Association Between Tacrolimus Pharmacokinetics and Cytochrome P450 3A5 and Multidrug Resistance Protein 1 Exon 21 Polymorphisms.

BACKGROUND: Individual differences in the pharmacokinetics (PK) of tacrolimus (TAC), an immunosuppressive drug, are reportedly associated with single-nucleotide polymorphisms (SNPs) of cytochrome P450 (CYP) 3A5 and multidrug resistance protein 1 (MDR1). We determined the effect of SNPs in CYP3A5 and MDR1 exons 21 and 26 on TAC PK parameters. METHODS: Thirty-eight Japanese patients who underwent renal transplantation were genotyped for CYP3A5 and exons 21 and 26 of MDR1 with the use of polymerase chain reaction-restriction fragment length polymorphism analysis. TAC concentrations were determined 3 weeks after renal transplantation and PK parameters calculated. RESULTS: The area under the blood concentration-time curve (AUC) in CYP3A5 expressers was significantly higher than that in CYP3A5 nonexpressers (CYP3A5*3/*3). Patients with the MDR1 exon 21 A allele (G2677A) showed higher dose-adjusted AUC (AUC/D) and lower doses of TAC than those who did not possess that allele. Furthermore, patients with both CYP3A5*3/*3 and MDR1 G2677A showed significantly lower TAC doses and higher dose-adjusted trough levels (C/D) and AUC/D than those without those genotypes. There was no significant association between MDR1 exon 26 polymorphism and the PK of TAC. CONCLUSIONS: Patients with both CYP3A5*3/*3 and MDR1 G2677A had higher blood TAC concentrations than those without those genotypes. Japanese patients should be carefully monitored for consideration of lower TAC doses, because 24% of Japanese patients have double mutations.

Spin/orbital and magnetic quantum number selective magnetization measurements for CoFeB/MgO multilayer films.

Spin selective magnetic hysteresis (SSMH) curves, orbital selective magnetic hysteresis (OSMH) curves and magnetic quantum number selective SSMH curves are obtained for CoFeB/MgO multilayer films by combining magnetic Compton profile measurements and superconducting quantum interference device (SQUID) magnetometer measurements. Although the SQUID magnetometer measurements do not show perpendicular magnetic anisotropy (PMA) in the CoFeB/MgO multilayer film, PMA behavior is observed in the OSMH and SSMH curves for the |m| = 2 magnetic quantum number states. These facts indicate that magnetization switching behavior is dominated by the orbital magnetization of the |m| = 2 magnetic quantum number states.

Comparison of viscoelastic characteristics in triceps surae between Black and White athletes.

The purpose of the present study was to investigate race differences in viscoelastic characteristics of triceps surae muscle group. Black and white college sprint type athletes (n=44) participated in this study. Viscoelastic properties were assessed using the free vibration technique: subjects sat with their forefeet on the edge of a force-plate (Kistler, Switzerland) and support a frame loaded with weights (0-40 kg) on the knees. Oscillations of the triceps surae and Achilles tendon system were initiated with a hand-held hammer by tapping the weight load. Oscillations occur at frequencies of 3-6 Hz and were slightly damped. The damped oscillations in conjunction with the equation of motion of a damped mass-spring model were used to calculate the viscosity of muscle (b), and the elasticity of muscle fibres (k(d)) and tendon (k(t)) in each subject. There were little significant differences in most of physical characteristic variables between black and white athletes. Black athletes have significantly greater muscle viscosity and elasticity than white athletes while tendon elasticity is equivalent. Thus, muscle stiffness is greater among black athletes. Greater muscle stiffness could contribute to greater sprint/jump performance among black athletes, compared with white athletes, through alteration of foot/ground contact and take-off phases during sprinting/jumping.

Asymptomatic brain tumor detected at brain check-up.

Brain check-up was performed in 4000 healthy subjects who underwent medical and radiological examinations for possible brain diseases in our hospital from April 1996 to March 2000. Magnetic resonance imaging revealed 11 brain tumors which consisted of six meningiomas, three pituitary adenomas, one astrocytoma, and one epidermoid cyst. The detection rate of incidental brain tumor in our hospital was 0.3%. Nine patients underwent surgery, with one case of morbidity due to postoperative transient oculomotor nerve paresis. The widespread use of brain check-up may increasingly detect asymptomatic brain tumors. Surgical indications for such lesions remain unclear, and the strategy for treatment should be determined with consideration of the patient's wishes.

[Cerebral arteritis and cerebritis caused by subdural empyema: two cases report].

We report two cases of cerebral angitis and cerebritis caused by subdural empyema. A 22-year-old man, who complained of a headache and high fever, suddenly developed unconsciousness and right hemiparesis. CT and MRI demonstrated left subdural empyema with diffuse brain swelling. CT angiography showed diffuse narrowing of the left internal carotid artery, middle cerebral artery, and anterior cerebral artery. Although we performed craniotomy, continuous irrigation with drainage, systemic injection of antibiotics for subdural empyema, antiplatelet therapy, and hyperbaric oxygen therapy for angitis, his condition remained unchanged. A 67-year-old man who had previously undergone burr hole surgery presented to our hospital for the treatment of scalp infection. He suddenly developed unconsciousness and right hemiparesis. CT and MRI demonstrated left subdural empyema with diffuse brain swelling, but MR angiography did not show any abnormal findings. Hemiparesis improved after the surgery and systemic injection of the antibiotics. Subdural empyema with sinusitis or meningitis around the skull base sometimes causes cerebral angitis. We considered that the angiographical evaluation for the subdural empyema was necessary to detect angitis.

In vivo determination of muscle viscoelasticity in the human leg.

The purpose of this study was to examine the methodological validity of the free vibration technique for determining individual viscoelastic characteristics of the human triceps surae muscle-tendon complex (MTC) in vivo. Six subjects sat with first phalangeal joint of the forefoot on the edge of a force-plate. The special frame on the knee was loaded with weight (0-40 kg) for testing. Oscillations of the triceps surae MTC system were initiated with a hand-held hammer by tapping the weight. In order to keep the same posture, the output of the force plate was displayed on the oscilloscope and subjects were asked to maintain the beam on the oscilloscope at a particular location in relation to a reference line. The damped oscillations in conjunction with the equation of motion of a damped mass-spring model were used to calculate the viscosity of muscle (b) and the elasticity of muscle fibres and tendon (k) in each subject, considering moment arm of the ankle joint. With this arrangement, we have obtained high reproducibility in this method. The coefficient of variations (CVs) of b and k in five trials at each weight were quite small (range: 0.5-18.7% in b and 1.0-15.1% in k). There were no significant differences in viscoelastic coefficients between right and left legs. Therefore, it appears that free vibration technique, used here, is adequate in describing the viscoelastic characteristics of the triceps surae in vivo in humans.

Computer-assisted neurosurgical navigational system for transsphenoidal surgery--technical note.

Transsphenoidal surgery carries the risk of carotid artery injury even for very experienced neurosurgeons. The computer-assisted neurosurgical (CANS) navigational system was used to obtain more precise guidance, based on the axial and coronal images during the transsphenoidal approach for nine pituitary adenomas. The CANS navigator consists of a three-dimensional digitizer, a computer, and a graphic unit, which utilizes electromagnetic coupling technology to detect the spatial position of a suction tube attached to a magnetic sensor. Preoperatively, the magnetic resonance images are transferred and stored in the computer and the tip of the suction tube is shown on a real-time basis superimposed on the preoperative images. The CANS navigation system correctly displayed the surgical orientation and provided localization in all nine patients. No intraoperative complications were associated with the use of this system. However, outflow of cerebrospinal fluid during tumor removal may affect the accuracy, so the position of the probe when the tumor is removed must be accurately determined. The CANS navigator enables precise localization of the suction tube during the transsphenoidal approach and allows safer and less-invasive surgery.

Characteristics of symptomatic chronic subdural haematomas on high-field MRI.

We studied the frequency of various features of the appearances on high-field MRI in symptomatic patients with chronic subdural haematomas (CSDH). The ability to predict recurrence after treatment with one burr-hole procedure using MRI was evaluated. A total of 40 patients with symptomatic CSDH underwent MRI at 1.5 T. All haematomas were evacuated within a few days of the MRI examination. Symptomatic CSDH were divided into five groups according to the MRI findings: group A (11 cases), isointense or low signal on T1- and low signal on T2-weighted images; group B (18 cases), high signal on T1- and low signal on T2-weighted images; group C (5 cases), high signal on both T1- and T2-weighting; group D (1 case), low signal on T1- and high signal on T2-weighted images; group E (5 cases), heterogeneous intensity on T1- and T2-weighting throughout the haematoma cavity. The mean interval between onset of symptoms and MRI for group A was 5.0 +/- 4.1 days, which was significantly shorter than that for group B (9.4 +/- 4.4 days, P < 0.02), group C (27.8 +/- 20 days, P < 0.005) or group E (17.8 +/- 12.2 days, P < 0.01). Recurrence was seen in three haematomas of group A and one of group B. Reoperation was most closely correlated with diffuse low signal on T2-weighted images but not with a multiloculated appearance. Low signal on T2 weighting was surprisingly high (72.5%) and the age of the haematomas as estimated on the MRI correlated well with the interval between the onset of symptoms and MRI. Our findings support the causative role of recurrent bleeding in the enlargement of CSDH.