Development of culture-sensitive clinical teacher evaluation sheet in the Japanese context

Aim: Many instruments for evaluating clinical teaching have been developed, albeit most in Western countries. This study aims to develop a validated cultural and local context sensitive instrument for clinical teachers in an East Asian setting (Japan), Japanese Clinical Teacher Evaluation Sheet (JaCTES).

Methods: A multicenter, cross-sectional evaluation study was conducted. We collected a total of 1368 questionnaires on 304 clinical teachers, completed by residents in 16 teaching hospitals. The construct validity was examined by conducting a factor analysis and using structural equation modeling (SEM). We also assessed the reliability using generalizability analysis and decision study.

Results: Exploratory factor analysis resulted in three-factor (role model, teaching activities, and accessibility) model including 18 items. Confirmatory factor analysis was performed, using SEM. The comparative fit index was 0.931 and the root mean square error of approximation was 0.087, meaning an acceptable goodness of fit for this model. To obtain a reliable dependability-coefficient of at least 0.70 or higher, 5–8 resident responses are necessary.

Discussion and conclusion: JaCTES is the first reported instrument with validity evidence of content and internal structure and high feasibility in Japan, an East Asian setting. Medical educators should be aware of the local context and cultural aspects in evaluating clinical teachers.     

Association between ApoE phenotypes and telomere erosion in Alzheimer's disease

Although several reports suggest that Alzheimer's disease (AD) is associated with shortened telomere length, the clinical relevance of this has not yet been fully elucidated. This study was conducted to clarify the correlation of telomere length with clinical characteristics and ApoE phenotypes in 74 AD patients. Telomere length was determined from genomic DNA extracted from whole blood by quantitative real-time polymerase chain reaction. We found no significant difference in telomere length between the AD and non-dementia elderly control (n = 35) groups. Furthermore, no significant correlation was found among telomere length and the severity of cognitive decline and disease duration, age, or gender difference. However, telomere length was significantly shorter in AD patients with the ApoE4 homozygote than in those with the ApoE4 heterozygote (p < .001) and noncarriers (p < .001). These findings suggest that shortened telomere length may be associated with the ApoE4 homozygote in AD patients.     

Complex translocations derived stepwise from standard t(15;17) in a patient with variant acute promyelocytic leukemia

We report the case of an elderly man with an acute promyelocytic leukemia variant carrying complex variant translocations. The Q-banded karyotype and spectral karyotyping method revealed a typical t(15;17), and two complex rearrangements caused by stepwise translocation derived from a typical t(15;17). Chromosomes 8 and 14 were related to these rearrangements. The patient received induction chemotherapy using all-trans retinoic acid and achieved complete remission. To our knowledge, a case with complex rearrangements, caused by apparent stepwise translocation, at diagnosis, has not been reported previously.     

Generation of a novel CD30+ B cell subset producing GM-CSF and its possible link to the pathogenesis of systemic sclerosis

Systemic sclerosis (SSc) is a T helper type 2 (Th2)-associated autoimmune disease characterized by vasculopathy and fibrosis. Efficacy of B cell depletion therapy underscores antibody-independent functions of B cells in SSc. A recent study showed that the Th2 cytokine interleukin (IL)-4 induces granulocyte–macrophage colony-stimulating factor (GM-CSF)-producing effector B cells (GM-B_effs) in humans. In this study, we sought to elucidate the generation mechanism of GM-B_effs and also determine a role of this subset in SSc. Among Th-associated cytokines, IL-4 most significantly facilitated the generation of GM-B_effs within memory B cells in healthy controls (HCs). In addition, the profibrotic cytokine transforming growth factor (TGF)-β further potentiated IL-4- and IL-13-induced GM-B_effs. Of note, tofacitinib, a Janus kinase (JAK) inhibitor, inhibited the expression of GM-CSF mRNA and protein in memory B cells induced by IL-4, but not by TGF-β. GM-B_effs were enriched within CD20⁺CD30⁺CD38^−/low cells, a distinct population from plasmablasts, suggesting that GM-B_effs exert antibody-independent functions. GM-B_effs were also enriched in a CD30⁺ fraction of freshly isolated B cells. GM-B_effs generated under Th2 conditions facilitated the differentiation from CD14⁺ monocytes to DC-SIGN⁺CD1a⁺CD14⁻CD86⁺ cells, which significantly promoted the proliferation of naive T cells. CD30⁺ GM-B_effs were more pronounced in patients with SSc than in HCs. A subpopulation of SSc patients with the diffuse type and concomitant interstitial lung disease exhibited high numbers of GM-B_effs. Together, these findings suggest that human GM-B_effs are enriched in a CD30⁺ B cell subset and play a role in the pathogenesis of SSc.     

Aortitis during intraarterial chemotherapy for cervical cancer

A 76-year-old woman with stage IIb cervical cancer with a bulky tumor experienced aortitis during continuous intraarterial cisplatin-based chemotherapy. The chemotherapy was administered through a catheter tip placed in the aorta abdominalis, utilizing an external infusion pump. During the third course of chemotherapy, she complained of left-sided lower back pain and moderate fever was observed. Elevated white blood cell count (WBC) and C-reactive protein (CRP) level were noted, and an abdominal X-ray and urgent computed tomography (CT) were performed. The catheter tip was displaced against the arterial blood flow. At this level of the aortic wall, soft tissue density surrounded the aorta completely. Aortitis caused by the intraarterial chemotherapy, was strongly suspected. It was thought that the maldistribution of drugs and changes in the drug flow occurrred due to the vertebral height movement of the catheter tip against the aortic blood flow, and there, flow to the vasa vasorum may have occurred. Chemical vasculitis of the vasa vasorum due to the anticancer drugs was strongly suspected as a contributing factor of the aortitis. Because of the long-term use of an intraarterial catheter, the maldistribution of drugs and changes in the drug flow occurred physically and biologically during the course of the chemotherapy. We recommend occasional monitoring of the location of the catheter tip and a repeat evaluation with contrast medium in regard to flow to the vasa vasorum. Received: August 29, 2001 / Accepted: December 17, 2001     

Increased formaldehyde in jet engine exhaust with changes to JP-8, lower temperature, and lower humidity irritates eyes and respiratory tract

BACKGROUND: Formaldehyde (FA) in exhaust from F-4 aircraft with low smoke combustor(LSC) J79 engines has been reported to be of sufficient concentration to cause irritation. It has also been noted that eye and respiratory irritation became more frequent and severe after the fuel was changed from JP-4 to JP-8. The present sturdy investigated the effect of jet fuel and power setting on formaldehyde concentrations in the exhaust. We also investigated the exposure to formaldehyde among pilots and flight line personnel. METHODS: The exhaust from LSC J79 engines using different types of fuel (JP-8 and JP-4) was sampled 50 m behind the engine at different power settings in July (summer season in Japan) and February (winter season ). It was also sampled at 75% power settings using JP-8 in July. RESULTS: At an idle power setting, the FA concentration was higher in the exhaust of engines using JP-8 (1.31 ppm in July and 2.78 ppm in February) than in engines using JP-4 (0.95 ppm in July and 1.84 ppm in February). The FA concentration increased as both ambient temperature and relative humility decreased in the sampling atmosphere. The FA concentration of JP-8 fuel at an idle power setting (65%) was higher than that at a 71.5% power setting (1.32 ppm and 0.86 ppm, respectively). CONCLUSIONS: The FA concentrations in LSCJ79 engine exhaust varies depending on the type of fuel, engine power settings, and ambient air conditions. A high FA concentration at ground level due to a change in the fuel type, low temperature, and humidity, causes frequent severe eye respiratory irritation.     

Pharmacokinetics of cisplatin and methotrexate in a patient suffering from advanced ureteral tumor accompanied by chronic renal failure, undergoing combined hemodialysis and systemic M-VAC chemotherapy

The pharmacokinetics of cisplatin and methotrexate were determined in a patient suffering from advanced ureteral tumor accompanied by chronic renal failure undergoing 4 consecutive cycles of M-VAC chemotherapy and hemodialysis. No significant difference was observed in t1/2, AUC or CLtot of total platinum between the patient with the chronic renal failure and patients with normal renal function. The AUC and CLtot of free platinum in the patient with the chronic renal failure were higher and lower, respectively, than in the patients with normal renal function. The free cisplatin rebounded remarkably after the end of dialysis, which may be partly attributed to an increase in the AUC and decrease in CLtot. However, the dialysis index was about 75 and 85% in the 3rd and 4th cycles, respectively. The t1/2 and CLtot of methotrexate in the patient with the chronic renal failure tended to be longer and smaller than those in patients with normal renal function, respectively. Seventy-two hours after administration, the methotrexate level was 0.02 microM, which was not at the high-risk level of high-dose therapy. After four cycles of M-VAC therapy, the rest of the right ureteral tumor was extirpated and the clinical response was CR. In conclusion, it is considered that cisplatin and methotrexate can be given to a patient with chronic renal failure. However, the cisplatin and methotrexate serum levels must be monitored, even after very low doses.     

Home care of an ALS patient using an artificial respirator

Due to social changes, advancement of medical technology and introduction of home care insurance, it has become a reality that a patient using an artificial respirator could be treated at home. We report specific problems associated with an ALS patient using an artificial respirator through home care support. A 68-year-old male had a back problem in 2001 and developed a sudden difficulty in breathing. Since 2002, the patient was forced to use an artificial respirator, and without taking his informed consent, was treated at home. Primary caregivers are his wife and daughter. The specific problems we identified are (1) patient's caregivers were unnecessary confused due to a lack of coordination between visiting nurses from two hospitals in giving home care treatment direction, (2) the care giver's burden tends to increase as the duration of care is extended because the short-stay facility or transferring system for patient is not well equipped, (3) there is no particular place to ask for assistance in case of an emergency or an established communication method as the patient's disease status will progress. It appears that these identified problems cannot be resolved by one hospital. However, we believe that we have to establish a community-wide home care system as quickly as possible. Meanwhile, it is important to have a nationwide coordination involving government, corporations, and political institutions to make it to be a success.     

Therapeutic effect of camostat mesilate on Duchenne muscular dystrophy in mdx mice

Duchenne muscular dystrophy is known to be caused by a defective gene of dystrophin, a 427-kDa cytoskeletal protein, but the effective therapeutic drug is presently unavailable. We previously reported that a trypsin-like protease designated as dystrypsin is markedly activated in the muscle microsomal fraction immediately before onset of the clinical signs in mdx mice, a dystrophin-deficient hereditary animal model for human Duchenne muscular dystrophy. In order to examine the possible participation of dystrypsin in the occurrence of the disease, we investigated the therapeutic effects of dystrypsin inhibitors on the occurrence and progress of muscular dystrophy. Here, we show that camostat mesilate, a low-molecular-weight inhibitor of trypsin-like proteases, including dystrypsin, is a candidate drug for Duchenne muscular dystrophy.