12 weeks after surgery (p < 0.0001, p < 0.0007, p < 0.0013, respectively).

Reliability of the transepicondylar line as a parameter of femoral axial alignment.

The purpose of this research was to determine the significance of the transepicondylar line as a parameter of femoral axial alignment. Standing full-length X-ray films of 124 knees of 91 patients (63 women, 28 men) with osteoarthritis, rheumatoid arthritis, or osteonecrosis were used in this study, in which the lateral angles formed by the femoral anatomical axis intersecting with the transepicondylar line (angle a'), horizontal line (angle b'), and femoral condylar line (angle r') were measured. The mean value of angle b' in knees with neutral alignment was significantly smaller than that in knees with varus alignment, and significantly larger than that in knees with valgus alignment; no significant difference was found in angle a'. Also, there was no significant difference in angle a' among the patients with osteoarthritis, rheumatoid arthritis, and osteonecrosis. These findings suggest that the transepicondylar line, which is a stable reference of femoral rotation, is also a very reliable parameter of axial alignment of the femur. In the future design of extramedullary guiding for total knee arthroplasty, the transepicondylar line may play an important role as a parameter for proper and accurate implant setting.