Relationship Between Initial Renal Function and the Inhibitory Effect of Dipeptidyl Peptidase-4 Inhibitor Treatment on Renal Function Decline.

We retrospectively investigated the renal function index of patients with type 2 diabetes mellitus (T2DM) to examine the influence of dipeptidyl peptidase-4 (DPP-4) inhibitors on renal function between patients up to early nephropathy and after overt nephropathy. Patients with T2DM (>18 years old) who had been prescribed hypoglycemic agents for ≥3 months at Gifu Municipal Hospital between March 2010 and April 2014 were included in the study. Renal function was evaluated as the estimated glomerular filtration rate (eGFR) decline from baseline at 12 months. Patients in the DPP-4 inhibitor-treated and untreated groups with an eGFR ≥60 (358 [58.2 %] and 257 [41.8 %], respectively) and eGFR <60 (115 [60.2 %] and 76 [39.8 %], respectively) were subjected to multiple logistic regression analysis. Among patients with an eGFR ≥60, no significant differences were observed in eGFR decline rates over time. However, among patients with an eGFR <60, significant decreases were observed in eGFR decline rates >10 % (6 months; odds ratio, 0.476; P = 0.043, 12 months; odds ratio, 0.413; P = 0.010). Similar results were obtained for an eGFR decline rate >20 % (12 months; odds ratio, 0.369; P = 0.049). DPP-4 inhibitors are renoprotective in patients with T2DM and an eGFR <60.

Leak-free million-fold DNA amplification with locked nucleic acid and targeted hybridization in one pot.

An isothermal cascade reaction that exponentially amplifies pre-designed, single-stranded DNA as a sensor and signal amplifier module for DNA-based computing and molecular robotics was developed. Taking advantage of the finding that locked nucleic acid can suppress problematic ab initio DNA synthesis, up to million-fold amplification rates and concurrent hybridization were achieved at a physiological temperature in a single reactor. Although the effect of locked nucleic acid introduction to the templates was complicated, undesired leak DNA amplification was generally suppressed in the amplification reaction for distinct DNA sequences. The present reaction that senses one DNA as an input and generates a large amount of another DNA as an output, exhibiting a high correlation between the molecular concentration and the amplification time, is applicable for nucleic acid quantification.

Is there association between human development index and tuberculosis mortality risk? Evidence from a spatial analysis study in the south of Brazil.

The goal of this study was to analyse the spatial pattern of tuberculosis (TB) mortality using different approaches, namely: mortality rates (MR), spatial relative risks (RR) and Bayesian rates (Global and Local) and their association with human development index (HDI), Global and its three dimensions: education, longevity and income. An ecological study was developed in Curitiba, Brazil based on data from Mortality Information System (2008-2014). Spatial scan statistics were used to compute RR and identify high-risk clusters. Bivariate Local Indicator of Spatial Associations was used to assess associations. MR ranged between 0 and 25.24/100.000 with a mean (standard deviation) of 1.07 (2.66). Corresponding values for spatial RR were 0-27.46, 1.2 (2.99) and for Bayesian rates (Global and Local) were 0.49-1.66, 0.90 (0.19) and 0-6.59, 0.98 (0.80). High-risk clusters were identified for all variables, except for HDI-income and Global Bayesian rate. Significant negative spatial relations were found between MR and income; between RR and HDI global, longevity and income; and Bayesian rates with all variables. Some areas presented different patterns: low social development/low risk and high risk/high development. These results demonstrate that social development variables should be considered, in mortality due TB.

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.

Changes in axial alignment of the ipsilateral hip and knee after total hip arthroplasty.

AIMS: We investigated changes in the axial alignment of the ipsilateral hip and knee after total hip arthroplasty (THA). PATIENTS AND METHODS: We reviewed 152 patients undergoing primary THA (163 hips; 22 hips in men, 141 hips in women) without a pre-operative flexion contracture. The mean age was 64 years (30 to 88). The diagnosis was osteoarthritis (OA) in 151 hips (primary in 18 hips, and secondary to dysplasia in 133) and non-OA in 12 hips. A posterolateral approach with repair of the external rotators was used in 134 hips and an anterior approach in 29 hips. We measured changes in leg length and offset on radiographs, and femoral anteversion, internal rotation of the hip and lateral patellar tilt on CT scans, pre- and post-operatively. RESULTS: The mean internal rotation increased by 11° (-15° to 46°) and was associated with underlying disease (OA), pre-operative range of internal rotation, gender, surgical approach, leg lengthening, and change of femoral anteversion (adjusted R(2) : 0.253, p < 0.001). The mean lateral patellar tilt increased by 4° (-5° to 14°) and was associated with age, leg lengthening, and increment of hip internal rotation (adjusted R(2): 0.193, p < 0.001). CONCLUSION: Both internal rotation of the hip at rest and lateral patellar tilt are increased after THA. Changes in rotation after THA may affect gait, daily activities, the rate of dislocation of the hip, and ipsilateral knee pain. TAKE HOME MESSAGE: Internal rotation of the hip at rest and lateral patellar tilt increase after THA.

Stable neutral radicals of planar N2O2-type dipyrrin platinum complexes: hybrid radicals of the delocalized organic π-orbital and platinum d-orbital.

Neutral radicals of N2O2-dipyrrin platinum complexes were synthesized by the reaction of dipyrrin ligands with PtCl2(cod) and successive one-electron oxidation. The radicals are very stable even under aerobic and ambient conditions. X-ray crystallographic analysis revealed the stacking array of the planar dipyrrin complex moieties. The ESR signals were broadened and significantly downfield shifted. The absorption spectra exhibited NIR bands. These results indicated a delocalized radical character with a contribution by the platinum d-orbital.

An investigation of visual hallucinations associated with voriconazole administration to patients with hematological malignancies.

Voriconazole (VRCZ) is commonly administered to treat fungal infections in patients with hematological malignancies. Some of these patients experience VRCZ-associated visual hallucinations. We conducted a retrospective survey to investigate the characteristic features of this side effect. Patients with hematological malignancies who were treated with VRCZ for a fungal infection after hospitalization at Ichinomiya municipal hospital between 1 October 2005 and 31 December 2015 were included in this study (n = 103). Fifteen of these (14.6%) reported visual hallucinations that started on day 1-7. Seven of these 15 patients developed this symptom rapidly (day 1 or 2). Three patients had transient symptoms (lasting 2-12 days), 6 patients experienced hallucinations throughout the treatment, and the duration was unknown in 6 patients. Eleven patients experienced visual hallucinations when their eyes were closed (73 %) and these disappeared when they opened their eyes. One patient had visual hallucinations with open eyes, while the state of the eyes was unknown in 3 patients. The patients saw a range of images including people, animals, landscapes, and foods; several reported seeing images like those found in movies. In addition, 9 of 15 patients (60%) with visual hallucinations had visual disturbances. This was a higher proportion than that observed in patients who did not develop hallucinations (17 of 88; 19.3 %; P < 0.05). However, we found no significant difference between the blood VCRZ concentrations of patients who developed or did not develop visual hallucinations. This study indicated that most of these patients had visual hallucinations that manifested on eye closure, and they did not progress to serious mental illness. Our findings emphasized the importance of fully explaining the features of this symptom to each patient prior to starting VRCZ administration in order to reduce anxiety. In addition, since VRCZ discontinuation will compromise patient management, therapeutic drug monitoring should be used to increase the likelihood of successful therapy.

Preliminary validation of an instrument to assess social support and tuberculosis stigma in patients' families.

SETTING: Ribeirão Preto, São Paulo, Brazil. OBJECTIVE: To develop and validate a preliminary instrument for assessing social support and tuberculosis (TB) stigma in families of TB patients. DESIGN: A literature review on social support and TB stigma was used to generate the theoretical domains for the instrument. A focus group was then conducted with TB patients and their families to revise the domains. Reviewers were invited to judge the appropriateness of the items in the instrument. A cross-sectional survey was carried out among 110 family members to assess the factorial structure using principal component analysis and confirmatory factor analysis to assess construct validity. Reliability was assessed in terms of internal consistency using Cronbach's alpha. RESULTS: After semantic validation and a pilot study, 23 items were selected for the scale. Examination of the factorial structure of the 16 items that were factorable using principal component analysis led to the extraction of two factors. The 16-item instrument was assessed for construct validity with confirmatory factor analysis, which confirmed a model with four items for each dimension. CONCLUSION: The study analysed the psychometric properties of an instrument that is still in its preliminary stages. Other studies on a similar scale in the Brazilian setting are required.

Contexte : Ribeirão Preto, Brésil.Objectif : Elaborer et valider un instrument préliminaire afin d'évaluer le soutien social et la stigmatisation liée à la tuberculose (TB) dans les familles des patients.Schéma : Une revue de littérature relative au soutien social et à la stigmatisation liée à la TB a permis de générer les domaines théoriques de l'instrument. Un groupe focal a ensuite été réalisé avec des patients tuberculeux et leurs familles afin de revoir ces domaines. Les réviseurs ont été invités à juger le caractère approprié des éléments de l'instrument. Une enquête traversable auprès de 110 membres des familles a été effectuée afin d'évaluer la structures factorielles grâce à l'analyse du composant principal, avec une analyse du facteur de confirmation qui a permis de vérifier la validité de la construction. La fiabilité a été évaluée par la cohérence interne grâce au coefficient α de Cronbach.Résultats : Vingt-trois éléments composaient l'échelle après la validation sémantique et l'étude pilote. L'exploration de la structure factorielle des 16 items qui étaient favorables grâce à l'analyse du composant principal a extrait deux facteurs. L'instrument à 16 items a été évalué en termes de validité de la construction avec une analyse du facteur de confirmation qui a confirmé un modèle à quatre items pour chaque dimension.Conclusion : L'étude a démontré les propriétés psychométriques d'un instrument encore au stade préliminaire. Cette échelle doit être testée à travers d'autres études dans le contexte brésilien.

Marco de referencia: Ribeirão Preto, en Brasil.Objetivo: Validar una herramienta preliminar de evaluación del apoyo social y los estigmas relacionados con la tuberculosis (TB) en las familias de los pacientes.Método: Mediante una recensión bibliográfica sobre el apoyo social y los estigmas relacionados con la TB se definieron los dominios teóricos de la herramienta. Luego, en un grupo de opinión conformado por pacientes con diagnóstico de TB y sus familiares se verificaron los dominios. Se invitaron revisores con el objeto de juzgar la idoneidad de los elementos de la escala. Se llevó a cabo una encuesta transversal a 110 miembros de las familias de pacientes con el propósito de evaluar la estructura factorial, mediante un análisis de componentes principales y se aplicó un análisis factorial confirmatorio a fin de apreciar la validez conceptual de la escala. Mediante un análisis de la consistencia interna se examinó la fiabilidad de la escala con medición del coeficiente α de Cronbach.Resultados: Tras la validación semántica y el estudio preliminar, la escala estaba compuesta por 23 elementos. Se exploró la estructura factorial de los 16 elementos factorizables mediante el análisis de componentes principales y se extrajeron dos factores. La validez conceptual del instrumento de 16 elementos se verificó mediante un análisis factorial confirmatorio, el cual ratificó un modelo con cuatro elementos en cada dimensión.Conclusión: El estudio puso en evidencia las propiedades psicométricas de un instrumento que se encuentra en fases preliminares de desarrollo. Es necesario poner a prueba esta escala en otros estudios en el contexto del Brasil.

Metastatic cutaneous carcinosarcoma to the tongue.

Carcinosarcoma is a rare malignant tumour composed of a mixture of carcinomatous and sarcomatous elements. Carcinosarcoma metastatic to the tongue is extremely rare. An 84-year-old woman presented with a rapidly growing mass on the tongue. She had a history of surgery for carcinosarcoma of the occipital skin 9 months before. An excisional biopsy of the tongue mass was performed, and the lesion was histopathologically diagnosed as carcinosarcoma. PET after diagnosis showed multiple hot uptakes in the whole body. The patient died of the disease 2 months after diagnosis. Therapies for patients with metastatic malignant tumours to the oral cavity are difficult, especially in aggressive case such as this. To the authors' knowledge, this is the first case of metastatic carcinosarcoma to the tongue.

Stereospecific oxidation of the (S)-enantiomer of RS-8359, a selective and reversible monoamine oxidase A (MAO-A) inhibitor, by aldehyde oxidase.

In a previous paper by the authors on RS-8359, a new selective and reversible monoamine oxidase A (MAO-A) inhibitor, it was reported that the (S)-enantiomer of RS-8359 is rapidly eliminated from rats, monkeys and humans as a result of the formation of a 2-oxidative metabolite. The present study investigates the properties of the enzyme responsible for the 2-oxidation of RS-8359. Subcellular localization, cofactor requirement and the inhibitory effects of typical compounds were studied using rat liver preparations. In addition, the enzyme was purified from rat liver cytosol for further characterization. The enzyme activity was localized in the cytosolic fraction without the need for any cofactor and was extensively inhibited by menadione, chlorpromazine and quinacrine. The purified enzyme was also a homodimer with a monomeric molecular weight of 140 kDa and it had an A280/A450 ratio of 5.1 in the absorption spectrum. The results suggest that the enzyme responsible for the biotransformation of RS-8359 to give the 2-keto derivative is aldehyde oxidase (EC 1.2.3.1). The reaction of aldehyde oxidase is highly stereoselective for the (S)-configuration of RS-8359 and the (9R)-configuration of cinchona alkaloids.

[Aortic valve replacement presence of anti-Jr(a) antibody].

A 65-year-old female with a heart murmur developed progressive symptom of chest oppression. She was diagnosed severe aortic valve stenosis with echocardiogram. Antibody screening revealed anti-Jr(a) antibody. Preoperatively, erythropoietin was administered. Over 14 days, a total 1,000 ml of her blood was drawn and stored for autologous transfusion. The aortic valve was replaced with ATS mechanical valve [18 mm advanced performance (AP)]. Following surgery, her stored blood was administered to him. But her HCT was 17% on the 1st postoperative day. Frozen thawed red cells were transferred 7th postoperative day.

[Surgical treatment for left ventricular false aneurysm caused by infective endocarditis; report of a case].

A 24-year-old man who had left ventricular (LV) false aneurysm, which is caused by mitral valve infective endocarditis, underwent aneurysmectomy, direct closure of aneurysmal mouth and concomitant mitral valve replacement. Post-operative course was uneventful. It has been reported that the etiology of this false aneurysm was due to the vegetations' friction, which could have caused an initial endocardial ulceration that progressively expanded into the myocardium. The false aneurysmal wall should be completely removed in order to eliminate the possibility of recurrence of the infective endocarditis. We believe that the surgical treatment should be carried out as soon as possible after completion of diagnosis because the aneurysmal wall is usually quite thin and could rupture easily.

[Prosthetic valve endocarditis after aortic valve replacement with freestyle stentless xenograft].

A 52-year-old man underwent aortic valve replacement with freestyle stentless xenograft, using subcoronary technique for active infective endocarditis in June, 2001. Eighteen month later he had late prosthetic valve endocarditis associated with aortic annular abscess due to Staphylococcus epidermidis infection. The abscess was debrided and gelatin-resorcin-formalin glue (GRF glue) was injected into the abscess cavity. Abscess cavity was closed with continuous running suture of 3-0 polypropylene stitches. Finally the aortic valve was replaced with ATS mechanical valve (20 mmAP). After administration of vancomycin and gentamicin for 4 weeks, he discharged on 57th postoperative day in good condition. We strongly suggest that GRF glue is essential to close the aortic annular abscess of combined with aortic regurgitation due to active infective endocarditis.

[Thymic carcinoma (mixed small cell undifferentiated squamous cell carcinoma); report of a case].

A 52-year-old man was admitted to our hospital on October, 1997 with complains of left anterior chest pain. A chest X-ray and computed tomography on admission showed evidence of a mass in the left anterior mediastinum. The patient was treated with combination chemotherapy [cisplatin (CDDP), etoposide (VP-16)] and radiation therapy (2 gray x 25 days), preoperatively. Median sternotomy revealed a tumor invading into the left anterior chest wall, the pericardium, and partial pleura. The tumor was extirpated with combined resection of invaded organs. Microscopically and immunohistochemically, the tumor was diagnosed mixed small cell and undifferentiated squamous cell carcinoma documented by Snover et al. The patient was discharge on March 1998, but 2 years later after operation, he was dead by recurrent. We reported a rare case of thymic carcinoma.

Renal involvement in rheumatoid arthritis: analysis of renal biopsy specimens from 100 patients.

Abstract We analyzed renal biopsy specimens from 100 patients to evaluate the characteristics of renal involvement in patients with rheumatoid arthritis (RA). Membranous nephropathy (MN) was the most common renal histological pattern (31%). Mesangial proliferative glomerulonephritis (GN) was found in 21% of cases (IgA nephropathy 12%, non-IgA GN 9%), minor changes in 17%, renal amyloidosis in 11%, interstitial nephritis in 9%, sclerotic GN in 4%, and crescentic GN in 2%. MN was relatively more frequent in men than in women, and most developed nephrotic syndrome, while a few developed renal failure. Disease-modifying antirheumatic drugs (DMARDs) correlated with MN in 26 of 31 cases. Mesangial proliferative GN showed high-grade hematuria. Amyloidosis correlated with long duration of RA; approximately half of the cases with amyloidosis also had nephrotic syndrome, and 82% developed renal failure. Of the 100 patients, 82% showed some tubulo-interstitial changes, which might be related to non-steroidal anti-inflammatory drugs. Because renal lesions in RA are very diverse, and early stage cases of MN and amyloidosis can be detected only by histological examinations, renal biopsy should be performed in cases with continuous urinary abnormalities or progressive renal failure.

Artificial ion channels showing rectified current behavior.

Voltage-dependent artificial ion channels 3 and 4 were synthesized. Two cholic acid derivatives were connected through a m-xylylene dicarbamate unit at 3-hydroxyl groups. Asymmetries were introduced by terminal hydrophilic groups, carboxylic acid and phosphoric acid for 3 and hydroxyl and carboxylic acid for 4. Under basic conditions, these headgroups in 3 and 4 are expected to be dissociate into -1/-2 (pH 8.2) and 0/-1 (pH 7.2), respectively. Single ion channel properties were examined by a planar bilayer lipid membrane method under symmetrical 500 mM KCl at pH 8.2 or 7.2. When 3 and 4 were introduced into the bilayer membrane under application of positive voltage (a positive-shift method), the current values at positive applied voltage were larger than the corresponding ones at the negative applied voltage. The current-voltage plots were fitted by curves through a zero point to show clear rectification properties. The direction of rectification could be controlled by positive- or negative-shift methods. Vectorial alignment of terminal headgroup charges by the voltage-shift incorporation is essential for giving voltage-dependent rectified ion channels.

Erythema multiforme associated with cytomegalovirus infection in nonimmunosuppressed patients.

BACKGROUND: It is widely known that cytomegalovirus (CMV) primarily brings about subclinical and asymptomatic infection in the early stages of life and can cause various dermatological and systemic disorders under immunosuppressed conditions. Nonimmunosuppressed individuals very rarely present with cutaneous CMV involvement. OBJECTIVE: In the present study, we described the clinical characteristics of 5 nonimmunosuppressed adult patients with positive IgM antibody to CMV. METHODS: The systemic symptoms and dermatological features of these 5 patients were described. Laboratory examinations including blood cell counts, liver and renal functions were performed. IgG and IgM antibodies to CMV were also examined at the first consultation and 2-3 months after the skin eruption. Polymerase chain reaction for CMV DNA was performed in the skin samples of the patients. RESULTS: All 5 patients had fever and complained of a sore throat. Multiple exudative erythema and target lesions with itching were observed mainly on the extremities. These symptoms and eruptions disappeared within 1 week after the onset and IgM antibody titers significantly decreased after 2-3 months. IgG antibody to CMV was already positive in 3 cases but was negative in 2 cases at the initial consultation. CONCLUSION: We propose that CMV infection may cause erythema multiforme by primary, recurrent infections or reactivation of CMV even in nonimmunosuppressed adults.

Immunomodulation based on a two-way paradigm with deoxyspergualin alleviates graft-versus-host reaction in small-bowel transplantation in rats.

In this study, we investigated whether or not deoxyspergualin used as donor pretreatment, with and without pretreatment using bone-marrow-cell injection, could alleviate graft-versus-host reaction (GVHR) following small-bowel transplantation in an unidirectional GVHR model with Lewis (LEW)-to-F1 rats. In addition, we studied the effect of deoxyspergualin plus bone-marrow-cell donor pre-operative treatment in combination with recipient postoperative treatment using deoxyspergualin. When the donor was pretreated with bone-marrow cells from recipient rats, the recipient died at 7.2+/-1.4 days, showing significantly shorter survival compared with the control group. Deoxyspergualin, when employed either alone as recipient post-treatment or as donor pretreatment, both with and without additional pretreatment with F1 recipient bone-marrow-cell injection, did not result in significant prolongation of recipient survival. The combination of donor pretreatment with deoxyspergualin plus F1 bone-marrow-cell injection followed by post-operative deoxyspergualin administration, however, resulted in significant prolongation in recipient survival compared with control (26.1+/-1.7 days). In addition, no severe cutaneous lesions on GVHR were seen throughout the observation period. This suggests that donor pretreatment with deoxyspergualin and recipient bone-marrow-cell injection combined with postoperative deoxyspergualin administration can lead to resistance to GVHR after parent-to-F1 small-bowel transplantation.