[A Case of Emphysematous Pyelonephritis Complicated by Bacterial Endophthalmitis in which Multidisciplinary Therapy Led to Preservation of the Kidney].

A 49-year-old male with untreated diabetes mellitus type 2 experienced eyesight deterioration and general malaise, and was treated for uveitis and orbital cellulitis. Later, he was taken to a local hospital via ambulance for a consciousness disorder and was diagnosed with bilateral infectious endophthalmitis, a right ureteral stone, and emphysematous pyelonephritis. He was then referred to our hospital for further examination and treatment. We immediately initiated intravenous antibiotic therapy with meropenem and glycemic control with continuous subcutaneous insulin infusion, and placed a ureteral and percutaneous drain tube into the right ureter and the emphysema, respectively. We performed a diagnostic and therapeutic vitrectomy on the patient's left eye. Urinary, blood, and vitreous cultures were positive for Klebsiella aerogenes. Abdominal contrast-enhanced computed tomography showed bilaterally comparable renal contrast enhancement. On the 60th hospital day, we performed endoscopic combined intrarenal surgery (ECIRS) and completely removed the urinary stone. Although he lost light sensitivity in his right eye, his left eyesight improved, and his blood glucose level was adequately managed by oral medication. Three months after the surgery, he was discharged from our hospital and he showed no sign of recurrence of the infection at ten months after surgery.

Predictive factors and radiological findings of adrenohepatic adhesion during laparoscopic adrenalectomy.

Purpose: This retrospective study aimed to identify predictive factors and imaging features of adrenohepatic adhesion found during laparoscopic right adrenalectomy. Materials and Methods: Altogether, 77 patients underwent laparoscopic right adrenalectomy between January 2005 and December 2018. Adrenohepatic adhesion was defined as strict adhesion that required either partial adrenalectomy with coagulation of residual tissue or partial hepatectomy to accomplish complete resection. We assessed their surgical video records to determine if adrenohepatic adhesion was present. Age, sex, body mass index, tumor size, tumor diagnosis and radiological findings (attachment between the liver and the adrenal gland, diameters of the right and left adrenal veins and its ratio) were evaluated as preoperative variables. Results: Adrenohepatic adhesion was present in 11 of the 77 patients (14.3%). Age, sex, and body mass index were not statistically significant factors. Tumor size was significantly small in adhesion group (14.2 mm vs. 25.9 mm, p=0.02). Attachment to the liver and adrenal gland was frequently seen regardless of the adhesion. The mean right/left adrenal veins diameters ratio was significantly lower in the adhesion group (0.8 vs. 1.1, p=0.01). Multivariate logistic regression analysis demonstrated the right/left adrenal veins diameters ratio was the only significant predictor of adhesion. The sensitivity, specificity, negative predictive value and positive predictive value were 0.82, 0.76, 0.43, and 0.95 respectively when the optimal cutoff value for the ratio was 0.9 (area under the curve, 0.75; 95% confidence interval, 0.60-0.90). Conclusions: The right/left adrenal veins diameters ratio was possible predictor of adrenohepatic adhesion.

[A Case of Castration-Resistant Prostate Cancer after Prostatectomy Treated with Resection of A Solitary Metastatic Site].

A 72-year-old man underwent a bilateral nerve-sparing radical retropubic prostatectomy (RRP) with pelvic lymph node dissection 11 years earlier. His prostate specific antigen (PSA) value at diagnosis was 61.024 ng/ml. Bone scans and computed tomographic (CT) scans showed no metastasis. Pathological findings and stage were adenocarcinoma, Gleason score 4+3, positive surgical margin, pT3b, and no lymph node metastasis. The postoperative PSA nadir was 0.218 ng/ml, and salvage radiotherapy (SRT, total 66 Gy) was performed six months after RRP. However, the PSA value continued to rise after SRT. Therefore, androgen deprivation therapy (ADT) was started 11 months after SRT. Nine years postoperatively, the PSA value showed a continuous rise despite ADT, and prostate cancer was considered to be castration-resistant. Although he was taking enzalutamide, his PSA value rose to 18. 271 ng/ml. Repeated bone scans and CT scans were negative. Eleven years after RRP, the fluoro-2-deoxy-D-glucosepositronemissiontomography (FDG-PET) revealed a nodule lesiondorsal to the left pubic bone. The patient underwent a resection of the lesion. Three months after the resection, his PSA level declined to 0.038 ng/ml, thus ADT was discontinued. Thirteen months after the resection, PSA re-elevation was absent, and follow-up without ADT is ongoing.

[A Case of Nivolumab-Induced Isolated Adrenocorticotropic Hormone Deficiency Presenting Dyspnea].

A 66-year-old man had undergone multiple treatments for metastatic renal cell carcinoma, including 11 cycles of nivolumab, which was discontinued because of disease progression. About three weeks after discontinuing nivolumab, he reported suffering from worsening of dyspnea. Pulse oximetry showed no desaturation. His cardiovascular and pulmonary functions were normal. His dyspnea slowly worsened with no underlying diagnosis. Two months after symptoms developed, he was diagnosed with isolated adrenocorticotropic hormone deficiency. His dyspnea disappeared soon after receiving hydrocortisone. Nivolumab-induced isolated adrenocorticotropic hormone deficiency may not present with typical symptoms, and can occur even after discontinuing nivolumab. Cortisol levels should be routinely monitored in patients who receive nivolumab.

Platelet responsiveness to in vitro aspirin is independent of COX-1 and COX-2 protein levels and polymorphisms.

Aspirin's inhibitory effect on platelet function has been shown to be highly heterogeneous. However, due to the considerable individual variation in pharmacokinetics after aspirin intake, it has been difficult to investigate the mechanism of aspirin resistance empirically. Our objective was to examine whether platelet responsiveness to in vitro aspirin treatment could be affected by cyclooxygenase (COX)-1/2 protein levels in platelets or single-nucleotide polymorphisms (SNPs), which could possibly change specific activity of enzymes and/or aspirin susceptibility. Collagen/epinephrine closure time (CEPI-CT) of PFA-100 in blood from 178 healthy males was assessed with/without aspirin. Platelet COX-1 protein levels and the sequences of COX-1 gene exons were examined in three groups categorized by CEPI-CT: PR (Poor responders to aspirin), 10 people showing the shortest CEPI-CT under aspirin; GR-High or GR-Low (good responders to aspirin with high or low platelet basal reactivity), 10 people showing CEPI-CT over 300 s under aspirin and having the shortest or longest basal CEPI-CT, respectively. We analyzed the three groups, representing phenotypic extremes, aiming to increase statistical power to investigate the possible relevance of COXs to platelet response to aspirin. Western blot analysis revealed that COX-1 was abundantly expressed in platelets at comparable levels among the three groups, whereas COX-2 was undetectable. The frequencies of nonsynonymous COX-1/2 SNPs were unlikely to explain the difference in aspirin responsiveness considering the observed genotype frequencies and wide individual variation in platelet response. These results suggest that heterogeneity in platelet responsiveness to in vitro aspirin is independent of COX-1/2 protein levels and SNPs.

Increased basal platelet activity, plasma adiponectin levels, and diabetes mellitus are associated with poor platelet responsiveness to in vitro effect of aspirin.

INTRODUCTION: Aspirin is one of the most effective antiplatelet agents and is now commonly used to prevent vascular events. In some patients, however, recurrent vascular events have been demonstrated despite aspirin therapy. Our objective was to characterize individuals showing poor response to in vitro effect of aspirin, using PFA-100. METHODS: One hundred sixty-eight healthy male subjects were analyzed. We assessed platelet function tests, including PFA-100, whole blood aggregation, and optical platelet aggregation. Also measured were hemostatic and other parameters including von Willebrand factor (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), soluble vascular adhesion molecule-1 (sVCAM-1), high sensitive C-reactive protein (hs-CRP), and adiponectin. Poor responders were defined as having a collagen/epinephrine-induced closure time (CEPI-CT) under 250 s with PFA-100 when incubated with 10 microM aspirin, whereas good responders were defined as having a CEPI-CT of more than 250 s. RESULTS AND CONCLUSIONS: PFA-100 tests revealed that 40 subjects (24%) were poor responders (PR) and 128 (76%) were good responders (GR). Poor responsiveness was significantly associated with (1) higher basal platelet activities in PFA-100, as well as in whole blood aggregation and aggregometer;(2) increased level of adiponectin (8.8+/-4.1 micro g/mL [PR] vs 7.3+/-2.9 micro g/mL [GR], p=0.010);and (3) the presence of diabetes mellitus (17.5% [PR] vs 4.7% [GR], p=0.009). Importantly, whereas 24% of the subjects showed insufficient inhibition in PFA-100 when incubated with 10 microM aspirin, almost all subjects showed maximum inhibition with 30 microM aspirin. These observations suggest that higher doses of aspirin might overcome aspirin resistance.

Long-term functional outcome of colonic J-pouch reconstruction after low anterior resection for rectal cancer.

PURPOSE: To evaluate the long-term functional outcome of colonic J-pouch reconstruction after low anterior resection (LAR) for rectal cancer in a prospective study. METHODS: We compared the functional outcome of 46 patients who underwent J-pouch reconstruction (J-group) and 49 patients who underwent straight anastomosis (S-group) after LAR for rectal cancer. We evaluated clinical function using a 17-item questionnaire about different aspects of bowel function. Physiologic reservoir function was evaluated by manovolumetry. RESULTS: Among the patients with an ultralow anastomosis (

Optimal ligation level of the primary feeding artery and bowel resection margin in colon cancer surgery: the influence of the site of the primary feeding artery.

PURPOSE: In colon cancer surgery, it is recommended that en bloc resection involving extended lymphadenectomy, characterized as a hemicolectomy, be performed by ligating the primary feeding artery at a high position and resecting proximal and distal with 5-cm to 10-cm bowel margins. However, there is little evidence to unequivocally support such extensive lymphovascular resection. METHODS: The distribution of nodal metastases was obtained by the clearing method in 164 patients with colon cancer. RESULTS: For pericolic spread, for pT1 tumors, the distance from the primary tumor to a diseased node was 2.5 cm; for pT2, the distance was less than 5 cm; for 97.0 percent of pT3 tumors and 93.3 percent of pT4 tumors with nodes involved, the distance was less than 7 cm. For central spread, for pT1 tumors, the rate of spread to central nodes was 0 percent; for pT2, the rate of spread was 20.0 percent to intermediate nodes (for tumors more than 5 cm from the feeding artery, the rate for central nodes was 0 percent); for pT3, the rate was 30.6 percent to intermediate nodes and 15.3 percent to main nodes; for pT4, the rate was 44.4 percent to intermediate nodes and 22.2 percent to main nodes. For curative resection cases with pT3 tumors more than 7 cm from the feeding artery, the rate to central nodes was 0 percent. CONCLUSIONS: In T1 tumors, central node dissection is not required, but resection with proximal and distal 3-cm margins are required; in T2, central node dissection that includes the intermediate node should be performed in addition to resection with proximal and distal 5-cm margins. In T3 and T4, central node dissection that includes the main node should be performed in addition to resection with proximal and distal 7-cm margins. However, for T2 more than 5 cm from the primary feeding artery, and for T3 more than 7 cm from the primary feeding artery, proximal and distal resection alone may be adequate.

Number versus distribution in classifying regional lymph node metastases from colon cancer.

BACKGROUND: Metastasis to regional lymph nodes from colon cancer is an important prognostic factor. In the TNM classification, node metastases are classified into three grades based on the number of metastatic nodes. In the Japanese General Rules for Clinical and Pathologic Studies on Cancer of the Colon, Rectum, and Anus (JGR), node metastases are classified into four grades based on the distribution of metastatic nodes. STUDY DESIGN: Based on the findings of node metastases in 164 patients with colon cancer obtained by the clearing method, node classifications by the JGR and TNM classifications were compared. RESULTS: The case distribution by the JGR grading was 41.5% in n (-), 29.3% in n1 (+), 18.3% in n2 (+), and 11.0% in n3 (+) disease. In the TNM classification, the distribution was 23.8% in pN1 and 34.8% in pN2 disease. The 5-year survival rate by the JGR was 98.4% in n (-), 74.3% in n1 (+), 51.2% in n2 (+), and 30.0% in n3 (+) disease; in TNM classification, this rate was 76.0% in pN1 and 45.0% in pN2 disease. CONCLUSIONS: In the classification of regional node metastases from colon cancer, the JGR classification showed a wider range in distribution and 5-year survival rate compared with the TNM system.

Physical and functional association of c-Src and adhesion and degranulation promoting adaptor protein (ADAP) in osteoclastogenesis in vitro.

c-Src plays a crucial role in osteoclastogenesis. In this study, we searched for c-Src-binding proteins using a combination of pull-down assays and mass spectrometric analysis, and identified the association of adhesion and degranulation promoting adaptor protein (ADAP) with c-Src in RAW264 cells and osteoclast precursors prepared from bone marrow cells. The kinase activity and the SH2 domain of c-Src were required for this association and Tyr807 in the extreme carboxyl terminus of ADAP was identified as a major recognition site. ADAP was found to be expressed in cells at the prefusion stage and localized mainly in the leading edge of lamellipodia and in pseudopodia. Tyrosine phosphorylation of ADAP was induced in an integrin-dependent manner, and the level was Src kinase-dependent. ADAP-knockdown RAW264 cells showed retarded migration and formed few multinucleated cells. Cas, known to be phosphorylated by c-Src, was identified as a major tyrosine-phosphorylated protein in differentiating RAW264 cells and the phosphorylation appeared to be decreased in ADAP-knockdown cells. ADAP thus may play an important role as a partner of c-Src for cell migration and progression to the multinucleated cell stage in osteoclastogenesis in vitro.

Genetic analysis of hereditary factor X deficiency in a French patient of Sri Lankan ancestry: in vitro expression study identified Gly366Ser substitution as the molecular basis of the dysfunctional factor X.

We investigated a new family with cross-reactive material-positive factor X (FX) deficiency. The proband was an 11-year-old French girl from Sri Lanka with a tendency towards severe bleeding. The FX antigen level was 67%, although the activity with extrinsic pathway was 1 U/dl. The complete nucleotide sequences of all exons and exon/intron junctions of the patient's genomic DNA revealed a homozygous G <-- A substitution in exon 8, which would result in replacement of Gly366 with Ser. The proband is the first reported case of homozygote for the FX Gly366Ser mutation. Heterozygosity for Gly366Ser substitution was previously reported in a Japanese patient (FX Nagoya 2). We studied the functional consequences by expressing mutant FX Gly366Ser protein in HEK293 cells. FX Gly366Ser was secreted into the culture media at levels similar to wild-type FX; however, mutant FX activities were only 0.04, 1.05, and 0.75% of wild-type FX upon activation by the extrinsic system, the intrinsic system, and Russell's viper venom, respectively. Moreover, the activity of FX Gly366Ser was undetectable when analyzed with chromogenic-activated FX and thrombin generation assays. These data suggest that the Gly366Ser substitution would cause a major defect in function of the FX molecule.

Protective effect of DY-9760e, a calmodulin antagonist, against neuronal cell death.

An excessive elevation of intracellular Ca(2+) levels is known to play a key role in the pathological events following cerebral ischemia. DY-9760e, 3-[2-[4-(3-chloro-2-methylphenylmethyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate, is a potent calmodulin antagonist that attenuates brain damage in focal ischemia models. In the present study, we investigated the effect of DY-9760e on neuronal cell death induced by a variety of cell-toxic stimuli that increase intracellular Ca(2+). Cell death was induced by the exposure of primary cultured neurons to excitotoxic agents such as glutamate and N-methyl-D-aspartate, membrane-depolarizing agents such as veratridine and high KCl, or thapsigargin an endoplasmic reticulum Ca(2+)-ATPase inhibitor. Treatment with DY-9760e resulted in a dose-dependent prevention of neuronal cell death elicited by excitotoxicity, voltage-gated channel opening, and inhibition of endoplasmic reticulum Ca(2+)-ATPase. These results indicate that DY-9760e can rescue neurons from various types of cell-toxic stimuli, which may contribute to attenuation of brain injury after cerebral ischemia.

Identification of novel mutations in ADAMTS13 in an adult patient with congenital thrombotic thrombocytopenic purpura.

Congenital thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) is associated with an inherited von Willebrand factor-cleaving protease (ADAMTS13 [a disintegrin and metalloprotease with thrombospondin type I domains 13]) deficiency. In this study, we identified novel mutations in the ADAMTS13 gene in a patient with TTP. The patient was a 51-year-old Japanese male who exhibited TTP symptoms at frequent intervals. The ADAMTS13 activity during acute episodes was less than 3% that of normal. The enzyme activities of the patient's father and mother were both 46%, and both parents were asymptomatic. Genetic analysis revealed that the patient was a compound heterozygote for 2 mutations. One mutation was a missense mutation in the metalloprotease domain (A250V, exon 7), and the other was a guanine to adenine substitution at the 5' end of intron 3 (intron 3 G-->A). In vitro expression studies revealed that the A250V mutation markedly reduced ADAMTS13 activity and the intron 3 G-->A mutation caused abnormal mRNA synthesis.

Detection of von Willebrand factor-cleaving protease (ADAMTS-13) in human platelets.

The hemostatic activity of von Willebrand factor (vWF) is strongly dependent on its multimeric structure, with the highest activity in 'unusually large' multimers secreted from endothelial cells. The multimeric structure is regulated by a plasma protease, vWF-cleaving protease (vWF-CP, or ADAMTS-13). ADAMTS-13 mRNA is variably expressed in liver and other tissues. Because 15-25% of circulating vWF is stored in platelets, the presence and function of ADAMTS-13 in platelets are important issues. Here we report ADAMTS-13 expression in human platelets. Western blot analysis and flow cytometric analysis on permeabilized platelets revealed the presence of ADAMTS-13 protein. Real-time PCR demonstrated that ADAMTS-13 mRNA is present in platelets of six healthy volunteers, with little quantitative difference. The presence of ADAMTS-13 in platelets may imply the functional role of this enzyme in the local regulation of platelet function at the site of vascular injury or thrombus formation, and provide a useful tool for the analysis of structure and function of this enzyme.

Influência do sombreamento no crescimento de mudas de cumaru (Dipteryx odorata (Aubl.) Willd. - Fabaceae), cultivadas em viveiro

This paper presents results of an experiment carried out in the nursery at the Tropical Silviculture Experiment Station of Inpa, in Manaus, Amazonas, Brazil, with Dipteryx odorata (Aubl.) Willd. seedlings. The objective was to assess the growth of the species in the nursery under different levels of shade. The experiment used fully randomised blocks with five treatments: two treatments with temporary shading which was removed later to provide full sun light (0%) and three treatments under shade (30%, 50% and 70%) using black polypropylene mesh. Stem diameter, height, root length, leaf, root, stem dry weights, shoot/root ratio and height/diameter ratio were assessed at three and five months after sowing. Height and root length were unaffected by shade levels at three and five months. Stem diameter was larger in full sun light, being statistically superior to the treatment with 70% shade, in both periods. Dry weight obtained under 70% shade was less than for other treatments at three months. At five months, there was a trend to increase dry weight as shade levels decreased. Smaller values of root/shoot ratio and height/diameter ratio were obtained in full sun. Dipteryx odorata, a species typical of the terra-firme (non-flooded) high forest, grows better under full sun light.

Este trabalho apresenta os resultados de um experimento realizado com mudas de Dipteryx odorata (Aubl.) Willd. no viveiro da Estação Experimental de Silvicultura Tropical, do Inpa, em Manaus, Amazonas. O objetivo foi avaliar o desempenho da espécie cultivada em viveiro sob diferentes níveis de sombreamento. O experimento foi instalado em blocos ao acaso, com cinco tratamentos: dois tratamentos com sombra temporária, passando a pleno sol e três tratamentos com sombreamento de 30%, 50% e 70%, obtidos com o uso de telas de poliolefinas, de cor preta. Aos 3 e 5 meses foram avaliados após a semeadura, diâmetro do colo, altura, comprimento das raízes, peso de matéria seca de raízes, caule e folhas e as relações altura/ diâmetro do colo e parte aérea/sistema radicular. Tanto aos 3 quanto aos 5 meses, o sombreamento não afetou o crescimento em altura e o comprimento das raízes. O diâmetro do colo foi maior sob 0% de sombreamento, sendo superior estatisticamente ao tratamento com 70% em ambos períodos. Com relação ao peso de matéria seca, o tratamento com 70% de sombreamento foi inferior aos demais na primeira medição. Na segunda medição verificou-se uma tendência de aumento do peso de matéria seca com a diminuição dos níveis de sombreamento. Os menores valores das relações altura/diâmetro do colo e parte aérea/sistema radicular foram obtidos a pleno sol. Dipteryx odorata, uma espécie típica das matas altas de terra-firme, cresce melhor a plena luz, quando cultivada em viveiro.