Case report: A rare case of extravesical, extraperitoneal metastasis after transuretheral resection of urothelial carcinoma.

Bladder perforation secondary to transurethral resection of bladder tumour (TURBT) increases the risk of tumour cell seeding and eventual extravesical metastasis. Here we presented a case where a patient with localised bladder tumour was initially managed with repeated TURBTs for tumour recurrence. Subsequently he was found to have extravesical pelvic metastasis. This was likely secondary to microperforation of bladder and tumour cell seeding. Microscopic bladder perforation is difficult to diagnose. However patients with confirmed bladder perforation during TURBT would justify systemic radiological cancer surveillance in view of higher risk of metastatic disease.

Harmine promotes periodontal ligament cell-induced tissue regeneration.

OBJECTIVE: to investigate whether harmine has a promotive effect on human periodontal ligament cells (hPDLCs)-induced tissue regeneration. MATERIALS AND METHODS: Various concentrations of harmine on hPDLCs proliferation were tested. Osteogenic and cementogenic characteristics were examined in hPDLC/rhBMP-2 and hPDLC/harmine by alizarin red S staining, real-time PCR, and Western blotting assay. The activity of harmine was investigated in an ectopic transplantation nude mouse model. RESULTS: We determined that 10 µM of harmine was the threshold concentration. hPDLC/harmine showed similar mineralized nodule formation in alizarin S staining compared to hPDLC/rhBMP-2. In real-time PCR, the highest gene expression level was observed for Runx2 in hPDLC/harmine at all time points. The level of CEMP-1 in hPDLC/harmine was higher at 7 days than hPDLCs alone. Thicker band of Runx2 in hPDLC/harmine was observed than in hPDLC/rhBMP-2 at 7 days by Western blotting. The band for CEMP-1 in hPDLC/harmine was thicker than hPDLCs alone at both 7 and 14 days. In ectopic transplantation, hPDLCs with harmine showed a comparable amount of mineralized tissue formation compared to rhBMP-2. hPDLCs with harmine or rhBMP-2 formed both bone and cementum-like tissue with Sharpey's fiber-like collagen insertion. CONCLUSION: Harmine can be a potential candidate for promoting hPDLCs-induced tissue regeneration.

Role of PIN1 on in vivo periodontal tissue and in vitro cells.

BACKGROUND: Although expression of peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) was reported in bone tissue, the precise role of PIN1 in periodontal tissue and cells remain unclear. MATERIAL & METHODS: To elucidate the roles of PIN1 in periodontal tissue, its expression in periodontal tissue and cells, and effects on in vitro 4 osteoblast differentiation and the underlying signaling mechanisms were evaluated. RESULTS: PIN1 was expressed in mouse periodontal tissues including periodontal ligament cells (PDLCs), cementoblasts and osteoblasts at the developing root formation stage (postnatal, PN14) and functional stage of tooth (PN28). Treatment of PIN1 inhibitor juglone, and gene silencing by RNA interference promoted osteoblast differentiation in PDLCs and cementoblasts, whereas the overexpression of PIN1 inhibited. Moreover, osteogenic medium-induced activation of AMPK, mTOR, Akt, ERK, p38 and NF-jB pathways were enhanced by PIN1 siRNA, but attenuated by PIN1 overexpression. Runx2 expressions were induced by PIN1 siRNA, but downregulated by PIN1 overexpression. CONCLUSION: In summary, this study is the first to demonstrate that PIN1 is expressed in developing periodontal tissue, and in vitro PDLCs and cementoblasts. PIN1 inhibition stimulates osteoblast differentiation, and thus may play an important role in periodontal regeneration.

The influence of surgical factors on dislocation of the meniscal bearing after Oxford medial unicompartmental knee replacement: a case-control study.

The aim of this study was to evaluate the risk factors for dislocation of the bearing after a mobile-bearing Oxford medial unicompartmental knee replacement (UKR) and to test the hypothesis that surgical factors, as measured from post-operative radiographs, are associated with its dislocation From a total of 480 UKRs performed between 2001 and 2012, in 391 patients with a mean age of 66.5 years (45 to 82) (316 female, 75 male), we identified 17 UKRs where bearing dislocation occurred. The post-operative radiological measurements of the 17 UKRs and 51 matched controls were analysed using conditional logistic regression analysis. The post-operative radiological measurements included post-operative change in limb alignment, the position of the femoral and tibial components, the resection depth of the proximal tibia, and the femoral component-posterior condyle classification. We concluded that a post-operative decrease in the posterior tibial slope relative to the pre-operative value was the only significant determinant of dislocation of the bearing after medial Oxford UKR (odds ratio 1.881; 95% confidence interval 1.272 to 2.779). A post-operative posterior tibial slope < 8.45° and a difference between the pre-operative and post-operative posterior tibial slope of > 2.19° may increase the risk of dislocation.

Evaluation of anatomical landmark position differences between respiration-gated MRI and four-dimensional CT for radiation therapy in patients with hepatocellular carcinoma.

OBJECTIVE: To measure the accuracy of position differences in anatomical landmarks in gated MRI and four-dimensional CT (4D-CT) fusion planning for radiation therapy in patients with hepatocellular carcinoma (HCC). METHODS: From April to December 2009, gated MR and planning 4D-CT images were obtained from 53 inoperable HCC patients accrued to this study. Gated MRI and planning 4D-CT were conducted on the same day. Manual image fusions were performed by matching the vertebral bodies. Liver volumes and three specific anatomical landmarks (portal vein conjunction, superior mesenteric artery bifurcation, and other noticeable points) were contoured from each modality. The points chosen nearest the centre of the four landmark points were compared to measure the accuracy of fusion. RESULTS: The average distance differences (±standard deviation) of four validation points were 5.1 mm (±4.6 mm), 5.6 mm (±6.2 mm), 5.4 mm (±4.5 mm) and 5.1 mm (±4.8 mm). Patients who had ascites or pulmonary disease showed larger discrepancies. MRI-CT fusion discrepancy was significantly correlated with positive radiation response (p<0.05). CONCLUSIONS: Approximately 5-mm anatomical landmark positional differences in all directions were found between gated MRI and 4D-CT fusion planning for HCC patients; the gap was larger in patients with ascites or pulmonary disease. ADVANCES IN KNOWLEDGE: There were discrepancies of approximately 5 mm in gated MRI-CT fusion planning for HCC patients.

The radiological parameters correlated with the alignment of the femoral component after Oxford phase 3 unicompartmental knee replacement.

The purpose of this study was to measure the radiological parameters of femoral component alignment of the Oxford Phase 3 unicompartmental knee replacement (UKR), and evaluate their effect on clinical outcome. Multiple regression analysis was used to examine the relative contributions of the radiological assessment of femoral component alignment in 189 consecutive UKRs performed by a single surgeon. The American Knee Society scores were compared between groups, defined as being within or outside recommended tolerances of the position of the femoral component. For the flexion/extension position 21 UKRs (11.1%) lay outside the recommended limits, and for posterior overhang of the femoral component nine (4.8%) lay outside the range. The pre-operative hip/knee/ankle (HKA) angle, narrowest canal distance from the distal femoral entry point of the alignment jig and coronal entry-point position had significant effects on the flexion/extension position. Pre-operative HKA angle had a significant influence on posterior overhang of the femoral component. However, there was no significant difference in American Knee Society scores relative to the position of the femoral component.

Oxford phase 3 unicompartmental knee replacement in Korean patients.

Medium-term survivorship of the Oxford phase 3 unicompartmental knee replacement (UKR) has not yet been established in an Asian population. We prospectively evaluated the outcome of 400 phase 3 Oxford UKRs in 320 Korean patients with a mean age at the time of operation of 69 years (48 to 82). The mean follow-up was 5.2 years (1 to 10). Clinical and radiological assessment was carried out pre- and post-operatively. At five years, the mean Knee Society knee and functional scores had increased significantly from 56.2 (30 to 91) pre-operatively to 87.2 (59 to 98) (p = 0.034) and from 59.2 (30 to 93) to 88.3 (50 to 100) (p = 0.021), respectively. The Oxford knee score increased from a mean of 25.8 (12 to 39) pre-operatively to 39.8 (25 to 58) at five years (p = 0.038). The ten-year survival rate was 94% (95% confidence interval 90.1 to 98.0). A total of 14 UKRs (3.5%) required revision. The most common reason for revision was dislocation of the bearing in 12 (3%). Conversion to a total knee replacement was required in two patients who developed osteoarthritis of the lateral compartment. This is the largest published series of UKR in Korean patients. It shows that the mid-term results after a minimally invasive Oxford phase 3 UKR can yield satisfactory clinical and functional results in this group of patients.

Long-term results of arthroscopic excision of unstable osteochondral lesions of the lateral femoral condyle.

The purpose of this study was to evaluate the long-term functional and radiological outcomes of arthroscopic removal of unstable osteochondral lesions with subchondral drilling in the lateral femoral condyle. We reviewed the outcome of 23 patients (28 knees) with stage III or IV osteochondritis dissecans lesions of the lateral femoral condyle at a mean follow-up of 14 years (10 to 19). The functional clinical outcomes were assessed using the Lysholm score, which improved from a mean of 38.1 (SD 3.5) pre-operatively to a mean of 87.3 (SD 5.4) at the most recent review (p = 0.034), and the Tegner activity score, which improved from a pre-operative median of 2 (0 to 3) to a median of 5 (3 to 7) at final follow-up (p = 0.021). The radiological degenerative changes were evaluated according to Tapper and Hoover's classification and when compared with the pre-operative findings, one knee had grade 1, 22 knees had grade 2 and five knees had grade 3 degenerative changes. The overall outcomes were assessed using Hughston's rating scale, where 19 knees were rated as good, four as fair and five as poor. We found radiological evidence of degenerative changes in the third or fourth decade of life at a mean of 14 years after arthroscopic excision of the loose body and subchondral drilling for an unstable osteochondral lesion of the lateral femoral condyle. Clinical and functional results were more satisfactory.

High tibial osteotomy using polycaprolactone-tricalcium phosphate polymer wedge in a micro pig model.

Medial open-wedge high tibial osteotomy has been gaining popularity in recent years, but adequate supporting material is required in the osteotomy gap for early weight-bearing and rapid union. The purpose of this study was to investigate whether the implantation of a polycaprolactone-tricalcium phosphate composite scaffold wedge would enhance healing of the osteotomy in a micro pig model. We carried out open-wedge high tibial osteotomies in 12 micro pigs aged from 12 to 16 months. A scaffold wedge was inserted into six of the osteotomies while the other six were left open. Bone healing was evaluated after three and six months using plain radiographs, CT scans, measurement of the bone mineral density and histological examination. Complete bone union was obtained at six months in both groups. There was no collapse at the osteotomy site, loss of correction or failure of fixation in either group. Staining with haematoxylin and eosin demonstrated that there was infiltration of new bone tissue into the macropores and along the periphery of the implanted scaffold in the scaffold group. The CT scans and measurement of the bone mineral density showed that at six months specimens in the scaffold group had a higher bone mineral density than in the control group, although the implantation of the polycaprolactone-tricalcium phosphate composite scaffold wedge did not enhance healing of the osteotomy.

Stabilizing the eIF4G1 α-helix increases its binding affinity with eIF4E: implications for peptidomimetic design strategies.

Eukaryotic initiation factor (eIF)4E is overexpressed in many types of cancer such as breast, head and neck, and lung. A consequence of increased levels of eIF4E is the preferential translation of pro-tumorigenic proteins such as c-Myc, cyclin D1, and vascular endothelial growth factor. Inhibition of eIF4E is therefore a potential therapeutic target for human cancers. A novel peptide based on the eIF4E-binding peptide eIF4G1, where the α-helix was stabilized by the inclusion of α-helix inducers as shown by CD measurements, was synthesized. The helically stabilized peptide binds with an apparent K(d) of 9.43±2.57 nM, which is ∼15.7-fold more potent than the template peptide from which it is designed. The helically stabilized peptide showed significant biological activity at a concentration of 400 µM, unlike the naturally occurring eIFG1 peptide when measured in cell-based cap-dependent translational reporter and WST-1 (4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate) assays. Fusion of the template peptide and the stabilized peptide to the cell-penetrating peptide TAT produced more active but equally potent inhibitors of cap-dependent translation in cell lines. They also equally disrupted cell metabolism as measured in a WST-1 assay. Propidium iodide staining revealed that the TAT-fused, helically stabilized peptide caused more cell death than the TAT-fused eIF4G1 template peptide with substantial decreases in the G1 and G2 cell populations. Annexin-staining experiments also indicated that the TAT-fused eIF4G1 derivative peptides caused cell death by apoptosis. The results presented should offer further insight into peptidomimetics development for eIF4E.

Assessment of Physical Activity Level among Individuals with Type 2 Diabetes Mellitus at Cheras Health Clinic, Kuala Lumpur.

A cross-sectional study was carried out to assess the physical activity levels among patients with type 2 diabetes mellitus (DM) at Cheras Health Clinic in Kuala Lumpur. A total of 132 subjects (62 men and 70 women) aged 30 years and above participated in this study. Data was collected using an interview based questionnaire to obtain socio-demographic and health profile information. Physical activity was assessed using a shortened version of the International Physical Activity Questionnaire (IPAQ). Anthropometric measurements and body fat were also taken. Glycaemic status, that is, HbA1c, fasting blood sugar (FBS) and 2 hours post-prandial (2-HPP) were obtained from medical records. Results showed that the mean age of the patients was 51.9 + 5.8 years. The majority of patients had poor glycaemic control based on HbA1c (70.7%), FBS (71.9%) and 2HPP (85.4%). Patients who were unmarried and aged(60 years and above had a lower physical activity level (p< 0.05). In the older age group, low physical activity was associated with poor glycaemic control (p< 0.05). Patients in the moderate and high physical activity level were motivated to perform physical activity so as to be healthy (68.1%). Low physical activity level among patients was due to lack of time (54.5%) and lack of energy (21.2%). In conclusion, physical activity levels of the patients were unsatisfactory and associated with poor glycaemic control, especially in the elderly. There is a need to encourage diabetic patients to undertake regular physical activity in order to achieve optimal glycaemic control.

Acute naphthalene poisoning following the non-accidental ingestion of mothballs.

Ingestional naphthalene mothball poisoning leading to prolonged haemolysis and methaemoglobinaemia can present with diagnostic and therapeutic challenges. A 19-year-old woman ingested 12 mothballs, and presented two days later with haemolysis and methaemoglobinaemia. She was treated with red blood cell transfusions, intravenous methylene blue, N-acetylcysteine and ascorbic acid. Continuous venovenous haemofiltration was conducted for 45 hours. Haemolysis with anaemia and methaemoglobinaemia persisted even after five days post-ingestion. Clinical and biochemical parameters improved. We describe a case of ingestional naphthalene poisoning with a good outcome after treatment.

Pathotypes and genetic relationship of worldwide collections of Elsinoë spp. causing scab diseases of citrus.

Two scab diseases are recognized currently on citrus: citrus scab, caused by Elsinoë fawcettii, and sweet orange scab, caused by E. australis. Because the two species cannot be reliably distinguished by morphological or cultural characteristics, host range and molecular methods must be used to identify isolates. Four pathotypes of E. fawcettii and two of E. australis have been described to date based on host range. The host specificity and genetic relationships among 76 isolates from Argentina, Australia, Brazil, Korea, New Zealand, and the United States were investigated. Based on pathogenicity tests on eight differential hosts, 61 isolates were identified as E. fawcettii and 15 as E. australis. Of 61 isolates of E. fawcettii, 24 isolates were identified as the Florida broad host range (FBHR) pathotype, 7 as the Florida narrow host range (FNHR) pathotype, 10 as the Tryon's pathotype, and 3 as the "Lemon" pathotype. Two new pathotypes, the "Jingeul" and the satsuma, rough lemon, grape-fruit, clementine (SRGC), are described, and four isolates did not fit into any of the known pathotypes of E. fawcettii. Of the 15 isolates of E. australis from Argentina and Brazil, 9 belonged to the sweet orange pathotype and 6 from Korea to the natsudaidai pathotype. E. fawcettii and E. australis were clearly distinguishable among groups by random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) assays and the E. fawcettii group was divided into three subgroups, A-1, A-2, and A-3. The A-1 group was composed of the FBHR, FNHR, and SRGC pathotypes; some Lemon pathotypes; and the uncertain isolates. The A-2 subgroup included all of the Tryon's pathotype isolates and one of the three Lemon pathotype isolates and the A-3 group contained the Jingeul pathotype isolates. E. australis was differentiated into two groups: B-1, the natsudaidai pathotype isolates, and B-2, the sweet orange pathotype isolates. Isolates of E. fawcettii and E. australis were clearly distinguishable by sequence analysis of the internal transcribed spacer (ITS) region and the translation elongation factor 1 alpha (TEF) gene. There were also fixed nucleotide differences in the ITS and TEF genes that distinguished subgroups separated by RAPD-PCR within species. We confirmed two species of Elsinoë, two pathotypes of E. australis, and at least six pathotypes of E. fawcettii and described their distribution in the countries included in this study.

Effects of irradiation on cytokine production in a mouse model of Behçet's disease.

OBJECTIVE: Low-dose whole-body irradiation is known to have anti-inflammatory effects. The objectives of this study were to verify that cytokine augmentation is induced by irradiation in vivo, and to assess the effectiveness of radiation in treating Behçet's disease (BD). METHODS: Whole-body and half-body irradiation with single doses of 10cGy, 2Gy and 10Gy were delivered to normal mice, and cytokine and chemokine levels were analyzed in PBMC and sera. BD-like mice were treated with low-dose, half-body 10cGy irradiation. RESULTS: In normal mice, PBMC cytokine mRNA levels peaked four days after irradiation. Of the cytokines and chemokines examined, the levels of IL-4, IL-6, IL-12p40, TNF-alpha, TGF-b, MIP-1alpha and IL-18 were all influenced by radiation treatment. Of these, IL-4, an ameliorating factor for BD, was the most elevated following low-dose irradiation (10cGy group). FACS analysis showed intracellular IL-4-staining of 7.24+/-0.92% of PBMC from irradiated mice compared to 1.3+/-0.1% from non-irradiated, normal mice (p<0.005). Serum IL-4 levels were also significantly increased (6.08+/-1.7 pg/ml) relative to control (1.83+/-0.8; p<0.005). CONCLUSION: Augmentation of cytokine production may contribute to the anti-inflammatory effects of low dose irradiation and amelioration of BD symptoms in this mouse model.

Arthrodesis of the knee using cannulated screws.

We retrospectively evaluated eight patients who underwent arthrodesis of the knee using cannulated screws. There were six women and two men, with a mean age of 53 years. The indications for arthrodesis were failed total knee arthroplasty, septic arthritis, tuberculosis, and recurrent persistent infection. Solid union was achieved in all patients at a mean of 6.1 months. One patient required autogenous bone graft for delayed union. One suffered skin necrosis which was treated with skin grafting. The mean limb-length discrepancy was 3.1 cm. On a visual analogue scale, the mean pain score improved from 7.9 to 3.3. According to the Knee Injury and Osteoarthritis Outcome score quality of life items, the mean score improved from 38.3 pre-operatively to 76.6 at follow-up. Cannulated screws provide a high rate of union in arthrodesis of the knee with minimal complications, patient convenience, and a simple surgical technique.

Development of PCR Assays for the Identification of Species and Pathotypes of Elsinoë Causing Scab on Citrus.

Two scab pathogens of citrus, Elsinoë fawcettii and E. australis, cause citrus scab and sweet orange scab, respectively, and pathotypes of each species have been described. The two species cannot be readily distinguished by morphological or cultural characteristics and can be distinguished only by host range and the sequence of the internal transcribed spacer (ITS) region. In this study, random amplified polymorphic DNA (RAPD) assays clearly distinguished E. fawcettii and E. australis, and the sweet orange and natsudaidai pathotypes within E. australis also could be differentiated. We developed specific primer sets, Efaw-1 for E. fawcettii; Eaut-1, Eaut-2, Eaut-3, and Eaut-4 for E. australis; and EaNat-1 and EaNat-2 for the natsudaidai pathotype within E. australis using RAPD products unique to each species or pathotype. Other primer sets, Efaw-2 and Eaut-5, which were specific for E. fawcettii and E. australis, respectively, were designed from previously determined ITS sequences. The Efaw-1 and Efaw-2 primer sets successfully identified E. fawcettii isolates from Korea, Australia, and the United States (Florida) and the Eaut-1 to Eaut-5 primer sets identified both the sweet orange pathotype isolates of E. australis from Argentina and the natsudaidai pathotype isolates from Korea. The EaNat-1 and EaNat-2 primer sets were specific for isolates of the natsudaidai pathotype. The Efaw-1 and Efaw-2 primer sets successfully detected E. fawcettii from lesions on diseased leaves and fruit from Korea and primer pairs Eaut-1, Eaut-2, Eaut-3, Eaut-4, and Eaut-5 detected E. australis from lesions on sweet orange fruit from Brazil.

Determination of molecular types and genetic heterogeneity of Cryptococcus neoformans and C. gattii in Malaysia.

The molecular types and genetic heterogeneity of Cryptococcus neoformans and C. gattii clinical isolates in Malaysia were determined in this study. Of 44 C. neoformans collected between 1980 and 2003, 42 (95.5%) were molecular type VNI, 2 (4.5%) were molecular type VNII. Of 17 C.gattii isolates, 13 (76.5%) were molecular type VGI, and 4 (23.5%) were molecular type VGII. A difference was noted when comparing the molecular types of cryptococcal isolates in the earlier and recent cases of cryptococcosis. While both molecular types VNI and VGI were equally predominant in the earlier cases of cryptococcosis, VNI was the most predominant molecular type isolated from the recent cases. VNII was a new molecular type, isolated from 5.1% of the recent cases. All the bird dropping isolates were molecular type VNI. The genetic heterogeneity of the two predominant molecular types, i.e., VNI, VGI clinical isolates and bird dropping isolates of C. neoformans were further determined by polymerase chain reaction (PCR) fingerprinting method, using (GTG)5 as single primer. Two clusters of cryptococcal isolates were distinguished at 68.5% of similarity, with cluster I consisting of VNI isolates and cluster II consisting of VGI isolates. Each cluster was further subdivided into three subtypes at >/=80% of similarity. Fourteen bird dropping isolates were grouped into a subtype within VN1, sharing 82.7% of similarity with the clinical isolates. A higher degree of similarities, ranging from 93.4-97.6% was noted between 3 bird dropping isolates with the clinical isolates in another subtype. This study demonstrated the existence of various molecular types of C. neoformans isolates in Malaysia and the genetic heterogeneity within the predominant molecular types. The study also provides evidence for genetic relatedness of clinical isolates with bird dropping isolates in the environment.

Kinetics of L-lysine fermentation: a continuous culture model incorporating oxygen uptake rate.

For process design and optimization, it is essential to have a mathematical model that represents the system well. Many past studies do not go beyond empirically fitting experimental data. In the present study, an unstructured model incorporating oxygen uptake and dissolved oxygen concentration was developed for a continuous culture of L-lysine. Specific rate expressions of cell growth, substrate consumption, product formation, and oxygen uptake were developed and incorporated in the model. The model predicts very well the effects of operational parameters, such as the dilution rate and the feed substrate concentration. It is also able to predict the unsteady-state dynamics of continuous L-lysine fermentation.

The use of sildenafil in patients with erectile dysfunction in relation to diabetes mellitus--a study of 1,511 patients.

Erectile dysfunction (ED) seriously impairs the quality of life. Patients with diabetes mellitus (DM) are prone to ED due to various factors, including vasculopathy, neuropathy and sex hormone abnormalities. This is a retrospective study involving 1,511 patients taking sildenafil. Patients with DM have significantly more comorbidities like hypertension and ischaemic heart disease. They are also more likely to be on medications which may affect erectile function, including various antihypertensive drugs. 77.9% of patients with DM reported success with sildenafil, as compared to 86.5% of patients without DM. A significant number of patients with DM require a higher dose of sildenafil as compared to those without DM.