A safe clinical system for nitric oxide inhalation therapy for pediatric patients

A safe clinical system for nitric oxide (NO) inhalation therapy was developed. The system consists of three parts: a NO controller, a NO monitor, and a patient circuit. NO gas flow and carrier gas flow are controlled by a special rust-proof thermal mass flowmeter. Standard gas quality NO gas (10,000 ppm, balance nitrogen) is used. The outlet of the NO gas tank is connected to the distal end of a heated humidifer that is very close (12 mL) to the patient, to decrease acidic water precipitation and decrease contact time between NO and oxygen (O₂). Fail-safe mechanisms to prevent the delivery of a hypoxic mixture or excessive NO concentration are incorporated. Inspiratory NO concentration is continuously monitored by a modified electrochemical NO meter. The patient circuit consists of a breathing circuit and a ventilator with a scavenging unit. A modified Mapleson D type circuit is used. Fresh gas, humidified and mixed with NO, is introduced to the patient connection port. A mechanical ventilator, either of conventional or of high-frequency oscillation type, is connected to the expiratory limb of the Mapleson D circuit. A coaxial scavenging unit including activated charcoal is placed in between the expiratory limb and the ventilator. The adjustment of inspiratory NO concentration (y) was accurate over a wide range (1–80 ppm) of concentrations (x) (y = 0.36 + 0.96x, R² = 0.999, n = 45) and showed good agreement with the chemiluminescence method. Inspiratory nitrous oxide (NO₂) concentration was less than 0.3 ppm, and acidic water accumulation as measured by NO⁻₂ and NO⁻₃ was less than 5 ppm, even at an extremely high NO concentration of 80 ppm with an F₁O₂ of 1.0 and 10 L/min of fresh gas flow. Environmental NO and NO₂ concentrations in the ICU remained below 0.005 and 0.05 ppm, respectively. This system was used clinically on 214 pediatric patients and proved to be accurate, safe, and useful. Pediatr Pulmonol. 1996; 22:174–181. © 1996 Wiley-Liss, Inc.     

Effect of age,height, and prechallenge respiratory resistance on bronchial hyperresponsiveness in childhood asthma using the forced oscillation technique

To evaluate the effects of age, height and prechallenge respiratory system resistance (Rrs) on bronchial responsiveness to methacholine inhalation (BRm) as measured by the oscillation technique in children with mild asthma, we studied BRm in 92 atopic children aged from 8 to 13 years (mean ± SD, 10.5 ± 1.7 years). Inhalation challenge was performed by administering progressively doubling doses of methacholine, until a twofold increase in Rrs from baseline had been reached. The minimum cumulative dose of methacholine (Dmin) at which Rrs deviated from baseline was identified by the point of deflection of the continuously recorded Rrs tracing. The Dmin represented the amount of methacholine which elicited BRm. By using single-regression analysis, height was negatively correlated with Rrs (p < 0.001). Height was positively and Rrs was negatively correlated with age (p < 0.001 and p < 0.001, respectively). Furthermore, height and age were correlated with Dmin (p < 0.001 and p < 0.001, respectively), but prechallenge Rrs was not correlated with Dmin (p > 0.1). To minimize the effect of height and prechallenge Rrs on BRm, the relationships between Dmin and age was studied in a subgroup with a narrow range of heights (135–155 cm, n = 32), and a narrow range of prechallenge Rrs (5.0–6.9 cmH₂ O/L/s, n = 42); there remained a statistically significant correlation between Dmin and age in the groups with comparable heights (p = 0.026) and Rrs (p = 0.003). These data suggest that the BHR in childhood asthma may be affected by height and age when measured by the oscillation technique. Considering the many advantages of the oscillation method, this technique may be very suitable for measuring BHR in childhood asthma. Pediatr Pulmonol. 1996;22:1–6. © 1996 Wiley-Liss, Inc.     

A novel automated assay for malate dehydrogenase isoenzymes

We have developed a new automated method for the determination of malate dehydrogenase (MDH) isoenzymes in serum employing guanidine hydrochloride. Our proposed method showed good reproducibility; within-run precision coefficient of variations (CVs) were less than 2.5 (mean 13.6–42.9 U/L) for total MDH (T-MDH) and less than 6.7% (mean 6.3–23.6 U/L) for mitochondrial MDH (m-MDH) (n = 10). The upper detection limit of the proposed method exhibited good linearity up to 1,000 U/L for both T-MDH and m-MDH. In the proposed m-MDH reagent, the presence of up to 2,000 U/L of cytosolic MDH(c-MDH) activity had no effect on the outcome of m-MDH assay. Results of our proposed method (y) correlated well with those of the electrophoretic method (x) giving the regression equation: y = 1.46 x + 6.87 (N = 30); r = 0.99. Normal concentrations of various anticoagulants and bilirubin did not affect the assay results. Both ascorbic acid and glucose exhibited a slight positive interference with the proposed assay. Clinically, we found that m-MDH activity in serum had greater diagnostic predictive value than T-MDH activity for judging successful outcome of reperfusion therapy; the prognosis was poor when the m-MDH/T-MDH ratio was greater than 20%. © 1996 Wiley-Liss, Inc.     

Sonographic diagnosis of fatty liver using a histogram technique that compares liver and renal cortical echo amplitudes

Accurate diagnosis of fatty liver using ultrasonography was attempted based on the difference between the echo intensities of the liver and kidney determined from ultrasonic histograms. Livers were then classified as having fatty infiltration, normal histology, or intermediate histology based on CT ratios established previously in earlier work comparing non-contrast-enhanced liver and spleen. The hepatorenal difference was significantly greater in the fatty liver group than in the normal liver group (8.9 ± 2.0 dB vs 2.5 ± 4.5 dB, p < 0.001). When a hepatorenal difference of ⩾7.0 dB was taken as the criterion, this method had a sensitivity of 91.3%, a specificity of 83.8%, and an accuracy of 86.7% for the diagnosis of fatty liver. Thus, quantitative ultrasonic diagnosis of fatty liver can be performed using echo intensity histograms. © 1996 John Wiley & Sons, Inc.     

Prediction of early progression of metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitor

Background:There are various alternative first-line therapeutic options besides tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). To inform therapeutic decision-making for such patients, this study aimed to identify predictive factors for resistance to TKI.Materials and methods:A total of 239 cases of mRCC patients who received first-line TKI therapy were retrospectively studied. Patients with a radiologic diagnosis of progressive disease within 3 months after initiating therapy were classified as primary refractory cases; the others were classified as non-primary refractory cases. The association between primary refractory cases and age, gender, pathology findings, serum c-reactive protein (CRP) level, metastatic organ status, and 6 parameters defined by the International Metastatic Renal Cell Carcinoma Database Consortium were analyzed.Results:Of 239 cases, 32 (13.3%) received a radiologic diagnosis of progressive disease within 3 months after initiating therapy. The rates of sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, presence of liver metastasis, anemia, and time from diagnosis to treatment interval of less than a year were significantly higher in the primary refractory group. Multivariate analysis showed that sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, and liver metastasis were independently associated with primary refractory disease. A risk-stratified model based upon the number of patients with these factors indicated rates of primary refractory disease of 4.0%, 10.1%, and 45.0% for patients with 0, 1, and 2 or more factors, respectively.Conclusions:Sarcomatoid differentiation, hypercalcemia, an elevated serum CRP level, and presence of liver metastasis were associated with primary refractory disease in mRCC patients receiving first-line TKI therapy. These results provide clinicians with useful information when selecting a first-line therapeutic option for mRCC patients.     

High seroprevalence of anti–HTLV-I antibody in rheumatoid arthritis

Objective. To investigate the association between human T lymphotropic virus type I (HTLV-I) infection and rheumatoid arthritis (RA) in Nagasaki, an area highly endemic for HTLV-I infection. Methods. Sera from 113 female patients with RA and 19,796 female blood donors were screened for anti–HTLV-I antibodies with a gelatin particle agglutination kit and confirmed using an immunoblotting kits. Results. The age-adjusted summary odds ratio of HTLV-I infection among RA patients, as compared with blood donors, was 2.8 (95% confidence interval [95% CI] 1.8–4.6). The etiologic fraction, i.e., the proportion of RA in the study population that is attributable to HTLV-I infection, was estimated to be 13.2% (95% CI 5.1–21.2). There was no significant difference in the clinical and laboratory findings between HTLV-I–infected and HTLV-I–uninfected RA patients. Conclusion. These epidemiologic findings support the idea that HTLV-I infection is a risk factor for RA, and suggest that ∼13% of the cases of RA in females living in Nagasaki are associated with HTLV-I infection.     

Food Protein-Induced Enterocolitis Syndrome in Children with Down Syndrome: A Pilot Case-Control Study

Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobin E-mediated food hypersensitivity disorder. However, little is known about the clinical features of FPIES in patients with Down syndrome (DS). Medical records of children with DS diagnosed at our hospital between 2000 and 2019 were retrospectively reviewed. Among the 43 children with DS, five (11.6%) were diagnosed with FPIES; all cases were severe. In the FPIES group, the median age at onset and tolerance was 84 days and 37.5 months, respectively. Causative foods were cow’s milk formula and wheat. The surgical history of colostomy was significantly higher in the FPIES group than in the non-FPIES group. A colostomy was performed in two children in the FPIES group, both of whom had the most severe symptoms of FPIES, including severe dehydration and metabolic acidosis. The surgical history of colostomy and postoperative nutrition of formula milk feeding may have led to the onset of FPIES. Therefore, an amino acid-based formula should be considered for children who undergo gastrointestinal surgeries, especially colostomy in neonates or early infants. When an acute gastrointestinal disease is suspected in children with DS, FPIES should be considered. This may prevent unnecessary tests and invasive treatments.     

Impact of the COVID-19 Pandemic on Glycemic Control and Blood Pressure Control in Patients with Diabetes in Japan

Objective In this study, we investigated whether and how the COVID-19 pandemic affected glycemic control and blood pressure (BP) control in patients with diabetes mellitus (DM). Methods DM patients whose HbA1c level was measured regularly before and after the declaration of a state of emergency were included in this study. Some patients were given questionnaires about changes in their lifestyle to determine the factors affecting glycemic control and BP control. Results The median HbA1c level of the 804 patients increased significantly from 6.8% before the state of emergency to 7.1% and 7.0% during and after the state of emergency, respectively. This was in contrast to the decrease one year earlier due to seasonal variations. In the 176 patients who responded to the questionnaire, the HbA1c level also increased significantly during and after the state of emergency. The worsening of glycemic control was more pronounced in the group that had achieved HbA1c of <7% before the state of emergency than in those with higher values. Unlike the rise in HbA1c, the BP did not rise during the state of emergency but did rise significantly afterwards. There was no marked decrease in HbA1c or BP after the state of emergency, even in patients who responded that they were much more careful with their diet, ate less, or exercised more. Conclusions The COVID-19 pandemic worsened glycemic control and BP control, even in patients who perceived no marked change in their diet or exercise, suggesting that more active lifestyle guidance is necessary for good treatment of DM patients.     

Mediastinal Malignant Melanoma Markedly Shrinking in Response to Nivolumab

Primary malignant melanoma (MM) of the mediastinum is rare, and there is a lack of consensus regarding the preferred treatment because non-cutaneous MM demonstrates an inferior response to systemic therapy. Herein, we describe the case of a 73-year-old man with MM of the anterior mediastinum with multiple liver metastases. Even though the size of lesions increased rapidly following diagnosis, nivolumab monotherapy caused remarkable tumor shrinkage. This is the first report of mediastinal MM showing a significant response to nivolumab. We, therefore, suggest that immunotherapy may be one of the treatment options for primary mediastinal MM.