Early-onset acute kidney injury is a poor prognostic sign for allogeneic SCT recipients.

Acute kidney injury (AKI) following stem-cell transplantation (SCT) contributes to a poor prognosis, yet its impact may vary depending on the timing of AKI onset. A prospective cohort study was performed to understand the significance of the onset timing in 103 allogeneic SCT (allo-SCT) recipients. AKI prior to stem-cell engraftment was defined as early AKI and subsequently occurring AKI as late AKI. Propensity score (PS) for early AKI was calculated using a logistic regression model to reduce confounding effects related to differences in clinical background between the early and late AKI groups. The cumulative incidences of early and late AKI were 22.3% and 54.9%, respectively. Non-relapse mortality (NRM) was 39.1% and 7.0%, and overall survival (OS) was 56.5% and 90.9% in early and late AKI at 100 days after AKI, respectively (P<0.001). The cumulative incidence of chronic kidney disease (CKD) over 2 years after SCT was 41.5% and 19.1% in early and late AKI, respectively (P=0.048). Logistic regression analysis adjusted for the PS showed that early AKI was significantly associated with OS (odds ratio (95% confidence interval); 4.63 (1.15-21.4), P=0.031) but with neither NRM (1.25 (0.28-5.33), P=0.766) nor CKD (1.85 (0.41-8.60), P=0.422). In conclusion, early AKI may portend a poor survival for allo-SCT recipients.

New-onset microalbuminuria following allogeneic myeloablative SCT is a sign of near-term decrease in renal function.

The emergence of microalbuminuria following conditioning chemotherapy may predict the development of renal dysfunction. To confirm this, a 1-year retrospective cohort study was conducted in 31 myeloablative allogeneic SCT patients who received five consecutive measurements of albuminuria before conditioning therapy and on days 0, 7, 14 and 28 following SCT. The cohort had neither microalbuminuria nor renal dysfunction at baseline. Microalbuminuria was defined as an albumin-creatinine (Cr) ratio over 30 mg/g, and renal dysfunction was as an estimated glomerular filtration rate <60 mL/min per 1.73 m(2). Cumulative incidence of renal dysfunction over time was analyzed by the Kaplan-Meier method. Multivariate Cox proportional hazards analysis was used to examine an association of de novo microalbuminuria with the incidence of renal dysfunction. In all, 16 patients (52%) developed microalbuminuria that was positive at least two times among the four measurements after SCT. The actuarial occurrence of chronic kidney disease was significantly higher in patients who developed microalbuminuria than in those who did not. Incidence of microalbuminuria had a significant risk of subsequent renal dysfunction (hazard ratio (95% confidence interval), 7.3 (1.2-140)). In conclusion, de novo microalbuminuria following conditioning therapy is a warning of near-term loss of renal function.

Doppler ultrasonography-aided early diagnosis of venous thromboembolism after total knee arthroplasty.

OBJECTIVES: Postoperative deep venous thrombosis (DVT) is usually asymptomatic but can result in a fatal pulmonary embolism (PE). To assess the ability of transcranial Doppler (TCD) ultrasound apparatus to detect venous emboli in patients who had undergone total knee arthroplasty (TKA). METHODS: Forty-eight patients undergoing TKA were examined postoperatively by using compression ultrasonography, computed tomographic angiography, and TCD ultrasonography that detected high-intensity transient signals (HITS) in femoral veins. An original scoring system based on both the number of HITS and the locations of DVT was tested for its accuracy in predicting PE development. RESULTS: Twenty-three of the 48 patients had DVT postoperatively, and 8 had an asymptomatic PE. The sensitivity and specificity of the HITS assessment alone in identifying PE development were 75% and 92.5%, respectively. The scoring system, however, had a sensitivity of 100% and a specificity of 85% and the area under the receiver operating characteristic (ROC) curve (AUC) was 0.96. CONCLUSIONS: Application of a scoring system based on the detection of both DVT and HITS may be an effective and efficient method of screening for PE after knee arthroplasty.

A comparative assessment of the RIFLE, AKIN and conventional criteria for acute kidney injury after hematopoietic SCT.

An observational cohort study was conducted to compare the performance of the RIFLE (risk, injury, failure, loss and end-stage kidney disease), AKIN (acute kidney injury network) and conventional graded criteria to identify acute kidney injury (AKI) following SCT and to predict long-term mortality in 141 myeloablative allogeneic SCT (m-allo), 60 non-myeloablative allogeneic SCT (nm-allo) and 48 autologous SCT (auto) cases. The AKIN criteria had less ability to identify patients as having the lowest category, stage 1 (analogous to RIFLE risk): 33% (37%) in m-allo, 23% (32%) in nm-allo and 8.3% (16.7%) in auto. Cox regression showed that categories higher than the intermediate stage were independent predictors of mortality in all three definitions. The areas under receiver operating characteristic curves showed that both definition systems had similar and significant ability to predict mortality (0.643-0.649 in m-allo and 0.734-0.766 in nm-allo, respectively). These abilities of the conventional graded criteria were comparable with those of the RIFLE criteria. The RIFLE criteria have greater sensitivity than the AKIN criteria to identify patients with AKI and therefore are more favorable as a uniform definition system for post-SCT AKI. However, the RIFLE criteria do not improve on the clinical relevance of the conventional graded criteria.

Synovial fluid-derived mesenchymal stem cells increase after intra-articular ligament injury in humans.

OBJECTIVE: The existence of mesenchymal stem cells (MSCs) in SF was previously reported. However, the behaviour and properties of MSCs derived from SF have not been fully elucidated. METHODS: Human SFs were obtained from 19 knee joints with anterior cruciate ligament injury around the time of reconstruction surgery, and from three healthy volunteers. SF was plated, cultured and examined for colony-forming number, in vitro differentiation, surface epitopes and gene profiles. Also, rabbit synovium-MSCs were injected into the knee joint in a rabbit partial anterior cruciate ligament defect model, and the injected cells were traced. RESULTS: SF-MSCs from IA ligament injury patients were 100 times more in number than those from healthy volunteers. Total colony number was positively correlated with post-injury period. No significant differences were observed among the cells derived from SF around the time of the surgery in relation to surface epitopes and differentiation potentials. Cluster analysis of gene profiles demonstrated that SF-MSCs were more similar to synovium MSCs than bone marrow MSCs. In rabbit experiments, the MSCs injected into the knee in which IA ligament was partially defective were observed more on the defected area than on the intact area of the ligament at 24 h. CONCLUSION: We demonstrated that SF-MSCs, similar to synovium MSCs, increased in number after IA ligament injury and surgery without marked alteration of the properties.

Duodenal follicular lymphomas share common characteristics with mucosa-associated lymphoid tissue lymphomas.

BACKGROUND: Follicular lymphomas occasionally arise in the extra-nodal organs and are frequently found in the duodenum. They are often localised tumours with multiple polyps around the ampulla of Vater. AIMS: To examine a IgH/bcl-2 hybrid gene and VH gene to investigate the nature of the lymphoma cells and how they differ from nodal follicular lymphomas and MALT lymphomas. METHODS: Of 40 patients reported previously, 35 with duodenal follicular lymphoma were studied in detail with respect to clinicopathological characteristics. RESULTS: 37/40 patients were in clinical stage I (n = 30) or stage II (n = 7). Clonal immunoglobulin gene rearrangement was detected in 53.3% of examined cases, and rearrangement of IgH/bcl-2 gene at the major break point was detected in 27% of cases. Three of 8 examined cases were VH4 (38%); 2 out of them were VH4-34. As VH4 deviation is one of the common characteristics of MALT lymphomas and 2/3 were identical, duodenal follicular lymphomas have a similar aetiology to MALT lymphomas. Clinical course was also similar to that of MALT lymphomas. CONCLUSIONS: Results suggest that duodenal follicular lymphomas have intermediate characteristics of MALT lymphomas and nodal follicular lymphomas.

Antibodies to E1 and E2/Protein X components of pyruvate dehydrogenase complex in sera of patients with primary biliary cirrhosis.

AIMS/METHODS: Using purified E1 component of pyruvate dehydrogenase complex (PDC) from bovine heart, we measured the levels of anti-E1 antibodies in PBC sera using ELISA and determined the degree of inhibition that these antibodies exerted on E1 enzyme activity. We also estimated levels of anti-E2/Protein X (Pro-X) antibodies in PBC sera using purified E2 and Pro-X of PDC which were copurified with E1. RESULTS/CONCLUSIONS: Anti-E1 antibodies were detected in 87.5% (35/40) of PBC sera. Some of these sera inhibited E1 enzyme activity but inhibition did not correlate with levels of anti-E1 antibodies. A high positive correlation (r = 0.918) was found between levels of anti-E1 and anti-E2/Pro-X antibodies, suggesting that anti-PDC antibody production was stimulated by PDC itself. Levels of IgG class anti-E2/Pro-X antibodies were significantly higher in sera of symptomatic PBC patients than in those of asymptomatic PBC patients. It was also found that patients who were positive for only IgM class anti-E2/Pro-X antibodies had early-stage PBC.

Familial positive ulnar variance with secondary radioulnar joint arthritis and extensor tendon ruptures.

A familial pattern of extensor tendon ruptures due to distal radioulnar osteoarthritis with underlying positive ulnar variance is described. Spontaneous ruptures occurred in four members of the family (one woman and three men) in middle age. Laboratory data did not indicate any sign of rheumatoid arthritis. All cases revealed significant positive ulnar variance and distal radioulnar osteoarthritis. Younger members of the family demonstrated positive ulnar variance although without osteoarthritic changes. The tendon ruptures presumably resulted from a hereditary disorder in conjunction with degenerative changes brought about by age.

[Two cases of allergic granulomatosis and angiitis (AGA); Churg-Strauss syndrome].

AGA is an angiitis syndrome that has some characteristic features, for example preceding asthma and polyneuritis. And histological findings are granulomatous angiitis or extravascular granuloma. We report two typical cases of AGA. Case 1; 51-year-old woman had been suffering from asthmatic dyspnea for one year and developed in 1987 multiple neuritis in her extremities. Eosinophilia and high level of IgE were noted. Pathologic diagnosis of the biopsied right calf muscle specimen was granulomatous angiitis. Case 2; 40-year-old woman had been suffering from asthmatic dyspnea for two years. She complained of severe cough and myalgia in 1986 and her chest X-ray showed homogeneous shadows in right upper and left lower fields. And her blood showed eosinophilia and high level of IgE. The histology of the biopsied subcutaneous nodules of hands showed extravascular granuloma. These two cases had specific features of AGA. About symptoms of angiitis, case 1 showed multiple neuritis and case 2 had subcutaneous nodules of hands. About laboratory data, case 1 showed WBC count of 9400/mm3 with 85% eosinophils and high level of IgE at 1400 IU/ml, case 2 had WBC count of 13200/mm3 with 22% eosinophils and IgE at 846 IU/ml. The vary of eosinophil count and IgE level were related to the degree and course of illness. These symptoms and laboratory data, except neuritis, improved by an administration of prednisolone. In early stage of AGA, prednisolone is effective, so the criteria of AGA and usage of corticosteroids must be considered.

The destructive effects of sclerosant ethanolamine oleate on mammalian vessel endothelium.

Ethanolamine oleate (EO) used widely in sclerotherapy against esophageal varices was studied for its pharmacological effect on blood coagulation and vascular damage in animals. Blood coagulation was completely inhibited by EO at a concentration of 0.31%. EO destroyed the endothelial cells of the vessel of dog and rat within one minute after injection into the vessels. An accumulation of fibrin and platelets on the surface of the damaged vessel was observed electron microscopically. Mural thrombus was formed in a few hours and the thrombus occluded the blood stream in the vein. From these animal experiment, intravasal injection of EO was considered to cause the disappearance of varices by the following two processes: collapse of varices because of occlusion of the blood stream and shrinking of the obstructed thrombus through organization.

Stimulatory effect of cefodizime on macrophage-mediated phagocytosis.

We evaluated the ingestion of anti-sheep erythrocyte (anti-E) IgG- and IgM-coated sheep erythrocytes by murine peritoneal macrophages exposed to cefodizime, a new semisynthetic cephalosporin, and other antibiotics. Cefodizime enhanced the ingestion of anti-E IgG-coated erythrocytes by peritoneal macrophages from CD-1 and BALB/c mice in a dose-dependent manner, but had no effect on uncoated or IgM-coated erythrocytes. Similar enhancement was observed only in the case of cefpimizole (AC-1370), among the other antibiotics examined. These results suggest that the favorable in vivo activity of cefodizime and cefpimizole may result from their phagocytosis-enhancing as well as antimicrobial properties.

[An autopsy case of a patient with myasthenia gravis who showed various symptoms of collagen diseases and complicated with malignant thymoma].

A 37-year-old man suffered from photosensitivity and urinary casts with serological findings of positive anti-DNA antibody, LE cells and false positive VD reaction in September of 1979. He developed general fatigue, dyspnea and diplopia with ptosis of bilateral eyelids in November of 1979, which were improved by the anti-cholinesterase drugs. In January of 1980, he had an attack of unconsciousness and his chest X-ray film showed several tumorous shadows in the anterior mediastinum and middle and lower lung fields. Treating him with chemotherapy of VEMP, the pulmonary shadows disappeared. However, he developed severe muscle weakness with an elevated CPK (430 mU/ml) and a myogenic EMG pattern along with an increased anti-acetylcholine receptor antibody (243 n Mol/l), dysphagia and eyelid-ptosis. He died in September of 1985 and his autopsy disclosed a malignant thymoma of mixed type in the anterior mediastinum and an atrophy and fibrosis with infiltration of inflammatory cells in the striated muscles.

Localization of nRNP antigen in mammalian cells stained with peroxidase-labelled IgG fraction of anti-nRNP antibody obtained from a patient with mixed connective tissue disease (MCTD).

The peroxidase-labelled IgG fraction of anti-nRNP antibody obtained from a MCTD patient stained the nuclei of almost any kind of cells of man and rat. In addition, the cytoplasma of anterior horn cells of the rat spinal cord was exclusively reacted with this antibody. Both cytoplasmic and nuclear staining of the anterior horn cells were reduced after treatment of tissue sections with RNase.

A competitive inhibition test of enzyme immunoassay for the anti-nRNP antibody.

A competitive inhibition test for anti-nRNP antibody was developed, using horseradish-peroxidase-labelled anti-nRNP IgG derived from the serum of a patient with mixed connective tissue disease. In this test, the anti-nRNP antibody was clearly distinguished from the anti-Sm antibody in the patients' sera, and the sensitivity of the assay for anti-nRNP antibody was close to 50 ng/ml.