Comparison of 5-year outcomes between pedicle screw and hybrid constructs in adolescent idiopathic scoliosis

Object Pedicle screw fixation has been theorized to provide better correction of scoliotic deformity, but controversy over the benefits of pedicle screw-only constructs remains, and the longer-term impact of pedicle screw fixation as compared with hybrid constructs is unclear. In this study, a retrospective review of a prospectively collected database was conducted to determine the longer-term impact of pedicle screw fixation as compared with hybrid constructs in patients with adolescent idiopathic scoliosis (AIS). Methods The authors retrospectively reviewed a multicenter database of pediatric patients (ages ≤ 18) from 1995 to 2006 and identified 127 patients with Lenke Type 1-4 AIS curves with a minimum 5 years of follow-up. Patients were divided into 2 cohorts based on whether they had undergone pedicle screw fixation or fixation with hybrid constructs. Results The mean main thoracic curvature of 56.1° ± 13.0°, which corrected to 14.9° ± 9.3°, translated into a mean correction of 73% (p < 0.01). The curve was 19.4° ± 10.6° at 2-year follow-up and 20.5° ± 10.4° at 5 years. When comparing preoperative parameters between the groups, differences were noted in the magnitude of the main thoracic curve (p = 0.04), flexibility of the main thoracic curve (p = 0.02), coronal balance (p = 0.04), T2-12 kyphosis (p = 0.02), and sex (p = 0.02). The pedicle screw cohort had fewer spinal segments instrumented (p < 0.01), fewer anterior releases performed (p = 0.02), and fewer thoracoplasties performed (p < 0.01). By 5 years of follow-up, significant differences were apparent between the two cohorts with respect to upper thoracic curvature (p = 0.01), T2-12 (p = 0.02) and T5-12 (p = 0.02) kyphosis, lumbar lordosis (p < 0.01), and sagittal balance (p = 0.01). Conclusions Although some preoperative differences did exist, outcomes were comparable between hybrid and screw constructs at 2 and 5 years. However, hybrid constructs required more concurrent anterior releases and thoracoplasties to achieve similar results.     

Peginterferon alpha and ribavirin combination therapy in patients with hepatitis C virus-related liver cirrhosis

Background/Aims

Pegylated interferon (peginterferon) and ribavirin combination therapy is less effective and associated with a higher frequency of serious complications in chronic hepatitis C patients with cirrhosis than in noncirrhotic patients. This study evaluated the efficacy and tolerability of peginterferon and ribavirin treatment in patients with hepatitis C virus (HCV)-related cirrhosis.

Methods

Eighty-six patients with clinically diagnosed liver cirrhosis were treated with either peginterferon alpha-2a (n=51) or peginterferon alpha-2b (n=35) plus ribavirin. The sustained virologic response (SVR) and adverse effects were analyzed retrospectively.

Results

Of the 86 patients (55 males), 48 patients (55.8%) had HCV genotype 1 infection and 38 (44.2%) had genotype non-1 infection. The overall SVR rate was 34.9% (30/86), and the rates of SVR in the genotype 1 and non-1 patients were 20.8% (10/48) and 52.6% (20/38), respectively. The multivariate analysis revealed that having HCV genotype 1 (P=0.003) and high baseline viral load (>8.0×10⁵ IU/mL, P=0.012) were the independent predictive factors for SVR failure. In 20.9% (18/86) of the patients, treatment was not completed due to adverse events (27.8%), loss to follow-up (50.0%), and other reasons (22.2%).

Conclusions

Peginterferon and ribavirin combination therapy was relatively effective and feasible for clinically diagnosed HCV patients, especially in those with genotype non-1 infection and low baseline viral load.     

N-(3,5-dimethylphenyl)-3-methoxybenzamide (A(3)B(5)) targets TRP-2 and inhibits melanogenesis and melanoma growth

Melanin protects the skin from harmful environmental factors such as UV light. However, excessive melanin production induces hyperpigmentation. Previously, N-(3,5-dimethylphenyl)-3-methoxybenzamide (A(3)B(5)), a biaryl amide derivative, was identified for its ability to inhibit melanin production. However, its detailed mechanism of action has not been investigated. We elucidated the inhibitory mechanisms of A(3)B(5) in melanin production. Our results showed that A(3)B(5) had no effect on the production and activity of tyrosinase, an enzyme involved in melanogenesis. However, A(3)B(5) markedly decreased both constitutively expressed and UVB-induced tyrosinase-related protein 2 (TRP-2), which plays an important role along with tyrosinase in melanogenesis. The TRP-2 downregulation caused by A(3)B(5) may occur through proteasomal degradation because the A(3)B(5)-induced TRP-2 downregulation was inhibited by the ubiquitination inhibitor, MG-132. In addition, A(3)B(5) inhibited the proliferation of melanocytes and melanoma cells by arresting cells in the G1 stage of the cell cycle and moderately suppressed tumor growth in vivo. Taken together, our results indicate that A(3)B(5) downregulates melanin production and melanoma cell growth via proteosomal degradation of TRP-2 and suggest that A(3)B(5) can be a possible therapeutic agent that effectively regulates both hyperpigmentation and melanoma growth in the skin.     

PRELIMINARY RESULTS OF HEPATIC RESECTION FOR CENTRALLY LOCATED LARGE HEPATOCELLULAR CARCINOMA

Resection of large hepatocellular carcinoma (HCC) located in the central portion of the liver remains a surgical challenge. Over a 2 year period, from July 1989, 19 HCC patients whose main tumour (mean diameter 11.3 cm, range 6–19cm) was located in the central part of the liver (defined as Couinaud's segments IV, V, VIII) had liver resections. Liver cirrhosis was found in 14 patients (73.7%). Extended major hepatectomy could be performed in only three patients. The operative morbidity and mortality were 26.3% and 0%, respectively. The resection margin in 14 patients was less than 1 cm. At the time this paper was written 11 patients were alive and disease free, five patients survived longer than 30 months. The 1 year disease free rate and survival rate were 73.7% and 84.2%, respectively. The preliminary results reveal that with careful preservation of non-tumourous liver, resection of centrally located large HCC is still advocated even in a cirrhotic liver, and that the resection margin width should not be a major concern.     

Neuropathological abnormalities of astrocytes, GABAergic neurons, and pyramidal neurons in the dorsolateral prefrontal cortices of patients with major depressive disorder

Human post-mortem brain studies have revealed reduced density and size of neurons and glial cells in the dorsolateral prefrontal cortex (dlPFC) in major depressive disorder (MDD). However, the basis of these cytoarchitectural abnormalities and the relationship between them are not understood. We hypothesized that the reduced density of GABAergic neurons and glial cells was associated with altered glutamate neurotransmission in the dlPFC. In order to test this hypothesis, we examined a specific marker type (i.e., calretinin, CR: as a marker of GABAergic neurons) and also attempted to identify the neuropathological markers that correlate with the density of CR-immunoreactive (IR) GABAergic neurons in the dlPFC, using the Stanley Neuropathology Consortium Integrative Database (SNCID, http://sncid.stanleyresearch.org/), which is a web-based tool used to integrate Stanley Medical Research Institute (SMRI) data sets. We found that the density of CR-IR GABAergic neurons was significantly lower in layer I of the dlPFC of MDD patients (n=15) than in that of unaffected controls (n=15) (p=0.021). CR-IR GABAergic neuronal changes were positively correlated with changes in several markers for glial cells and pyramidal neurons in the dlPFC of all SNC subjects (n=60). We also found that the glutamate changes negatively correlated with glial fibrillary acidic protein (GFAP) expression levels and CR-IR GABAergic neuronal density in the prefrontal cortex of all SNC subjects (P<0.05). These findings yield some insight into the mechanism by which increased glutamatergic neurotransmission leads to excitotoxic damage both in neurons and glial cells in the dlPFC of MDD patients.     

Enhanced expression of cathepsin L in metastatic bone tumors.

Cathepsin L is a kind of cystein proteases which are known to facilitate the invasion and metastasis of tumor cells by degrading the components of basement membrane and extracellular matrix. This study was undertaken to investigate the expression of cathepsin L by Northern blot analysis with radiolabeled cDNA specific for cathepsin L in six normal tissues, two osteosarcoma cell lines, MG-63 and Saos-2, six primary bone tumors and six metastatic bone tumors. In six normal tissues, the highest level of cathepsin L was expressed in liver with the descending order of liver > lung > thymus > ovary > kidney > esophagus. One of the two osteosarcoma cell lines established from the primary sites expressed a high level of cathepsin L mRNA. Out of six primary bone tumors, three (50%) expressed cathepsin L mRNA, while all (100%) of six metastatic bone tumors expressed the mRNA. These results demonstrating the higher frequency of expression of cathepsin L in metastatic bone tumors suggest that cathepsin L may participate in tumor invasion and metastasis.     

Reconstruction of Disrupted Extensor Mechanism After Total Knee Arthroplasty

Background

Disruption of the extensor mechanism after total knee arthroplasty (TKA) is a debilitating complication that results in extension lag, limited range of motion, difficulty in walking, frequent falls, and chronic pain. This study presents the clinical and radiographic results of reconstruction after extensor mechanism disruption in TKA patients.

Immune response to p53 and HPV-16 E6 proteins in patients with cervical cancer

Park JS, Kim CJ, Um SJ, Hwang ES, Kim HS, Park SN, Namkoong SE, Kim SJ. Immune response to p53 and HPV-16 E6 proteins in patients with cervical cancer. Int J Gynecol Cancer 1998; 8 : 328–335.
To investigate whether p53 autoantibodies could be found in the sera of patients with cervical cancers, we have therefore studied by radioimmunoprecipitation assay, using in vitro translated p53 protein, sera from such patients. The sero-positive patients for p53 were also evaluated in relation to immunoreactivity to p53 antigens by immunohistochemistry, for genomic alterations of p53 by PCR-SSCP, and for the presence of HPV-16/18 DNAs in the cervical cancer cells. In immunohistochemistry, expression of p53 protein was seen in 47% (14/30) of HPV-16 or -18 positive cervical cancers and 13 % (2/15) of HPV-16/18 negative cervical cancers ( P < 0.01). Eight out of 12 control ovarian cancers (67%) showed positive p53 staining in most tumor cells. Cases of cervical cancer and ovarian cancer, which were positively expressed p53 protein in the tissue or the sera, were studied for genomic alterations in exons 5–8 of the p53 by PCR-SSCP. Serum antibodies to in vitro translated p53 protein were found in two cases from 63 cervical cancers; one patient was stage IIA, having HPV-16 DNA in a tumor of squamous cell type, and another patient was stage IIIB, having HPV-16 and -18 DNAs in an adenocarcinoma. The cervical cancer tissues from the two sero-positive patients were also positive for p53 immunostaining. None of the cervical cancer samples showed aberrant bands, but three of eight cases of ovarian cancer which were positive for p53 protein by immunostaining were shown to have aberrant bands by PCR-SSCP. In contrast to ovarian cancers, alteration of p53 tumor suppressor gene and positive antibody response to p53 protein seem to be rare events in patients with cervical cancer.     

A randomized study of the utility of human immunodeficiency virus RNA measurement for the management of antiretroviral therapy.

To compare frequent measurement with infrequent measurement of human immunodeficiency virus (HIV) RNA levels in the management of antiretroviral therapy, we conducted a clinical strategy study of 206 HIV-infected patients who had <500 CD4 cells/mm(3). Patients were randomized (1.5:1) to undergo frequent monitoring (at baseline and every 2 months) or infrequent monitoring (at baseline and twice yearly), with CD4 cell counts determined every 2 months. Patients received unrestricted antiretroviral therapy. In the primary analysis (at month 6), the frequent group had a mean HIV RNA reduction (+/- standard deviation) of 0.93+/-0.79 log(10) copies/mL, versus 0.48+/-0.83 log(10) copies/mL for the infrequent group (P=.0002). A trend (P=.1) toward improved survival was seen in the frequent group. Given this improved virological response, more frequent HIV RNA measurement than is recommended in published guidelines (every 3-4 months) may be appropriate.     

In Vitro Activity of Tigecycline Against Orientia tsutsugamushi

Scrub typhus is a zoonosis caused by Orientia tsutsugamushi (O. tsutsugamushi) occurring mainly in autumn in Korea. The need of new antibiotics has arisen with a report on strains resistant to antibiotics and chronic infection. This study aims to identify susceptibility of tigecycline in-vitro as a new therapeutic option for O. tsutsugamushi. Antibacterial activity of tigecycline against the O. tsutsugamushi was compared with doxycycline using flow cytometry assay. The inhibitory concentration 50 (IC₅₀) was 3.59×10^-3 µg/mL in doxycycline-treated group. Whereas in 0.71×10^-3 µg/mL tigecycline-treated group. These findings indicate that tigecycline may be a therapeutic option for the treatment of scrub typhus.