It has been suggested that reactivation of human herpesvirus 6 (HHV-6) infection may be involved in the pathogenesis of drug-induced hypersensitivity syndrome. We report a 45-year-old Japanese man who developed a generalized papuloerythematous rash, fever, hepatitis, lymphadenopathy and lymphocytosis with an increased number of atypical lymphocytes. He was diagnosed with DIHS due to mexiletine hydrochloride based on laboratory data, results of a patch test and the clinical course of his complaint, and was treated with systemic steroids. In order to determine whether HHV-6 or -7 was associated with the patient’s disease, serological assays and PCR were carried out. Significant increases in antibody titers against HHV-6 and -7 were observed from day 12 to 24. From PCR analysis, none of the peripheral blood mononuclear cells or skin tissue samples contained HHV-6 DNA. All samples, however, were found to contain HHV-7 DNA. Reactivation of HHV-7 could be responsible for drug-induced hypersensitivity syndrome.

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INTRODUCTION Heated tobacco products (HTPs) appear to be less harmful to health than conventional cigarettes (CCs). However, limited analytical data are available to support this claim. This study aimed to compare the cytotoxic, genotoxic, and toxicogenomic effects of HTPs and CCs in carcinogenesis via multistep gene mutations in the oral mucosal cells. METHODS Cigarette smoke extract (CSE) was obtained from HTPs and CCs. Primary human oral keratinocytes (HOKs) were treated with 5% and 20% CSE from HTPs and CCs. Cell survival rate assays were performed after 6, 12, and 24 h. After 6 h, DNA double-strand breaks (DSBs) were evaluated using anti-γH2AX antibodies with immunohistochemistry. mRNAs expressions of mediator of DNA damage checkpoint 1 (MDC1) and ataxia telangiectasia and Rad3-related protein (ATR), were analyzed. Expressions of miR-22 and miR-185 were analyzed because miR-22 targets MDC1 and miR-185, ATR. RESULTS The HOKs had equivalent survival rates after exposure to the same concentrations of CSE from CCs and HTPs. HTPs increased foci formation of γH2AX in HOKs, as did CCs (without CSE vs 20% HTP, p<0.05; without CSE vs 20% CC, p<0.05). Expressions of MDC1 and ATR decreased in cells exposed to CSE from CCs and HTPs (MDC1: without CSE vs 20% HTP, p<0.05; without CSE vs 20% CC, p<0.05; ATR: without CSE vs 20% HTP, p<0.05; without CSE vs 20% CC, p<0.05). Expressions of miR-22 and miR-185 were not significantly increased when exposed to CSE from CCs or HTPs. CONCLUSIONS HTPs and CCs had similar cytotoxic effects. HTPs are genotoxic, can cause DSBs, and have toxicogenomic damage because they inhibit the MDC1 and ATR-CHK1 DNA repair pathways in the oral mucosa. The miRNA-mRNA axis was not related to these inhibitions.

We mailed questionnaires to 748 registered medical sonographers [RMSs (cardiology)] to gather information for a large-scale survey of RMSs in May 2000. We wanted to evaluate the current state of routine echocardiography in Japan. Altogether, 530 (70.9%) of these sonographers responded; 18 respondents employed by equipment manufacturers were excluded from the start of the study, and 20 others later found to be employed by equipment manufacturers were also excluded. Responses from all personnel at a single institution were treated as a single response; 436 institutions were thus included in the survey. Most or all examinations were carried out by sonographers at 77.3% of the responding institutions but were performed mainly by physicians at 11.1% of the institutions. At least 80% of sonographer or physician working hours were used for echocardiographic examination at 18.9% of the surveyed institutions, whereas up to half the working hours were devoted to echocardiographic examinations at 67.0% of the institutions. The most frequently reported examination time was 30-40 min [35.6% (n ϭ 116) of the institutions], whereas 32.8% (n ϭ 107) of the institutions indicated durations of 10-20 min per examination. Left ventricular (LV) dimensions and wall thickness were measured on M-mode images in all patients at 14.1% (n ϭ 59) of the institutions and mainly on M-mode images but from twodimensional echocardiography in problematic patients at 74.2% (n ϭ 311) of the institutions. The LV ejection frac-tion was calculated from LV dimensions at 55.7% (n ϭ 205) of the institutions and from the LV cross-sectional area at 44.3% (n ϭ 163) of the institutions. The LV ejection fraction was estimated visually at 57.0% of the institutions. Only 5.5% (n ϭ 22) of the facilities always scored the wall motion. Pulsed Doppler echocardiography was used to assess LV inflow in all patients at 65.9% of the institutions; regurgitation and shunting were always assessed quantitatively at only 2% (n ϭ 8). Comments concerning image quality were reported in all cases or in cases of poor image quality at 98% of the institutions, and the sonographer was also involved in writing the diagnostic report at 94% of institutions. Echocardiography is less expensive than other diagnostic imaging methods, and its importance is thus likely to continue to increase. Echocardiographic examinations should be carried out by skilled RMSs and physician echocardiographers; and an accurate, readily comprehensible report of the findings should be provided promptly to the referring physician. More such surveys are required to ensure that these practices are adopted.

Peripheral blood stem cell transplantation (PBSCT) has increasingly been used for hematologic cancer therapy, resulting in improved survival rates. However, risks include graft-versus-host disease (GVHD) and secondary solid tumors. Here, we describe a case of tongue squamous cell carcinoma (SCC) complicated by bronchiolitis obliterans (BO) following PBSCT. A 42-year-old man with a history of acute lymphocytic leukemia treated with PBSCT presented with multiple white lesions and erosions on the tongue and buccal mucosa that are compatible with oral chronic GVHD (NIH criteria: score 2). The lesions were presented for 8 years. The patient had a history of BO manifested as GVHD. During follow-up, an exophytic mass was rapidly developed on the left dorsum of the tongue. Biopsy of this lesion confirmed SCC (cT2N0M0). Pulmonary function testing for general anesthesia was almost normal. Hemiglossectomy, supraomohyoid neck dissection, and tongue reconstruction were performed. Thirteen months after surgery, the patient showed neither recurrence of tumor nor progression of oral GVHD. However, the patient died of respiratory failure due to repeated pneumothoraxes and deterioration of BO.