Minimally Invasive Total Hip Arthroplasty in a Patient with Hereditary Multiple Exostoses: A Case Report.

Hip geometry abnormalities found in patients with hereditary multiple exostoses (HME) could promote premature hip joint degeneration which needs treatment. We report the case of a 45-year old male with right hip arthrosis who underwent two-incision minimally invasive (MIS-2) total hip arthroplasty (THA), with satisfactory outcome. This technique could be an alternative approach for performing THA in patients with hereditary multiple exostoses.

Disrupted cortical brain network in post-traumatic stress disorder patients: a resting-state electroencephalographic study.

This study aimed to examine the source-level cortical brain networks of post-traumatic stress disorder (PTSD) based on the graph theory using electroencephalography (EEG). Sixty-six cortical source signals were estimated from 78 PTSD and 58 healthy controls (HCs) of resting-state EEG. Four global indices (strength, clustering coefficient (CC), path length (PL) and efficiency) and one nodal index (CC) were evaluated in six frequency bands (delta, theta, alpha, low beta, high beta and gamma). PTSD showed decreased global strength, CC and efficiency, in delta, theta, and low beta band and enhanced PL in theta and low beta band. In low beta band, the strength and CC correlated positively with the anxiety scores, while PL had a negative correlation. In addition, nodal CCs were reduced in PTSD in delta, theta and low beta band. Nodal CCs of theta band correlated negatively with rumination and re-experience symptom scores; while, nodal CCs in low beta band correlated positively with anxiety and pain severity. Inefficiently altered and symptom-dependent changes in cortical networks were seen in PTSD. Our source-level cortical network indices might be promising biomarkers for evaluating PTSD.

Generation of potent cytotoxic T lymphocytes against castration-resistant prostate cancer cells by dendritic cells loaded with dying allogeneic prostate cancer cells.

To induce a potent cytotoxic T lymphocyte (CTL) response in dendritic cell (DC)-based immunotherapy against prostate cancer, various tumour antigens should be loaded onto DCs. The aim of this study was to establish a method of immunotherapy for castration-resistant prostate cancer (CRPC) using prostate cancer-specific CTLs generated in vitro by DCs. Monocyte-derived DCs from patients with CRPC were induced to mature using a standard cytokine cocktail (in IL-1ß, TNF-α, IL-6 and PGE(2) : standard DCs, sDCs) or using an α-type 1-polarized DC (αDC1) cocktail (in IL-1ß, TNF-α, IFN-α, IFN-γ and polyinosinic:polycytidylic acid) and loaded with the UVB-irradiated CRPC cell line PC-3. Antigen-loaded DCs were evaluated by morphological and functional assays. The αDC1s significantly increased the expression of several molecules related to DC maturation, regardless of whether the αDC1s were loaded with tumour antigens or not, compared to sDCs. The αDC1s showed a higher production of interleukin-12 both during maturation and after subsequent stimulation with CD40L, which was not significantly affected by loading with tumour antigens, as compared to standard DCs (sDCs). Prostate cancer-specific CTLs against autologous CRPC cells were successfully induced by αDC1s loaded with dying PC-3 cells. Autologous αDC1s loaded with an allogeneic CRPC cell line can generate greater CRPC-specific CTL responses as compared to sDCs and may provide a novel source of DC-based vaccines that can be used for the development of immunotherapy in patients with CRPC.

Mannose-binding lectin gene-2 polymorphisms and serum mannose-binding lectin levels in Behçet's disease.

OBJECTIVE: Behçet's disease (BD) is an autoimmune disease with an unknown etiology and mannose-binding lectin (MBL) is a pattern recognition receptor in the innate immune system, which is associated with some autoimmune diseases. We investigated MBL2 gene polymorphisms and serum MBL levels in BD patients and controls. METHODS: MBL2 gene polymorphisms in exon 1 (MBL2 54 Gly/Asp, (A/B)), promoter (MBL2 H/L (G-550C), MBL2 Y/X (G-221C)), and 5' UTR region (MBL2 P/Q (C+4T)) were investigated using polymerase chain reaction and restriction fragment length polymorphism in 119 BD patients and 252 healthy controls. Serum MBL levels were measured by enzyme linked immunosorbent assay in 49 BD patients and 102 sex-/genotype-matched controls. RESULTS: No significant difference was found between BD patients and controls in terms of MBL2 polymorphisms and MBL serum levels. However, the presence of genital ulcer and neurologic involvement were found to be associated with MBL2 54 allele A (OR=2.415, OR=6.632, respectively). Eye involvement was found to be related to the presence of the MBL2 54 AA or AB genotypes (OR=12.46), MBL2-G-550C allele H (OR=1.829). High serum MBL level (> or =500 ng/ml) was associated with skin lesions (p=0.002). CONCLUSION: The frequencies of the four MBL2 genetic polymorphisms examined were not different in BD patients and healthy controls. However, the presence of genital ulcer, eye involvement, and neuro-Behcet's disease were found to be associated with MBL2 polymorphisms that are associated with the production of high levels of MBL or functional MBL.

Receptor activator of nuclear factor kappa B ligand-mediated osteoclastogenesis is elevated in ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis (AS) is an inflammatory arthritis involving the axial skeleton. Decreased bone mineral density has also been reported in AS patients. This study sought to determine whether osteoclastogenesis and osteoclast activity are increased in AS. METHODS: Twenty patients with AS were evaluated using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and other clinical parameters. Mononuclear cells were separated out from peripheral blood samples taken from AS patients and normal healthy controls and cultured with monocyte colony stimulating factor and receptor activator of the nuclear factor kappa B ligand (RANKL). Multi-nucleated, tartrate-resistant acid phosphatase stain-positive osteoclasts were counted after 9 days, and the areas of calcium absorption on calcium-coated plates were determined. RESULTS: Osteoclastogenesis was significantly greater in AS patients than in normal controls (number of osteoclasts/1106 mononuclear cells, median, 518.0 vs. 362.5, p=0.036). No differences were observed between AS patients and controls in terms of calcium absorption areas or the serum concentrations of tumor necrosis factor and RANKL. Osteoclastogenesis was greater in AS patients with sacroiliac joint ankylosis than in those without. Osteoclastogenesis and the calcium absorption area were not found to be correlated with BASDAI nor with other clinical parameters including age, erythrocyte sedimentation rate, and C-reactive protein levels. CONCLUSION: Osteoclastogenesis is elevated in AS patients, especially in those with sacroiliac joint ankylosis. Increased osteoclastogenesis may be related to osteopenia in AS patients.

Association of the ABCB1 gene polymorphisms 2677G>T/A and 3435C>T with clinical outcomes of paclitaxel monotherapy in metastatic breast cancer patients.

BACKGROUND: ABCB1 is responsible for multidrug resistance, the principal mechanism by which many cancers develop resistance to chemotherapeutic drugs. There is a controversy whether ABCB1 gene polymorphisms correlate with survival and response in cancer patients treated with chemotherapy. We evaluated the association between clinical outcome (safety and efficacy) of paclitaxel monotherapy in metastatic breast cancer patients with ABCB1 gene polymorphisms 2677G>T/A or 3435C>T. PATIENTS AND METHODS: Patients with metastatic breast cancer were treated with 175 mg/m(2) paclitaxel per 3-week cycle. Peripheral blood mononuclear cells from patients were used to genotype ABCB1 2677G>T/A and 3435C>T polymorphisms. Genotypes were investigated for their association with tumor response, survival, toxicity, and chemoresistance. RESULTS: ABCB1 3435 CT showed a significantly lower disease control rate than the CC genotype (P = 0.025). ABCB1 3435 CT was correlated with shorter overall survival (OS) in Cox regression analysis (P = 0.026). The 2677 GG genotype showed a significant association with chemoresistance to paclitaxel and anthracycline (P = 0.04 and 0.04, respectively). None of the ABCB1 genotypes correlated with toxicity. CONCLUSIONS: ABCB1 genotypes may be a predictor of paclitaxel activity as well as a prognostic factor in metastatic breast cancer patients.

Survival benefit of combined curative resection of the stomach (D2 resection) and liver in gastric cancer patients with liver metastases.

BACKGROUND: The benefit of surgical resection of liver metastases from gastric cancer has not been well established. The aim of this study was to evaluate the rationale for hepatic resection in patients with hepatic metastases from gastric cancer. METHODS: Among 10 259 patients diagnosed with gastric adenocarcinoma in the Yonsei University Health System from 1995 to 2005, we reviewed the records of 58 patients with liver-only metastases from gastric cancer who underwent gastric resection regardless of hepatic surgery. RESULTS: The overall 1-year, 3-year, and 5-year survival rates of 41 patients who underwent hepatic resection with curative intent were 75.3%, 31.7%, and 20.8%, respectively, and three patients survived >7 years. Of the 41 patients, 22 had complete resection and 19 had palliative resection. Between the curative and palliative resections, survival rates after curative intent were not different. The number of liver metastasis (solitary or multiple) was a marginally significant prognostic factor for survival. CONCLUSIONS: Surgery for liver metastases arising from gastric adenocarcinoma is reasonable if complete resection seems feasible after careful preoperative staging, even if complete resection is not actually achieved. Hepatic resection should be considered as an option for gastric cancer patients with hepatic metastases.

Phase II study of combination chemotherapy of 5-fluorouracil, low-dose leucovorin, and oxaliplatin (FLOX regimen) in pretreated advanced gastric cancer.

BACKGROUND: This phase II study describes the efficacy and safety of combination chemotherapy of 5-fluorouracil (5-FU), low-dose leucovorin, and oxaliplatin (FLOX regimen) for pretreated advanced gastric cancer. PATIENTS AND METHODS: Patients who had been previously treated with greater than or equal to one regimen were enrolled. Patients received an oxaliplatin 75 mg/m(2) on day 1, 5-FU 1000 mg/m(2) on days 1-3, and leucovorin 20 mg/m(2) on days 1-3, every 3 weeks. The primary end point was overall survival (OS). RESULTS: Among the 52 patients enrolled, 26 patients were treated as second line, and the remaining 26 patients were enrolled as third- or fourth line. A total of 203 cycles of chemotherapy were administered with the median being three cycles (range 1-15) per patient. The median OS was 6.6 months [95% confidence interval (CI) 4.5-8.8] and the median progression-free survival was 2.5 months (95% CI 1.9-3.0). The response rate was 4% (95% CI 0-9%), and the disease control rate was 48% (95% CI 34-62%). The most common toxic effects of grade 3/4 were neutropenia (16%) and vomiting (6%). CONCLUSIONS: The FLOX regimen showed modest activity as a salvage treatment in pretreated advanced gastric cancer with a favorable compliance.

Interstitial lung disease in patients with polymyositis, dermatomyositis and amyopathic dermatomyositis.

OBJECTIVE: To assess the prevalence, characteristics and prognostic factors of interstitial lung disease (ILD) in Korean patients with polymyositis (PM), dermatomyositis (DM) and amyopathic dermatomyositis (ADM). METHODS: We reviewed the medical records of 72 consecutive PM and DM patients, including six patients with ADM, who were seen at the Rheumatology Clinic of Seoul National University Hospital between 1984 and 2003. RESULTS: Twenty-nine PM/DM patients (40.3%) developed ILD. Anti-Jo-1 antibody and arthralgia were associated with the presence of ILD (P = 0.022 and P = 0.041, respectively), whereas dysphagia was more frequently found in patients without ILD (P = 0.041). Lung biopsies revealed diffuse alveolar damage (DAD) (n = 2), usual interstitial pneumonia (UIP) with DAD (n = 2), UIP (n = 1), and non-specific interstitial pneumonia (n = 2). Of the 29 patients, 11 (37.9%) died. The mean survival time in ILD patients was significantly shorter than in those without ILD (13.8+/-1.8 vs 19.2+/-0.9 yr, P = 0.017). Poor survival in ILD patients was associated with a Hamman-Rich-like presentation (P = 0.0000), ADM features (P = 0.0001) and an initial forced vital capacity (FVC) < or =60% (P = 0.024). CONCLUSIONS: ILD was observed in 40.3% of Korean PM/DM patients and was associated with poor survival. A Hamman-Rich-like presentation, ADM features and an initial FVC < or =60% were associated with poor survival in ILD.

Effect of platelet-rich plasma on bone regeneration in autogenous bone graft.

In this study, we evaluated the effect of platelet-rich plasma (PRP) on bone regeneration in an autogenous bone graft in a canine model. The mandibular premolar teeth had been bilaterally extracted previously, and the ridges had been allowed to heal for 3 months. After this period, continuity resection was performed on both sides of the mandible. One defect (the PRP group) was reconstructed with the original particulate bone mixed with PRP. As a control, the contralateral defect (non-PRP group) was reconstructed with the original particulate bone alone. Biopsies after 6 weeks showed lower levels of bone formation in the PRP group than in the non-PRP group, and fluorescence microscopy revealed a delay in the remodelling of grafts loaded with PRP. These findings suggest that the addition of PRP does not appear to enhance new bone formation in autogenous bone grafts.

Ultrasound diagnosis of postpartum ovarian vein thrombosis: case report.

Postpartum ultrasound investigation of a woman with unremitting fever and right flank pain after Cesarean section revealed an extensive thrombosis of the right ovarian vein which extended into the inferior vena cava. Computed tomography was required to substantiate the diagnosis. Medical treatment with intravenous urokinase and heparin and antibiotics was successfully performed. During the postpartum period, the possibility of ovarian vein thrombosis should be considered in febrile patients with abdominal pain who are not responding to antibiotics, and imaging studies such as ultrasound and computed tomography should be performed early for prompt diagnosis and therapy.

Identification of possible signal transduction components mediating light induction of the Gsa gene for an early chlorophyll biosynthetic step in Chlamydomonas reinhardtii.

Light-induced expression of the Gsa gene encoding the heme and chlorophyll biosynthetic enzyme glutamate 1-semialdehyde aminotransferase in Chlamydomonas reinhardtii was previously shown to involve Ca2+ and calmodulin (CaM) (C. lm et al. 1996, Plant Cell 8: 2245-2253). To further analyze the signal transduction pathway for light-induced Gsa expression, the effects of several pharmacological agents were examined. Treatment of light-dark synchronized cells with the heterotrimeric G-protein agonist Mas-7 caused partial induction of Gsa in the dark. The phospholipase C inhibitor U73122 inhibited light induction of Gsa. Exposure of cells to light caused a sustained 3-fold increase in cellular D-inositol 1,4,5-trisphosphate (InsP3) concentration. KN-93, a specific inhibitor of Ca2+/CaM-dependent protein kinase II, inhibited light induction of Gsa. In contrast, cyclosporin A, a specific inhibitor of the Ca2+/CaM-dependent phosphoprotein phosphatase calcineurin, did not affect light induction of Gsa. These results, together with the earlier results, suggest the involvement of a canonical signal transduction pathway for light-regulated Gsa expression that involves a heterotrimeric G-protein activation, phospholipase C-catalyzed InsP3 formation, InsP3-dependent Ca2+ release, and activation of a downstream signaling pathway through a Ca2+/CaM-dependent protein kinase.

Synthesis of 6-exomethylenepenams as beta-lactamase inhibitors.

The 6,6-dibromopenam (6) was treated with CH3MgBr and carbaldehyde 5 to afford the hydroxy compound 7, which was reacted with acetic anhydride to give acetoxy compound 8. The deacetobromination of 8 with zinc and acetic acid gave 6-exomethylenepenams, E-isomer 10 and Z-isomer 9, which was oxidized to sulfone 11 by m-CPBA. The p-methoxybenzyl compounds were deprotected by AlCl3 and neutralized to give the sodium salts 12, 13 and 14.

Light-regulated expression of the gsa gene encoding the chlorophyll biosynthetic enzyme glutamate 1-semialdehyde aminotransferase in carotenoid-deficient Chlamydomonas reinhardtii cells.

Expression of the Chlamydomonas reinhardtii gsa gene encoding the chlorophyll biosynthetic enzyme glutamate 1-semialdehyde aminotransferase was previously shown to be induced by blue light. Possible blue light photoreceptors include flavins and carotenoids. Light induction of gsa was investigated in carotenoid-deficient mutant C. reinhardtii cells. Strain CC-2682 cells are sensitive to light, produce only small amounts of chlorophyll, and do not exhibit phototaxis. Solvent extracts show the absence of carotenoids and carotenoid precursors beyond phytoene in dark-grown mutant cells. Although apparently devoid of carotenoids, the cells did show light induction of gsa. The gsa transcript level was very low in dark-grown cells but increased significantly after 2 h of exposure to dim (1.5 x 10(-5) mol m(-2) s(-1)) green (480-585 nm) light. This light regime was previously determined not to injure these photosensitive cells and to fully induce gsa in wild-type cells. Exposure to this light did not cause the mutant cells to produce measurable carotenoids or to become phototactic. Growth of the mutant cells in the presence of exogenous beta-carotene or all-trans retinol restored phototaxis but did not affect the degree of gsa induction by light. The induction of gsa by light in the absence of carotenoids, and the fact that incorporation of physiologically usable carotenoids (as indicated by the restoration of phototaxis) did not affect the degree of light induction, indicate that the photoreceptor for light induction of gsa in C. reinhardtii is not a carotenoid. The flavin antagonist diphenyleneiodonium blocked light induction of gsa in both wild-type and mutant cells under conditions where respiration was not inhibited. These results suggest that the photoreceptor or a signal transduction effector for light induction of the C. reinhardtii gsa gene is a flavoprotein.

Detection of a dup(17q) and inv(16) by fluorescence in situ hybridization in acute myelomonocytic leukemia.

Two cases of acute myelomonocytic leukemia (AMMoL) of FAB type M4Eo are described in which a primary subclone containing a dup(17)(q21q25) and a subclone containing dup(17)(q21q25), inv(16)(p13q22) were seen in one patient, and -7, dup(17)(q21q25) in another. Fluorescence in situ hybridization (FISH) was carried out for the confirmation of the duplicated segment and breakpoint of inv(16). Inv(16) is a well known anomaly in AMMoL, whereas dup(17q) is rare though as not yet confirmed, this anomaly could be a nonrandom or novel change in AMMoL.

Synthesis of 6-[1-[4-(benzoxazol-2-yl)thiobuthyl]-1,2,3-triazole-4-yl]methylenepenam as beta-lactamase inhibitors.

The 6,6-dibromopenam6 was treated with CH(3)MgBr and carbaldehyde5 to afford the 6-bromo-6-(1-hydroxy-1-methyl)penicillanate7, which was reacted with acetic anhydride to give acetoxy compound8. The deacetobromination of8 with zinc and acetic acid gave 6-exomethylenpenams, Z-isomer9 and E-isomer10, which were oxidized to sulfones11 and12 by m-CPBA. The p-methoxybenzyl compounds were deprotected by AlCl(3) and neutralized to give the sodium salts13, 14, and15.

(1)H-NMR and NOE studies of 2-cephems and 3-cephems.

The(1)H-NMR signals of 2-cephems and 3-cephems have been assigned and the Nuclear Overhauser Effect (NOE) study of these compounds was undertaken.

Calcium and calmodulin are involved in blue light induction of the gsa gene for an early chlorophyll biosynthetic step in Chlamydomonas.

The Chlamydomonas reinhardtii nuclear gene gsa, which encodes the early chlorophyll biosynthetic enzyme glutamate 1-semialdehyde aminotransferase (GSAT), is specifically induced by blue light in cells synchronized in a 12-hr-light and 12-hr-dark regime. Light induction required the presence of a nitrogen source in the incubation medium. Maximal induction also required acetate. However, in the absence of acetate, partial induction occurred when Ca2+ was present in the medium at concentrations of > or = 1 microM. The Ca2+ channel-blocking agents Nd3+ and nifedipine partially inhibited the external Ca(2+)-supported induction of GSAT mRNA but did not inhibit acetate-supported induction. The calmodulin antagonists trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide inhibited both external Ca(2+)-supported and acetate-supported induction. The Ca2+ ionophore A23187 caused a transient induction in the dark. These results suggest that Ca2+ and calmodulin are involved in the signal transduction pathway linking blue light perception to the induction of GSAT mRNA. The electron transport uncoupler carbonyl cyanide m-chlorophenylhydrazone inhibited acetate-supported induction of GSAT mRNA but did not inhibit external Ca(2+)-supported induction. It is proposed that in the presence of acetate, an internal pool of Ca2+ can be mobilized as a second message, whereas in the absence of acetate, internal Ca2+ is not available but the requirement for Ca2+ can be partially met by an external Ca2+ source. The mobilization of internal Ca2+ may require energy derived from metabolism of acetate.

Synthesis and beta-lactamase inhibitory activity of 6-[(1-heteroarylthioethyl-1,2,3-triazol-4-yl)-methylene]penam sulfones.

The synthesis of beta-lactamase inhibitory activity of a series of sodium 6-[(1-heteroarylthioethyl-1,2,3-triazol-4-yl)methylene]pe nicillanate, 1,1-dioxides are described. Their activity was compared with tazobactam and sulbactam. The Z-isomers were more active than the E-isomers. The in vitro activity of the Z-isomers of the phenylthiadiazole derivatives (13a and 15a) was better than sulbactam against the tested beta-lactamases and comparable to tazobactam especially against TEM-2 and cephalosporinase. But their synergistic activity with five antibiotics was inferior to tazobactam.