Evaluation of patient dose from diagnostic X-ray using glass badges

Radiography is used in medical practices based on the principles of justification and optimization. Patients' exposure doses should be kept as low as still allows for image quality that does not disturb the diagnostic processes. To optimize diagnostic radiological procedures, the international commission on radiological protection (ICRP) advocated the establishment of diagnosis reference levels (DRLs) in the new basic recommendation (Publication 103) in 2007 by stating that "The DRL should be expressed as a readily measurable patient-dose-related quantity for the specified procedure." In this context, a simple and standardized dosimetric method is needed to verify the adaptability of a radiation dose to the DRLs. As a measuring instrument that has good availability, high accuracy, and easy operability, we adopted the glass badge system, which has been used for individual exposure dose management. We evaluated the accuracy of the system as a tool of simplified dosimetry of diagnostic X-rays by comparing it to the standard dosimetry of an ionization chamber. In an energy range of 50 to 140 kV for X-ray exposure, the glass badge showed values within 7% of or closer to those measured by the standard ionization chamber. Moreover, the glass badge measurement was independent of the rectification modes of the X-ray tubes. In conclusion, glass badge measurement is feasible for verifying diagnostic X-ray doses in relation to DRLs and can be widely used in hospitals and clinics.     

Potential use of beards for single-follicle micrografts: convenient follicle-harvesting technique using an injection needle.

The authors developed a convenient hair-harvesting procedure using a disposable 18-gauge injection needle, which is common in every clinical scene. The needle was used as a skin puncher to harvest single follicles. The harvested micrografts were transplanted without trimming any of the adjacent tissue around the follicle. Clinical applications for the reconstruction of eyebrows in cases of anhydrotic ectodermal dysplasia and facial scars are demonstrated. Each patient showed a favorable result, and there was no scar formation at the donor site. This procedure makes hair harvesting smooth, speedy, and less traumatic. Beards as well as occipital hairs can be used as donors for single-follicle micrografts with this method in male patients.     

Myocardial blood flow, alternans of ST segment elevation, conduction delay and ventricular arrhythmia during acute myocardial ischemia with and without retrograde blood flow in canine hearts

The technique of retrograde blood flow has been shown to decrease collateral flow into the ischemic myocardium, and to cause severe myocardial ischemia in dogs. Ischemia with retrograde blood flow in dogs is similar to ischemia in human hearts. Therefore, we examined the effect of retrograde blood flow on myocardial blood flow, ST segment elevation, alternans of ST segment elevation, conduction delay and ventricular arrhythmia in dogs. Sixty dogs were divided into two groups. In group A (N = 32), the left anterior descending coronary artery was occluded for 10 min. In group B (n = 28), ischemia was induced by the technique of retrograde blood flow for 10 min. During ischemia, the myocardial blood flow at the ischemic zone measured by a H2 gas clearance method was 11.2 +/- 1.6 in group A and 5.7 +/- 0.7 ml/min/100 g in group B (p less than 0.01). The maximal ST segment elevation was 13.6 +/- 1.9 in group A and 27.2 +/- 2.1 mV in group B (p less than 0.001); the maximal alternans of ST segment elevation was 5.3 +/- 1.1 in group A and 10.1 +/- 1.4 mV in group B (p less than 0.01); the maximal conduction delay was 51.6 +/- 8.4 in group A and 111.1 +/- 6.2 msec in group B (p less than 0.001); and the incidences of ventricular premature beats (greater than 5/min), ventricular tachycardia and fibrillation were 34%, 41% and 22% in group A, and 68%, 79% and 25% in group B (p less than 0.01, p less than 0.01 and not significant, respectively). It is concluded that ischemia with retrograde blood flow can be used to examine occlusive and reperfusion ventricular arrhythmia in dogs, because the incidences of ventricular premature beats and ventricular tachycardia were high, but that of ventricular fibrillation was not high despite the severe ischemia.     

Neurological manifestations of thoracic myelopathy

Introduction

Investigation of preoperative manifestations of thoracic myelopathy in a large population has not been reported. The aim of this study was to identify symptoms specific to anatomical pathology or compressed segments in thoracic myelopathy through investigation of preoperative manifestations.

Materials and methods

Subjects were 205 patients [143 men, 62 women; mean age, 62.2 (range 21–87 years)] with thoracic myelopathy who underwent surgery at our affiliate institutions from 2000 to 2011. The disease distribution included ossification of the ligamentum flavum (OLF) in 106 patients, ossification of the posterior longitudinal ligament (OPLL) in 17, OLF with OPLL in 17, intervertebral disc herniation (IDH) in 23, OLF with IDH in 3, and spondylosis in 39. We assessed (1) initial and preoperative complaints, (2) neurological findings, (3) Japanese Orthopaedic Association scores (JOA, full score, 11 points), (4) the compressed segments, and (5) preoperative duration. Multivariate analyses were performed to examine potential relationships between preoperative manifestations and anatomical pathology or compressed segments.

Results

The multivariate analyses revealed relationships between lower limb muscle weakness and T10/11 anterior compression; lower limb pain and T11/12 anterior compression; low back pain and T11/12 compression; and hyporeflexia in the patellar tendon reflex/foot drop and T12/L1 anterior compression.

Conclusion

This study elucidated symptoms specific to anatomical pathology or compressed segments in thoracic myelopathy. These relationships can be helpful in the initial investigation of thoracic diseases, although additional measures such as MRI or CT are necessary for definitive diagnosis.     

Prediction of interindividual differences in hepatic functions and drug sensitivity by using human iPS-derived hepatocytes

Interindividual differences in hepatic metabolism, which are mainly due to genetic polymorphism in its gene, have a large influence on individual drug efficacy and adverse reaction. Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem (iPS) cells have the potential to predict interindividual differences in drug metabolism capacity and drug response. However, it remains uncertain whether human iPSC-derived HLCs can reproduce the interindividual difference in hepatic metabolism and drug response. We found that cytochrome P450 (CYP) metabolism capacity and drug responsiveness of the primary human hepatocytes (PHH)-iPS-HLCs were highly correlated with those of PHHs, suggesting that the PHH-iPS-HLCs retained donor-specific CYP metabolism capacity and drug responsiveness. We also demonstrated that the interindividual differences, which are due to the diversity of individual SNPs in the CYP gene, could also be reproduced in PHH-iPS-HLCs. We succeeded in establishing, to our knowledge, the first PHH-iPS-HLC panel that reflects the interindividual differences of hepatic drug-metabolizing capacity and drug responsiveness.Drug-induced liver injury (DILI) is a leading cause of the withdrawal of drugs from the market. Human induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (HLCs) are expected to be useful for the prediction of DILI in the early phase of drug development. Many groups, including our own, have reported that the human iPS-HLCs have the ability to metabolize drugs, and thus these cells could be used to detect the cytotoxicity of drugs that are known to cause DILI (1, 2). However, to accurately predict DILI, it will be necessary to establish a panel of human iPS-HLCs that better represents the genetic variation of the human population because there are large interindividual differences in the drug metabolism capacity and drug responsiveness of hepatocytes (3). However, it remains unclear whether the drug metabolism capacity and drug responsiveness of human iPS-HLCs could reflect those of donor parental primary human hepatocytes (PHHs). To address this issue, we generated the HLCs differentiated from human iPSCs which had been established from PHHs (PHH-iPS-HLCs). Then, we compared the drug metabolism capacity and drug responsiveness of PHH-iPS-HLCs with those of their parental PHHs, which are genetically identical to the PHH-iPS-HLCs.Interindividual differences of cytochrome P450 (CYP) metabolism capacity are closely related to genetic polymorphisms, especially single nucleotide polymorphisms (SNPs), in CYP genes (4). Among the various CYPs expressed in the liver, CYP2D6 is responsible for the metabolism of approximately a quarter of commercially used drugs and has the largest phenotypic variability, largely due to SNPs (5). It is known that certain alleles result in the poor metabolizer phenotype due to a decrease of CYP2D6 metabolism. Therefore, the appropriate dosage for drugs that are metabolized by CYP2D6, such as tamoxifen, varies widely among individuals (6). Indeed, in the 1980s, polymorphism in CYP2D6 appears to have contributed to the withdrawal of CYP2D6-metabolized drugs such as perhexiline from the market in many countries (7). If we could establish a panel of HLCs that better represents the diversity of genetic polymorphisms in the human population, it might be possible to determine the appropriate dosage of a drug for a particular individual. However, it is not known whether the drug metabolism capacity and drug responsiveness of HLCs reflect the genetic diversity, including SNPs, in CYP genes. Therefore, in this study we generated HLCs from several PHHs that have various SNPs on CYP2D6 and then compared the CYP2D6 metabolism capacity and responses to CYP2D6-metabolized drugs between the PHH-iPS-HLCs and parental PHHs.To this end, PHHs were reprogrammed into human iPSCs and then differentiated into the HLCs. To examine whether the HLCs could reproduce the characteristics of donor PHHs, we first compared the CYP metabolism capacity and response to a hepatotoxic drug between PHHs and genetically identical PHH-iPS-HLCs (12 donors were used in this study). Next, analyses of hepatic functions, including comparisons of the gene expression of liver-specific genes and CYPs, were performed to examine whether the hepatic characteristics of PHHs were reproduced in the HLCs. To the best of our knowledge, this is the first study to compare the functions between iPSC-derived cells from various donors and their parental cells with identical genetic backgrounds. Finally, we examined whether the PHH-iPS-HLCs exhibited a capacity for drug metabolism and drug responsiveness that reflect the genetic diversity such as SNPs on CYP genes.     

Participation of food antigens in increased polyclonal antibody production induced by alcohol

In order to obtain a better understanding of hyperglobulinemia in chronic alcoholism, we investigated whether food antigens participated in the effects of long-term oral alcohol (AL) administration on serum immunoglobulin levels and polyclonal antibody production in spleen, Peyer's patch and bone marrow of C57BL/6 mice in specific pathogen free (SPF) circumstances. In animals fed antigen food (AF), three weeks of oral AL administration elicited an increase in polyclonal IgA antibody production in Peyer's patch. Moreover, seven weeks of oral AL administration elicited increases in both polyclonal IgA antibody production and serum IgA level. However, in animals fed antigen free food (AFF), oral AL administration failed to elicite increases in serum IgA level and polyclonal antibody production in spleen, Peyer's patch and bone marrow. Furthermore, in animals fed AF or AFF, oral AL administration failed to elicite increases in polyclonal IgM and IgG antibody production in any organ and serum IgM and IgG level. It is suggested that food antigens participated greatly in the elevation of serum IgA level in chronic alcoholism and that Peyer's patch is the major site of polyclonal IgA antibody production.