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.

Biphasic regulation of Fc-receptor mediated phagocytosis of rabbit alveolar macrophages by surfactant phospholipids.

Dipalmitoyl phosphatidylcholine (DPPC) is a major phospholipid constituent in the pulmonary surfactant, whereas lysophosphatidylcholine (Lyso-PC) is a minor constituent, this membrane phospholipid being produced at inflammatory sites in association with activation of phospholipase A2. To determine the role of these two different forms of phospholipids in the phagocytic function of alveolar macrophages (AM), we examined the effects of DPPC or Lyso-PC on Fc-mediated phagocytosis. We demonstrated a significant decrease of the ingestion activity of AM for anti-sheep erythrocyte immunoglobulin G-coated sheep erythrocytes (EA: IgG) by DPPC. On the other hand, Lyso-PC caused significantly increased ingestion of EA: IgG by AM. These data indicate that increase of Lyso-PC due to the hydrolysis of DPPC through activation of phospholipase A, may up-regulate AM-mediated phagocytic functions in the alveolar milieu associated with infections and inflammation. DPPC may suppress and stabilize the AM-mediated phagocytosis in the normal alveolar environment.

Two sister cases of autoimmune hepatitis.

Two sister cases of autoimmune hepatitis are described. Case 1 involved a 49-year-old woman who suffered from bleeding gums and general fatigue. Her laboratory data showed a marked increase in transaminase levels, an elevated IgG level with titers 1:80 or more of both antinuclear and smooth muscle antibodies and thrombocytopenia. Histology of the biopsied liver revealed chronic active hepatitis with a moderate infiltration of mononuclear cells. A complication of idiopathic thrombocytopenic purpura was determined based on higher titers of PA-IgG and a normal bone marrow findings. Case 2 involved a 54-year-old woman, an elder sister of case 1, who suffered from general fatigue with jaundice. Her laboratory data showed a severe damage of liver function and an elevated IgG level with positive antibodies to nuclear and smooth muscle antigen. Histology of the biopsied liver revealed chronic active hepatitis. Both patients were negative to markers of hepatotrophic agents. Under diagnosis of autoimmune hepatitis, they have been treated with prednisone followed by a significant clinical improvement. HLA types of two patients were Bw54-DR4 and DR4. Among 4 other siblings, the eldest sister suffered from rheumatoid arthritis. The occurrence of two sister cases of type-1 autoimmune hepatitis has rarely reported and the fact would support a role of enviromental factors besides genetic factors for the onset of this disease.

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.

Idiopathic thrombocytopenic purpura complicated by intracranial hemorrhage in a 78-year-old male.

A 78-year-old male was admitted to our hospital with cutaneous hemorrhage, aphasia and somnolence. On physical examination, he appeared drowsy and complained of epistaxis and multiple purpura. His platelet count was 8,000/microliters with a high level of PA-IgG, but the coagulation time was normal. A CT scan of the head revealed a left temporal and right frontal hemorrhage. Bone marrow aspiration revealed abundant megakaryocytes. He was diagnosed as having idiopathic thrombocytopenic purpura with intracranial hemorrhage. He was treated with prednisolone and azathioprine in addition to platelet infusions and high doses of gamma-globulin. After two months of treatment, the platelet count had risen to 40,000/microliters and his symptoms had subsided.

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.

[A case of Sjögren's syndrome accompanied by lymphadenopathy and IgG4 hypergammaglobulinemia].

A 78-year-old male patient suffered from slight dryness of his mouth and eyes, which was followed by swelling of the parotid and submandibular glands on both sides. Subsequently, he developed generalized lymphadenopathy accompanied by hypergammaglobulinemia IgG 7740 mg/dl, main subclass: IgG4, 5800 mg/dl. Histopathological examination of lymph nodes from his left neck showed follicular proliferation of plasma cells containing cytoplasmic kappa and lambda chains of IgG4, without destruction of the lymph node structure. His serum showed very low levels of complement: 0 U/ml of CH 50, 14 mg/ml of C3 and less than 11 mg/ml of C4. During treatment with prednisolone at 30 mg/day, the swelling of the salivary glands and lymph nodes reduced the IgG and IgG4 decreased and the complement increased. Finally, all lymph nodes, IgG and complement abnormalities were normalized. Anticomplementariness of IgG4 was demonstrated in this patient.

[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 antimicrobial activity of fluoroquinolone agents against pathogenic organisms in respiratory tract infections and its clinical effect].

The efficacy rate, minimal inhibitory concentrations (MICs), and resistance of fluoroquinolone agents against causative organisms in respiratory tract infections from January to March, 1988 were investigated. Of 333 pathogenic strains 85% consisted of 5 major causative organisms of respiratory tract infection (Haemophilus influenzae, Pseudomonas aeruginosa, Streptococcus pneumoniae, Branhamella catarrhalis, and Staphylococcus aureus). In 61 (59 cases) of these 333 strains, including 3 cases of acute pharyngitis, 5 of acute bronchitis, 3 of pneumonia, and 48 of chronic lower respiratory tract infection fluoroquinolone agents were administered. The efficacy rate was 76.3% in all cases, and 75% in cases with chronic lower respiratory tract infection. The fluoroquinolone agents were 100% effective in H. influenzae and B. catarrhalis, though the efficacy rate was 67% in S. aureus and 40% in P. aeruginosa. The susceptibility of all strains to fluoroquinolone agents were investigated. There was no resistant strain in H. influenzae and B. catarrhalis, though resistant strains to fluoroquinolone agents have increased in S. aureus and P. aeruginosa. The efficacy rate was investigated using the MIC of administered fluoroquinolone agent against causative organisms. It is surmised that the efficacy of that agent has an MIC of 1.56-3.13 micrograms/ml.

[The significance of autoantibodies coexisting with anti-centromere antibodies in sera of patients with primary biliary cirrhosis].

Anti-centromere antibody (ACA) has been believed to be specific to patients with CREST syndrome, a variant of scleroderma (PSS). This study was undertaken to clarify the distribution of ACA in various diseases and the significance of autoantibodies coexisting with it. The sera of patients with primary biliary cirrhosis (PBC) along with collagen diseases and aged subjects were examined for ACA by immunofluorescence method (IF) using cultured HEp-2 cells and chromosomes prepared from K 562 cells. ACA were found in sera of 10 patients with PBC, one with scleroderma, one with cerebral infarction and one with chronic renal failure respectively. ACA positive sera were examined for antibodies against other nuclear antigens including nRNP, Sm, Scl-70, SS-A and SS-B and cytoplasmic antigens by double immunodiffusion methods using rabbit thymus extract etc. as the antigens and by IF method using cryostat sections of rat kidney and stomach. In 13 sera with ACA, antimitochondrial antibody (AMA), anti-smooth muscle antibody (ASMA) and anti SS-A antibody were found in 10, 4 and one sera respectively. In 10 PBC patients with ACA, various collagen disease-related disorders were found to coexist; CREST syndrome in one, CRST syndrome in one, Raynaud's phenomenon in two and Sjögren's syndrome in 5. These results would indicate that ACA may be one of the common serological abnormalities among patients with PBC, CREST syndrome and Sjögren's syndrome.

[Eosinophilia in primary biliary cirrhosis].

The numbers and the percent of eosinophils in peripheral blood of thirty patients with primary biliary cirrhosis were serially measured and were compared with their clinical data. eosinophils of 22 patients at non icteric stage (total bilirubin less than 2.0 mg/dl) were significantly higher (P less than 0.05) than those of 8 patients at icteric stage (total bilirubin more than 2.0 mg/dl). Seven patients (23.3%) showed eosinophilia with value of 6% or more and in which four patients (13.3%) showed eosinophilia more than 8%. These eosinophilia was found in non icteric patients alone but not in icteric. In two patients who have shown eosinophilia at their non icteric stage, numbers of their eosinophils decreased gradually following the increment of their total bilirubin levels. These results would indicate that eosinophils in the peripheral bloods of PBC patients could reflect some clinical conditions at their non icteric stage.