Development and validation of a tuberculosis prognostic score for smear-positive in-patients in Japan.

BACKGROUND: No scoring system has ever been used to estimate the prognosis of individual tuberculosis (TB) patients. OBJECTIVE: To develop and validate a tuberculosis prognostic score. METHODS: This retrospective cohort study conducted in Japan comprised the development (n = 179; mean age 65.9 ± 18.8 years) and validation (n = 244; mean age 64.3 ± 20.1 years) of a tuberculosis prognostic score among patients with newly diagnosed smear-positive non-multidrug-resistant pulmonary tuberculosis without human immunodeficiency virus infection. The score (raw score) was defined by modifying a logistic regression formula using known risk factors as independent variables and in-patient death as a dependent variable. RESULTS: The raw score was calculated as follows: age (years) + (oxygen requirement, 10 points) - 20 × albumin (g/dl) + (activity of daily living: independent, 0 point; semi-dependent, 5 points; totally dependent, 10 points). The raw scores were grouped into risk groups 1 (raw score < -30) to 5 (raw score ≥ 60) using 30-point intervals. Every increase in risk group was equivalent to a 7.3-fold increase in the odds ratio for in-hospital death (P < 0.001). The area under the receiver operating characteristics curve by risk group for in-patient death was 0.875 (P < 0.001). CONCLUSIONS: In this study we were able to develop and validate a tuberculosis prognostic score.

Association of incompleteness of the anterior part of the circle of Willis with the occurrence of lacunes in the basal ganglia.

BACKGROUND AND PURPOSE: This study investigated whether incompleteness of the anterior part of the circle of Willis affects the occurrence of lacunes in the basal ganglia. METHODS: One thousand and seventy-seven healthy individuals examined by magnetic resonance (MR) imaging and MR angiography were divided into eight subgroups according to our new classification. RESULTS: Logistic regression analysis demonstrated that healthy individuals with incompleteness of the anterior circle of Willis had significantly higher frequency of lacunes [odds ratio (OR): 2.121, 95% confidence interval (CI): 1.477-3.108; or OR: 2.46, 95% CI: 1.377-4.384 in cases without or with fetal type posterior communicating artery, respectively] and higher numbers of lacunes (P < 0.001 or P < 0.001 in cases without or with fetal type posterior communicating artery, respectively) compared to patients with complete circle of Willis. CONCLUSIONS: Incompleteness of the anterior part of the circle of Willis significantly affected the occurrence of lacunes.

Thoracic chordoma: review and role of FDG-PET.

Chordoma is an uncommon primary bone tumor and the thoracic spine is the least common of all sites for a chordoma. It may recur despite slow-growing nature. Precise literature review will be performed and possible use of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) for detection of both primary and recurrent diagnosis will be discussed. This article presents the case of a 73-year-old male patient who complained of back pain. Magnetic resonance (MR) imaging, computed tomography (CT) and FDG-PET demonstrated thoracic lesion and biopsy revealed chordoma. The patient was operated on and histological findings showed the tumor was chondroid chordoma. He suffered recurrence after 7 months by FDG-PET. He received 6,000 rads radiation therapy and is neurological free but, suffered backache 15 months after initial diagnosis. Only 12 cases including this case were reported precisely and this is the first report of FDG-PET for both initial and recurrent diagnosis of chordoma.

Localized mediastinal lymph node amyloidosis showing an unusual unsynchronized pattern of enlargement and calcification on serial CT.

Amyloidosis is an unusual cause of mediastinal lymphadenopathy. A localized form of amyloidosis manifesting solely in the intrathoracic lymphnode is extremely rare. We describe a case of intrathoracic lymphadenopathy caused by a localized form of amyloidosis. Calcification has been reported in amyloidosis; however, it has been considered as non-specific. In our case, serial CT carried out over a period of 3 years and 3 months showed an unusual and unsynchronized pattern of enlargement and calcification.

Ossification of the ligamentum flavum of the cervical spine.

AIM: Ossification of ligamentum flavum (OLF) mainly occurs in the thoracic spine, and rarely in the cervical spine. To clarify its etiology; the features of OLF in the cervical spine were reviewed in 50 reported cases. METHODS: Age, sex, location of OLF, classification of OLF, radiographic findings, computed tomography (CT) findings, magnetic resonance imaging findings, association of ossification of the posterior longitudinal ligament (OPLL), association of OLF in other spinal regions, and association of diffuse idiopathic skeletal hyperostosis (DISH) were analyzed in 23 detailed cases. RESULTS: Association of OPLL was observed in 7 of 20 cases and 4 of these 7 OPLL cases were at C2-4. Association of OLF in other spinal regions was recognized in 7 of 15 cases. DISH was also present in 3 of 7 cases. Local kyphosis was recognized in 10 of 12 cases by radiography. CT showed facet hypertrophy in 13 of 15 cases and lamina hypertrophy in 14 of 16 cases. Patients with OLF at C2-4 had high rates of local kyphosis and association of hyperostotic state, suggesting both local factors and systemic hyperostotic factors are involved in the formation of OLF of the upper cervical spine. CONCLUSION: Local factors may be strongly related to the formation of OLF of the middle or lower cervical spine.

Risk factors for the association of intracranial and aortic aneurysms.

This study investigated the association of intracranial aneurysms and abdominal aortic aneurysms to elucidate the incidence and independent risk factors for this association. Ultrasonography of the abdominal aorta was performed in 181 patients with 224 intracranial aneurysms. Six patients had suffered subarachnoid haemorrhage and the others had chronic disease or no symptoms. Magnetic resonance angiography was performed for confirmation if abdominal aortic aneurysm was identified by ultrasonography. Thirteen patients (7.2%) with 23 intracranial aneurysms had abdominal aortic aneurysms. Univariate analysis demonstrated that age (p < 0.01), size of intracranial aneurysms (p < 0.001), male sex (p < 0.01), multiplicity of intracranial aneurysms (p < 0.001), history of cerebrovascular diseases (p < 0.05), and current smoking (p < 0.0001) were significantly different between patients with and without this association. Multiple logistic analysis indicated that age (odds ratio [OR] 1.27, 95% confidence interval 1.08-1.48, p < 0.01), multiplicity (OR 22.1, 95% confidence interval 1.83-266.3, p = 0.01), size of intracranial aneurysms (OR 1.30, 95% confidence interval 1.10-0.54, p < 0.01), and current smoking (OR 33.3, 95% confidence interval 2.43-456.7, p = 0.01) were independent risk factors for the association. Patients with intracranial aneurysms who are older males with multiple or large intracranial aneurysms, and current smokers should be examined for abdominal aortic aneurysms using ultrasonography.

[Probable toxic shock syndrome following pleural drainage].

Toxic shock syndrome (TSS) is rare complication after minor surgical procedure. A 22-year-old man was admitted our hospital with spontaneous pneumothorax on the right side. Few days after pleural drainage, he developed a high fever often over 40 degrees C and a rash, most demonstrating a truncal, "sunburn" pattern. Initially, he was diagnosed as right pylothorax, but the clinical course was not typical and antibiotic treatment was not effective. Two weeks later, desquamation of the hands and feet were noted, and methicillin-resistant Staphylococcus aureus (MRSA) isolated from the pleural effusion were identified as TSS toxin (TSST)-1 and enterotoxin-C producing. He was diagnosed as probable TSS, and recovered by steroid therapy. Early awareness and recognition of this disease is necessary for surgeons.

Genetic variation in hypoxia-inducible factor 1alpha and its possible association with high altitude adaptation in Sherpas.

Hypoxic stress at high altitude requires adaptations in several physiological functions to ensure the optimal oxygenation of all cells. Several lines of evidence suggested that high-altitude native populations such as Sherpas have been genetically adapted to their stressful environment. We investigated the genetic variation in the hypoxia-inducible factor (HIF)-1alpha gene in Sherpas as compared with Japanese, native lowlanders, and found a novel dinucleotide repeat polymorphism in intron 13 of the HIF-1alpha gene. GT15 allele was more frequent in Japanese than in Sherpas with statistical significance, while GT14 allele was significantly more frequent in Sherpas as compared with Japanese. A possible genetic variation in the HIF-1alpha gene might function in adaptation to living at high altitude. Because the activity of HIF-1 is regulated by multiple steps including the transcriptional level, the effect of the polymorphism in intron 13 on the cellular hypoxic responses remains to be elucidated.

Embryonic stem cells injected into the mouse knee joint form teratomas and subsequently destroy the joint.

OBJECTIVE: To determine whether the joint space is a suitable environment for embryonic stem (ES) cells to grow and form cartilage. METHOD: We transplanted ES cells into the knee joint and a subcutaneous space of mice with severe combined immunodeficiency. RESULTS: Teratomas formed in both areas. Those in the joints grew and destroyed the joints. The incidence of cartilage formation was the same in the knee joint and subcutaneous space, but the ratio of cartilage to teratoma was higher in the knee joint than in the subcutaneous space. The teratomas were proved to have been derived from the transplanted ES cells by detection of the neomycin-resistance gene that had been transfected into the ES cells. CONCLUSIONS: It is currently not possible to use ES cells to repair joint tissues. Further optimization of donor ES cells to differentiate as well as inhibit tumour growth may help to meet these challenges.

Tandem single-step construction of chiral hexahydrophenanthrenes: a concise route to (+)-ferruginol.

An efficient enantio- and diastereocontrolled construction of hydrophenanthrenes having either a quaternary or a tertiary benzylic stereogenic center has been developed by employing a tandem retro-aldol and intramolecular Friedel-Crafts alkylation sequence. Its application to a diastereocontrolled synthesis of an abietane diterpenoid (+)-ferruginol has also been demonstrated.

Long-term follow-up of asymptomatic patients with major artery occlusion: rate of symptomatic change and evaluation of cerebral hemodynamics.

BACKGROUND AND PURPOSE: The natural history of asymptomatic major cerebral artery occlusive disease is unclear. Rate of symptomatic change, appearance of new lesions on MR images, and cerebral hemodynamics were analyzed for patients with asymptomatic major cerebral artery occlusion. METHODS: This prospective study included asymptomatic patients who had occlusive disease between 1992 and 1995. MR imaging and MR angiography were used to detect internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion in 3965 neurologically asymptomatic patients and for follow-up of affected patients for 67 to 105 months (mean, 79 months). Regional cerebral blood flow and cerebrovascular reserve capacity were examined by xenon-enhanced CT at rest and after the administration of acetazolamide, respectively. RESULTS: Eighteen patients had MCA occlusion and 17 had ICA occlusion. During the follow-up period, five patients became symptomatic (four with MCA occlusion and one with ICA occlusion), with no significant difference (P = .332) in the rate of symptomatic change. Among these five patients, new infarction occurred on the ipsilateral side in three patients, contralateral side in one, and bilateral sides in one. New stenotic or occlusive changes occurred in three patients. The patients were divided into groups: group A, without new lesions on MR images (n = 23), and group B, with new lesions (n = 12). There was no significant difference in regional cerebral blood flow value between groups A and B in the whole hemisphere, anterior cerebral artery territory, or MCA territory. There was a significant difference in cerebrovascular reserve capacity between groups A and B between the affected side (P = .00051 and P = .00068, respectively) and the contralateral side (P = .00101 and P = .00115, respectively) for the whole hemisphere and MCA territory, and the difference was more severe on the affected side in both regions. CONCLUSION: These pilot data suggest that asymptomatic MCA occlusion has a worse prognosis than does ICA occlusion. Silent events are common bilaterally. This may be because of hemodynamic factors or perhaps MCA occlusion is a marker for a more progressive type of atherosclerosis. A prospective study involving assessment of hemodynamics and baseline stroke risk factors in patients with MCA occlusion is indicated.

Adenovirus serotype 7 retention in a late endosomal compartment prior to cytosol escape is modulated by fiber protein.

The intracellular trafficking of adenovirus (Ad) subgroup B (e.g., Ad7) differs from that of subgroup C (e.g., Ad5) in that Ad5 rapidly escapes from endocytic compartments following infection whereas Ad7 accumulates in organelles. To assess the hypothesis that Ad7 is targeted to the lysosomal pathway, Ad7 and Ad5 were conjugated with fluorophores and their trafficking in A549 epithelial cells was analyzed by fluorescence microscopy. Within 1 h after infection, Ad7, but not Ad5, accumulated in the cytoplasm of A549 cells. The pH in the environment of Ad5 was nearly neutral (pH 7), while Ad7 occupied acidic compartments (pH 5) over the first 2 h with a gradual shift toward neutrality by 8 h. Ad7 partially colocalized with alpha(2)-macroglobulin and late endosomal and lysosomal marker proteins, including Rab7, mannose-6-phosphate receptor, and LAMP-1. The pH optimum for membrane lysis by Ad7, as well as a chimeric Ad5 capsid that expressed the Ad7 fiber (Ad5fiber7), was pH 5.5, while that for lysis by Ad5 was pH 6.0. Thus, the native trafficking pathway for Ad7 involves residence in late endosomes and lysosomes, with information encoded in the Ad7 fiber acting as a pH-dependent trigger for membrane lysis and escape to the cytosol.

Evaluation of crossed cerebellar diaschisis in 30 patients with major cerebral artery occlusion by means of quantitative I-123 IMP SPECT.

Quantitative crossed cerebellar diaschisis (CCD) and the correlation with a reduction in supratentorial regional cerebral blood flow (rCBF) and cerebrovascular reserve capacity (CVR) were investigated in clinically stable patients with major cerebral artery occlusion by the iodine-123-N-isopropyl-p-iodoamphetamine (I-123 IMP) single photon emission computed tomography (SPECT) method. Thirty patients with major cerebral artery occlusion underwent SPECT by the I-123 IMP autoradiographic method. Regional CBF was measured in the cerebral hemisphere, frontal and parietal lobes, temporo-parietal lobe, and cerebellum both at rest and after administration of acetazolamide. Eighteen of 30 patients (60%) had CCD. CCD was significantly related to magnetic resonance imaging evidence of infarction. Quantitative CCD was 17% and the CVR in the cerebellum was preserved in patients with CCD. There was a significant difference in CBF and CVR between the affected and normal sides in all regions of interest in the patients without CCD [CBF (ml/100 g/min): hemisphere (H), normal side (N): 31.4 +/- 6.8, affected side (A): 27.5 +/- 7.4; p < 0.05. CVR: H, N: 0.56 +/- 0.38, A: 0.42 +/- 0.18; p < 0.01]. CCD is common in patients with major cerebral artery occlusion, and quantitative I-123 IMP SPECT is helpful in detecting CCD in clinically stable patients with occlusion of major cerebral arteries.

Tumor regression induced by intratumor administration of adenovirus vector expressing CD40 ligand and naive dendritic cells.

We have previously shown that in vivo genetic modification of tumors with an adenovirus (Ad) vector engineered to express CD40 ligand (AdmCD40L) induces tumor-specific CTLs and suppresses tumor growth in vivo. In the present study, we investigate the hypothesis that this treatment can be made more efficient with 10(2)-fold less Ad vector by also administering bone marrow-generated dendritic cells (DCs) to the tumor. Using AdmCD40L and the number of DCs that alone had no effect on tumor growth, the data show that the growth of CT26 (colon adenocarcinoma; H-2d) and B16 (melanoma; H-2b) murine s.c. tumors is significantly suppressed by direct administration of DCs into s.c. established tumors that had been pretreated with AdmCD40L 2 days previously. The antitumor effect produced by the combination therapy AdmCD40L + DCs correlated with in vivo priming of tumor-specific CTLs. The antitumor cell-mediated immunity was transferable to naive mice by spleen cells from AdmCD40L + DC-treated animals. The interactions between CD40L and CD40 within treated tumors were critical because tumor suppression was abrogated by coadministration to the tumors of neutralizing monoclonal antibody against CD40L along with the DCs. Finally, in vivo depletion and knockout mice experiments demonstrated that tumor regression produced by this combination therapy depends on CD8+ T cells, but not on CD4+ T cells. These findings should be useful in designing strategies for use of DCs and AdmCD40L in cancer immunotherapy.

Protective effect of FK506 in the reperfusion model after short-term occlusion of middle cerebral artery in the rat: assessment by autoradiography using [125I]PK-11195.

The protective effect of the immunosuppressant agent FK506 in the reperfusion after short-term occlusion of the middle cerebral artery in the rat model was evaluated using [125I]PK-11195 autoradiography. FK506 0.5 mg kg-1 day-1 was administered intramurally to Wistar rats weighing 260-300 g from one day prior to ischemia to seven days after ischemia. Reperfusion was performed after 30 or 60 min occlusion. Infarct area was evaluated by [125I]PK-11195 autoradiography on the seventh day following occlusion. FK506 significantly reduced the infarct area in the caudate nucleus following 30 and 60 min occlusion, but significantly reduced the infarct area in the cortex only following 60 min occlusion. These results suggest that FK506 has a protective effect against reperfusion after short-term occlusion of the middle cerebral artery.

Dynein- and microtubule-mediated translocation of adenovirus serotype 5 occurs after endosomal lysis.

Modified viruses are used as gene transfer vectors because of their ability to transfer genetic material efficiently to the nucleus of a target cell. To better understand intracellular translocation of adenovirus serotype 5 (Ad), fluorophores were covalently conjugated to Ad capsids, and movement of fluorescent Ad within the cytoplasm was observed during the first hour of infection of a human lung epithelial carcinoma cell line (A549). Ad translocation was characterized with respect to its ability to achieve nuclear envelope localization as well as directed movement in the cytoplasm. Whereas Ad achieved efficient nuclear localization 60 min after infection of A549 cells under control conditions, depolymerization of the microtubule cytoskeleton by addition of 25 microM nocodazole reversibly inhibited development of nuclear localization. In contrast, depolymerization of microfilaments by addition of 1 microM cytochalasin D had no effect on nuclear localization. Direct video observation of Ad motility showed that nocodazole, but not cytochalasin D, caused a reversible decrease in rapid linear translocations of Ad in the cytoplasm of A549 cells. Microinjection of function-blocking antibodies against the microtubule-dependent motor protein, cytoplasmic dynein, but not kinesin, blocked nuclear localization of Ad, consistent with net minus end-directed motility indicated by accumulation of Ad at mitotic spindles. Fluorescence ratio imaging revealed a neutral pH in the environment of translocating Ad, leading to a model in which the interaction of Ad with an intact microtubule cytoskeleton and functional cytoplasmic dynein occurs after escape from endosomes and is a necessary prerequisite to nuclear localization of adenovirus serotype 5.

MRI at 1.5 T of intramedullary ependymoma and classification of pattern of contrast enhancement.

We retrospectively reviewed the MRI findings in 28 patients with an intramedullary spinal cord ependymoma who underwent surgical treatment. There were 26 tumours in the cervical and two in the thoracic spine. T1- and T2-weighted and contrast-enhanced images at 1.5 T were obtained in all cases. T1-weighted imaging showed solid tumour as isointense in 13 patients, high-signal in ten and low signal in five. In contrast, T2-weighted imaging showed all tumours as high signal. Contrast enhancement was heterogeneous 13 patients, homogeneous 10, heterogeneous with cyst wall enhancement in three, and a nodule on a cyst wall was seen in two. Cases with these latter patterns require careful differential diagnosis from astrocytoma or haemangioblastoma.

Statistical analysis of factors affecting the outcome of patients with ruptured distal anterior cerebral artery aneurysms.

The clinical factors affecting the outcome of patients with ruptured distal anterior cerebral artery (ACA) aneurysms were analyzed using multiple logistic regression analysis. The medical records were reviewed of 52 patients (57 aneurysms) with ruptured distal ACA aneurysms operated on by the same neurosurgeon over 25 years. The standard policy was early surgery for patients in Hunt and Kosnik grades I to IV. Age, sex, Hunt and Kosnik grade, timing of operation, size of aneurysms, number of aneurysms, association of intracerebral haemorrhage (ICH), intraventricular haemorrhage, and azygos ACA, use of temporary clipping, occurrence of premature rupture, and presence of psychiatric change were investigated. Univariant analysis disclosed that clinical grade (P = 0.0006), size of aneurysm (P = 0.005), and size of ICH (P = 0.012) affected the outcome of patients. Multiple logistic regression analysis found that Hunt and Kosnik grade (P = 0.010) and timing of operation (P = 0.033) affected the outcome. There was no significant relationship between long-term outcome and clinical factors, although a close relationship was found with Hunt and Kosnik grade (P = 0.071). Clinical grade and timing of the operation affected the outcome of patients with ruptured distal ACA aneurysms. Patients harboring ICH of over 3 cm diameter in poor grades should also be carefully treated.

Exhaled nitric oxide before and after montelukast sodium therapy in school-age children with chronic asthma: a preliminary study.

Exhaled nitric oxide (ENO) is a surrogate marker of airway inflammation in asthma. In 12 children aged 6-11 years with mild to moderate persistent asthma, ENO concentrations were measured before and after 4 weeks of treatment with montelukast sodium, a leukotriene receptor antagonist, and 2 weeks after withdrawal of therapy. Baseline ENO levels (mean and 95% confidence interval) were significantly elevated in patients with asthma compared to age-matched nonasthmatic control subjects, with levels of 83 (42-123) vs. 13 (11-15) ppb (P < 0.001). After treatment with montelukast sodium, there was a significant (P < 0.01) reduction in ENO to 58 (27-89) ppb which again rose to 69 (38-99) ppb 2 weeks after treatment was withdrawn. During treatment, the fall in ENO was accompanied by nonsignificant improvements in prebronchodilator forced expiratory volume in 1 s (FEV(1)) from 81-85% predicted or reductions in use of albuterol from a mean of 2.5 to 1.6 puffs/day. Individual ENO measurements and change in ENO concentrations with treatment did not correlate with either pulmonary function changes or use of bronchodilator. These data show that ENO is elevated in children with relatively mild asthma treated with bronchodilator alone, and that treatment with montelukast sodium for 4 weeks results in a significant reduction in ENO concentrations, even in the absence of significant changes in pulmonary function. These findings suggest an anti-inflammatory role for leukotriene D(4) receptor antagonism in the treatment of children with mild to moderate asthma.