Late-onset type ornitine transcarbamirase deficiency (OTCD) with fulminant onset following a fatal prognosis]

A 16-year-old man was admitted to our hospital with nausea, general fatigue, and consciousness disturbance along with extreme hyperammoniemia eight days after the onset of symptoms. Familial history and the high concentration of orotic acid in urine lead us to a diagnosis of OTCD. We immediately initiated intensive treatment such as continuous hemodiafiltration and sodium benzoate administration; however, the patient died twelve days after admission. Since OTCD is not so rare and can be found in all ages, it should be considered fundamental for evaluation of hyperammoniemia. This case suggested that for a better prognosis of OTCD patients it is very important to prevent such an onset, and to make an as early as possible diagnosis and start to treatment.     

Health-related quality of life among persons living in Japan with a permanent colostomy.

OBJECTIVE: To compare the health-related quality of life (HRQOL) of persons with a permanent colostomy to that of the general Japanese population and explore the factors influencing HRQOL. DESIGN: A cross-sectional survey. SETTING AND SUBJECTS: A total of 255 persons with an ostomy who attended a meeting of the Japan Ostomy Association in the Kanto region of Japan. INSTRUMENTS: The HRQOL was assessed using Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), Japanese version 1.2. Factors potentially influencing the HRQOL were age, sex, marital status, employment status, number of people in the household, time since colostomy, and diagnosis. METHODS: Questionnaires were distributed to the subjects and SF-36 scores were determined and compared with the corresponding national-norm data by Wilcoxon signed rank sum test. A logistic regression analysis was used to explore the influencing factors. RESULTS: The questionnaire response rate was 66.7%. Subjects with a urostomy or an ileostomy and those with missing data were excluded. Data from 102 subjects with a permanent colostomy were analyzed. The subjects' scores were significantly lower than the national-norm scores in the role-physical and social functioning scales. Being employed was associated with significantly lower scores or associated with a tendency toward lower scores. CONCLUSIONS: Scores in two scales in these subjects were lower than those of national-norm scores. Being employed had a negative impact on the HRQOL of subjects with a permanent colostomy. The results of this study provide reference data for future research and underscore the importance of support for persons with a colostomy.     

Chronic myelogenous leukemia with a complex Ph1 translocation in an XYY male

We encountered a 38-year-old Japanese male patient with chronic myelogenous leukemia (CML), whose bone marrow and peripheral blood cells during the chronic and blastic phases contained a complex Ph¹ translocation and an extra Y chromosome [i.e., 47,XYY,t(9;22;13)(q34;q11;q14)]. A karyotypic analysis of PHA-stimulated lymphocytes showed the constitutional karyotype to be 47,XYY. Thus, it was considered that CML with a complex Ph¹ translocation developed in an XYY male; such a case has not been reported, so far. A B-lymphocyte cell line with the complex Ph¹ translocation was established by the procedure of Epstein-Barr virus transformation. The presence of the complex Ph¹ translocation in the B-lymphocyte cell line suggests that some of the B lymphocytes in this patient originated from the CML clone.     

Evidence for feeding elicited through antihistaminergic effects of tricyclic antidepressants in the rat hypothalamus

We studied central mechanisms of antidepressants that affect feeding behavior in rats. The tricyclic compounds amitriptyline, doxepin and imipramine significantly induced feeding after their infusion into the third cerebral ventricle in the light phase, but the tricyclic, desipramine, and the dicyclic zimelidine, did not. Drinking was not affected by any compound tested. The relative order of potency in eliciting feeding was: amitriptyline and doxepin > imipramine > desipramine and zimelidine. To clarify the involvement of neuronal histamine in antidepressant-induced feeding, alpha-fluoromethylhistidine (FMH), a suicide inhibitor of histidine decarboxylase, was intraperitoneally administered before infusion of amitriptyline. FMH attenuated the amitriptyline's effect. Bilateral microinfusion of amitriptyline into the ventromedial hypothalamus or the paraventricular nucleus verified that these are loci for the modulation of feeding by amitriptyline. In the lateral hypothalamus, amitriptyline was less effective. These findings indicate that tricyclic antidepressants directly facilitate feeding, which is, at least in part, mediated by histamine in the hypothalamus.     

Genomic determinants impacting the clinical outcome of mogamulizumab treatment for adult T-cell leukemia/lymphoma

In order to identify genomic biomarkers for the outcome of mogamulizumab-containing treatment, an integrated molecular analysis of adult T-cell leukemia/lymphoma (ATL) was conducted on 64 mogamulizumab-naïve patients. Among driver genes, CCR4 and CCR7 alterations were observed in 22% and 11% of the patients, respectively, both consisting of single nucleotide variants (SNV)/insertion-deletions (indels) in the C-terminus. Patients with CCR4 alterations or without CCR7 alterations exhibited a more favorable clinical response (complete response [CR] rate 93%, 13/14; P=0.024, and CR rate 71%, 40/56; P=0.036, respectively). Additionally, TP53, CD28, and CD274 alterations were identified in 35%, 16%, and 10% of the patients, respectively. TP53 alterations included SNV/indels or copy number variations (CNV) such as homozygous deletion; CD28 alterations included SNV, CNV such as amplification, or fusion; CD274 alterations included CNV such as amplification, or structural variants. Univariate analysis revealed that TP53, CD28 or CD274 alterations were associated with worse overall survival (OS) (hazard ratio [HR]: 2.330, 95% confidence interval [CI]: 1.183-4.589; HR: 3.191, 95% CI: 1.287-7.911; HR: 3.301, 95% CI: 1.130-9.641, respectively) but that CCR4 alterations were associated with better OS (HR: 0.286, 95% CI: 0.087-0.933). Multivariate analysis indicated that in addition to performance status, TP53, CCR4 or CD274 alterations (HR: 2.467, 95% CI: 1.197-5.085; HR: 0.155, 95% CI: 0.031-0.778; HR: 14.393, 95% CI: 2.437-85.005, respectively) were independently and significantly associated with OS. The present study contributes to the establishment of precision medicine using mogamulizumab in ATL patients.     

Dielectric property measurement of human sweat using attenuated total reflection terahertz time domain spectroscopy

Sweat is one of the essential biofluids produced by the human body, and it contains various physiological biomarkers. These biomarkers can indicate human health conditions such as disease and illness. In particular, imbalances in the concentration of electrolytes can indicate the onset of disease. These same imbalances affect the dielectric properties of sweat. In this study, we used attenuated total reflection terahertz time domain spectroscopy to obtain the frequency-dependent dielectric properties of human sweat in a frequency range from 200 GHz to 2.5 THz. We have investigated the variation of dielectric properties of sweat collected from different regions of the human body, and we have observed that the real and imaginary part of dielectric permittivity decreases with the increase in frequency. A combination of left-hand Jonscher and Havriliak-Negami processes is used to model the results and reveal the presence of relaxation processes related to sodium and calcium ions concentrations. This information may help design novel biosensors to understand the human health condition and provide a hydration assessment.     

Effects of tranexamic acid on coagulofibrinolytic markers during the early stage of severe trauma: A propensity score–matched analysis

Tranexamic acid (TXA) reduces the risk of bleeding trauma death without altering the need for blood transfusion. We examined the effects of TXA on coagulation and fibrinolysis dynamics and the volume of transfusion during the early stage of trauma. This subanalysis of a prospective multicenter study of severe trauma included 276 patients divided into propensity score–matched groups with and without TXA administration. The effects of TXA on coagulation and fibrinolysis markers immediately at (time point 0) and 3 hours after (time point 3) arrival at the emergency department were investigated. The transfusion volume was determined at 24 hours after admission. TXA was administered to the patients within 3 hours (median, 64 minutes) after injury. Significant reductions in fibrin/fibrinogen degradation products and D-dimer levels from time points 0 to 3 in the TXA group compared with the non-TXA group were confirmed, with no marked differences noted in the 24-hour transfusion volumes between the 2 groups. Continuously increased levels of soluble fibrin, a marker of thrombin generation, from time points 0 to 3 and high levels of plasminogen activator inhibitor-1, a marker of inhibition of fibrinolysis, at time point 3 were observed in both groups. TXA inhibited fibrin(ogen)olysis during the early stage of severe trauma, although this was not associated with a reduction in the transfusion volume. Other confounders affecting the dynamics of fibrinolysis and transfusion requirement need to be clarified.     

The first recognized patient withLegionella pneumophila serogroup 9 pneumonia in Japan

A 77-year-old female was admitted because of high fever, cough and sputum. She had been receiving corticosteroid therapy for 4 years for multiple myeloma and was immunosuppressed. A physical examination on admission showed coarse crackles in the right lower lung field, a chest radiograph showed consolidation in the right middle and lower lung fields, and a blood gas analysis revealed marked hypoxemia. The patient was diagnosed as having refractory pneumonia associated with acute respiratory failure and treated with intravenous cefmetazole followed by imipenem. On hospital day 5, erythromycin therapy was started because of a poor response to the previous antibiotics. The patient became afebrile on the tenth day and was in good health on day 15. A sputum culture on day 4 revealed aLegionella organism on Wadowsky-Yee-Okuda medium, which was subsequently confirmed to beLegionella pneumophila by a DNA hybridization test. This strain was identified at the Centers for Disease Control (Atlanta, GA, USA) by slide agglutination asL. pneumophila serogroup 9. Although our patient's symptoms are not apparently different from those caused by other serogroup strains ofL. pneumophila, this is the first recognized patient with culture-provenL. pneumophila serogroup 9 pneumonia in Japan. The clinical course of the disease and the diagnostic difficulties in identifying this type of pneumonia are discussed.     

Absolute lymphocyte count and C-reactive protein-albumin ratio can predict prognosis and adverse events in patients with recurrent esophageal cancer treated with nivolumab therapy

Predicting the prognosis and adverse events (AEs) of nivolumab therapy for recurrent esophageal cancer is very important. The present study investigated whether a simple blood biochemical examination could be used to predict prognosis and AEs following nivolumab treatment for relapse of esophageal cancer. A total of 41 patients who received nivolumab treatment for recurrent esophageal cancer after esophagectomy were analyzed. The absolute lymphocyte count (ALC), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) and C-reactive protein-albumin ratio (CAR) were assessed at the time of nivolumab induction as indices that can be calculated by blood biochemical examinations alone. Median values were 1,015 for ALC, 3.401 for NLR, 242.6 for PLR, 0.458 for MLR and 0.119 for CAR, and patients were divided into two groups according to values. A high ALC, low NLR, low PLR, low MLR and low CAR were associated with a better response to nivolumab. In addition, patients with the aforementioned indices, with the exception of low PLR, or better response were more likely to develop AEs in univariate analysis. In multivariate analysis, a high ALC [odds ratio (OR): 4.857, P=0.043] and low CAR (OR: 9.099, P=0.004) were identified as independent risk factors for AEs. Survival analysis revealed that overall survival and progression-free survival (PFS) rates after nivolumab treatment differed significantly between the high and low groups of ALC, NLR, PLR, MLR and CAR. The multivariate analysis identified a low ALC [hazard ratio (HR): 3.710, P=0.003] and high CAR (HR: 2.953, P=0.007) as independent poor prognostic factors of PFS. In conclusion, ALC and CAR have potential as biomarkers for outcomes of recurrent esophageal cancer following nivolumab treatment.