The Japanese respiratory society guidelines for the management of cough and sputum (digest edition)

Cough and sputum are common complaints at outpatient visits. In this digest version, we provide a general overview of these two symptoms and discuss the management of acute (up to three weeks) and prolonged/chronic cough (longer than three weeks). Flowcharts are provided, along with a step-by-step explanation of their diagnosis and management. Most cases of acute cough are due to an infection. In chronic respiratory illness, a cough could be a symptom of a respiratory infection such as pulmonary tuberculosis, malignancy such as a pulmonary tumor, asthma, chronic obstructive pulmonary disease, chronic bronchitis, bronchiectasis, drug-induced lung injury, heart failure, nasal sinus disease, sinobronchial syndrome, eosinophilic sinusitis, cough variant asthma (CVA), atopic cough, chronic laryngeal allergy, gastroesophageal reflux (GER), and post-infectious cough. Antibiotics should not be prescribed for over-peak cough but can be considered for atypical infections. The exploration of a single/major cause is recommended for persistent/chronic cough. When sputum is present, a sputum smear/culture (general bacteria, mycobacteria), cytology, cell differentiation, chest computed tomography (CT), and sinus X-ray or CT should be performed. There are two types of rhinosinusitis. Conventional sinusitis and eosinophilic rhinosinusitis present primarily with neutrophilic inflammation and eosinophilic inflammation, respectively. The most common causes of dry cough include CVA, atopic cough/laryngeal allergy (chronic), GER, and post-infectious cough. In the last chapter, future challenges and perspectives are discussed. We hope that the clarification of the pathology of cough hypersensitivity syndrome will lead to further development of “pathology-specific non-specific therapeutic drugs” and provide benefits to patients with chronic refractory cough.     

Increased Efficiency of Exogenous Messenger RNA Translation in a Krebs Ascites Cell Lysate

Addition of a 0.5 M KCl wash fraction from rabbit reticulocyte ribosomes causes a 3- to 10-fold increase in the extent of translation of natural mRNAs by Krebs-cell lysates. In the presence of the wash fraction, 1 pmol of rabbit or mouse 10S RNA directs the incorporation of 80 pmol of leucine into rabbit globin. The addition of human 10S RNA results in the synthesis of equal amounts of human alpha and beta chains, identified by column chromatography. The stimulation by the wash fraction is almost completely dependent on added mammalian tRNA. In contrast to the wash fraction from rabbit reticulocytes, the wash fraction isolated from Krebs-cell ribosomes is inhibitory to both endogenous and exogenous mRNA translation. The stimulation by the wash fraction from rabbit ribosomes is not specific for globin mRNAs, but also increases endogenous, phage Qbeta, and viral RNA-directed protein synthesis.     

Change in the membranous lipid composition accelerates lipid peroxidation in young rat hearts subjected to 2 weeks of hypoxia followed by hyperoxia.

BACKGROUND: The effects of chronic hypoxia on cardiac membrane fatty acids and on lipid peroxidation were examined, as well as the effect of l-carnitine (LCAR), which suppresses lipid peroxidation, on this process. METHODS AND RESULTS: Four-week-old Sprague-Dawley rats were exposed to 10% oxygen for 14 days ("Hypoxia"), and then to 100% oxygen for 12 h (O2). LCAR (200 mg/kg) was administered by intraperitoneal injection daily for 2 weeks. Fatty acid composition, malondialdehyde (MDA) as a lipid peroxidation product, and antioxidants (superoxide dismutase (SOD), glutathione peroxidase and catalase) were measured. The concentration of linoleic acid was lower, and that of docosahexaenoic acid, which has more double bonds than linoleic acid, was increased in hypoxic hearts. SOD activity decreased in hypoxia, whereas MDA was unchanged, but significantly increased in "Hypoxia"+O2. LCAR reduced the increase in MDA, and had no effect on SOD activity or fatty acid composition. The administration of LCAR caused an increase in the ventricular levels of acetylcarnitine. CONCLUSIONS: These results suggest that chronic hypoxia changes the cardiac fatty acid composition of juvenile rats to fatty acids that contain more double-bonds and reduce SOD activity, and that lipid peroxidation was augmented by exposure to oxygen.     

QT dispersion correlates with systolic rather than diastolic parameters in patients receiving anthracycline treatment

OBJECTIVE: The aim of this study was to investigate the relation of QT dispersion to left ventricular (LV) systolic and diastolic function in patients undergoing anthracycline therapy. METHODS: We used echocardiography to evaluate LV systolic and diastolic function and electrocardiography to evaluate QT dispersion and corrected QT dispersion (QTcD) in patients with hematological diseases, who received anthracycline therapy. PATIENTS: Seventy-two patients with hematological diseases who were receiving anthracycline treatment were enrolled in the present study. RESULTS: LV end-diastolic diameter or LV end-systolic diameter had a significant positive correlation to QTcD (r = 0.35, p < 0.01, r = 0.43, p < 0.01). Also left ventricular ejection fraction of (LVEF) or fractional shortening had a significant negative correlation to QTcD (r = -0.46, p < 0.001, r = -0.27, p = 0.02). The highest QTcD group had a significantly larger LV end-diastolic diameter or LV end-systolic diameter than the lowest QTcD [48.5 +/- 5.7 vs. 44.4 +/- 4.5 (mm), p < 0.001, 34.1 +/- 6.4 vs. 28.8 +/- 4.3 (mm), p < 0.001] and the highest QTcD group had a significantly lower LVEF than the lowest QTcD [57.5 +/- 8.0 vs. 65.5 +/- 6.4 (%), p < 0.001]. On the other hand, none of the diastolic function markers were significantly correlated with QTcD. CONCLUSION: We concluded that increased QTcD is correlated with LV dilation and systolic dysfunction induced by anthracycline therapy, and does not reflect a dispersion of ventricular repolarization or asynchronous motion.     

Neuroendocrine differentiation of periodic-acid Schiff and Alcian blue-negative signet-ring cell-like cells and tubular adenocarcinoma cells within a gastric cancer

A case of a Borrmann type 2 advanced gastric cancer with endocrine differentiation is described. Histologically, the cancer was either composed of cells arranged in a tubular pattern or formed solid nests of various sizes. The tubular pattern was composed of a moderately differentiated tubular adenocarcinoma. The histology showed partial carcinoid tumor-like features. Cancer cells inside solid nests had a signet-ring cell-like appearance. Periodic-acid Schiff (PAS) staining was positive in the cytoplasm of a few of the cells found in the tubular pattern and in the mucus in some lumens and on the apical surface of cells in some lumens, but PAS did not stain cancer cells in the solid nests. Neither cancer cells nor mucus in the lumens were stained with alcian blue. All cancer cells were strongly positive for Grimelius silver stain, and most of the cancer cells stained positively for chromogranin A. Electron microscopic examination showed electron dense neuroendocrine granules in the cytoplasm of cancer cells. Cancer cells were stained positively for pancytokeratin, cytokeratin 8/18 and carcinoembryonic antigen. Muc 1 mucin glycoprotein staining was positive along the cell surfaces of cancer cells, but Muc 2, 5AC and 6 stainings were negative, although Muc 3 stained positively in the cytoplasm of a few cancer cells. The present case is a gastric tubular adenocarcinoma with Muc 1-positive, neutral- and acid mucin-negative signet-ring cell-like cells, which is associated with neuroendocrine differentiation.     

A 13-year study of Japanese cedar pollinosis in Japanese schoolchildren.

BACKGROUND: Japanese cedar pollen (JCP) sensitization and Japanese cedar pollinosis (JCPS) appear to be increasingly prevalent in younger children. The present study investigated factors affecting JCP sensitization and JCPS development in school children. METHODS: In May or June each year from 1994 to 2006, 275-510 children were assessed for serum JCP-IgE and house dust mite (HDM)-IgE levels, and surveyed regarding rhinoconjunctival symptoms. RESULTS: Strong JCP sensitization (IgE > or = 17.5 U(A)/ml) was associated with age (odds ratio (OR) = 2.65), the amount of dispersed pollen in the observed year (OR = 2.03) and in the year following birth (OR = 1.51), the month of birth (OR = 2.18), and the recent birth cohort (OR = 1.96). Symptoms were negatively correlated with the recent birth cohort (OR = 0.69) after adjusting for JCP-IgE levels. Strong HDM sensitization was associated with gender (OR = 0.65 for girls) and the recent birth cohort (OR = 1.76). CONCLUSIONS: JCP sensitization appeared to be associated with the recent birth cohort and to increases in dispersed pollen just after birth and in the observed season. Although the recent birth cohort was more easily sensitized, they were not more likely to develop symptoms. In contrast to JCP sensitization, strong HDM sensitization appeared to develop prior to commencement of primary school and was more likely to affect boys.     

Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT lymphoma) in Ulcerative Colitis

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) occurring in inflammatory bowel diseases, including ulcerative colitis (UC) and Crohn''s disease, has been reported, although it is extremely rare. An 18-year-old man with a two-years history of UC underwent colon endoscopy, and was found to have active total UC ranging from anus to cecum. Six biopsies were obtained. The microscopic examinations showed severe infiltrations of atypical small lymphocytes. They showed hyperchromatic nuclei and increased nucleocytoplasmic ratio and scattered immunoblastic cells. Centrocyte-like atypical lymphocytes, monocytoid cells, and plasma cells were seen in some places. Vague germinal centers were present, and apparent lymphoepithelial lesions were seen. No crypt abscesses were seen, and there were few neutrophils. No apparent other findings of UC were seen. Immunohistochemically, the atypical lymphocytes were positive for vimentin, CD45, CD20, CD79α, CD138, κ-chain, λ-chain, and p53 and Ki-67 antigen (labeling index = 63%). They were also positive for CD45RO, CD3, and CD15, but these positive cells were very scant compared with CD20 and CD79α. They were negative for CD10, CD30, CD56, cytokeratin (CK) AE1/3, CK CAM5.2, CK34BE12, CK5, CK6, CK7, CK8, CK14, CK18, CK19, CK20, EMA, chromogranin, synaptophysin, NSE, S100 protein, CEA, CA19-9, p63, and HMB45. Without clinical information, the appearances are those of MALT lymphoma. However, with clinical information, making the diagnosis of MALT lymphoma was hesitated. It is only mentioned herein that atypical lymphocytic infiltrations indistinguishable from MALT lymphoma occurred in an 18-year-old male patient with a two-year history of UC.