Accuracy of composite diagnostic standards for pneumococcal pneumonia in vaccine trials.

Because of a lack of gold standard diagnostics, a combination of multiple diagnostic tests, or composite diagnostic standard, has been used to measure pneumococcal pneumonia (PP) in pneumococcal vaccine trials. We estimated the accuracy of composite diagnostic standards for PP used in previous randomised controlled trials by simple formulas. A systematic literature review identified five eligible trials and all trials had used different combinations of diagnostic tests for PP. The estimated values of sensitivity and minimum specificity of composite diagnostic standards varied substantially between trials: 48.4% to 98.1% and 71.0% to 97.3%, respectively. Without standardizing the outcome measurements, pneumococcal vaccine efficacy estimates against PP are not comparable between trials and their pooled estimates are biased.

High incidence of acute traumatic spinal cord injury in a rural population in Japan in 2011 and 2012: an epidemiological study.

STUDY DESIGN: Retrospective questionnaire-based epidemiological study. BACKGROUND: Physicians treating acute traumatic spinal cord injury (SCI) in Japan noticed an increased occurrence of cervical SCI without skeletal injury. OBJECTIVE: To elucidate the precise epidemiology of acute cervical SCI with the aim of planning a prevention program. METHODS: Questionnaires were posted to all hospitals in Tokushima prefecture (around 780,000 inhabitants) to investigate the annual incidence of SCI in 2011 and 2012. RESULTS: The response rate was 79% in 2011 and 64% in 2012. The returned questionnaires reported on 95 patients in 2011 and 91 patients in 2012, with a mean age of 67.6 and 64.3 years and an annual incidence (per million population) of 121.4 and 117.1, respectively. More than two-thirds of the cases suffered cervical SCI without skeletal injury, and 61% of these were categorized as Frankel D neurological deficits due to low-energy impact as the main cause. CONCLUSION: The incidence of incomplete cervical SCI does appear to be increasing, and significant regional differences in the incidence of cervical SCI exist across Japan. We speculate that factors other than age are contributing to this increase.

www.elearnSCI.org: a global educational initiative of ISCoS.

OBJECTIVE: To develop a web-based educational resource for health professionals responsible for the management of spinal cord injury (SCI). The resource:www.elearnSCI.org is comprised of seven learning modules, each subdivided into various submodules. Six of the seven modules address the educational needs of all disciplines involved in comprehensive SCI management. The seventh module addresses prevention of SCI. Each submodule includes an overview, activities, self-assessment questions and references. DEVELOPMENT OF THE RESOURCE: Three hundred and thirty-two experts from The International Spinal Cord Society (ISCoS) and various affiliated societies from 36 countries were involved in developing the resource through 28 subcommittees. The content of each submodule was reviewed and approved by the Education and Scientific Committees of ISCoS and finally by an Editorial Committee of 23 experts. KEY FEATURES: The content of the learning modules is relevant to students and to new as well as experienced SCI healthcare professionals. The content is applicable globally, has received consumer input and is available at no cost. The material is presented on a website underpinned by a sophisticated content-management system, which allows easy maintenance and ready update of all the content. The resource conforms to key principles of e-learning, including appropriateness of curriculum, engagement of learners, innovative approaches, effective learning, ease of use, inclusion, assessment, coherence, consistency, transparency, cost effectiveness and feedback. CONCLUSION: www.elearnSCI.org provides a cost effective way of training healthcare professionals that goes beyond the textbook and traditional face-to-face teaching.

A crucial role of sialidase Neu1 in hyaluronan receptor function of CD44 in T helper type 2-mediated airway inflammation of murine acute asthmatic model.

CD44 is a highly glycosylated cell adhesion molecule that is involved in lymphocyte infiltration of inflamed tissues. We have demonstrated previously that sialic acid residues of CD44 negatively regulates its receptor function and CD44 plays an important role in the accumulation of T helper type 2 (Th2) cells in the airway of a murine model of acute asthma. Here we evaluated the role of sialidase in the hyaluronic acid (HA) receptor function of CD44 expressed on CD4+ T cells, as well as in the development of a mite antigen-induced murine model of acute asthma. Splenic CD4+ T cell binding of HA was examined with flow cytometry. Expression of sialidases (Neu1, Neu2, Neu3 and Neu4) in spleen cells was evaluated by quantitative real-time reverse transcription-polymerase chain reaction. Airway inflammation and airway hyperresponsiveness (AHR) were evaluated in the asthmatic Neu1-deficient mouse strain SM/J model. Splenic CD4+ T cells from asthmatic model mice displayed increased HA receptor activity of CD44 after culture with the antigen, along with characteristic parallel induction of sialidase (Neu1) expression. This induction of HA binding was suppressed significantly by a sialidase inhibitor and was not observed in SM/J mice. Th2 cytokine concentration and absolute number of Th2 cells in the bronchoalveolar lavage fluid, and AHR were decreased in SM/J mice. In conclusion, HA receptor activity of CD44 and acute asthmatic reactions, including Th2-mediated airway inflammation and AHR, are dependent upon Neu1 enzymatic activity. Our observation suggests that Neu1 may be a target molecule for the treatment of asthma.

The effect of rheumatoid arthritis on the anatomy of the female cervical spine: a radiological study.

The effect of rheumatoid arthritis on the anatomy of the cervical spine has not been clearly documented. We studied 129 female patients, 90 with rheumatoid arthritis and 39 with other pathologies (the control group). There were 21 patients in the control group with a diagnosis of cervical spondylotic myelopathy, and 18 with ossification of the posterior longitudinal ligament. All had plain lateral radiographs taken of the cervical spine as well as a reconstructed CT scan. The axial diameter of the width of the pedicle, the thickness of the lateral mass, the height of the isthmus and internal height were measured. The transverse diameter of the transverse foramen (d1) and that of the spinal canal (d2) were measured, and the ratio d1/d2 calculated. The width of the pedicles and the thickness of the lateral masses were significantly less in patients with rheumatoid arthritis than in those with other pathologies. The area of the transverse foramina in patients with rheumatoid arthritis was significantly greater than that in the other patients. The ratio of d1 to d2 was not significantly different. A high-riding vertebral artery was noted in 33.9% of the patients with rheumatoid arthritis and in 7.7% of those with other pathologies. This difference was statistically significant. In the rheumatoid group there was a significant correlation between isthmus height and vertical subluxation and between internal height and vertical subluxation.

Transglutaminase down-regulates the dimerization of epidermal growth factor receptor in rat perivenous and periportal hepatocytes.

OBJECTIVE: Recently, we found that transglutaminase 2 (TG2) might be involved in the difference in proliferative capacities between periportal hepatocytes (PPH) and perivenous hepatocytes (PVH) through down-regulation of high-affinity epidermal growth factor receptor (EGFR). However, it is uncertain whether this high-affinity EGFR contributes to the hepatocyte growth signalling pathway. Here, we have investigated the influence of TG2 on EGF-induced EGFR dimerization and its phosphorylation, which are important steps in the hepatocyte proliferative/growth signalling pathway, in PPH and PVH. MATERIALS AND METHODS: PPH and PVH were isolated using the digitonin/collagenase perfusion technique. Amounts of TG2, EGFR dimerization and its phosphorylation were determined by Western blot analysis. RESULTS: Pretreatment with monodansylcadaverine, an inhibitor of TG2, greatly increased EGF-induced EGFR dimerization and its phosphorylation in PVH compared with PPH. Conversely, treatment with retinoic acid, an inducer of TG2, significantly decreased EGF-induced EGFR dimerization and its phosphorylation with a significant increase in TG2 expression and its catalysed products, isopeptide bonds, in both subpopulations. It was found that EGFR served as a substrate for TG2. CONCLUSION: The present data showed good correlation with our previous data on EGF-induced DNA synthesis and EGFR-binding affinity to EGF. These results suggest that zonal difference in cell growth between PPH and PVH may be caused by down-regulation of EGFR dimerization and subsequent autophosphorylation through TG2-mediated cross-linking of EGFR.

Effect of combined application of bFGF and inorganic polyphosphate on bioactivities of osteoblasts and initial bone regeneration.

Basic fibroblast growth factor (bFGF) and inorganic polyphosphate (poly(P)) have been recognized as therapeutic agents that enhance bone regeneration. It has also been shown that poly(P) may enhance the mitogenic activity of bFGF. The purpose of this study is to evaluate the combined effect of bFGF and poly(P) on bioactivities of osteoblasts and initial bone regeneration in vitro and in vivo. MC3T3-E1 cells were treated with bFGF, poly(P) or bFGF+poly(P), then subjected to cell proliferation assay, alkaline phosphatase (ALP) activity measurement, quantitative real-time reverse transcription-polymerase chain reaction and Alizarin S Red staining. In an in vivo study, bFGF-, poly(P)- and bFGF+poly(P)-modified interconnected porous hydroxyapatite (IPHA) complexes were fabricated, and placed into the femurs of rabbits to evaluate new bone formation histologically and histomorphometrically. The highest enhancement of cell proliferation were observed in those treated with bFGF+poly(P) on days 5 and 7. Cells treated with bFGF+poly(P) also exhibited increased ALP activity on days 5 and 10, up-regulated mRNA levels of osteocalcin and osteopontin, and enhanced calcification when compared to the non-treated cells. In vivo, the highest bone formation ratio was observed in bFGF+poly(P)-modified IPHA complexes. This study indicated that co-application of bFGF and poly(P) may provide enhanced bone formation by modulating cell proliferation and the mineralization process. It is anticipated that a combined application of bFGF and poly(P) can provide a novel method for bone regeneration in clinical use.

Minimally invasive excision of lumbar epidural lipomatosis using a spinal endoscope.

In this report, we describe the case of a patient with a long-term radiculopathy due to epidural lipomatosis at the L3-4 intervertebral disc level. The fatty tissue was located on the dorsal side of the dural sac in the spinal canal and compressed the dural sac. The fatty tissue was removed endoscopically. After surgery, the symptoms disappeared, and neurological deficits normalized. We would like to state that epidural lipomatosis is a good candidate for minimally invasive endoscopic surgery because of its anatomic location.

Minimally invasive endoscopic removal of a herniated nucleus pulposus that had migrated to the S1 nerve root foramen.

In this report, we described an adult case with a lumbar herniated nucleus pulposus that had migrated to the S1 nerve root foramen from L5-S1 disc space. Endoscopically, the migrated mass was successfully removed after laminectomy at the S1 with a small skin incision of 20 mm in length. Unlike the other levels, the intraforaminally migrated mass along the S1 root can be excised without any removal of the facet joints; therefore, additional spinal fusion is not necessary. Thus, an S1 foraminal migrated mass can be a good surgical candidate for minimally invasive endoscopic surgery.

Minimally invasive technique for direct repair of the pars defects in young adults using a spinal endoscope: a technical note.

Pars defect (spondylolysis) of the lumbar spine can cause chronic low back pain, and it sometimes requires surgical intervention. Direct repair is selected for the surgery if young adult patients do not present significant disc degeneration and lumbar instability. In order to lessen damages of back muscles during surgery, we added the use of a spinal endoscope to the "Buck's screwing procedure" the direct repair. There are four steps in this procedure: 1) identification of the defect, 2) curettage (refresh) of the defect, 3) percutaneous insertion of the annulated screws and 4) cancellous bone grafting. All these steps can be done endoscopically. We treated 3 young adults--a baseball player, a professional cycle-racer and a sculptor--using this endoscopic procedure. There were no complications during or after the operation. Union was obtained in all defects within 3 months, and they returned to their previous activities within 6 months after the surgery.

The alpha2 type IX collagen tryptophan polymorphism is associated with the severity of disc degeneration in younger patients with herniated nucleus pulposus of the lumbar spine.

Tryptophan alleles in COL9A2 (Trp2) and COL9A3 (Trp3) have been linked to lumbar disc diseases in the Finnish population. Although such diseases consist of various pathogenetically different conditions, detailed analysis of each has not been well documented. The aim of this study was to clarify whether the collagen IX tryptophan alleles influence the symptomatic degeneration of the lumbar disc in Japanese patients with herniated nucleus pulposus. We performed a prospective study of 84 patients who underwent lumbar discectomy. The degree of disc degeneration was evaluated by magnetic resonance images in relation to the collagen IX genotype. Twenty patients (21.4%) had the Trp2 allele and no patients had the Trp3 allele. Patients under 40 years with the Trp2 allele showed more severe disc degeneration at the surgical level than did those without the Trp2 allele (odds ratio 6.00, P=0.043). In contrast, patients aged 40 years or over did not show significant association between disc degeneration and collagen IX genotype. Our results suggest that the Trp2 allele is an age-dependent risk factor for the severity of disc degeneration in younger patients with symptomatic herniated nucleus pulposus of the lumbar spine.

Preservation of C7 spinous process does not influence the long-term outcome after laminoplasty for cervical spondylotic myelopathy.

Axial pain is one of the major complications after laminoplasty, and preservation of C7 spinous process during the procedure can reduce the axial pain. However, it has not been elucidated whether laminoplasty preserving the C7 spinous process can maintain neurological improvement for a long time. The purpose of our retrospective study was to investigate the long-term neurological outcome after open-door laminoplasty preserving the C7 spinous process for cervical spondylotic myelopathy (CSM). Clinical and radiological outcomes were analysed in 42 patients who underwent open-door laminoplasty preserving C7 spinous process and followed up for more than 5 years. Neurological function was evaluated by means of the Japanese Orthopaedic Association (JOA) scoring system for cervical myelopathy. Axial pain was assessed using a visual analog scale (VAS) at the last examination. Alignment and motion of the cervical spine were measured from radiographs, and magnetic resonance imaging (MRI) was used to evaluate postoperative compression at C7. The mean JOA score was 9.4 before surgery and 12.0 at the latest follow-up. The mean VAS score in 26 patients score was 9.7/100. No compression of the spinal cord was observed in any MRI at the latest follow-up. Preservation of the C7 spinous process does not influence the long-term outcome of CSM after laminoplasty. Although we did not have a comparative group, the procedure described here should be considered as the solution.

Extruded lumbar osseous endplate causing long-term radiculopathy in an adult: an endoscopic excision.

In this report, we described an adult case that had a long-term radiculopathy due to an extruded osseous endplate of the lumbar spine at the L5-S1 intervertebral disc level. The osseous material inside the extruded material was not absorbed, and it had continued compressing the nerve root for one year. Endoscopically, the bony fragment was successfully removed. After the surgery, the patient's symptom disappeared, and neurological deficits became normalized. In conclusion, we propose that surgical intervention should be taken into account for the treatment of HNP, when the extruded material contains bony fragment such as osseous endplate.

Maternal smoking during pregnancy and genetic polymorphisms in the Ah receptor, CYP1A1 and GSTM1 affect infant birth size in Japanese subjects.

Genetic susceptibility to tobacco smoke might have relation to adverse pregnancy outcomes. To estimate the effects of maternal smoking and genetic polymorphisms on infant birth weight and length, we conducted a prospective cohort study of 293 women who delivered singleton live births in Sapporo, Japan. Birth weight and length were significantly lower among infants born to continuously smoking women having the aryl hydrocarbon receptor (AhR) wild type genotype (Arg/Arg; 211 g +/- 76 g; 1.2 cm +/- 0.4 cm, p < 0.01 and p < 0.01, respectively), the CYP1A1 variant genotype (m1/m2 + m2/m2; 170 g +/- 64 g, 0.8 cm +/- 0.3 cm, p < 0.01 and p < 0.05, respectively), or the GSTM1 null genotype (171 g +/- 58 g, 0.6 cm +/- 0.3 cm, p < 0.01 and p < 0.05, respectively). When combinations of these genotypes were considered, birth weight and length were significantly lower for infants of continuously smoking women in the AhR wild type + CYP1A1 variant group (315 g +/- 116 g; 1.7 cm +/- 0.6 cm, p < 0.01 and p < 0.01, respectively) and in the CYP1A1 variant + GSTM1 null group (237 g +/- 92 g; 1.3 cm +/- 0.5 cm, p < 0.05 and p < 0.01, respectively). These genotypes did not confer adverse effects among women who had never smoked; therefore, maternal smoking in combination with maternal AhR, CYP1A1 and GSTM1 genetic polymorphisms may adversely affect infant birth size.

Sex differences in cardiovascular and total mortality among diabetic and non-diabetic individuals with or without history of myocardial infarction.

AIMS/HYPOTHESIS: We investigated the associations of type 2 diabetes and a history of myocardial infarction (MI) with coronary heart disease, stroke, cardiovascular and total mortality, and whether these effects are different in men and women. METHODS: Study cohorts included 51,735 Finnish men and women aged 25-74 years. Smoking status and the history of MI and type 2 diabetes were recorded, and height, weight, blood pressure and serum cholesterol levels were measured at baseline. Additional data on the occurrence of diabetes and MI prior to baseline survey were obtained from national hospital discharge and drug registers through computerised register linkage. Mortality data were obtained from the national mortality register. RESULTS: During a mean follow-up period of 17.2 years, 9,201 deaths were recorded. Hazard ratios (HRs) for coronary mortality were 2.1, 4.0 and 6.4 among men with diabetes alone, men with MI alone, and men with diabetes and MI, respectively, compared with men with neither diabetes nor a history of MI. The corresponding HRs among women were 4.9, 2.5 and 9.4, respectively. The equivalent HRs for cardiovascular and total mortality were 2.2, 3.3 and 6.0, and 1.8, 2.3 and 3.7 in men, and 4.4, 2.4 and 6.5, and 3.2, 1.7 and 4.4 in women, respectively. Diabetic men and women had similar total mortality rates, whereas total mortality rates were markedly higher among men in the other three diabetes-MI categories. CONCLUSIONS/INTERPRETATION: Diabetes and MI markedly increase cardiovascular and all-cause mortality. In women, the association between diabetes and mortality was stronger than that between MI and mortality, whereas the converse was true among men.

Elevated interleukin-18 levels in bronchoalveolar lavage fluid of patients with eosinophilic pneumonia.

BACKGROUND: Interleukin (IL)-18 can induce Th2 cytokine production particularly in collaboration with IL-2. Accumulation of Th2 cells and increased levels of Th2 cytokines are found in bronchoalveolar lavage fluid (BALF) from patients with eosinophilic pneumonia (EP). To evaluate the role of IL-18 in the pathogenesis of EP, we measured the concentration of IL-2, IL-12, IL-18, and Th2 cytokines in BALF from patients with EP. METHODS: The concentrations of interferon (IFN)-gamma, IL-2, IL-5, IL-10, IL-12, IL-13, and IL-18 in BALF were measured in patients with idiopathic acute eosinophilic pneumonia (AEP), with idiopathic chronic eosinophilic pneumonia (CEP), with sarcoidosis and healthy volunteers (HV). RESULTS: The BALF concentrations of Th2 cytokines, IL-5, IL-10, and IL-13, were higher in patients with EP than in sarcoidosis and control. The IL-2 level in BALF was higher in EP than in sarcoidosis and control. The IL-18 and IL-12 (p40 + p70) levels were higher in patients with EP than sarcoidosis, while the level of IL-12 (p70) was below the detection limit in patients with EP. There was a significant correlation between IL-2 level and both IL-5 and IL-13 in BALF of patients with EP. CONCLUSIONS: Our findings suggest that IL-18 may contribute to Th2 cytokine-dominant responses in patients with EP in collaboration with IL-2.

[Computed tomography findings of pulmonary benign lesion in the peripheral region].

We evaluated computed tomography (CT) images in 22 cases of pulmonary granulomas less than 2 cm in diameter which preoperative diagnosis was difficult. In these lesions, air-containing type, irregular undulation of margin, pleural indentation, accompanying shadow and involvement of pulmonary artery was observed on CT images. The accompanying shadow and the absence of pulmonary vein relate to the lesion may have relevance in pulmonary benign lesion.

Union of defects in the pars interarticularis of the lumbar spine in children and adolescents. The radiological outcome after conservative treatment.

Lumbar spondylolysis can heal with conservative treatment, but few attempts have been made to identify factors which may affect union of the defects in the pars. We have evaluated, retrospectively, the effects of prognostic variables on bony union of pars defects in 134 young patients less than 18 years of age with 239 defects of the pars who had been treated conservatively. All patients were evaluated by CT scans when first seen and more than six months later at follow-up. The results showed that the spinal level and the stage of the defects were the predominant factors. The site of the defects in the pars, the presence or development of spondylolisthesis, the condition of the contralateral pars, the degree of lumbar lordosis and the degree of lumbar inclination all significantly affected union.

Photodynamic therapy may be useful in debulking cutaneous lymphoma prior to radiotherapy.

Photodynamic therapy (PDT) with topical 5-aminolaevulinic acid (5-ALA) is a promising new treatment for superficial malignant nonmelanoma tumours, including cutaneous malignant lymphoma. Here, we report a case of cutaneous anaplastic large cell lymphoma effectively treated by PDT with topical 5-ALA in combination with radiotherapy.

[Pulmonary sequestration associated with fungal infections; report of a case].

A 45-year-old female was admitted to our hospital complaining of cough and purulent sputum. Enhanced chest computer tomography(CT) showed that abnormal mass shadow in left lower lobe of the lung and an aberrant artery originated from the discending aorta and penetrated the lesion. Left lower lobectomy was performed and intralobar sequestration was diagnosed. Moreover, fungus which were suspected Aspergillus were found in the cystic lesion. The postoperative course was uneventful and she was discharged.