Search

Describes a medical case of rhabdomyolysis induced by levofloxacin, a quinolone antibacterial agent. Medical history of the patient; Common causes of rhabdomyolysis; Pathological changes induced by quinolones; Treatment of rhabdomyolysis.

Background: Alport syndrome (AS) is a genetic kidney disease caused by a mutation in type IV collagen α3, α4, and α5, which are normally secreted as heterotrimer α345(IV). Nonsense mutation in these genes causes severe AS phenotype. We previously revealed that the exon-skipping approach to remove a nonsense mutation in α5(IV) ameliorated the AS pathology. However, the effect of removing an exon on trimerization is unknown. Here, we assessed the impact of exon deletion on trimerization to evaluate their possible therapeutic applicability and to predict the severity of mutations associated with exon-skipping., Methods: We produced exon deletion constructs (ΔExon), nonsense, and missense mutants by mutagenesis and evaluated their trimer formation and secretion activities using a nanoluciferase-based assay that we previously developed., Results: Exon-skipping had differential effects on the trimer secretion of α345(IV). Some ΔExons could form and secrete α345(IV) trimers and had higher activity compared with nonsense mutants. Other ΔExons had low secretion activity, especially for those with exon deletion near the C-terminal end although the intracellular trimerization was normal. No difference was noted in the secretion of missense mutants and their ΔExon counterpart., Conclusion: Exon skipping is advantageous for nonsense mutants in AS with severe phenotypes and early onset of renal failure but applications may be limited to ΔExons capable of normal trimerization and secretion. This study provides information on α5(IV) exon-skipping for possible therapeutic application and the prediction of the trimer behavior associated with exon-skipping in Alport syndrome., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

A useful perioperative nutritional therapy for highly invasive esophageal cancer surgical cases needs to be developed. We clarified the usefulness of amino-acid-enriched nutritional therapy using glutamine (Gln)/arginine (Arg)/calcium β-hydroxy-β-methylbutyrate (HMB) products on the short-term postoperative outcomes of minimally invasive esophagectomy for esophageal cancer. Altogether, 114 patients (Gln/Arg/HMB group) received perioperative nutritional therapy with Gln/Arg/HMB products, and we retrospectively investigated the change in nutritional parameters including skeletal muscle mass, occurrence of postoperative complications, and short-term postoperative outcomes in this group. The results were compared between the Gln/Arg/HMB and control groups (79 patients not receiving the Gln/Arg/HMB products). The incidence of all postoperative complications, sputum expectoration disorder, and pleural effusion of grade ≥ III was significantly lower in the Gln/Arg/HMB group (62.0% vs. 38.6%, p = 0.001; 44.3% vs. 28.1%, p = 0.020; 27.8% vs. 13.2%, p = 0.011, respectively). The psoas muscle area and postoperative body weight were significantly higher at 1 month and 1 year after surgery in the Gln/Arg/HMB group than in the control group (93.5% vs. 99.9%, p < 0.001; 92.0% vs. 95.4%, p = 0.006). Perioperative amino-acid-enriched nutritional therapy may improve the short-term postoperative outcomes, nutritional status, and skeletal muscle mass of esophageal cancer surgical patients.

Purpose: Distant metastasis develops in approximately one-third of patients with colorectal cancer (CRC) who undergo radical surgery, and colorectal liver metastasis (CRLM) is the most common form of distant metastasis in CRC. Hepatectomy is the only potentially curative treatment for CRLM, but few patients with metastatic CRC meet the criteria for this radical resection, and the 5-year survival rate is poor. Identifying risk factors for CRLM is critical. Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for CRC. However, the effect of NAFLD on CRC liver metastasis after radical surgery remains unclear. Therefore, we examined the impact of NAFLD-associated hepatic fibrosis on liver metastasis after radical surgery for CRC., Methods: We retrospectively analyzed data from 388 patients who underwent curative surgery for CRC at our hospital between April 2008 and March 2015. The patients' clinical results, surgical procedures, postoperative course, and pathological and survival data were collected from the hospital records. The NAFLD fibrosis score was calculated and used to divide the patients into two groups (NAFLD and non-NAFLD)., Results: Recurrence was observed in 83/388 (21.4%) patients after a mean follow-up of 65.6 ± 15.1 months. Twenty-five patients had liver metastasis: 8 in the NAFLD group (8/45; 17.8%) and 17 in the non-NALFD group (17/343; 5.0%) (p = 0.004). Liver metastasis-free survival was significantly worse in the NAFLD than non-NAFLD group (p < 0.001). NAFLD and cancer stage were independent risk factors for liver metastasis recurrence., Conclusion: NAFLD may be a risk factor for liver metastasis in patients with CRC who undergo curative surgery., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A 62-year-old male presented with right intercostal muscle pain. Clinical examination revealed muscular defense in the same area. Abdominal ultrasonography revealed a distended gallbladder and ascites effusion, but no gallstones or polyps were present. Contrast-enhanced computerized tomography was performed, which revealed luminal obstruction due to arterial dissection of the celiac artery and intrinsic hepatic artery. This finding suggested gangrenous cholecystitis; thus, urgent cholecystectomy was performed. Only a few cases of celiac artery dissection and only one case of gangrenous cholecystitis without stones have been reported. We report here an extremely rare case of celiac artery dissection.

Alport syndrome (AS) is a hereditary glomerular nephritis caused by mutation in one of the type IV collagen genes α3/α4/α5 that encode the heterotrimer COL4A3/4/5. Failure to form a heterotrimer due to mutation leads to the dysfunction of the glomerular basement membrane, and end-stage renal disease. Previous reports have suggested the involvement of the receptor tyrosine kinase discoidin domain receptor (DDR) 1 in the progression of AS pathology. However, due to the similarity between DDR1 and DDR2, the role of DDR2 in AS pathology is unclear. Here, we investigated the involvement of DDR2 in AS using the X-linked AS mouse model. Mice were treated subcutaneously with saline or antisense oligonucleotide (ASO; 5 mg/kg or 15 mg/kg per week) for 8 weeks. Renal function parameters and renal histology were analyzed, and the gene expressions of inflammatory cytokines were determined in renal tissues. The expression level of DDR2 was highly elevated in kidney tissues of AS mice. Knockdown of Ddr2 using Ddr2 -specific ASO decreased the Ddr2 expression. However, the DDR2 ASO treatment did not improve the proteinuria or decrease the BUN level. DDR2 ASO also did not significantly ameliorate the renal injury, inflammation and fibrosis in AS mice. These results showed that Ddr2 knockdown by ASO had no notable effect on the progression of AS indicating that DDR2 may not be critically involved in AS pathology. This finding may provide useful information and further understanding of the role of DDRs in AS.

Background: Bardoxolone methyl activates nuclear factor erythroid 2-related factor 2 (Nrf2) via covalent binding and irreversible inhibition of Kelch-like ECH-associated protein 1 (Keap1), the negative regulator of Nrf2. Ongoing clinical trials of bardoxolone methyl show promising effects for patients with CKD. However, the direct inhibition of Keap1-Nrf2 protein-protein interaction (PPI) as an approach to activate Nrf2 is less explored., Methods: We developed a noncovalent Nrf2 activator UBE-1099, which highly selectively inhibits Keap1-Nrf2 PPI, and evaluated its efficacy on the progressive phenotype in an Alport syndrome mouse model ( Col4a5 -G5X)., Results: Similar to bardoxolone methyl, UBE-1099 transiently increased proteinuria and reduced plasma creatinine in Alport mice. Importantly, UBE-1099 improved the glomerulosclerosis, renal inflammation, and fibrosis, and prolonged the life span of Alport mice. UBE-1099 ameliorated the dysfunction of Nrf2 signaling in the renal tissue of Alport mice. Moreover, transcriptome analysis in the glomerulus showed that UBE-1099 induced the expression of genes associated with the cell cycle and cytoskeleton, which may explain its unique mechanism of improvement such as glomerular morphologic change., Conclusions: UBE-1099 significantly ameliorates the progressive phenotype in Alport mice. Our results revealed the efficacy of Keap1-Nrf2 PPI inhibitor for glomerulosclerosis and present a potential therapeutic drug for CKD., Competing Interests: H. Kai received research funding from Grants-in-Aid for Scientific Research from the Ministry of Education, Sciences, Sports, and Culture (MEXT) of Japan. S. Kaseda received research funding from the Japan Society for the Promotion of Science. T. Shuto reports received research funding from Grants-in-Aid for Scientific Research from the Ministry of Education, Sciences, Sports, and Culture (MEXT) of Japan. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

The purpose of this study is to design and develop a comprehensive model of teaching basic nursing skills on GBS theory and Four-Stage Performance Cycle. We designed a basic nursing skill program that consists of three courses: basic, application and multi-tasking. The program will be offered as blended study, utilizing e-learning.

SiOxNy films with a low nitrogen concentration (< 4%) have been prepared on Si substrates at 400°C by atmospheric-pressure plasma oxidation-nitridation process using O2 and N2 as gaseous precursors diluted in He. Interface properties of SiOxNy films have been investigated by analyzing high-frequency and quasistatic capacitance-voltage characteristics of metal-oxide-semiconductor capacitors. It is found that addition of N into the oxide increases both interface state density (Dit) and positive fixed charge density (Qf). After forming gas anneal, Dit decreases largely with decreasing N2/O2 flow ratio from 1 to 0.01 while the change of Qf is insignificant. These results suggest that low N2/O2 flow ratio is a key parameter to achieve a low Dit and relatively high Qf, which is effective for field effect passivation of n-type Si surfaces.

A 20 year-old male patient was admitted to our department for the treatment of recurrence of fever and pancytopenia developed despite of temporal remission of hemophagocytosis syndrome that had been treated with large doses of methylprednisolone in our hospital. Superficial lymph nodes were not palpable. CT scan and echography revealed neither findings of splenohepatomegalia or enlargement of intraabdominal lymph nodes. Bone marrow aspiration showed an increase of histiocytes, the cells phagocytizing erythrocytes and platelets, and a negative test for peroxidase stain. Analysis of surface antigens showed that 11.3% of cells were blast cells positive for CD10, CD19, CD20, CD34 and TdT. Bone marrow biopsy revealed a localized increase in tumor cells positive for L26, CD10 and negative for UCHL-1. Because of the absence of detectable tumor masses and the difficulty in differentiating between malignant lymphoma and lymphatic leukemia, we diagnosed the condition as B precursor lymphoblastic leukemia/lymphoma. If diagnosed with malignant lymphoma preceded by hemophagocytic syndrome(LAHS), he might have a rare type of LAHS-associated malignant lymphoma since histological examination did not reveal diffuse large cell lymphoma, a condition found in most patients with LAHS-associated malignant lymphoma. Whereas if diagnosed as ALL, he was the first adult patient with ALL with HPS at onset as far as we know. In any of these possibilities, the case was considered rare.

Findings for 41 patients with non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy (HDC) and/or autologous peripheral blood stem cell transplantation (PBSCT) are reported. Two of the 41 patients were treated with HDC alone without PBSCT. At transplant, 20 patients were in complete remission, while 19 had resistant NHL and had failed to achieve a complete remission (CR) after several courses of conventional chemotherapy. The conditioning regimens used were mainly ACE (cytarabine, cyclophosphamide, etoposide) and MEAC (MCNU, etoposide, cytarabine, cyclophosphamide). The treatment-related mortality rate was 4.9%. Two patients treated with MEAC died from intractable congestive heart failure. Nine of the 19 patients with resistant NHL achieved CR, and at a median follow-up of 26 months (range, 3 to 93 months) the estimated two-year disease-free survival rate for these patients was 44.4%. Four patients in CR at present were in partial remission before HDC and PBSCT. Fifteen of the 20 patients in CR before HDC were transplanted in first CR and 5 in 2nd CR. At a median follow-up of 49 months (range, 3 to 96 months), the estimated 3-year DFS for the group of all patients was 73.7%. Five relapses occurred between 5 and 35 months post-transplantation. In conclusion, HDC and PBSCT as induction therapy was only effective for patients with resistant NHL who responded to conventional chemotherapy, and may improve the survival of patients in CR as consolidation therapy.

By use of flow cytometry, we have investigated intracellular activated eosinophil cationic protein (ECP) in eosinophils and mitogen-induced cytokine production of T cells in peripheral blood from children with acute severe asthma. In addition, we measured ECP releasability (serum ECP/lysate ECP) as a maker of activated eosinophils. The monoclonal antibody EG2 (anti-activated ECP/EPX antibody) was used for measuring the amount of intracellular activated ECP. ECP releasability and mean fluorescence intensity (MFI) values of EG2-positive eosinophils increased at the time of asthmatic attack and reduced after treatment with improvement in peak expiratory flow. Furthermore, the frequency of T cells which produced IL-4, IL-5 and IFN-gamma stimulated with phorbol myristate acetate and ionomycin increased and reduced in parallel with MFI of EG2-positive cells. These observations suggest that flow cytometric analysis for intracellular ECP and mitogen-induced cytokine production reflects the activation of T cells in bronchial mucosa, and is useful for monitoring airway inflammation in bronchial asthma.

One hundred thirty-eight patients with severe infections associated with hematopoietic disorders were treated with cefclidin (CFCL), and the efficacy and the safety of the drug were evaluated. The results obtained are summarized below. 1. Of the 126 patients in whom the efficacies were evaluable, 22 (17.5%) responded markedly well and 48 (38.1%) moderately, and the overall efficacy rate was 55.6%. 2. Efficacy rates for different infections were: 20.0% in septicemia, 61.2% in suspected septicemia, 46.7% in respiratory tract infection and 25.0% in others. 3. Significantly different efficacy ratings were observed between a group of patients with neutrophil counts of less than 100/mm3 and that with neutrophil counts of higher than 501/mm3. 4. Out of 138 patients in whom the safety was evaluable, side effects were observed in 5 patients (3.6%) and abnormal laboratory test values in 9 (6.5%). None was serious, however.

Forty-three patients with severe infections which were complicating hematological disorders were treated with panipenem/betamipron, and the efficacy and the safety of the drug were evaluated. The results obtained are summarized below. 1. Out of 40 patients in whom efficacies are evaluable, the clinical responses were excellent in 17 patients, good in 4, fair in 7 and poor in 12, and the total clinical efficacy rate was 52.5%. 2. The efficacy rate in 7 patients who had failed to respond to prior treatment with other antibiotics was 57.1%. Thus, no significant difference was observed in efficacy rates between the patients who had failed to respond to prior treatment with other antibiotics and the patients who received no preceding antibiotics therapy. 3. Out of the 43 patients in whom the safety was evaluable, no side effects nor abnormal laboratory findings were found.

A 55-year-old woman developed a secondary leukemia following 1-year treatment of Hodgkin's disease. She was admitted to our hospital because of the celiac lymphadenopathy. Open laparotomy was performed. Biopsy specimens of the lymph node demonstrated Reed Sternberg cells with mature lymphocytes. She was diagnosed as having Hodgkin's disease (lymphocyte predominant type). She was treated by the combination chemotherapy consisting of mitoxantrone, cyclophosphamide, vincristine and prednisolone for Hodgkin's disease in November 1986. Hodgkin's disease achieved complete remission and she was regularly followed. No abnormal findings were observed in the peripheral blood and bone marrow. But thrombocytopenia and the blastoid cells appeared in the peripheral blood in February 1988. The bone marrow specimen was hypercellular and occupied by 90% of blastoid cells that were positive for peroxidase staining. She was diagnosed as having AML from the bone marrow aspiration and biopsy specimens. She did not respond to several chemotherapy regimens and now she is treated by low dose Ara C.

One hundred ninety-eight patients with severe infections associated with hematopoietic disorders were treated with imipenem/cilastatin sodium (IPM/CS), and the efficacy and safety of the drug were evaluated. The results obtained are summarized below. 1. Out of 182 patients in whom efficacies are evaluable, responses were excellent in 50 patients, good in 52, fair in 21 and poor in 59, and the efficacy rating was 56.0%. 2. The efficacy rating in 87 patients who had failed to respond to prior treatment with other antibiotics was 58.6%. 3. There were significant differences in efficacy ratings when patients were grouped according to differences the number of neutrophils after treatment, less than 100, 101 approximately 500 and over 501/mm3. 4. The eradication rate in 38 patients from whom causative organisms were isolated was 75.8%. 5. Out of 197 patients in whom the safety was evaluable, side effects were observed in 19 patients (9.6%) and abnormal laboratory test values in 15 (7.6%).

A 30-year-old man was admitted to our hospital because of fever and cervical lymphadenopathy. Hematological examination revealed leukocytosis with atypical lymphocytes in peripheral blood. Mature histiocytes with erythrophagia were detected in the bone marrow. GOT and GPT were elevated. Anti-EB virus antibody titer was high. The titers of VCAIgM and VCAIgG on admission were 1:320 and 1:160, respectively, and those at convalescence stage were 1: less than 10 and 1:640. The diagnosis of virus associated hemophagocytic syndrome (VAHS) due to EB virus was made. Immunosuppressive and cytotoxic therapy are thought to be contraindicated in the treatment of VAHS. In this case only a febrifuge was administrated and the condition of the patient was improved.

Combination Chemotherapy with Adriamycin (VEPA) was applied to 16 patients with non-Hodgkin's lymphoma. The effects of VEPA therapy were compared with those of combination chemotherapy without Adriamycin (non-VEPA). Complete remission rate achieved with VEPA therapy was 37.5% while that with non-VEPA therapy was 27.6%. Histologically, the complete remission rate in cases of large-cell type treated with VEPA therapy was 40%, while that with non-VEPA therapy was 14.3%. No cases of stage IV showed complete remission, whereas the complete remission rate for cases of stage III was 37.5% for VEPA therapy, but 27.6% for non-VEPA therapy. From these results we concluded that VEPA therapy is more effective for non-Hodgkin's lymphoma, especially large-cell type, than non-VEPA therapy.

We examined the effects of two inhibitors of aggregation of human platelets the, Forskolin and Cilostazol on clot retraction. Both substances suppressed clot retraction in a dose-dependent way. Both suppress platelet aggregation because of an increase in intercellular cyclic AMP, but there was no close correlations were shown between suppression rate for clot retraction and cyclic-AMP content in platelets in the clot in each substance. Furthermore, although it has been considered that actomyosin in platelets is a major contractile source for clot retraction and that failure of actin polymerization results suppression of clot retraction. As it was difficult to obtain active actin from platelets of the reagents on the polymerization. Cilostazol accelerated actin polymerization, whereas Forskolin did not. From these findings, it was considered that the effects of both substances on clot retraction could not be interpreted directly just by the increasing effect for intracellular cyclic-AMP. Clot retraction is consider to be a in vitro model of hemostasis and its contractile force is supplied from platelets (1,2,3). Experiments used prostaglandin E-1 revealed that elevation of cyclic-AMP (c-AMP) would regulate the clot retraction, and experiments used cytochalasin B demonstrated that actomyosin is responsible to the retraction (4,5). Many date demonstrate that elevation of c-AMP level suppresses platelet aggregation (6,7). c-AMP, therefore, should play a key role on platelet activation. Forskolin and Cilostazol are newly-developed reagents as a suppress for platelet functions. Pharmacological action of these substances have been interpreted to process increase effect for intracellular c-AMP of platelets(8,9). If so, both substances should show some effect on clot retraction. Under this assumption, we examined the effects.

The effects of one-day intravenous therapy with gamma-globulin in a 25-year-old man with idiopathic thrombocytopenic purpura are reported. The patient showed resistance to prednisolone and had bleeding tendency. The thrombocytopenia improved after the intravenous administration of gamma-globulin at a dose of 1 g/kg. Splenectomy was carried out. The results suggested that the usual dose of gamma-globulin is not always necessary. The half-dose increased the platelet count.

A 58-year-old male was admitted to Osaka City University Hospital because of diplopia in May, 1987. Hematological examinations revealed abnormal blastoid cells in his peripheral blood and bone marrow. We found many mitochondria and polysomes in the cytoplasm of the blastoid cells by the electron microscopy. Moreover, left axillary lymph node biopsy specimen disclosed the typical "starry sky" pattern. The blastoid cells in the bone marrow had chromosomal abnormality; 47XY, 8q-, 14q+, 22q-, +mar. Therefore, the diagnosis of Burkitt's lymphoma (leukemic change) was performed. He was treated with chemotherapy, but the blastoid cells resisted many anticancer agents and he died in September 30. On admission left ocular motor disturbance was revealed. Generally, it was reported that meningitis with CNS involvement of lymphoma is accompanied by cranial nerves palsy. However in this case lymphoma cells was not found in the cerebrospinal fluid. The cause of ocular motor disturbance was the adhesion to the medial rectus muscle and compression to the ocular motor nerves of the lymphoma mass.

High doses of methotrexate (MTX) and leucovorin (LCV) as a rescue treatment were applied to five patients with non-Hodgkin's lymphoma, refractory to standard combination chemotherapy. Two of 5 patients showed a complete remission, and 2 patients showed a partial remission. One patient with massive pleural effusion showed an improvement by the treatment without any severe side effect under monitoring and controlling the dose of MTX. However, the remission duration of the treatment was short; therefore, additive therapy was required of later. From these results we assumed that the high dose of MTX and LCV could be effective for malignant lymphoma being resistant to other combination therapies.