High cervical midline punctate myelotomy in the management of visceral pain in the mouse

Increasing evidence implies the existence of a visceral pain pathway in the dorsal column of the spinal cord. Limited midline myelotomy has been used to treat intractable pelvic cancer pain. However, no obvious evidence has been provided that high cervical punctate midline myelotomy (CPMM) relieves visceral pain originating from the abdomen. This study was designed to examine the pain relief effect of CPMM in a mouse model of visceral pain. Thirty-six Institute of Cancer Research (ICR) mice were divided into three groups: Group 1, healthy controls; Group 2, treated with CPMM at C1 and C2; and Group 3, a sham group that underwent laminectomy at C1 and C2 without CPMM. All animals were tested for antinociception in the writhing test 24 hours after surgery. Visceral pain-related behaviors were counted from 5-20 minutes after intraperitoneal injection of 0.6% acetic acid. Writhing test scores were not significantly different between Groups 1 (56.7 +/- 10.7) and 3 (50.7 +/- 17.4). However, Group 2 (30.0 +/- 14.3) showed more than 40% antinociception after treatment, and writhing test scores were significantly different from those of Groups 1 and 3 (p < 0.001). Our results confirm that midline punctate myelotomy can relieve visceral pain and imply that there is a pathway in the posterior funiculus that signals visceral pain. Punctate midline myelotomy at the cervical or high thoracic level may be an alternative strategy in the management of intractable visceral pain due to abdominal or pelvic cancers.     

Gene transfer of pro-opiomelanocortin prohormone suppressed the growth and metastasis of melanoma: involvement of alpha-melanocyte-stimulating hormone-mediated inhibition of the nuclear factor kappaB/cyclooxygenase-2 pathway

Pro-opiomelanocortin (POMC) is a prohormone of various neuropeptides, including corticotropin, alpha-melanocyte-stimulating hormone (alpha-MSH), and beta-endorphin (beta-EP). POMC neuropeptides are potent inflammation inhibitors and immunosuppressants and may exert opposite influences during tumorigenesis. However, the role of POMC expression in carcinogenesis remains elusive. We evaluated the antineoplastic potential of POMC gene delivery in a syngenic B16-F10 melanoma model. Adenovirus-mediated POMC gene delivery in B16-F10 cells increased the release of POMC neuropeptides in cultured media, which differentially regulated the secretion of pro- and anti-inflammatory cytokines in lymphocytes. POMC gene transfer significantly reduced the anchorage-independent growth of melanoma cells. Moreover, pre- or post-treatment with POMC gene delivery effectively retarded the melanoma growth in mice. Intravenous injection of POMC-transduced B16-F10 cells resulted in reduced foci formation in lung by 60 to 70% of control. The reduced metastasis of POMC-transduced B16-F10 cells could be attributed to their attenuated migratory and adhesive capabilities. POMC gene delivery reduced the cyclooxygenase-2 (COX-2) expression and prostaglandin (PG) E(2) synthesis in melanoma cells and tumor tissues. In addition, application of NS-398, a selective COX-2 inhibitor, mimicked the antineoplastic functions of POMC gene transfer in melanoma. The POMC-mediated COX-2 down-regulation was correlated with its inhibition of nuclear factor kappaB (NFkappaB) activities. Exogenous supply of alpha-MSH inhibited NFkappaB activities, whereas application of the alpha-MSH antagonist growth hormone-releasing peptide-6 (GHRP-6) abolished the POMC-induced inhibition of NFkappaB activities and melanoma growth in mice. In summary, POMC gene delivery suppresses melanoma via alpha-MSH-induced inhibition of NFkappaB/COX-2 pathway, thereby constituting a novel therapy for melanoma.     

Growing skull fractures

Growing skull fractures are rare complications of severe closed head injury occurring almost exclusively in infants and children under the age of three. The reported incidence is between 0.05% and 0.6%. Two such cases were treated at our institution. Both cases presented with bulging mass and underlying skull defect two months after head injury. They received surgical treatment and achieved excellent results. Early diagnosis and surgical intervention are essential for these patients to prevent progressive brain damage. Therefore, close follow-up for patients at risk of developing growing skull fracture is necessary.     

Multiple spinal meningiomas--a case report

Multiple spinal meningiomas are relatively rare and account for only 2 to 3.5% of all spinal meningiomas. A case of multiple meningiomas of the thoracic (T) spine was reported. This 77-year-old woman was admitted with progressive motor weakness and sensation disturbance in both legs for 4 months. Neurological findings on admission revealed paraparesis, hyperesthesia, and hypalgesia below the dermatome of T10 level and hyporeflexia of both ankles. Urinary and stool incontinence were also noted. Magnetic resonance imaging (MRI) documented two intradural extramedullary lesions with different intensity at the T9 and T12 levels. Both tumors were totally resected. Histopathologic examination showed all psammomatous meningiomas with more or less psammoma bodies. There were no any manifestations of von Recklinghausen's disease in this patient. MRI is a choice of diagnostic tool to detect spinal tumors, especially multiple spinal meningiomas. Different intensities in MRI may infer different components of meningiomas. Follow-up study after operation three months later disclosed she could walk very well.     

Expression and mutation analysis of the p53 gene in astrocytoma.

The role of p53 gene mutations in the formation or progression of human astrocytic tumors is controversial. We studied the distribution pattern of p53 immunoreactivity and analyzed p53 gene mutations to define the significance of p53 gene mutations in astrocytoma tumorigenesis or malignant progression. Twenty-three astrocytic tumors were evaluated with immunohistochemistry, single-strand conformation polymorphism (SSCP) analysis, and sequence analysis. We also searched MEDLINE to collect data on p53 gene mutation frequencies in astrocytic tumors in order to evaluate the association of p53 mutations and tumor grade. Strong immunoreactivity with a diffuse clustering pattern was found in three of five glioblastomas and seven of 12 anaplastic astrocytomas. Three of four low-grade astrocytomas were immunonegative. The p53 immunopositive cells in the only positively staining low-grade astrocytoma in our study appeared sparsely scattered. The results of immunostaining suggested that clonal expansion was associated with astrocytoma progression. Mutations of the p53 gene were detected in four of the 23 astrocytomas (one glioblastoma and three anaplastic astrocytomas). In the genetic data analysis, 76 of 367 astrocytomas had p53 gene mutations. A significantly greater p53 gene mutation frequency was found in anaplastic astrocytomas or glioblastomas than in the low-grade astrocytomas. The results of these immunohistochemical and genetic studies support the view that p53 gene mutation is associated with the malignant progression from low-grade to high-grade astrocytomas rather than with tumor initiation or promotion.     

Analysis of surgically treated intraspinal tumors in southern Taiwan

The medical records of 117 patients with spinal tumors who underwent surgery with pathologic confirmation from January 1999 to April 2004 at Kaohsiung Medical University Hospital were reviewed. Data from this review were compared with those obtained from the same institution 10 years earlier (covering the period 1988-1995) and from other reported series. There were 69 male and 48 female patients aged from 13 to 87 years old (mean age, 51.9). The most common pathologic findings were metastasis in 45.3% (53/117), nerve sheath tumors in 28.2% (33/117), meningiomas in 12% (14/117) and neuroepithelial tumors in 6% (7/117). The peak ages at diagnosis were 41-50 years and 61-70 years. A slight male predominance was noted for all tumors, except meningiomas. Motor weakness, even paralysis, was the major clinical presentation (64-86%), followed by sensory deficits (50%) and pain (42%). The location of tumors was most often in the thoracic (50.4%; 59/117), lumbosacral (27.4%; 32/117) and cervical spine (22.2%; 26/117) segments. Among the metastatic tumors, the lung (22.6%) and breast (15.1%) were the most common primary sites of origin, followed by unknown origin, the liver (hepatocellular carcinoma), the gastrointestinal tract and the nasopharynx (nasopharyngeal cancer).     

The alteration of plasma TGF-β1 levels in patients with brain tumors after tumor removal

Transforming growth factor (TGF) β1 may be a candidate for a serologic tumor marker. In this study, the plasma levels of TGF-β1 in patients with brain tumors were measured using enzyme-linked immunosorbent assay before and after tumor removal. Patients were divided into four groups, the control group and the benign, malignant, and metastatic brain tumor groups. All brain tumor groups showed significant increases in the levels of TGF-β1 before tumor removal (6.36 ± 3.94, 17.0 ± 9.7, and 12.2 ± 10.3 ng/ml for the benign, malignant, and metastatic groups, respectively). When compared with the results obtained in the control group (1.12 ± 0.74 ng/ml), significant decreases in TGF-β1 concentrations after total tumor removal were found in both the benign and malignant brain tumor groups (2.55 ± 2.00 and 8.93 ± 5.73 ng/ml, respectively; p = 0.0001 and p = 0.003, respectively). On the other hand, plasma TGF-β1 levels in the metastatic brain tumor group showed a slight but significant increase (14.7 ± 9.3 ng/ml, p = 0.035) after tumor removal. In a case of low-grade astrocytoma, plasma levels of TGF-β1 were found to be 3.6 and 1.1 ng/ml before and after tumor removal, respectively. However, recurrent tumor was noted in this patient 7 months later, and the levels of TGF-β1 were 26.2 and 8.4 ng/ml before and after the second operation, respectively. The data show that plasma TGF-β1 was elevated in the circulation of patients with brain tumors and that significant decreases in TGF-β1 levels were observed after the removal of benign and malignant tumors. The results also suggest that TGF-β1 may be a useful serologic marker for brain tumors.     

Association between Hemorrhagic Fever with Renal Syndrome Epidemic and Climate Factors in Heilongjiang Province,China

The purpose of this study was to quantify the relationship between climate variation and transmission of hemorrhagic fever with renal syndrome (HFRS) in Heilongjiang Province, a highly endemic area for HFRS in China. Monthly notified HFRS cases and climatic data for 2001–2009 in Heilongjiang Province were collected. Using a seasonal autoregressive integrated moving average model, we found that relative humidity with a one-month lag (β = –0.010, P = 0.003) and a three-month lag (β = 0.008, P = 0.003), maximum temperature with a two-month lag (β = 0.082, P = 0.028), and southern oscillation index with a two-month lag (β = –0.048, P = 0.019) were significantly associated with HFRS transmission. Our study also showed that predicted values expected under the seasonal autoregressive integrated moving average model were highly consistent with observed values (Adjusted R² = 83%, root mean squared error = 108). Thus, findings may help add to the knowledge gap of the role of climate factors in HFRS transmission in China and also assist national local health authorities in the development/refinement of a better strategy to prevent HFRS transmission.