The Changes in Relative Blood Volume during Dialysis Are Characterized by Ultrafiltration Rate and Predialysis Blood Test Values.

INTRODUCTION: Continuous monitoring of relative blood volume (percentage BV) in hemodialysis (HD) is critical for determining dry weight and preventing intradialytic hypotension. However, the cause of the BV variation remains unknown. This research aimed to examine factors that influence the percentage BV. METHODS: We devised a formula based on coefficients ("a," "τ," and "b") to predict changes in percentage BV. "a" denotes a significant decrease in percentage BV in the early stages of HD. "τ" represents the transition from early to late phase of HD. "b" denotes the slope of the decrease in percentage BV in the late phase of HD. We measured the percentage BV in 18 patients with end-stage renal disease. The coefficients were estimated by fitting experimental data from patients using a least squares optimization algorithm. A correlation analysis of these parameters and patient predialysis data was performed. RESULTS: Ultrafiltration rate (UFR) was found to be negatively correlated with "b" (r = -0.851, p < 0.01). However, UFR was not significantly related to "a." Predialysis serum total protein level was negatively correlated with "a" (r = -0.531, p = 0.042). Predialysis serum albumin and predialysis sodium were not significantly correlated with "a" and "τ." Plasma osmolarity did not have a significant relationship with "a" and "τ." DISCUSSION/CONCLUSION: UFR influenced the decrease in percentage BV in the late phase but did not influence the decrease of percentage BV in the early phase. "a" was associated with predialysis serum total protein level but not with plasma osmolality or predialysis sodium. This implies that colloid oncotic pressure is important for plasma refilling immediately after dialysis begins. During the change of percentage BV, the decrease in the early phase of dialysis was not related to UFR, but related to other parameters, especially predialysis total protein level. A decrease in the late phase of dialysis is related to UFR.

Predilution On-Line Hemodiafiltration Improves Albumin Redox in Maintenance Hemodialysis Patients.

BACKGROUND/AIM: In this study, we compared the dialysis efficiency, oxidative stress, and nutritional conditions between predilution on-line hemodiafiltration (pre-OL-HDF) and conventional hemodialysis (HD) using a super-flux dialyzer (CHD). METHOD: This was a crossover study of 38 maintenance HD patients. All patients were treated with CHD for the first 4 months (1st CHD period), then were switched to pre-OL-HDF for 4 months (pre-OL-HDF period), and were returned to CHD for the next 4 months (2nd CHD period). RESULTS: We found no significant difference in the removal ratio of small uremic substances or the indices of inflammation or nutritional states between the pre-OL-HDF and CHD periods. However, we found higher removal of ß2 micro-globulin in the pre-OL-HDF period, and the human mercapto-albumin (Alb)/human serum Alb ratio was significantly higher in the pre-OL-HDF period. CONCLUSION: Treatment with pre-OL-HDF enabled enhanced removal of middle molecule uremic toxins and better Alb redox than did CHD.

Ubiquitin-interacting motifs confer full catalytic activity, but not ubiquitin chain substrate specificity, to deubiquitinating enzyme USP37.

Ubiquitin-specific proteases (USPs) consist of a family of deubiquitinating enzymes with more than 50 members in humans. Three of them, including USP37, contain ubiquitin-interacting motifs (UIMs), an ∼20-amino acid α-helical stretch that binds to ubiquitin. However, the roles of the UIMs in these USP enzymes remain unknown. USP37 has three UIMs, designated here as UIMs 1, 2, and 3 from the N-terminal side, between the Cys and His boxes comprising the catalytic core. Here, we examined the role of the UIMs in USP37 using its mutants that harbor mutations in the UIMs. The nuclear localization of USP37 was not affected by the UIM mutations. However, mutations in UIM2 or UIM3, but not UIM1, resulted in a significant decrease in USP37 binding to ubiquitinated proteins in the cell. In vitro, a region of USP37 harboring the three UIMs also bound to both Lys(48)-linked and Lys(63)-linked ubiquitin chains in a UIM2- and UIM3-dependent manner. The level of USP37 ubiquitination was also reduced by mutations in UIM2 or UIM3, suggesting their role in ubiquitination of USP37 itself. Finally, mutants lacking functional UIM2 or UIM3 exhibited a reduced isopeptidase activity toward ubiquitinated proteins in the cell and both Lys(48)-linked and Lys(63)-linked ubiquitin chains. These results suggested that the UIMs in USP37 contribute to the full enzymatic activity, but not ubiquitin chain substrate specificity, of USP37 possibly by holding the ubiquitin chain substrate in the proximity of the catalytic core.

Longer virus shedding in influenza B than in influenza A among outpatients treated with oseltamivir.

OBJECTIVE: To compare the persistence, susceptibility and resistance of influenza A and influenza B viruses in oseltamivir therapy in outpatients of various ages. METHODS: Virus isolation was done before and 4-6 days after the initiation of oseltamivir therapy for 148 patients with influenza A/H3N2 and for 66 with influenza B in the 2003-2004 and 2004-2005 influenza seasons. Neuraminidase inhibition assay and neuraminidase or hemagglutinin sequence analysis were done using influenza viruses isolated from these patients. RESULTS: The virus isolation rate after oseltamivir therapy was significantly higher for influenza B (33.3%) than for influenza A/H3N2 (12.8%, p<0.001). The mean IC(50) values before and after oseltamivir therapy were significantly higher in patients with influenza B (10.82 and 11.32nM, respectively) than in patients with influenza A/H3N2 (0.94 and 0.81nM, respectively, both p<0.001). No significant differences in IC(50) among each age group, or no significant increase in IC(50) from before to after oseltamivir therapy was observed. Neuraminidase or hemagglutinin sequence analysis revealed no known genotype with resistance to oseltamivir. CONCLUSION: Virus persistence after oseltamivir therapy was longer and IC(50) values were higher in influenza B than influenza A.

Factors influencing the effectiveness of oseltamivir and amantadine for the treatment of influenza: a multicenter study from Japan of the 2002-2003 influenza season.

BACKGROUND: To evaluate the effectiveness of oseltamivir and amantadine for the treatment of influenza with respect to various clinical factors, a prospective multicenter study of the influenza season of 2002-2003 was done with 2163 patients whose condition was diagnosed by an antigen-detection test kit. METHODS: Oseltamivir was administered to 803 patients with influenza A (A+Os group) and 684 patients with influenza B (B+Os group). Amantadine was administered to 676 patients with influenza A (A+Am group). RESULTS: For each group, the duration of fever (i.e., body temperature, > or = 37.5 degrees C) was significantly shorter in patients who received the drug within 12 h after the onset of symptoms than in patients who received the drug > 12 h after the onset. For all 3 groups, the duration of fever was shorter in patients with a highest temperature < 39 degrees C than in patients with temperatures > or = 39 degrees C. The duration of fever was significantly longer for the B+Os group than for the A+Os group. Multiple regression analysis found that the type of influenza, the highest body temperature, and the time between the onset of symptoms and the start of treatment are independent factor that influence the duration of fever. CONCLUSIONS: Early administration increases the benefit of anti-influenza drugs--not only the benefit of oseltamivir treatment for influenza A, but also the benefit of amantadine treatment for influenza A and oseltamivir treatment for influenza B. Oseltamivir may be less effective as a treatment for influenza B than for influenza A. A highest body temperature of > or = 39 degrees C was an indicator of a longer duration of fever.

[Clinical symptoms of influenza infection in the 2002-2003 season].

The highest body temperature and clinical symptoms during the influenza infection were analyzed on 2,145 patients with influenza, (type A: 1,408cases, type B: 737cases: confirmed by a rapid diagnosis kit, Capilia FluA, B), and for 670 patients with a negative response to the rapid diagnosis kit (controls). The study was a multi-center study of the 2002-2003 influenza season. The percentages of patients with fever over 38 degrees C, 38.5 degrees C and 39 degrees C were significantly higher in influenza A than in influenza B or controls (16-64 yrs). Over 80% of the patients in all age groups of 0-6 yrs, 7-15 yrs, 16-64 yrs or over 64 yrs with influenza A or B had a cough. The percentage of patients with cough was significantly higher for patients with influenza A or B than for controls under 65 yrs. The percentages of influenza A or B patients with rhinorrhea or loss of appetite were significantly higher than in controls under 65 yrs. The percentage of patients reporting fatigue, headache or myalgia was significantly higher for influenza A than for controls of 16-64 yrs. Differences in symptoms, including fever, were minimal between influenza A and B patients under 16 yrs, and also among influenza A, B and controls in patients over 64 yrs. The percentage of patients with cough was not different among the three age groups by influenza A or B. However, the percentage of patients with rhinorrhea, loss of appetite, vomiting or diarrhea was higher in children under 16 yrs than in adults aged 16-64 yrs in influenza A or B. In conclusion, consideration must be given to the patient's age and the type of influenza when doing a symptomatic diagnosis of influenza. In addition, the use of a rapid diagnosis kit seems necessary for the diagnosis of influenza in elderly patients, who may have no specific symptoms of influenza.

[An analysis of the 2002-2003 influenza epidemic focusing on patients infected with types A and B in the same season sequentially].

A total of 2,320 cases of influenza A (1,517 cases) and B (803 cases) in the 2002-2003 influenza season were analyzed. Influenza infection was confirmed by a rapid diagnosis kit, based on the immunochromatography method, at 24 clinics in 18 of the 47 prefectures of Japan. Influenza A/H3N2 was reported between November 22 and April 12 (the median at January 21), and influenza B was reported between December 24 and April 20 (the median at February 16). The mean age of type B patients (16.7 years old) was significantly younger than that of type A patients (26.7 years old) (p < 0.001). Pneumonia was more frequently a complication of type A (0.63%) than of type B (0%, p < 0.05). Although 5 type A patients needed hospitalization, neither hospitalization nor death was associated with type B. Of the 2,293 cases, 27 (1.2%) were infected with both influenza of A and B. The age of these 27 patients ranged from 2 to 51 years (mean of 11.2 years), but 20 of the 27 patients were 9 years of age or under. Type B followed type A in 25 patients. The median date of these 25 type A patients was January 22, similar to that of all cases of type A, January 21. However, the median date of type B infection was March 3, 15 days later than that of all patients with type B, February 16. The mean age of the 27 cases was significantly younger than that of all cases of type A (p < 0.001) and type B (p < 0.05). In epidemics consisting of multiple types of influenza viruses, patients may be infected by more than one virus. This is especially true for children.

[Effectiveness of oseltamivir on influenza and influencing factors: age of patients, type of influenza virus and timing of initial administration].

A multi-center open study using the internet was performed during the influenza season of 2001-2002 to evaluate the effectiveness of the anti-influenza agent, oseltamivir, on influenza in relation to: (1) age of patients; (2) type of influenza virus; and (3) timing of initial administration after the onset of the first symptoms of influenza. The study comprised of 779 cases of influenza confirmed by rapid detection tests from 44 clinics in Japan. Patients consisted of 4 age groups, 0-6, 7-15, 16-64 and 65-85 years. All patients were administered oseltamivir within 24 hours, at 25-48 or after 48 hours from the onset of the first symptoms of influenza. Data collected from each age group were the highest body temperature and duration of fever (> or = 37.5 degrees C). The percentage of afebrile patients was calculated at 24, 48 and 72 hours after the initial administration; data were also evaluated by the type of influenza virus A and B. The highest body temperature was higher with statistical significance as patients' age decreased. The duration of febrile period (days) was significantly longer in 0-6 years (2.57 +/- 0.95) than in 65-85 years (2.18 +/- 0.93). Evaluation of the percentage of afebrile patients revealed: the percentage at 24 hours was significantly lower in 0-6 years (28.4%) than in 16-64 years (44.0%); the percentage at 48 and 72 hours showed similar results in each age group; the percentage at 48 and 72 hours was significantly higher when administered initially within 24 hours than over 48 hours after the onset of the first symptoms of influenza; the percentage at 24 and 48 hours was significantly higher when administered within 24 hours than at 25-48 hours; and the type of influenza virus did not affect the percentage. In conclusion, effectiveness of oseltamivir seemed to be affected to an extent by the patients' age and little by the type of influenza virus. Oseltamivir was more effective when administered as early as possible after the onset of the symptoms of influenza.