Efficacy and safety of anti-CD20 antibody rituximab for patients with refractory systemic lupus erythematosus.

Objective We examined the efficacy and safety of rituximab in patients with refractory systemic lupus erythematosus (SLE). Methods The study enrolled 63 SLE patients who were treated with rituximab between 2002 and 2015. The participants underwent a battery of tests before treatment and at one year. Treatment ranged from two to four times at 500 or 1000 mg. Results Baseline characteristics were males:females = 6:57, age 33.9 years, and disease duration 87.2 months. The primary endpoint: The rate of major clinical response (MCR) was 60% while the partial clinical response (PCR) was 25%. Thirty of 36 (83%) patients with lupus nephritis (WHO II: 2, III: 5, IV: 22, V: 4, IV+V: 2, not assessed: 1) and 22 of 24 patients (92%) with neuropsychiatric SLE, who could be followed at one year, showed changes from BILAG A or B score to C or D score at one year. Multivariate analysis identified high anti-dsDNA antibody and shorter disease duration as significant determinants of MCR at one year. Repeat examination was conducted at five years. Primary failure was recorded in 8.8% and secondary failure in 32.4% (time to relapse: 24.4 months). Rituximab was well tolerated although 65 adverse events, mostly infections, were recorded within one year. Conclusion Rituximab is potentially efficacious for the treatment of patients with refractory SLE.

A case of refractory lupus nephritis complicated by psoriasis vulgaris that was controlled with secukinumab.

It has been reported that T helper 17 cells are involved in the pathogenesis of systemic lupus erythematosus, but there is no report on interleukin-17-targeted therapy. We report a case of a 62-year-old female who presented with psoriasis vulgaris and refractory lupus nephritis. Because her conditions were resistant to conventional treatment, and flow cytometry confirmed the proliferation of activated T helper 17 cells in peripheral blood, and examination of a renal biopsy tissue sample confirmed infiltration of numerous interleukin-17-positive lymphocytes to the renal interstitium, administration of the anti-interleukin-17A antibody secukinumab was initiated. After starting secukinumab the clinical and biological features were improved.

Cisplatin, an antineoplastic drug, inhibits catecholamine secretion from bovine adrenal chromaffin cells.

Long-term pretreatment (12-120 h) of cultured bovine adrenal chromaffin cells with cis-diamminedichloroplatinum (cisplatin, Pt(NH3)2Cl2) (33 microM), an antineoplastic drug, resulted in a decrease in the secretion of catecholamines from the cells stimulated by acetylcholine. Acetylcholine-induced 45Ca2+ influx into the cells was also reduced in the cells pretreated with cisplatin for 48 h. The concentration-response curves (3-66 microM) for cisplatin inhibition of the secretion and 45Ca2+ influx were quite similar. Pretreatment of cells with 33 microM Pt4+ or carboplatin, an analog of cisplatin, for 48 h also led to a decrease in acetylcholine-evoked secretion, but not with 33 microM Pt2+ or other metals (Au+, Au3+, Ni2+, Os3+, Pd2+, Ir3+, and Ir4+) that have properties similar to Pt4+. These results strongly suggest that in bovine adrenal chromaffin cells, cisplatin (3-66 microM) inhibits catecholamine secretion by the suppression of the Ca2+ influx into the cells evoked by acetylcholine and that the inhibitory effect of cisplatin is attributable to the tetravalent platinum ion in its molecule.

Changes in collagen matrix composition in human posterior tibial tendon dysfunction.

OBJECTIVE: To investigate whether tendon degeneration in posterior tibial tendon dysfunction syndrome is associated with changes in extracellular matrix collagen composition. METHODS: Specimens from grossly abnormal tendon regions from 9 patients with posterior tibial tendon dysfunction syndrome were prepared for routine histology. Collagens I, III and V were typed by immunoblotting and quantified by densitometry after SDS-PAGE. Proline and hydroxyproline residues were determined by liquid chromatography. Four other samples from grossly normal homologous tendon regions and one surgical specimen from a healthy patient undergoing arthrodesis of the ankle after an accident were included as control. RESULTS: In the grossly abnormal surgical posterior tibial tendon specimens we observed three types of histopathologic conditions present to varying degrees: increased mucin content, fibroblast hypercellularity and neovascularization. Analysis of degenerate tendons demonstrated a 79.3% increase in total proline and a 32.4% increase in 4-hydroxyproline. In addition, damaged tissue contained a higher proportion of collagen type III (mean increase: 53.6%) associated with a concomitant increase in type V collagen (mean increase: 26.4%). These alterations were accompanied by a reduction in type I collagen (mean decrease: 41.4%). CONCLUSIONS: In posterior tibial tendon dysfunction syndrome, the degenerative process results from marked changes in both structural organization and molecular composition of matrix collagens. The higher proportion of type V and type IlI collagens in degenerated tendons is likely to contribute to a decrease in the mechanical resistance of the tissue.

Mechanical test methods for biomedical membranes.

It is important to estimate the mechanical characteristics and strength of biomedical membrane. For this purpose, previously we have proposed several mechanical test methods for biomedical membranes. To establish the safety design for biomedical membrane, such as cellophane membrane for hemodialysis, it is important to estimate the viscoelastic characteristics of these materials. On the other hand, artificial biomedical membrane such as tympanic membrane, are subjected to noncontact internal air pressure under the membranous state. To estimate mechanical characteristics of such membrane, it is necessary to develop a well-simulated test under the gaseous pressure and the other mechanical test under the membranous state. In this paper, several test methods for these purposes were shown. Furthermore, results obtained by these methods were shown and related to clinical problems. These proposed test methods are quite different from the axial tensile test. But they are also important to estimate the mechanical property of biomedical membrane. Each result obtained by these test methods has its own significance. By selection of the most suitable test method for each purpose and revealing these mutual relations, safety design of artificial organs can be performed from the viewpoint of the strength.

Mechanical test methods of biomedical membranes such as used for otolaryngology.

Biomedical membranes, such as artificial tympanic membranes, are subject to noncontact internal air pressure. To estimate mechanical characteristics of such membranes, it is necessary to carry out the noncontact pressure test and membranous contact test, in addition to the usual monotonic tensile test, by using a rectangular specimen cut from the membranes. In this paper, these mechanical test methods and results on such biomedical membranes were studied. Some of the authors have already presented the mechanical test methods of cellophane membrane for hemodialysis under applied water pressure. Herein, we are concerned with the mechanical test methods of biomedical membranes such as tympanic membrane, in which gaseous pressure was applied.

Theoretical foundation on a noninvasive estimation for viscoelastic mechanical property of blood vessels by ultrasonic Doppler effect.

The method used in this paper is developed to estimate the degree of viscoelasticity of the blood vessel wall in a noninvasive mechanical method. In this proposed method, we can obtain an output waveform connected with mechanical behavior of blood vessels by using Ultrasonic Doppler Effect Sensory (UDES). Characterizing parameters on this waveform are established to estimate the mechanical properties of blood vessels. By analyzing the characteristics of these parameters, we attempt to estimate the viscoelastic property of blood vessels. Previously, it was found that these parameters are related to viscoelastic mechanical properties of materials. In this paper, we carried out computer analysis on the mechanical viscoelastic model and compared the theoretical behavior of blood vessels with the experimental output waveform by UDES. From these results, it was proved that values of these parameters connect with the change of the viscoelastic mechanical property of blood vessels. Therefore, the characterizing parameters of experimental output waveforms can be used to estimate the viscoelastic property of blood vessels in a noninvasive method.

Acoustical imaging and processing of blood vessel and the related materials using ultrasound Doppler effect.

In the present paper a method is proposed to measure the degree of the degradation of the elasticity in natural blood vessel and the related materials by using ultrasound Doppler effect. It was found that the deformation rate and its acceleration in the radial direction of the blood vessel can be detected by acoustical imaging and processing using this method. These results were proven to correspond to the degree of the degradation of the elasticity, that is, the degree of viscoelasticity in the blood vessel from the wave versus time pattern detected and its simple analysis. This method was applied to predicting the arteriosclerosis of blood vessels of humans by acoustical imaging and processing uninvadedly, as the characteristics of viscoelasticity in blood vessels.

Algorithm of the noninvasive diagnosis method on the atherosclerosis by ultrasonic Doppler effect.

Previously we proposed Acoustical Imaging and Processing Method to measure the viscoelastic property of the blood vessels of a canine and the related materials using Ultrasonic Doppler Effect Measurement. Furthermore, its theoretical foundation was presented. In this paper, this method is applied to measure the viscoelastic mechanical property, that is, the mechanical degradation of human blood vessels by a percutaneous noninvasive method. Based on these results, we proposed the algorithm of the noninvasive estimation method on the viscoelastic mechanical property of the blood vessel by using Doppler Effect Sensor. This method makes it possible to discriminate the blood vessel with arteriosclerosis from a normal blood vessel. Clinical applications were successfully performed using our developed computer software based on our proposed algorithm.

Hybrid concept on the mechanical test method of small caliber blood vessel.

A mechanical test on small caliber blood vessel is difficult because the strength is very low and the dimension is very small. In the present paper a multifunctional axial test apparatus design is proposed. This has the characteristics such that the load cell and the environmental container for the specimen are built up in terms of cassette, respectively, and thus both are easy to equip and take off, that is, easy to replace. Also, the test methodology by internal pressure for small caliber blood vessels has been proposed. By using both of these methodologies, the characteristics of the mechanical behavior of small caliber blood vessels, such as compliance, stress relaxation, and viscoelastic property have been clarified. An attempt has been made on the application of this method to a clinical case.

[Experimental study of biochemical modulation of 5-fluorouracil with l-leucovorin against human esophageal cancer].

Potentiation of cytotoxic effects of 5-fluorouracil (5-FU) were investigated by simultaneous or sequential combination of l-leucovorin (LV) against human esophageal cancer cell line (TE-1, TE-2) and 23 human clinical cancer samples in vitro. LV enhanced the cytotoxic effects of 5-FU on human esophageal cancer cell line as a dose dependent manner, and increased the cytotoxic effect of 5-FU about 1.5-fold with 10 microM and about 2-fold with 100 microM. The incubation time did not affect the effects. The potentiation with LV was also demonstrated against human clinical cancer samples, and the cytotoxic effects of 5-FU increased 7.6% in esophageal cancer, 20.9% in gastric cancer and 25.5% in colorectal cancer. As a result, the potentiating effects of LV against 5-FU seemed to be limited on human esophageal cancer.

Acute promyelocytic leukemia in Crohn's disease. Case report and review of the literature.

A 19-year-old man with a documented 2-year history of Crohn's disease abruptly developed leukopenia and thrombocytopenia. A diagnosis of acute promyelocytic leukemia was established by bone marrow cytology. Chromosomal analysis of bone marrow aspirate revealed aberrations of no. 8 trisomy and translocation between no. 15 and no. 17 [46,XY,t(15q+,17q-)/47,XY,+8,t(15q+,17q-)]. Nine cases of Crohn's disease complicated by leukemia have been reported, including the present one; once again, a relationship between Crohn's disease and leukemia is suggested.

Pharmacokinetics of cisplatin in combined cisplatin and 5-fluorouracil therapy: a comparative study of three different schedules of cisplatin administration.

BACKGROUND: Cisplatin is widely used in combination chemotherapy against a variety of tumors; however, the optimal administration schedule of cisplatin is still controversial. To clarify the pharmacokinetic differences according to the administration schedules of cisplatin, we compared three different administration schedules of cisplatin such as single short-term infusion, daily short-term infusion and daily continuous infusion in combination with 5-fluorouracil. Preliminary clinical responses and toxicities were also investigated. METHODS: A total of 12 courses in combination of cisplatin and 5-fluorouracil therapy was studied. The schedules of cisplatin tested were as follows: single short-term infusion (80 mg/m2, day 1,2 h div., n = 4), daily short-term infusion (20 mg/m2, days 1 to 5, 2 h div., n = 4), daily continuous infusion (100 mg/m2, 120 h, n = 4). In all schedules, 5-fluorouracil was continuously administered at a dose of 800 mg/m2/day on days 1 to 5. The area under the time-concentration curve (AUC) and the maximum concentration (Cmax) of total and free Pt were investigated. RESULTS: The highest AUC of total and free Pt and the lowest Cmax of free Pt were observed in the daily continuous infusion (total AUC; 162.53 +/- 18.39 micrograms h/ml, free AUC; 5.50 +/- 0.9 micrograms h/ml, free Cmax; 0.07 +/- 0.01 microgram/ml, mean +/- SEM). Two patients in the single short-term infusion and one patient in the daily continuous infusion indicated partial responses clinically. No nephrotoxicity or ototoxicity was observed. All toxicities were mild and tolerable in all regimens; however, the incidence of GI toxicity in daily continuous infusion seemed to be relatively higher. CONCLUSIONS: Daily continuous infusion of cisplatin gave the best pharmacokinetic results and to evaluate the clinical advantage of this schedule a prospective randomized trial should be conducted with sufficient numbers of patients.