Complement profile in microscopic polyangiitis and granulomatosis with polyangiitis: analysis using sera from a nationwide prospective cohort study.

OBJECTIVE: The complement cascade, especially the alternative pathway of complement, has been shown in basic research to be associated with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). We aimed to elucidate relationships between serum complement components and clinical characteristics in AAV. METHOD: In a nationwide prospective cohort study (RemIT-JAV-RPGN), we measured the serum levels of C1q, C2, C3, C3b/iC3b, C4, C4b, C5, C5a, C9, factor B, factor D, factor H, factor I, mannose-binding lectin, and properdin in 52 patients with microscopic polyangiitis (MPA) and 39 patients with granulomatosis with polyangiitis (GPA). RESULTS: The properdin level of MPA and GPA was significantly lower than that of healthy donors. The properdin level was negatively correlated with the Birmingham Vasculitis Activity Score (BVAS) (ρ = -0.2148, p = 0.0409). The factor D level at 6 months was significantly positively correlated with the Vasculitis Damage Index (VDI) at 6, 12, and 24 months (ρ = 0.4207, 0.4132, and 0.3115, respectively). Patients with a higher ratio of C5a to C5 had higher neutrophil percentage and serum immunoglobulin G levels, and significantly lower creatinine levels. Cluster analysis divided the MPA and GPA patients into three subgroups. A principal component (PC) analysis aggregated 15 types of complements into alternative pathway-related PC 1 and complement classical pathway and common pathway-related PC 2. CONCLUSIONS: The serum levels of properdin and factor D were correlated with the BVAS and the VDI in MPA and GPA, respectively. Our analyses suggested the pathological heterogeneity of MPA and GPA from the aspect of complement components.

Factors predictive of long-term mortality in lupus nephritis: a multicenter retrospective study of a Japanese cohort.

BACKGROUND: Lupus nephritis (LN) is a major determinant of mortality in systemic lupus erythematosus (SLE). Here we evaluated the association between complete renal response (CR) and mortality in LN. METHODS: We retrospectively analyzed the cases of 172 of 201 patients with LN for whom data on the therapeutic response at 6 and 12 months after induction therapy were available. The patients underwent a renal biopsy at Nagasaki University Hospital and community hospitals in Nagasaki between the years 1990 and 2016. We determined the CR rates at 6 and 12 months after induction therapy initiation and evaluated the predictive factors for CR and their relationship with mortality. We performed univariate and multivariable competing risks regression analyses to determine the factors predictive of CR. The patients' survival data were analyzed by the Kaplan-Meier method with a log-rank test. RESULTS: The median follow-up duration after renal biopsy was 120 months (interquartile range: 60.3-191.8 months). The 5-, 10-, 15- and 20-year survival rates of our cohort were 99.3, 94.6, 92.0 and 85.4%, respectively. During follow-up, nine patients (5.2%) died from cardiovascular events, infection, malignancy and other causes. The multivariate analysis revealed that the following factors were predictive of CR. At 6 months: male gender (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.08-0.65, p = 0.0028), proteinuria (g/gCr) (OR 0.83, 95% CI 0.71-0.97, p = 0.0098) and index of activity (0-24) (OR 0.84, 95% CI 0.71-0.99, p = 0.0382). At 12 months: male gender (OR 0.25, 95% CI 0.09-0.67, p = 0.0043) and index of activity (0-24) (OR 0.82, 95% CI 0.69-0.98, p = 0.0236). The Kaplan-Meier analysis showed that compared to not achieving CR at 12 months, achieving CR at 12 months was significantly correlated with the survival rate (OR 0.18, 95% CI 0.04-0.92, p = 0.0339). CONCLUSIONS: Our results suggest that the survival rate of patients with LN is associated with the achievement of CR at 12 months after induction therapy, and that male gender and a higher index of activity (0-24) are the common predictive factors for failure to achieve CR at 6 and 12 months.

Complete renal response at 12 months after induction therapy is associated with renal relapse-free rate in lupus nephritis: a single-center, retrospective cohort study.

BACKGROUND: Lupus nephritis (LN) is a major risk factor for overall morbidity and mortality in systemic lupus erythematosus (SLE). METHODS: We retrospectively analyzed cases of proliferative and membranous LN patients who underwent a renal biopsy at our hospital in 1993-2016. We analyzed the association between complete renal response (CR) rates at 12 months after induction therapy and predictive factors for CR and their association with renal flares. RESULTS: Of the 95 cases analyzed, we were able to track the therapeutic responses of 81 patients at 12 months after their induction therapy. The median follow-up duration after renal biopsy was 51 months (interquartile range: 16.5-154.5 months). The Cox proportional hazards model showed that, compared to not attaining CR at 12 months, the attainment of CR at 12 months was correlated with being free from renal flares. The multivariate logistic analysis revealed that the predictive factors for CR at 12 months were the anti-La/SSB antibodies (U/ml) (odds ratio (OR) 1.22, 95% confidence interval (CI) 1.01-1.63, p = 0.0220), blood urea nitrogen (BUN) (OR 0.68, 95% CI 0.44-0.90, p = 0.00048) and serum ß2 microglobulin (MG) (OR 0.26, 95% CI 0.06-0.74, p = 0.00098) levels. CONCLUSIONS: Among LN patients, being free from renal flares was associated with attaining CR at 12 months after induction therapy. Anti-La/SSB antibodies were a positive predictive factor, and BUN and serum ß2MG levels were negative predictive factors of CR at 12 months.

Development of Collaterals to the Spinal Cord after Endovascular Stent Graft Repair of Thoracic Aneurysms.

OBJECTIVES: In thoracic and thoraco-abdominal aortic aneurysm repair, spinal cord injury (SCI) is devastating. Detection of the Adamkiewicz artery might be important for preventing SCI. Although thoracic endovascular stent grafts often occlude the segmental artery, the incidence of SCI in thoracic endovascular aortic repair is thought to be low compared with open repair. This study aimed to evaluate how the Adamkiewicz artery is supplied after segmental arteries are occluded by stent grafts. METHODS: From March 2007 to August 2015, 32 patients were enrolled whose segmental arteries that were connected to the Adamkiewicz arteries were occluded by stent grafts. Segmental arteries, Adamkiewicz arteries, collateral circulation into the Adamkiewicz arteries, and anterior spinal arteries were pre- and post-operatively evaluated by computed tomography angiography. RESULTS: Post-operatively, Adamkiewicz arteries were detected in 24 (75%) patients, except for two patients with paraplegia and six without paraplegia. Post-operative Adamkiewicz arteries were the same as pre-operative Adamkiewicz arteries, except for one Adamkiewicz artery that was located at two vertebral levels below the pre-operative level. SCI occurred in two (6.3%) patients. The distribution of feeding arteries into the Adamkiewicz artery post-operatively was divided into three patterns as follows: a segmental artery below the distal landing zone of the stent graft (53%), branches of the left subclavian artery (33%), and a branch of the left external iliac artery (13%). CONCLUSIONS: The length of the stent graft should be as short as possible. Blood supply to the left subclavian artery should be maintained because segmental arteries below the segmental artery occluded by the stent graft and branches of the left subclavian artery can become collaterals post-operatively.

A mild hand cleanser, alkyl ether sulphate supplemented with alkyl ether carboxylic acid and alkyl glucoside, improves eczema on the hand and prevents the growth of Staphylococcus aureus on the skin surface.

OBJECTIVE: Washing the hands using cleansers with antiseptic materials is the most popular method for hand hygiene and helps maintain health by preventing food poisoning and bacterial infections. However, repeated hand washing tends to induce eczema of the hand, such as dryness, cracking and erythema. Moreover, eczema on the hand leads to increased levels in Staphylococcus aureus (S. aureus) on the skin surface in contrast to expectations. Thus, mild hand cleansers which induce less eczema even with repeated washings are desired. Here, we evaluated the efficacy of a hand cleanser formulated with alkyl ether sulphate (AES), alkyl ether carboxylic acid (AEC) and alkyl glucoside (AG) that contains isopropyl methylphenol (IPMP) on skin symptoms and S. aureus levels. METHODS: Eczema of the hand and the presence of S. aureus on the skin surface were analysed prior to and following 4 weeks of usage of the hand cleanser. A soap-based hand cleanser with IPMP was used as a reference cleanser. Eczema and cutaneous conditions were evaluated by visual grading, transepidermal water loss (TEWL), stratum corneum moisture-retention ability (MRA) and skin surface pH. RESULTS: The repeated use of the soap-based hand cleanser significantly worsened the hand dryness, scaling and cracks on the tips of the fingers and significantly increased the TEWL and decreased the MRA. In contrast, usage of the test cleanser only induced a significant increase in skin dryness but did not induce skin scaling or cracking and did not increase TEWL or decrease the MRA. Corresponding to these changes in skin symptoms, the presence of S. aureus increased the following use of the reference cleanser but not the test cleanser. There was no significant difference in skin surface pH between the two cleansers. Moreover, the increase in S. aureus was significantly correlated to the worsening of skin dryness and scaling. CONCLUSION: These results suggest that not only antimicrobial activity but also the mildness, which minimizes cutaneous effects, are important for hand cleansers to prevent the growth of S. aureus. The cleanser formulated with AES, AEC and AG containing IPMP is mild and is effective to promote hand hygiene.

Early and mid-term results of total laparoscopic bypass for aortoiliac occlusive lesions.

AIM: The aim of this study was to investigate the early and mid term results of total laparoscopic bypass for aortoiliac occlusive lesions. METHODS: From December 2001 to January 2007, we performed 32 laparoscopic bypasses for aortoiliac lesions. The mean age was 52.9 years. Clinical stages included: severe intermittent claudication (N.=24) ischemic rest pain (N.=5) and tissue loss or gangrene (N.=3). According to the TASC classification, the lesions were type B in three cases, C in nine cases and D in 20 cases. Graft patency was controlled by means of duplex scan before discharge and during the follow-up. The patency rates were calculated using Kaplan-Meier analysis. RESULTS: In 27 out of 32 patients the total laparoscopic bypass was successful (84%). Conversion was necessary in five patients. The mean operative time was 338 minutes (range, 200-620 minutes), the mean aortic clamping time was 73 minutes (range, 35-144 minutes). Mortality was 0%. The postoperative course was uneventful in 19 patients (70%). The mean follow-up was 32.1 months. In this period we had two deaths, one from breast cancer after 12 months. The second patient has committed suicide after 48 months. Two graft occlusions occurred at 3 and 21 months. No other late complications were observed. The primary and secondary graft patency rate was estimated by Kaplan-Meier analysis at 92% and 96% on the first year and 87% and 93% at three years, respectively. CONCLUSION: Early and mid-term results of total laparoscopic bypass are good in selected patients and comparable to these of conventional surgery.

Late referrals to home palliative care service affecting death at home in advanced cancer patients in Japan: a nationwide survey.

BACKGROUND: To identify factors influencing place of death among home palliative care patients with advanced cancer, focusing on the timing of referrals from hospital to home care settings. METHODS: A cross-sectional nationwide questionnaire survey was conducted on home palliative care patients at 1000 randomly selected home care agencies in Japan. A total of 568 responses were analyzed (effective response rate, 69%). RESULTS: Multivariate logistic regression analysis revealed that (i) predischarge health care supports in hospital (e.g. early referral 8 days or more before discharge; clear explanation by hospital staffs to patients and families regarding discharge to live and die at home) and (ii) postdischarge health care supports after transferring home care (e.g. signing a 24-h support insurance contract of network between primary physician and nurse as a home palliative care team; primary nurse consultation with primary physician >3 times during the first week after discharge) have an effect on place of death among home palliative care patients. CONCLUSION: An early and carefully coordinated referral support system for smooth discharge by hospital staffs as well as intensive and highly qualified support just after discharge by the home care team would help to increase the number of patients who could die at home.

Cloning and expression of the L-1-amino-2-propanol dehydrogenase gene from Rhodococcus erythropolis, and its application to double chiral compound production.

The gene encoding NADP(+)-dependent L-1-amino-2-propanol dehydrogenase (AADH) of Rhodococcus erythropolis MAK154 was cloned and sequenced. A 780-bp nucleotide fragment was confirmed to be the gene encoding AADH by agreement of the N-terminal and internal amino acid sequences of the purified AADH. The gene (aadh) codes a total of 259 amino acid residues, and the deduced amino acid sequence shows similarity to several short-chain dehydrogenase/reductase family proteins. An expression vector, pKKAADH, which contains the full length aadh was constructed. Escherichia coli cells possessing pKKAADH exhibited a 10.4-fold increase in specific activity as to catalysis of the reduction of (S)-1-phenyl-2-methylaminopropan-1-one (MAK), as compared with that of R. erythropolis MAK154 induced by 1-amino-2-propanol (1 mg/ml). Coexpression of aadh with a cofactor regeneration enzyme (glucose dehydrogenase) gene was also performed, and a system for sufficient production of d-pseudoephedrine from racemic MAK was constructed.

Vascular endothelial growth factor expression in pituitary adenomas.

Vascular endothelial growth factor (VEGF) is known to be a mediator of angiogenesis and vascular permeability. A cystic component and hemorrhage are often found in pituitary adenomas. In the present study we assess the VEGF expression based on immunohistochemical examinations in 48 pituitary adenomas. All the adenomas showed some VEGF immunoreactivity mainly in the cytoplasm of tumor cells. Of the 48 adenoma-cases, 16 cases had a strong VEGF immunoreactivity, 26 cases had a moderate one, and 6 cases had a weak one. On the MR images, a cystic component was found in 16 cases (33.3%), and a hemorrhage was found in 18 cases (37.5%). The VEGF immunoreactivity had a significant relationship with the cystic component but neither the hemorrhage, size, recurrence, or HE classification. These findings suggest that VEGF might play a potential role in the pathogenesis of cystic formation in pituitary adenomas.

[Subglottic granuloma with extubating mini-trach II: report of a case].

A case of subglottic granuloma after extubating Mini-trach II is described. The patient went aorto-coronary bypass and Mini-trach II was inserted for suction of sputum. Mini-trach II was extubated 6 days after insertion. The patient complained of dyspnea 3 months later. Examination showed subglottic granuloma. First, we burned the granuloma by laser under local anesthesia. Because the visual field was not good due to vocal cord movement, we failed to resect the granuloma completely. Therefore, we performed laryngo microsurgery under general anesthesia and resected the granuloma perfectly. The patient is in good health without signs of recurrence 6 months after granuloma removal. When we used Mini-trach II, the most important issues are insertion to the cricothyroid membrane, preventing infection, and careful follow-up after removing the Mini-trach II.

Video-assisted thoracic lobectomy by the substernal hand-assisted method for a metastatic lung tumor.

In lobectomy by video-assisted thoracic surgery (VATS), the surgeon is required to have experience and a high degree of skill in performing the operation. We applied substernal hand-assisted thoracoscopic lobectomy to remove a metastatic lung tumor that originated from colon cancer in one patient and obtained satisfactory results. This method compensates for a current limitation of VATS lobectomy, namely, the fact that the surgeon cannot touch the lesion. The reported method is safe and useful for thoracoscopic surgery. It can be performed easily, even if the surgeon is not experienced in performing VATS lobectomy.

Hand-assisted thoracoscopic resection for anterior mediastinal masses.

We report three cases of anterior mediastinal disease (pericardial cyst, thymoma, and myasthenia gravis) in which we used a hand-assisted method in combination with thoracoscopic resection via an infrasternal approach in order to improve the maneuverability and safety of the operation. This technique combines the advantages of both thoracoscopic and incisional resection. It shows promise of becoming a less invasive operation that can be used to treat certain mediastinal tumors, both malignant and benign.

[Critical ischemia of the leg. A technique for distal anastomosis in a a small caliber artery]. / Ischémie critique des membres inférieurs. Un artifice pour anastomose distale sur artère de petit calibre.

CRITICAL ISCHEMIA OF THE LOWER LIMBS: This type of lesion, which spontaneously progresses to gangrene and amputation, is encountered more and more frequently. Emergency endoluminal revascularization or bypass surgery is required. When conventional endoluminal techniques cannot be used, a distal graft using the autologous saphenous vein is a promising alternative to achieve patent vascularization and salvage the limb. IF VENOUS MATERIAL IS NOT AVAILABLE: Usable venous material is not always available due to varicosities, thrombus formation, small size or previous surgery (stripping, coronary surgery, prior revascularization procedure); rates reported range from 20 to 40%. For such patients, other veins (external saphenous, arm veins, superficial femoral veins) may be useful but are not always appropriate for distal repair. Different prostheses might also be used but again do not always provide improved permeability. Most teams however use a polytetrafluoroethylene stent for revascularization of the distal leg. Different technical improvements favor success of prosthetic bypasses, but when used below the knee, flow remains less satisfactory than with venous bypasses. VEIN CUFFS: This procedure is a common adjuvant technique positioning a venous cuff between the recipient artery and the prosthesis. The cuff avoids the direct contact between the prosthesis and the fragile artery that is often difficult to suture. RESULTS: Several series have demonstrated that the rate of success of vein cuff procedures remains lower than venous bypass procedures, but also that flow is better than with simple femorotibial prostheses. PATHOGENIC HYPOTHESES: The reduction of the neo-intimal hyperplasia observed in experimental models is insufficient to explain entirely the observed in vivo benefit. The fact that the suture is easier to make is one possible reason. Indeed the rate of failure of simple prosthetic bypass surgery is high in the immediate postoperative period. These cases of thrombosis result from technical insufficiencies and are undoubtedly overcome by the use of the venous cuff.

Participation in psychosocial group intervention among Japanese women with primary breast cancer and its associated factors.

Though psychosocial group intervention is considered in the West to be an important source of support for reducing psychosocial distress in cancer patients, in Asian countries, there has been no research as yet on the needs for such intervention. This study investigated the level of participation and interest in psychosocial group intervention plus any associated factors in 151 primary breast cancer patients. All were less than 65 years old at 4-18 months post-surgery. Of the 126 subjects who responded (response rate 83%), 53 (42%) participated (participants) and 73 (58%) did not (non-participants). Participation was greater among those with a high level of anxiety measured by the Hospital Anxiety and Depression Scale (HADS) (odds ratio [OR], 3.25; 95% confidence interval [CI], 1.07-10.42), those who had undergone surgery within the last 12 months (OR, 3.10; 95% CI, 1.35-7.55), and those who were 50-65 years old (OR, 3.08; 95% CI, 1.33-7.66). Among the non-participants, 53 (73%) were interested in the intervention while 20 (27%) were not. Non-participants without any interest in the psychosocial group intervention had significantly higher anxiety levels than those with interest (t=-2.08; df=71; p=0.03). These results suggest that most Japanese breast cancer patients who need psychological support can be sought out by asking whether they are willing to participate in a psychosocial group intervention. However, the minority not interested in any psychological group intervention might need other supports such as medication or individual psychotherapy.

Peduncular hallucinosis due to a pineal meningioma. Case report.

The authors report the case of a 53-year-old woman who experienced visual hallucinations diagnosed as peduncular hallucinosis (PH). The cause of the PH was compression of the quadrigeminal plate and/or the splenium due to a meningioma originating from the falcotentorial junction (pineal meningioma). The nature of the visual hallucinations was depicted in drawings created by the patient herself. This is the first report of PH caused by a tumor located in the pineal region.

Evaluation of spontaneous intracranial hypotension: assessment on ICP monitoring and radiological imaging.

We describe two recent cases of spontaneous intracranial hypotension. A 38-year-old woman developed a severe postural headache. Magnetic resonance imaging (MRI) showed marked dural enhancement. Histopathological findings of dural biopsy showed numerous dilated vessels in the dura, rather than hypertrophic change. Lumber CSF pressure was 5 cmH2O and RI cisternography suggested CSF leakage. A 58-year-old woman with postural headache and vertigo had bilateral subdural haematoma associated with diffuse dural enhancement on MRI. Lumber CSF monitoring confirmed persistent low pressure ranging from 0-5 cm H2O. MRI myelography revealed multiple CSF pouches along the whole spinal axis. CSF leakage was demonstrated on Radioisotope (RI) cisternography. Both cases described in this report were diagnosed as spontaneous intracranial hypotension caused by CSF leakage from spinal meningeal diverticula and were successfully treated by intravenous Factor XIII administration.

Comparison of the expression of cell surface poly-N-acetyllactosamine-type oligosaccharides in PC12 cells with those in its variant PC12D.

To explore the biological role of carbohydrate chains in the process of nerve cell differentiation, we carried out a characterization of the carbohydrate structure of glycoproteins by comparing conventional PC12 cells with variant cells (PC12D). In vitro metabolic labeling of cells with either [(3)H] glucosamine or [(3)H] threonine, together with tomato lectin staining, revealed that nerve growth factor (NGF) stimulation caused a decrease in the poly-N-acetyllactosamine synthesis of high-molecular-weight glycopeptides from PC12 cells. By comparison, the amount of glycopeptides with poly-N-acetyllactosamine from PC12D cells was already significantly low and it was not changed by NGF stimulation. By assaying the glycosyltransferases that participate in poly-N-acetyllactosamine synthesis, the decrease in the amount of the poly-N-acetyllactosamine in PC12D cells as well as NGF-stimulated PC12 cells could be accounted for by a reduction in the activity of poly-N-acetyllactosamine extension enzyme (GnT-i), because the amount of poly-N-acetyllactosamine in both cells precisely correlated with changes in GnT-i activity, whereas the activities of N-acetylglucosaminyltransferase V (GnT-V) and beta 1-4 galactosyltransferase remained unchanged. These results demonstrate that the decrease in poly-N-acetyllactosamine synthesis in PC12 cells occurred prior to neurite formation, whereas PC12D cells were insensitive to this effect. Next, we showed that GnT-i but not GnT-V catalyzed a rate-limiting reaction in the expression of poly-N-acetyllactosamine chains, especially in pheochromocytoma.