Online and offline health information seeking and the demand for physician services

The European Journal of Health Economics - We examine the relationship between Internet-based health information seeking and the demand for physician services, using data collected from the 28...     

Podocyte EGFR Inhibits Autophagy Through Upregulation of Rubicon in Type 2 Diabetic Nephropathy

Renal epidermal growth factor receptor (EGFR) signaling is activated in models of diabetic nephropathy (DN), and inhibition of the EGFR signaling pathway protects against the development of DN. We have now determined that in cultured podocytes, high glucose led to increases in activation of EGFR signaling but decreases in autophagy activity as indicated by decreased beclin-1 and inhibition of LC3B autophagosome formation as well as increased rubicon (an autophagy inhibitor) and SQSTM1 (autophagy substrate). Either genetic (small interfering [si]EGFR) or pharmacologic (AG1478) inhibition of EGFR signaling attenuated the decreased autophagy activity. In addition, rubicon siRNA knockdown prevented high glucose–induced inhibition of autophagy in podocytes. We further examined whether selective EGFR deletion in podocytes affected the progression of DN in type 2 diabetes. Selective podocyte EGFR deletion had no effect on body weight or fasting blood sugars in either db/db mice or nos3^−/−; db/db mice, a model of accelerated type 2 DN. However selective podocyte EGFR deletion led to relative podocyte preservation and marked reduction in albuminuria and glomerulosclerosis, renal proinflammatory cytokine/chemokine expression, and decreased profibrotic and fibrotic components in nos3^−/−; db/db mice. Podocyte EGFR deletion led to decreased podocyte expression of rubicon, in association with increased podocyte autophagy activity. Therefore, activation of EGFR signaling in podocytes contributes to progression of DN at least in part by increasing rubicon expression, leading to subsequent autophagy inhibition and podocyte injury.     

Right axillary arterial perfusion for a ruptured type B aortic dissection: Report of a case

The results of surgical treatment for a ruptured type B aortic dissection remain far from satisfactory. It is believed that additional perfusion from the right axillary artery might be more beneficial than perfusion from only the femoral artery during surgery for a ruptured thoracic aneurysm. The right axillary perfusion is more likely to perfuse the vital organs proximal to the ruptured area, and thus avoid retrograde emboli. In addition, if the open proximal method is performed, then the right axillary perfusion is able to facilitate the evacuation of air from the aortic lumen. We present herein the case of a patient in whom a ruptured type B acute aortic dissection was successfully treated by applying right axillary perfusion through a left thoracotomy.     

Total Esophagectomy versus Proximal Esophagectomy for Esophageal Cancer at the Cervicothoracic Junction

To investigate the adequate extent of esophagectomy and lymphadenectomy for an esophageal cancer localized at the cervicothoracic junction, the mortality and morbidity rates, survival rates, and patterns of recurrence were retrospectively analyzed in two groups—14 patients who underwent total esophagectomy with or without laryngectomy and 15 patients who underwent proximal esophagectomy with or without laryngectomy—at Kurume University Hospital from 1981 to 1996. Proximal esophagectomy with or without laryngectomy resulted in a lower hospital mortality rate and better overall survival for patients who underwent curative esophagectomy compared with total esophagectomy with or without laryngectomy. Multivariate analysis indicated that the extent of esophagectomy (total esophagectomy versus proximal esophagectomy) was not a prognostic factor. The incidence of recurrence was not different between the two groups. Lymph node metastasis or recurrence from such esophageal cancers was localized to the neck and upper mediastinum. For an esophageal cancer localized at the cervicothoracic junction, therefore, proximal esophagectomy with or without laryngectomy and with cervical and upper mediastinal lymphadenectomy could be better indicated for preselected patients.     

Video-assisted Thoracoscopic Lobectomy Achieves a Satisfactory Long-term Prognosis in Patients with Clinical Stage IA Lung Cancer

We designed a prospective trial to determine the long-term prognosis of video-assisted thoracoscopic (VATS) lobectomy versus conventional lobectomy for patients with clinical stage IA (T1N0M0) lung cancer. Between January 1993 and June 1994, 100 consecutive patients with clinical stage IA non-small cell lung carcinoma underwent either conventional lobectomy through an open thoracotomy (open group; n= 52) or VATS lobectomy (VATS group; n= 48). Lymph node dissections were performed in a similar manner in both groups. No significant differences were observed in the number of dissected lymph nodes between the 2 groups. Pathologic N1 and N2 disease was found in 3 and 1 patients, respectively, from the open group, and in 2 and 1 patients, respectively, from the VATS group. During the follow-up period, distant metastases and local or regional recurrences developed in 7 and 3 of the open group patients, respectively, and in 2 and 3 of the VATS group patients, respectively. Two and one of the open and VATS group patients developed second primary cancers, respectively. The overall survival rates 5 years after surgery were 85% and 90% in the open and VATS groups, respectively (log-rank test, p= 0.74; generalized Wilcoxon test, p= 0.91). VATS lobectomy with lymph node dissection achieved an excellent 5-year survival, similar to that achieved by the conventional approach.     

Coracoacromial arch decompression in rotator cuff surgery

In rotator cuff surgery it is important to obtain adequate decompression of the coracoacromial arch. However, it is difficult to localize the impingement site preoperatively. Based on histological and morphological studies and the clinical findings in 45 patients and 15 cadavers, we have tried to determine the impingement site. In addition, as a part of these investigations, we assessed the clinical outcome for 100 patients. Soft tissue decompression was indicated in 12 shoulders, anterior acromioplasty in 67 and anterior acromioplasty with coracoplasty in 21. According to Neer’s criteria there were 92 satisfactory and 8 unsatisfactory results. The mean postoperative UCLA score was 33.4 points and the results were rated excellent in 78, good in 18 and fair in 4.

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Résumé  Dans la chirurgie de la coiffe des rotateurs, il est important d’obtenir une décompression adéquate sous-acromiale, mais il est difficile de localiser la zone de conflit avant l’opération. A partir d’études histologiques, morphologiques et des conclusions cliniques chez 45 malades et 15 cadavres, nous avons essayé de déterminer l’emplacement du conflit. De plus, nous avons évalué le résultat clinique de 100 cas. La décompression des parties molles était indiquée dans 12 épaules, l’acromioplastie antérieure dans 67 et l’acromioplastie antérieure avec coracoplastie dans 21 cas. D’après les critères de NEER, il y avait 92 résultats satisfaisants et 8 médiocres. Le score UCLA moyen postopératoire était à 33,4 points avec 78 résultats jugés excellents, 18 jugés bons, et 4 médiocres.

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Accepted: 19 March 2000     

Acute cerebellar ataxia of a patient with SLE

We described a 28-year-old woman with systemic lupus erythematosus (SLE) presented with digestive tract, skin and renal symptoms and afterwards developed acute cerebellar ataxia, a paresis of the right inferior rectus muscle, left abducens paralysis and left facial palsy which seemed to be consistent with a brainstem lesion visible on magnetic resonance imaging (MRI). This lesion disappeared within 9 days of corticosteroid treatment. It is suggested that this lesion is focal edema induced by acute changes in the blood brain barrier secondary to a vasculopathy. Other causes, including local infarction, are unlikely.     

Inhibition of homodimerization of Toll-like receptor 4 by curcumin

Toll-like receptors play a key role in sensing microbial components and inducing innate immune responses. Ligand-induced dimerization of TLR4 is required for the activation of downstream signaling pathways. Thus, the receptor dimerization may be one of the first lines of regulation in activating TLR-mediated signaling pathways and induction of subsequent immune responses. LPS induces the activation of NF-kappaB and IRF3 through MyD88- or TRIF-dependent pathways. Curcumin, a polyphenol found in the plant Curcuma longa, has been shown to suppress the activation of NF-kappaB induced by various pro-inflammatory stimuli by inhibiting IKKbeta kinase activity in MyD88-dependent pathway. Curcumin also inhibited LPS-induced IRF3 activation. These results imply that curcumin inhibits both MyD88- and TRIF-dependent pathways in LPS-induced TLR4 signaling. However, in TRIF-dependent pathway, curcumin did not inhibit IRF3 activation induced by overexpression of TRIF in 293T cells. These results suggest that TLR4 receptor complex is the molecular target of curcumin in addition to IKKbeta. Here, we report biochemical evidence that phytochemicals (curcumin and sesquiterpene lactone) inhibit both ligand-induced and ligand-independent dimerization of TLR4. Furthermore, these results demonstrate that small molecules with non-microbial origin can directly inhibit TLRs-mediated signaling pathways at the receptor level. These results imply that the activation of TLRs and subsequent immune/inflammatory responses induced by endogenous molecules or chronic infection can be modulated by certain dietary phytochemicals we consume daily.     

A tumor metastasis‐associated molecule TWIST1 is a favorable target for cancer immunotherapy due to its immunogenicity

Although neoantigens are one of the most favorable targets in cancer immunotherapy, it is less versatile and costly to apply neoantigen‐derived cancer vaccines to patients due to individual variation. It is, therefore, important to find highly immunogenic antigens between tumor‐specific or associated antigens that are shared among patients. Considering the cancer immunoediting theory, immunogenic tumor cells cannot survive in the early phase of tumor progression including two processes: elimination and equilibrium. We hypothesized that highly immunogenic molecules are allowed to be expressed in tumor cells after an immune suppressive tumor microenvironment was established, if these molecules contribute to tumor survival. In the current study, we focused on TWIST1 as a candidate for highly immunogenic antigens because it is upregulated in tumor cells under hypoxia and promotes tumor metastasis, which is observed in the late phase of tumor progression. We demonstrated that TWIST1 had an immunogenic peptide sequence TWIST1_140–162, which effectively activated TWIST1‐specific CD4⁺ T‐cells. In a short‐term culture system, we detected more TWIST1‐specific responses in breast cancer patients compared with in healthy donors. Vaccination with the TWIST1 peptide also showed efficient expansion of TWIST1‐reactive HTLs in humanized mice. These findings indicate that TWIST1 is a highly immunogenic shared antigen and a favorable target for cancer immunotherapy.     

Treatment of secondary pneumothorax with interstitial lung disease: the surgical indications at the start of treatment is important

BackgroundSecondary pneumothorax with interstitial lung disease (ILD) is often difficult to treat in comparison to primary pneumothorax. The purpose of this study was to analyze the actual management and outcome, and to find the most effective treatment.MethodsAmong 180 patients with pneumothorax caused by ILD, who were managed between January 2000 and April 2021, 129 patients were included. Fifty-one patients with observation only were excluded. In the present study, a patient was considered to be cured if their chest tube could be removed.ResultsThe managements included chest tube drainage alone (n=41), pleurodesis (n=67), bronchoscopic treatment (n=14), and surgery (include overlapping cases) (n=25). The mean number of pleurodesis treatments was 2.4 (range, 1–9), and the most frequently used agent was blood-patch. All patients who received bronchoscopic treatment underwent bronchial occlusion with silicon spigots. The surgical procedures included bullectomy (n=20), lung cyst ligation (n=3), pleural covering with oxidized cellulose sheet (n=1), and spraying of fibrin glue alone (n=1). One hundred patients (77.5%) were curatively treated, 27 patients (20.9%) died, and 2 patients were transferred without chest tube removal. Among 25 patients who received surgery [including 6 patients with performance status (PS) ≥2], 24 patients (96.0%) were cured, and 1 patient died due to an acute exacerbation of ILD after surgery. The univariate analysis revealed that PS ≥2 and >3 pleurodesis treatments were significant non-curative factors, while steroid treatment before the development of pneumothorax was not.ConclusionsThe outcomes of surgery for pneumothorax in patients with ILD were good, and it is desirable to consider the surgical indications.