We reported previously that exercise significantly increases plasma adrenaline and oxidized low-density lipoprotein (oxLDL) in healthy subjects but not in persons with spinal cord injury (SCI). Since ...oxLDL and adrenaline levels are associated with oxidant/antioxidant balance, and exercise training elicits production of reactive oxygen species, we elucidated the effects of exercise on adrenaline, oxidant/antioxidant balance and oxLDL in individuals with SCI.
Eight subjects with cervical spinal cord injury (CSCI) and nine subjects with lower lesion of SCI (lower SCI (LSCI)) participated in a wheelchair half marathon race, and blood samples were collected before (pre), immediately after (post) and 1 h after the race (post 1 h). The blood samples were used to determine adrenaline, derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP), both as markers for oxidant/antioxidant balance.
Pre-serum oxLDL levels were 147.2±8.1 and 97.0±10.4 U l
(mean±s.e.m.) in LCSI and CSCI subjects, respectively, and remained stable throughout the study. Adrenaline levels were higher in LSCI athletes than in CSCI athletes, especially post half marathon. Serum d-ROMs level did not change between pre and post in both groups. The mean BAP was significantly higher in LSCI than in CSCI subjects (2574±94.6 vs 2118±94.6 μmol l
) at post, whereas the oxidative stress index (d-ROMs/BAP) was similar in the two groups throughout the study. In conclusion, exercise did not increase the d-ROMs or d-ROMs/BAP ratio in CSCI and LSCI subjects. The lack of increase in the plasma oxLDL level in SCI subjects was not due to the lack of response of adrenaline to exercise.
The steady-state concentrations of digoxin at trough levels were studied to establish the role of patient characteristics in estimating doses for digoxin using routine therapeutic drug monitoring ...data.
The data (n = 448) showing steady state after repetitive oral administration in 172 hospitalized neonates and infants were analyzed using Nonlinear Mixed Effect Model (NONMEM), a computer program designed to analyze pharmacokinetics in study populations by allowing pooling of data. Analysis of the pharmacokinetics of digoxin was accomplished using a simple steady-state pharmacokinetic model. The effects of a variety of developmental and demographic factors on the clearance of digoxin were investigated.
Estimates generated using NONMEM indicated that clearance of digoxin (l.h-1) was influenced by the demographic variables of age, total body weight, serum creatinine, the coadministration of spironolactone, and the presence or absence of congestive heart failure. The interindividual variability in digoxin clearance was modeled with proportional errors with an estimated coefficient of variation of 32.1%, and the residual variability was 28.9%. In the validation set of 66 patients, the performance (bias, precision) of the final population model was good (mean prediction error -0.04 ng.ml-1; mean absolute prediction error 0.20 ng.ml-1).
To clarify the observed variability of digoxin disposition by performing a population pharmacokinetic analysis in a Japanese population.
Retrospective analysis of clinical pharmacokinetic data.
Data ...were obtained from 106 patients with heart failure and atrial fibrillation (43 males and 63 females).
Digoxin concentrations in serum were measured by fluorescence polarisation immunoassay. Population pharmacokinetic analysis was performed using a 2-compartment open pharmacokinetic model with the computer program NONMEM.
246 serum concentrations were obtained. Final pharmacokinetic parameters were: CL (L/h) = (0.036 x TBW + 0.112 x CL(CR)) x 0.77SPI x 0.784CCB, V1 = 1.83 L/kg, V2 = 22.6 L/kg and Q = 0.629 L/h/kg, where CL is total body clearance, V1 and V2 are the apparent volumes of distribution in the central and peripheral compartments, Q is intercompartmental clearance, TBW is total bodyweight (in kg), CL(CR) is creatinine clearance (in ml/min), SPI = 1 for concomitant administration of spironolactone (and zero otherwise) and CCB = 1 for concomitant administration of calcium antagonists (and zero otherwise). Concomitant administration of digoxin and spironolactone resulted in a 23% decrease in digoxin clearance. Concomitant administration of digoxin and calcium antagonists (diltiazem, nicardipine, nifedipine or verapamil) resulted in a 21.6% decrease in digoxin clearance.
The estimated population parameter values may assist clinicians in the individualisation of digoxin dosage regimens.
Blood volume is influenced by physical activity. Physical activity in patients with spinal cord injury is lower than able-bodied individuals and associated with the level of lesion. We hypothesized ...that blood volume in patients with cervical spinal cord injury might be lower than able-bodied individuals and influenced by the level of lesion. To eliminate the effect of the lesion level, we determined blood volume by Evans blue dilution technique in 9 male patients with cervical spinal cord injury (age; 25.9 ± 1.9 years, mean ± SEM) whose level of lesions were C6 and compared them with 5 male able-bodied individuals (age; 27.6 ± 1.9). Plasma volume and blood volume in patients with cervical spinal cord injury were similar to those in able-bodied individuals. Despite the lower activity level of patients with cervical spinal cord injury in a wheelchair, blood volume did not change. Maintenance of blood volume in patients with cervical spinal cord injury is probably due to a reduction of central blood volume. The mechanism underlying reduced central blood volume appears to be lower vessel tension caused by autonomic nervous system dysfunction and/or lack of the muscle pump below the level of spinal cord lesion.
Chimerism analysis by polymerase chain reaction amplification of short tandem repeats (PCR-STR) has become a routine diagnostic procedure for evaluating grafts and assessing the likeliness of ...original disease recurrence after allogeneic stem cell transplantation. Following a sex-mismatched hematopoietic stem cell transplantation (HSCT), we monitored the clinical course of a 61-year old male AML M6 patient with trisomy 8 using PCR-STR with a TH01 locus on 11p15 and fluorescence in situ hybridization (FISH) analysis specific for alpha satellite DNA on chromosome 8. Ten months after HSCT, FISH analysis showed 24.8% recipient cells, but PCR-STR demonstrated 100% donor type chimerism. Further XY FISH analysis of May-Grünwald-Giemsa-stained bone marrow samples clearly demonstrated relapse of the original disease and G-banding analysis of bone marrow samples at relapse showed that an additional chromosomal abnormality, del(11) (p10), had deleted the PCR-STR detection site in all recipient type cells. As such, clinicians should consider the possibility that unexpected karyotype changes may invalidate PCR-STR analysis findings, especially when conflicting results appear among chimerism analyses.
IntroductionPatients with coronavirus disease, especially solid organ transplant recipients, are more susceptible to developing cytokine release syndrome than those with other viral infections. ...However, currently, treatment methods for such patients have not been established. Here, we describe two cases of successful immunomodulation in Japanese kidney transplant recipients with cytokine release syndrome following coronavirus disease. Case presentationTwo patients who had been receiving long-term immunosuppressant therapy developed coronavirus disease-associated pneumonia caused by cytokine release syndrome, following immunosuppressant dosage reduction. However, they recovered immediately after administration of tocilizumab with or without dexamethasone. ConclusionThe immunosuppressant dosage should be reduced to restore host immunity; however, immunomodulation should be considered in cases of suspected cytokine release syndrome.
Blood volume is influenced by physical activity. Physical activity in patients with spinal cord injury is lower than able-bodied individuals and associated with the level of lesion. We hypothesized ...that blood volume in patients with cervical spinal cord injury might be lower than able-bodied individuals and influenced by the level of lesion. To eliminate the effect of the lesion level, we determined blood volume by Evans blue dilution technique in 9 male patients with cervical spinal cord injury (age; 25.9 ± 1.9 years, mean ± SEM) whose level of lesions were C6 and compared them with 5 male able-bodied individuals (age; 27.6 ± 1.9). Plasma volume and blood volume in patients with cervical spinal cord injury were similar to those in able-bodied individuals. Despite the lower activity level of patients with cervical spinal cord injury in a wheelchair, blood volume did not change. Maintenance of blood volume in patients with cervical spinal cord injury is probably due to a reduction of central blood volume. The mechanism underlying reduced central blood volume appears to be lower vessel tension caused by autonomic nervous system dysfunction and/or lack of the muscle pump below the level of spinal cord lesion.
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