Sphenoparietal sinus and superficial middle cerebral vein thrombosis: A case report and review of literature.

BACKGROUND: Cerebral venous sinus thrombosis is rare and might be overlooked by healthcare providers. It often occurs in the transverse sinuses, superior sagittal sinus, and the vein of Trolard. Sphenoparietal sinus (SPS) and/or superficial middle cerebral vein (SMCV) thrombosis is rare and only 12 cases reported in the literature. CASE DESCRIPTION: We report a 47-year-old woman with iron deficiency anemia associated with myoma uteri who developed left SPS and SMCV thrombosis. She presented with sudden unconsciousness, right hemiplegia, and aphasia. Brain computed tomography showed subcortical hemorrhages in the left frontal and temporal lobes. Magnetic resonance imaging did not reveal the cause of the bleeding. Although antihypertensive treatment with nicardipine was initiated, she deteriorated into coma the next day and underwent emergency decompressive craniectomy. Thrombosis of the SMCV was identified during surgery. Re-examination of preoperative T2 star-weighted imaging revealed thrombosis of the SPS and SMCV. CONCLUSION: All but one of the reviewed cases had the thrombosis develop on the left side, which may be attributed to anatomical and brain functional laterality. When an edematous change or cortical hemorrhage of unknown cause is encountered within the perisylvian region, especially on the left side, the possibility of SPS and SMCV thrombosis should be considered.

STAT6 and IL-10 are required for the anti-arthritic effects of Schistosoma mansoni via different mechanisms.

To investigate possible roles of T helper type 2 (Th2) cytokines in the anti-arthritic effects of a blood fluke, Schistosoma mansoni (Sm), for mouse collagen-induced arthritis (CIA), wild-type (WT), signal transducer and activator of transcription 6 (STAT6) knock-out (KO) and interleukin (IL)-10 KO mice were infected with Sm. Three weeks after infection, the mice were immunized with bovine type II collagen (IIC). Arthritis severity was monitored by scoring, measurement of paw thickness and the presence of ankylosis. Serum anti-IIC IgG levels, splenic cytokine production and cytokine gene expression in the popliteal lymph nodes (PLNs) were measured and compared among WT and gene-KO mice. Consistent with our previous findings, Sm infection reduced the arthritis severity in WT mice. Splenic production of IL-17A and tumor necrosis factor (TNF)-α was reduced by the infection. In contrast, Sm infection markedly exacerbated CIA in STAT6 KO mice. In the KO mice, IL-17A production was increased by the infection. Conversely, Sm infection did not affect the exacerbated arthritis in IL-10 KO mice, although IL-17A production was reduced by the helminth. Our results suggest that signaling via STAT6 (presumably IL-4 and/or IL-13) and IL-10 is required for the suppression of CIA by Sm infection, but through different mechanisms. STAT6 was essential for helminth-induced reduction of IL-17A, whereas regulation of the basal arthritis severity by IL-10 was needed in order for it to be sufficiently suppressed by the helminth.

Three-dimensional finite element model to predict patterns of pterygomaxillary dysjunction during Le Fort I osteotomy.

The aim of this study was to determine whether non-linear three-dimensional finite element analysis (3D-FEA) can be applied to simulate pterygomaxillary dysjunction during Le Fort I osteotomy (LFI) not involving a curved osteotome (LFI-non-COSep), and to predict potential changes in the fracture pattern associated with extending the cutting line. Computed tomography (CT) image data (100 snapshots) after LFI were converted to 3D-CT images. 3D-FEA models were built using preoperative CT matrix data and used to simulate pterygomaxillary dysjunction. The pterygomaxillary dysjunction patterns predicted by the 3D-FEA models of pterygomaxillary dysjunction were classified into three categories and compared to the pterygomaxillary dysjunction patterns observed in the postoperative 3D-CT images. Extension of the cutting line was also simulated using the 3D-FEA models to predict the risk and position of pterygoid process fracture. The rate of agreement between the predicted pterygomaxillary dysjunction patterns and those observed in the postoperative 3D-CT images was 87.0% (κ coefficient 0.79). The predicted incidence of pterygoid process fracture was higher for cutting lines that extended to the pterygomaxillary junction than for conventional cutting lines (odds ratio 4.75; P<0.0001). 3D-FEA can be used to predict pterygomaxillary dysjunction patterns during LFI-non-COSep and provides useful information for selecting safer procedures during LFI-non-COSep.

Revision laryngeal framework surgery performed by directly pulling the lateral cricoarytenoid muscle.

BACKGROUND: Revision laryngeal framework surgery is usually performed for medialisation laryngoplasty failure, rather than for failure after arytenoid adduction. We describe a new method for revision arytenoid adduction surgery, performed by directly pulling the lateral cricoarytenoid muscle ('lateral cricoarytenoid muscle pull surgery'). METHODS: We describe a case of revision laryngeal framework surgery, present a literature review and describe the advantages of lateral cricoarytenoid muscle pull surgery over the original method of arytenoid adduction using a posterior approach. RESULTS: Medialisation laryngoplasty combined with arytenoid adduction was performed following unilateral vocal fold paralysis from mediastinal surgery, resulting in severe glottic insufficiency. The patient's voice improved after the initial surgery, but had deteriorated 18 months later. Revision surgery was performed using lateral cricoarytenoid muscle pull surgery, and her voice recovered normally in terms of perceptual impression. The post-operative course was uneventful for 10 months following revision surgery. CONCLUSION: To our knowledge, this is the first case of revision arytenoid adduction performed using a lateral cricoarytenoid muscle pull approach. Lateral cricoarytenoid muscle pull surgery should therefore be considered as a new fenestration approach for arytenoid adduction.

Prediction of neurosensory alterations after sagittal split ramus osteotomy.

Prediction of neurosensory deficit in the lower lip and chin after sagittal split ramus osteotomy (SSRO) is challenging. This study aimed to elucidate factors related to the development and improvement of neurosensory disturbance (NSD) after SSRO with respect to surgical procedure and the anatomical and structural characteristics of the craniomaxillofacial skeleton. Subjects comprised 50 patients treated by a single experienced surgeon. Anatomical data and landmarks were obtained by computed tomography (CT) imaging. There was a significant difference between patients with or without NSD for the surgical space on the medial side of mandibular ramus 1 week after SSRO (P=0.006). Less than 15.0mm between the lingula and mandibular notch (relative risk, 6.7; 95% CI, 1.7-33.8) and 195.0mm(2) or more space on the medial side of the mandibular ramus (relative risk, 17.2; 95% CI, 3.9-100.4) indicated a significant risk of NSD development at 6 months postoperatively. These results suggested that the development of NSD is related to the surgical space on the medial side of the mandibular ramus and subsequent manipulation of the inferior alveolar nerve (IAN) in that region. Limited periosteal degloving prevents excessive stretching of the IAN during SSRO, thus lowering NSD incidence.

KIT and platelet-derived growth factor receptor α gene expression in laryngeal small cell carcinoma.

OBJECTIVE: Small cell carcinoma has the worst prognosis of all laryngeal neoplasms. In order to further characterise this tumour, with a view to development of new therapeutic approaches, we report the results of KIT gene and platelet-derived growth factor receptor α gene expression analysis, for two extremely rare cases of primary small cell carcinoma of the larynx. METHOD: Case reports, including immunohistochemical study, and review of the literature. RESULTS: We present two patients with laryngeal small cell carcinoma, who died from tumour metastasis to the lungs and brain despite aggressive treatment. Immunohistochemical studies revealed positive reactions for KIT gene expression and platelet-derived growth factor α gene expression in patient one, and for KIT gene expression in patient two. Molecular genetic analysis, using polymerase chain reaction direct sequencing, identified no mutations of the KIT or platelet-derived growth factor receptor α genes. CONCLUSION: Although further investigation is necessary regarding KIT gene expression and platelet-derived growth factor receptor α gene expression in laryngeal small cell carcinoma, the reported results suggest that these genes may be significant in the development of molecular targeted therapy.

Long-term results of Tokyo Children's Cancer Study Group trials for childhood acute lymphoblastic leukemia, 1984-1999.

We report the long-term results of Tokyo Children's Cancer Study Group's studies L84-11, L89-12, L92-13, and L95-14 for 1846 children with acute lymphoblastic leukemia, which were conducted between 1984 and 1999. The value of event-free survival (EFS)+/-s.e. was 67.2+/-2.2% at 10 years in L84-11, which was not improved in the following two studies, and eventually improved to 75.0+/-1.8% at 10 years in L95-14 study. The lower EFS of the L89-12 reflected a high rate of induction failure because of infection and delayed remission in very high-risk patients. The L92-13 study was characterized by short maintenance therapy; it resulted in poor EFS, particularly in the standard-risk (SR) group and boys. Females did significantly better than males in EFS in the early three studies. The gender difference was not significant in overall survival, partly because >60% of the males survived after the testicular relapse. Randomized studies in the former three protocols revealed that intermediate- or high-dose methotrexate therapy significantly reduced the testicular relapse rate. In the L95-14 study, gender difference disappeared in EFS. Contrary to the results of larger-scale studies, the randomized control study in the L95-14 reconfirmed with updated data that dexamethasone 8 mg/m(2) had no advantage over prednisolone 60 mg/m(2) in the SR and intermediate-risk groups. Prophylactic cranial irradiation was assigned to 100, 80, 44, and 44% of the patients in the studies, respectively. Isolated central nervous system relapse rates decreased to <2% in the last two trials. Secondary brain tumors developed in 12 patients at 8-22 years after cranial irradiation. Improvement of the remission induction rates and the complete omission of irradiation are currently main objectives in our studies.

Maxillary haemangioma successfully resected by endoscopic approach.

OBJECTIVE: We report an extremely rare case of maxillary haemangioma. METHOD: Case report and review of the literature concerning haemangioma arising from the nasal cavity and paranasal sinuses. RESULTS: Maxillary haemangioma is rare and sometimes requires wider resection than nasal haemangioma if a large tumour is found. We present a case of maxillary haemangioma in a 37-year-old Japanese woman, which was completely resected by pre-operative embolisation and endoscopic sinus surgery. CONCLUSION: Our findings suggest that if a large maxillary haemangioma is diagnosed pre-operatively, the treatment of choice is pre-operative embolisation followed by endoscopic sinus surgery, in order to avoid the surgical complications associated with wide resection.

Family-based association testing strongly implicates DRD2 as a risk gene for schizophrenia in Han Chinese from Taiwan.

The gene that codes for dopamine receptor D2 (DRD2 on chromosome 11q23) has long been a prime functional and positional candidate risk gene for schizophrenia. Collectively, prior case-control studies found a reliable effect of the Ser311Cys DRD2 polymorphism (rs1801028) on risk for schizophrenia, but few other polymorphisms in the gene had ever been evaluated and no adequately powered family-based association study has been performed to date. Our objective was to test 21 haplotype-tagging and all three known nonsynonymous single-nucleotide polymorphisms (SNPs) in DRD2 for association with schizophrenia in a family-based study of 2408 Han Chinese, including 1214 affected individuals from 616 families. We did not find a significant effect of rs1801028, but we did find significant evidence for association of schizophrenia with two multi-marker haplotypes spanning blocks of strong linkage disequilibrium (LD) and nine individual SNPs (Ps<0.05). Importantly, two SNPs (rs1079727 and rs2283265) and both multi-marker haplotypes spanning entire LD blocks (including one that contained rs1801028) remained significant after correcting for multiple testing. These results further add to the body of data implicating DRD2 as a schizophrenia risk gene; however, a causal variant(s) in DRD2 remains to be elucidated by further fine mapping of the gene, with particular attention given to the area surrounding the third through fifth exons.

Effects of menstrual cycle on gene transfection through mouse vagina for DNA vaccine.

Human immunodeficiency virus (HIV) infections mainly occur through the vaginal and rectal mucosal membranes. In the present study, to develop a DNA vaginal vaccine against viral and bacterial infections, the effects of the menstrual cycle on DNA transfection through the vaginal mucosa in female mice and transfection enhancement by electroporation, a chelating agent, cell-penetrating peptides (CPP) and nuclear localizing signals (NLS) were investigated. The transfection efficiencies of a marker plasmid DNA (pDNA), pCMV-Luc, on the vaginal mucosal membrane in mice at the stages of metestrus and diestrus were significantly higher than those at the stages of proestrus and estrus. The gene expression was markedly enhanced by electroporation and by pretreatment with the chelating agent. The highest level of expression was obtained by 2h pretreatment with 5% citric acid solution combined with electroporation with 15 pulses at 250 V/cm for 5 milliseconds (ms). Furthermore, a synergistic promoting effect on pDNA transfection was obtained by co-administration of CPP, the Tat peptide analog, and NLS, the NF-kappaB analog. These results indicate that effective DNA vaccination administered through the vaginal tract is possible by selecting the menstrual stage and overcoming the mucosal barrier using a combination of methods that promotes uptake.

Unusual pressure-induced rupture of colonic volvulus in a patient with long-term corticosteroid therapy.

Perforation due to colonic volvulus is typically considered to occur following ischemic necrosis of the intestinal wall. In this report, we report a rare case of sigmoid colon volvulus rupture caused by increasing intraluminal pressure without any sign of ischemia. The patient was an 88-year old Japanese male, who had been treated with 5 mg of oral prednisolone daily for 8 years. He consulted for severe abdominal pain that had lasted for three days. X-ray and computed tomography showed free peritoneal air, suggesting peritonitis. He was diagnosed with sigmoid colon volvulus perforation and underwent emergency surgery. Pathological examination showed no ischemic necrosis around the perforations in the resected intestine. As a result, we came to believe that the fragility of the colonic wall, caused by the patient's long-term use of corticosteroid, had lowered the threshold for pressure-induced colonic rupture.

Galanin and galanin receptor type 1 suppress proliferation in squamous carcinoma cells: activation of the extracellular signal regulated kinase pathway and induction of cyclin-dependent kinase inhibitors.

Galanin receptor 1 (GALR1) maps to a common region of 18q loss in head and neck squamous cell carcinomas and is frequently inactivated by methylation. To investigate effects of GALR1 and its signaling pathways, we stably expressed hemaglutinin-tagged GALR1 in a human oral carcinoma cell line (UM-SCC-1-GALR1) that expresses no endogenous GALR1. In transfected cells, galanin induced activation of the extracellular-regulated protein kinase-1/2 (ERK1/2) and suppressed proliferation. Galanin stimulation mediated decreased expression of cyclin D1 and increased expression of the cyclin-dependent kinase inhibitors (CKI), p27(Kip1) and p57(Kip2). Pretreatment with the ERK1/2-specific inhibitor U0126 prevented these galanin-induced effects. Phosphatidylinositol 3-kinase (PI3K) pathway activation did not differ in UM-SCC-1-GALR1 and UM-SCC-1-mock cells after galanin treatment. Pertussis toxin and LY294002 inhibition demonstrated that galanin and GALR1 induce ERK1/2 activation via Galphai, not the PI3K pathway-linked to the Gbetagamma subunit. Galanin and GALR1 also inhibit colony formation and tumor growth in vivo. Our results implicate GALR1, a Gi protein-coupled receptor, as a tumor suppressor gene that inhibits cell proliferation via ERK1/2 activation.

Chromosome 18q deletion and Smad4 protein inactivation correlate with liver metastasis: A study matched for T- and N- classification.

Smad4 protein, whose gene is coded at chromosome 18q21.1, is an important tumour suppressor that mediates transforming growth factor-beta. It has been reported that inactivation of the Smad4 gene and allelic loss of chromosome 18q correlate with liver metastasis and poorer prognosis in colorectal cancers. Utilising a recently developed method of immunohistochemical staining for Smad4 protein, we focused on the specific impact of Smad4 protein expression on liver metastasis in colorectal cancer. We also evaluated the association between chromosome18q deletion and liver metastasis. We selected 20 colorectal cancers with liver metastasis for the experimental group, and 20 cases without liver metastasis for the control. In order to exclude the influence of lymph node metastasis, all cases were lymph node negative. In addition, the two groups were matched for tumour depth, tumour differentiation and tumour location. We compared the expression level of Smad4 protein immunohistochemically in these 20 matched pairs. We also compared the loss of heterozygosity status at chromosome 18q in these 20 matched pairs. Immunohistochemical staining revealed a significant difference (P = 0.024) in the level of Smad4 protein between the two groups. We also observed a significantly different (P=0.0054) ratio of allelic deletion at chromosome 18q21. Smad4 protein expression level and allelic loss at 18q21 are associated with the process of liver metastasis in colorectal cancers evaluated when excluding clinical and pathological features except for liver metastasis.

An immunohistological study of the integration at the bone-tendon interface after reconstruction of the anterior cruciate ligament in rabbits.

We studied bone-tendon healing using immunohistochemical methods in a rabbit model. Reconstruction of the anterior cruciate ligament was undertaken using semitendinosus tendon in 20 rabbits. Immunohistochemical evaluations were performed at one, two, four and eight weeks after the operation. The expression of CD31, RAM-11, VEGF, b-FGF, S-100 protein and collagen I, II and III in the bone-tendon interface was very similar to that in the endochondral ossification. Some of the type-III collagen in the outer layer of the graft, which was deposited at a very early phase after the operation, was believed to have matured into Sharpey-like fibres. However, remodelling of the tendon grafted into the bone tunnel was significantly delayed when compared with this ossification process. To promote healing, we believe that it is necessary to accelerate remodelling of the tendon, simultaneously with the augmentation of the ossification.

Successful induction of immune tolerance by continuous infusion of recombinant factor VIII in a haemophilia A patient with high-inhibitor titres.

The successful and persistent abolition of the inhibitor is of significant clinical benefit, as it allows for the restoration of the usual treatment with clotting factor concentrate. We describe a successful induction of immune tolerance by continuous infusion of recombinant factor VIII (rFVIII) in a 5-year-old boy with severe haemophilia A and high-responding inhibitor. He had previously been subjected to immune tolerance induction (ITI) with rFVIII at 100 units (U) kg(-1) three times weekly. One year after the beginning of therapy tolerance was not achieved and a high titer of inhibitor was detected (15 Bethesda Units). The patient had a sudden onset of severe neck pain. The diagnosis of spinal epidural haematoma was revealed by magnetic resonance imaging, and emergency laminectomy with evacuation of the haematoma was required. The patient received sequential therapy for surgery first as bolus rFVIII injection of 500 U kg(-1) in order to overwhelm the inhibitor and then as continuous infusion at 6 to 12 U kg(-1) hour(-1) to avoid bleeding episodes in the postoperative period. After the 3 weeks of continuous infusion, the inhibitor became undetectable. Thereafter, prophylactic treatment with rFVIII was started three times weekly, and the inhibitor has remained undetectable for 6 months. The, present case suggests that continuous infusion of rFVIII may be an effective therapy to induce immune tolerance.

Tumour budding at the deepest invasive margin correlates with lymph node metastasis in submucosal colorectal cancer detected by anticytokeratin antibody CAM5.2.

In the past few years, tumour budding at the invasive margin has been reported as a new risk factor for lymph node metastasis in advanced colorectal cancers, but it is sometimes difficult to detect tumour budding in submucosal colorectal cancer by haematoxylin and eosin staining. We immunohistochemically examined tumour budding at the deepest invasive margin of 56 surgically resected submucosal colorectal carcinomas using anticytokeratin antibody CAM5.2, furthermore checked by AE1/AE3, and determined the relation between tumour budding and clinicopathological factors. Moreover, we used the monoclonal antibody D2-40 for immunohistochemistry to detect lymphatic involvement. Tumour budding was detected in 42 cases (75.0%), and the budding-positive group showed a significantly higher rate of lymph node metastasis (including isolated tumour cells) (16/42 vs 0/14; P=0.004) than the budding-negative group. The sensitivity and negative predictive value of tumour budding alone for lymph node metastasis were superior to those of lymphatic invasion alone. Furthermore, the specificity and positive predictive value of the combination of either lymphatic invasion or tumour budding were superior to those of lymphatic invasion alone. Tumour budding detected immunohistochemically by using CAM5.2 is a newly found risk factor for lymph node metastasis and may help to avoid oversurgery in the future.