Neurological Improvement Associated with Resolution of Irradiation-Induced Myelopathy: Serial Magnetic Resonance Imaging and Positron Emission Tomography Findings

We document serial magnetic resonance imaging (MRI) and [¹⁸F] 2-fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET) findings in the process of improvement from delayed radiation necrosis of the spinal cord. A 61-year-old woman underwent radiotherapy for an oral carcinoma. Forty-six months later she developed a left-sided Brown-Séquard syndrome, suggesting incomplete cervical cord transection below the cervico-thoracic junction. Two months after starting steroid therapy, she had gradual clinical improvement, which continues 8 years after the termination of radiotherapy. Neurological improvement was associated with gradual resolution of an extensive high-intensity area within the cervico-thoracic spinal cord on MRI. Initially, the FDG-PET showed linear and uniform increase in FDG uptake throughout the cervical spinal cord with standardized uptake value of 2.68 ± 0.16 (mean ± SD), but it returned to normal value (1.90 ± 0.14) at final follow-up. Considering that the normalization of FDG uptake correlated with neurological recovery, the uniform- and diffuse-increased FDG uptake noted in the initial course of myelopathy could reflect the metabolic activity of the compromised spinal cord.     

Complete genome analysis of a novel intertypic recombinant human adenovirus causing epidemic keratoconjunctivitis in Japan

For 4 months from September 2008, 102 conjunctival swab specimens were collected for surveillance purposes from patients across Japan suspected of having epidemic keratoconjunctivitis (EKC). Human adenovirus (HAdV) DNA was detected in 61 samples by PCR, though the HAdV type for 6 of the PCR-positive samples could not be determined by phylogenetic analysis using a partial hexon gene sequence. Moreover, for 2 months from January 2009, HAdV strains with identical sequences were isolated from five conjunctival swab samples obtained from EKC patients in five different regions of Japan. For the analyses of the 11 samples mentioned above, we determined the nucleotide sequences of the entire penton base, hexon, and fiber genes and early 3 (E3) region, which are variable regions among HAdV types, and compared them to those of other HAdV species D strains. The nucleotide sequences of loops 1 and 2 in the hexons of all 11 samples showed high degrees of identity with those of the HAdV type 15 (HAdV-15) and HAdV-29 prototype strains. However, the fiber gene and E3 region sequences showed high degrees of identity with those of HAdV-9, and the penton base gene sequence showed a high degree of identity with the penton base gene sequences of HAdV-9 and -26. Moreover, the complete genome sequence of the 2307-S strain, which was isolated by viral culture from 1 of the 11 samples, was determined. The 2307-S strain was a recombinant HAdV between HAdV-9, -15, -26, -29, and/or another HAdV type; however, the recombination sites in the genome were not obvious. We propose that this virus is a novel intertypic recombinant, HAdV-15/29/H9, and may be an etiological agent of EKC.     

Overexpression of CD-11b and CXCR1 on circulating neutrophils: its possible role in COPD

BACKGROUND: It has been shown that the beta2-integrin molecule is up-regulated in circulating neutrophils in COPD subjects. However, little has been reported about the expression of the cell surface molecules in such patients and their relationship with pulmonary function. The aim of the present study was to investigate the surface expression of molecules in circulating neutrophils and to clarify their possible role in the airflow limitation of COPD. METHODS: The surface expression of Mac-1 cells (ie, CD-11b and CD-18 cells) and CXC chemokine receptor (CXCR) 1 and CXCR2 of circulating neutrophils obtained from COPD patients and healthy subjects (HSs) was measured by flow cytometry analysis. The serum levels of interleukin (IL)-8 were measured by enzyme-linked immunosorbent assay. RESULTS: Both CD-11b and CXCR1 expression were significantly higher in COPD patients than in HSs (mean [+/- SE] CD-11b concentration: HSs, 9.7 +/- 1.0; COPD patients, 14.2 +/- 1.8 [p < 0.05]; mean CXCR1 concentration: HSs, 9.6 +/- 0.5; COPD patients, 11.9 +/- 0.4 [p < 0.01]). Although aging was positively correlated with the expression of CXCR1 (r = 0.440; p < 0.01), none of the other background factors, including smoking and body mass index, showed a correlation with the expression of the molecules. Although serum IL-8 levels were higher in patients with COPD than in HSs, no significant correlation between serum IL-8 levels and the expression of any molecule was seen. The expression of CD-11b (r = -0.317) and CXCR1 (r = -0.383) showed a significant negative correlation with the severity of airflow limitation (both p < 0.05). CONCLUSIONS: The overexpression of CD-11b and CXCR1 in circulating neutrophils may be associated with the development of airflow limitation in COPD patients.     

Adenovirus-mediated retrograde transfer of neurotrophin-3 gene enhances survival of anterior horn neurons of twy/twy mice with chronic mechanical compression of the spinal cord

Chronic mechanical compression of the spinal cord causes neural tissue damage, including loss of anterior horn cells around the level of injury. Exogenous delivery of neurotrophins to neuronal cells could provide neuroprotection to a spinal cord subjected to mechanical injury. We investigated the efficacy of retrograde gene delivery of adenoviral vector (AdV) carrying neurotrophin-3 (NT-3) gene into twy (twy/twy) mouse spinal cord anterior horn neurons with chronic and progressive mechanical compression at C1-C2 level. AdV-NT-3 was used for retrograde delivery via the sternomastoid muscle to the cervical spinal accessory motoneurons in 16-week-old adult twy mice with relatively mild spinal cord compression. Four weeks after the AdV-NT-3 or AdV-beta-galactosidase cDNA (LacZ) as a marker gene injection, the compressed cervical spinal cord was examined histologically, immunohistologically, and by immunoblot analysis. Immunoreactivity to NT-3 was significantly enhanced in the AdV-NT-3-injected twy mice compared with the AdV-LacZ-injected mice. The numbers of anterior horn neurons of Nissl-, choline acetyltransferase (ChAT)-, and trkC-stained and wheat germ agglutinin-horseradish peroxidase (WGA-HRP)-labeled neurons at the spinal cord level with maximum compression were significantly higher in AdV-NT-3-transfected than in AdV-LacZ-transfected twy mice. Retrograde NT-3 gene transfer to twy mouse anterior horn neurons increased neurite axonal length and arborization of WGA-HRP-labeled neurons. Our results suggest that targeted retrograde NT-3 gene delivery is feasible in the intact animal and that it enhances neuronal survival even under chronic mechanical compression of the spinal cord.     

Atlantoaxial subluxation-induced myelopathy in cleidocranial dysplasia. Case report

The authors describe the clinical course and treatment of a patient with cleidocranial dysplasia in whom spastic myelopathy developed due to atlantoaxial subluxation. This 27-year-old woman with cleidocranial dysplasia and a history of atlantoaxial subluxation presented with spastic myelopathy. Surgery was performed twice for cervical myelopathy and atlantoaxial subluxation, including laminectomy at the atlas and cervicooccipital fusion in which the Luque rod system was used, as well as C1-2 fusion via the transpharyngeal route. Solid bone fusion was achieved by 7 months postsurgery. Postoperative magnetic resonance imaging studies demonstrated that spinal cord compression was relieved, but atrophy persisted. At 2 years postsurgery there was no neurological disease progression, but spasticity persisted. The patient could walk with a cane. Cleidocranial dysplasia is an extremely rare cause of myelopathy in patients with atlantoaxial subluxation; the authors know of only two reports of this condition. When managing cleidocranial dysplasia, the practitioner should always be aware that atlantoaxial subluxation may be the cause of cervical myelopathy.     

Economic evaluation of the prevention and treatment of breast cancer-present status and open issues

BACKGROUND: More effective methods of preventing and treating breast cancer are being sought by clinicians every day, and new drugs and interventions for overcoming this cancer are being energetically evaluated. At present, there are wide treatment options and many different objectives for breast cancer. These circumstances led us to seek information about the relative costs of the different medical options for the prevention and treatment of breast cancer and to try to ascertain whether one course of action is more efficient than other courses. Economic evaluation of healthcare is indispensable for selection of the best alternatives among medical interventions which are becoming more diverse day after day. The total medical expenditure continues to rise each year and some sort of evaluation from an objective and external viewpoint is required to provide the information with which to suppress this rise. METHODS: This paper surveys the three major reports published on this topic to date, for the purpose of demonstrating the importance and necessity of performing an economic analysis of the treatment and prevention of breast cancer. The three reports to be surveyed pertain to: (1) cost-effectiveness analysis of adjuvant chemotherapy for patients with lymph node negative breast cancer, (2) cost utility analysis of first-line hormonal therapy in advanced breast cancer, namely comparison of two aromatase inhibitors to tamoxifen, and (3) cost-effectiveness analysis of tamoxifen in the prevention of breast cancer. In addition, this paper discusses the advantages, limitations and perspective for the future of the economic evaluation of healthcare for breast cancer. RESULTS: (1) The authors concluded that if the average risk of all women of undergoing recurrence after this therapy is assumed to be 4% per year, adjuvant chemotherapy is definitely of benefit for node-negative, estrogen receptor-negative breast cancer patients. They additionally stated that this benefit decreases markedly if the changes in long-term survival are less than those in disease-free survival. In this connection, they pointed out that the benefit is considerably smaller among postmenopausal 60-year-old women. (2) The incremental cost per quality-adjusted progression-free life year (QAPFY) for letrozole and anastrozole, relative to tamoxifen, was Can $12,500-19,600, which was lower than the criterion level (US $50,000). On the basis of this result, the authors concluded that these two drugs are economically acceptable. Furthermore, when efficacy and cost effectiveness were analyzed together, it was concluded that letrozole is in fact preferable to anastrozole. (3) The model analysis of tamoxifen's cost effectiveness among women at increased risk for breast cancer yielded the following results. In the base-case analysis, involving the calculation of the costs and benefits of 5-year tamoxifen administration, the incremental cost effectiveness of tamoxifen was $41,372 per life-year gained for women age 35 to 49 years, whereas for women age 50 to 59 years and 60 to 69 years, these values were $68,349 and $74,981, respectively. For women who had undergone hysterectomy and thus had no risk of the onset of endometrial cancer, the incremental cost effectiveness of tamoxifen was $46,060 per life-year gained. CONCLUSION: Medico-economic evaluation of breast cancer is very significant and valuable and is expected to stimulate efficient utilization of healthcare resources. It can provide important information to physicians, patients, insurers, pharmaceutical and other industries, healthcare policy planners, and others.