Signet Ring Cell Carcinoma of Unknown Primary Complicated with Pulmonary Tumor Thrombotic Microangiopathy and Krukenberg Tumor

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare disease that shows hypoxia with severe pulmonary hypertension related to malignant tumor. Diagnosis is difficult due to rapid clinical progression and the need to demonstrate pathological findings from lung biopsy. A 64-year-old woman visited our hospital with hypoxia and pulmonary hypertension. Diffuse granular shadows in the centrilobular area and ground-glass shadows in both lungs and left ovarian tumor were found on radiological imaging. PTTM was suspected, but pulmonary artery blood aspiration by right cardiac catheter failed to detect cancer cells. We could not obtain lung or ovary biopsies because of hypoxia or pulmonary hypertension. The patient died due to respiratory failure. Signet ring cell carcinoma of unknown primary, PTTM, and Krukenberg tumor were diagnosed on autopsy. Since early diagnosis facilitates adequate treatment, physicians should not miss the opportunity for biopsy in cases of suspected PTTM

Markers that can Reflect Asthmatic Activity before and after Reduction of Inhaled Corticosteroids: A Pilot Study

Evaluation of airway inflammation is important in achieving adequate dosing of inhaled corticosteroids (ICS) for treating bronchial asthma. However, there is no evaluation tool that can be used in clinical settings. We examined biomarkers that can precisely reflect airway inflammation when ICS are decreased in stable asthmatic patients. This was a 12-week, single-arm, open-label clinical study performed at a single university hospital. Twenty-five patients (6 male and 19 female) with stable asthma were included in this study. We investigated whether the levels of nitrite and nitrate in exhaled breath condensate (EBC) increase after ICS reduction. We also investigated whether blood eosinophils, serum immunoglobulin E (IgE), high-sensitivity C reactive protein (hs-CRP), interleukin (IL)-13, IL-17, and periostin are different before and after ICS reduction. Peak expiratory flow (PEF), pulmonary function tests, asthma control test (ACT), and asthma quality of life questionnaire (AQLQ) were also examined. We considered an unscheduled hospital visit due to asthmatic symptoms and decline in average PEF over one week by more than 10% to indicate disease instability, and compared patients with stable and unstable disease for analysis. Unstable status was detected in 5 patients. Age, sex, asthma duration, ACT and AQLQ scores, and the level of serum IgE did not differ between stable and unstable groups. In the unstable group, the total concentration of nitrite and nitrate at the last visit was 9.84 (6.65–11.24) μM. Surprisingly, this was similar to the concentration at the first visit (5.58 (2.94–17.29) μM). Serum periostin before ICS reduction (141.9 [107.7–147.7] pg/mL) was higher in the unstable group than in the stable group (91.5 [78.75–103.5] pg/mL). The unstable group had a higher peripheral blood eosinophil count and wider diurnal variation of PEF at the first visit compared to the stable group. Higher eosinophils in peripheral blood and wider diurnal variation of PEF were predictive markers for unstable disease after ICS reduction. Serum periostin is another candidate for the predictive marker

最近16年間における日本人児童の体組成の変化

この研究は,1952-1960年と1968-1976年に実施された九州大学発育発達研究の縦断的な身長と体重の測定値を資料として用いている。すなわち,1946年と1962年生まれの児童の6歳から14歳までの体組成を身長と体重から推定し,16年間の変化を考察している。total body waterはMellits等の方法によって推定し,lean body weightはPace-Rathbunの式から推定している。body fatはWT-(TW/0.72)によって求めている。Secular trends of body composition in Japanese children and abolescents were studied. The material for the present study consisted of serial anthropometric measurements on males and females ranging in age from 6 to 14 years. Fukuoka city born participants in the Kyushu University Longitudinal Growth Study. A total of 137 males and 155 females were divided into two cohorts ; one cohort included the individuals born in 1946 and the other in 1962. Height and body weight measurements from 6 to 14 year old children were colleceted in the years from 1952-60 and 1968-76. Total body water and lean body weight were estimated by the methods of Mellits et al and by the formula of Pace Rathbun, respectively. Body fat was calculated by the equation : FAT WT (TW/0.72). The data indicated that the secular difference of TW and LBW per kg of body weight during this age period is not. significant for males. However, the modern Japanese adolescent females have large FAT per kg of body weight and small TW and LBW per kg of body weight. The LBW height relation, with height held constant, between both the cohorts did not differ during this age period, in both sexes. Only FAT weight relation, with weight held constant, showed that FAT of the modern Japanese adolescents increases at. a faster relative rate than that of the predecessors of 16 years ago. These findings provided a basis for the inferiority of physical performance in the modern Japanese which is known to exist in adolescence

Recommendation of Nymegen Growth Study\u27s Design and Its Case Study

In growth and development research, the traditional models based on cross-sectional and longitudinal models have usually been employed. In these models, growth and development is assumed to be a function of the two factors of age, time of measurement or cohort. The literatures on tri-factorial model in which growth and development is accout for as a function of age, time of measurement and cohort were summarized by Kessen (1960) and Schaie (1965). The Nymegen Growth Study develops these models and average value on each groups is described by the formula, G0=B+A+C+T+L (where B refers to the base line value ; A, the age effect ; C, the cohort effect ; T, the time of measurement effect ; L, the learning or testing effect). The present paper attempts to analyze the development of running long jump following the tri-factorial model in Nymegen Growth Study. The materials for this study are obtained by testing elementary school children. The measurements of both cohorts were administrated twice at 5-months intervals in 1978. A total of 22 boys is divided into two groups according to their birth periods (cohort). In addition, independently selected control group from younger cohort is employed to assess the impact of testing effect. The results obtained are as follws. 1) Cross-sectionally, the difference between two cohorts in the first measurement was significant. nevertheless, in the second measurement it is not significant. 2) Longitudinally, the younger cohort develops, while the elder cohort develops with non significance. 3) When the corresponding groups compared, it proves that neither the testing effect nor the time of measurement is significant in this design. 4) Consequently, the development or growth of running long jump is due to the net age effect, especially so in the younger cohort. We hope to expand the tri-factorial model by adding more data. Because there are evidences which support the application of this model to our area, and because the present approach would be of great value to the study of growth and development.古典的な発育・発達研究のデザインのうち,横断的な方法はDX＝f(A,C),縦断的な方法はDLO＝f(A,T)という関数式で表現されているが,KessenやSchaieの三要因モデルは心理学,社会心理学の領域にとり入れられ一定の成果をあげている。本稿では三要因モデルの拡張版としたNymegen Growth Studyのデザインがデータとは年令(A),コホート(C),測定時(T),テスト効果(L)の合成値(Go＝B＋A＋T＋C＋L)として表現できるものであることを紹介し,このミニマムなタイプをもちいて小学校男子児童の走り幅とびについて適用した事例を報告した。この適用事例の結果を要約すると,以下のようになる。1.春季の5年生と6年生の間には有意な年令効果(a)が認められた。2.春季と秋季の比較では,5年生に有意な年令効果が認められたが,6年生では認められなかった。3.テスト効果(L),測定時効果(t)には有意な効果は認められなかった。4.走り幅とびの時期は5年生の春季頃にピークが一つ存在し,これは正味の年令効果,生理機能の生物学的変化によるものと考えられる。一変数について少数標本を用い,ミニマムなデザインを示して適用を行なったが,デザインのタイプを拡大し,多変数・大標本を用いていく必要性が今後にのこされている

Mechanisms of acquired resistance to afatinib clarified with liquid biopsy.

Although mechanisms of acquired resistance to 1st and 3rd generation EGFR-TKI continue to be elucidated, there have been few clinical investigations into the mechanisms of acquired resistance to the 2nd generation EGFR-TKI afatinib. We analyzed data from 20 patients with advanced lung adenocarcinoma who acquired resistance to afatinib, including resistance during EGFR-TKI re-challenge. We examined EGFR T790M and C797S mutations, BRAF V600E mutation, and MET amplification with the MBP-QP method and with droplet digital PCR using ctDNA and re-biopsy samples obtained before and after afatinib treatment. Just before afatinib treatment, 15 of the 20 patients were T790M negative and five were positive. Among the T790M negative patients, 40.0% (6/15) became positive at the time of PD under afatinib. In patients positive for T790M, changes in T790M allele frequency were correlated with afatinib treatment efficacy. C797S was not detected in any patients just before afatinib treatment, but it appeared after treatment in three patients, although with very low allele frequency. Two of these three patients, although positive for both C797S and T790M, achieved PR to osimertinib. However, PFS of these patients was somewhat shorter than that of patients positive for T790M only. BRAF V600E was detected in one patient at PD under afatinib. MET amplification was not detected in this study. T790M is associated with acquired resistance to afatinib, as with 1st generation EGFR-TKI, but with somewhat lower frequency. The influence of C797S on resistance to afatinib is less than that of T790M, but C797S might cause shorter PFS under osimertinib

日本人児童の握力,立幅とびと体組成との関連における年代差

この研究は,握力と立幅とびにおける年代差を体組成との関連から考察している。資料は九州大学発育研究に参加した福岡市生まれの男女児童の人体計測値と運動能力測定値から得られている。男子児童664人,女子児童796人は,1946年生まれと1962年生まれの2集団に分けられている。身長,体重の計測と握力,立幅とびの測定は,各集団とも9歳から14歳までの1956-60年と1971-76年に実施されている。体水分量と除脂肪体重はMellitsらとPace Rathbunの方法によって推定され、体脂肪量は体重-（体水分量10.72）の式によって計算されている。結果は次のように要約できる。1　近年の日本人児童は15年前の児童に比較して,体重1kgあたりの体脂肪量が増加し,除脂肪体重が減少している。2　男子児童の除脂肪体重1Kgあたりの握力と立幅とびには年代差が認められない。3　女子児童の体重1kgあたりと除脂肪体重1kgあたりの立幅とびには年代差が認められ,近年の女子児童が15年前の児童より劣っている。立幅とびにおける近年の女子児童の劣位は体重1kgあたりの大きな体脂肪量と小さな除脂肪体重に帰するようである。Secular trends of hand-grip strength and standing long jump of Japanese children were studied in relation to their body composition. The materials for the present study were obtained from serial anthropometric and physical performance measurements on boys and girls, who were Fukuoka city-born participants in the Kyushu University Longitudinal Growth Study. A total materials of 664 boys and 796 girls from the age of 9 to 14 were divided into two cohorts, the one consisting of individuals born in 1946 and the other those born in 1962. Height, body weight, hand-grip strength and standing long jump measurements on children from 9 to 14 year-old were carried out covering the periods, 1956-60 and 1971-76. Total body water (TW) and lean body weight (LBW) were estimated according to the method of Mellits et al. and the formula of Pace-Rathbun, respectively. Body fat (Fat) was calculated according to the equation : Fat=WT-(TW/0.72). The results showed that modern Japanese children contain more Fat and less LBW per unit body weight than those of 15 years ago. The secular differences in hand-grip strength and standing long jump per LBW of Japanese boys were found not significant. On the other hand, modern Japanese girls showed lower standing long jump per body weight and LBW than those of 15 years ago. The inferiority of modern Japanese girls in standing long jump could be ascribed to large Fat and small LBW per unit body weight. This might result from their two characteristics, i.e., excessive caloric intake and inactivity

Sjögren Syndrome Complicated with Cystic Lung Disease and Pulmonary Amyloidosis

A 72-year-old Japanese woman was noted to have multiple cystic lung shadows and infiltrates on chest radiography and computed tomography (CT). She complained of dryness of the mouth and eyes, but she did not have respiratory symptoms, such as cough, sputum production, and dyspnea. Her laboratory findings showed high titers of anti-SSA/Ro and anti-SSB/La antibodies. Surgical lung biopsy was performed and demonstrated pathologic findings of amyloid light-chain deposition and bronchiolitis with lymphocytic infiltration. Taken altogether, she was diagnosed as Sjögren syndrome with bronchiolitis and pulmonary amyloidosis. Since then, she has been carefully followed up without treatment. After 6 years, the cystic lung lesions on CT gradually enlarged and increased in number, but she remained to have no respiratory symptoms and no manifestations of lymphoma. Here, we report a rare case of Sjögren syndrome complicated with cystic lung disease and pulmonary amyloidosis

最近16年間における日本人児童の体組成の変化

この研究は,1952-1960年と1968-1976年に実施された九州大学発育発達研究の縦断的な身長と体重の測定値を資料として用いている。すなわち,1946年と1962年生まれの児童の6歳から14歳までの体組成を身長と体重から推定し,16年間の変化を考察している。total body waterはMellits等の方法によって推定し,lean body weightはPace-Rathbunの式から推定している。body fatはWT-(TW/0.72)によって求めている。Secular trends of body composition in Japanese children and abolescents were studied. The material for the present study consisted of serial anthropometric measurements on males and females ranging in age from 6 to 14 years. Fukuoka city born participants in the Kyushu University Longitudinal Growth Study. A total of 137 males and 155 females were divided into two cohorts ; one cohort included the individuals born in 1946 and the other in 1962. Height and body weight measurements from 6 to 14 year old children were colleceted in the years from 1952-60 and 1968-76. Total body water and lean body weight were estimated by the methods of Mellits et al and by the formula of Pace Rathbun, respectively. Body fat was calculated by the equation : FAT WT (TW/0.72). The data indicated that the secular difference of TW and LBW per kg of body weight during this age period is not. significant for males. However, the modern Japanese adolescent females have large FAT per kg of body weight and small TW and LBW per kg of body weight. The LBW height relation, with height held constant, between both the cohorts did not differ during this age period, in both sexes. Only FAT weight relation, with weight held constant, showed that FAT of the modern Japanese adolescents increases at. a faster relative rate than that of the predecessors of 16 years ago. These findings provided a basis for the inferiority of physical performance in the modern Japanese which is known to exist in adolescence

Nymegen Growth Study の研究デザインの紹介と適用事例

In growth and development research, the traditional models based on cross-sectional and longitudinal models have usually been employed. In these models, growth and development is assumed to be a function of the two factors of age, time of measurement or cohort. The literatures on tri-factorial model in which growth and development is accout for as a function of age, time of measurement and cohort were summarized by Kessen (1960) and Schaie (1965). The Nymegen Growth Study develops these models and average value on each groups is described by the formula, G0=B+A+C+T+L (where B refers to the base line value ; A, the age effect ; C, the cohort effect ; T, the time of measurement effect ; L, the learning or testing effect). The present paper attempts to analyze the development of running long jump following the tri-factorial model in Nymegen Growth Study. The materials for this study are obtained by testing elementary school children. The measurements of both cohorts were administrated twice at 5-months intervals in 1978. A total of 22 boys is divided into two groups according to their birth periods (cohort). In addition, independently selected control group from younger cohort is employed to assess the impact of testing effect. The results obtained are as follws. 1) Cross-sectionally, the difference between two cohorts in the first measurement was significant. nevertheless, in the second measurement it is not significant. 2) Longitudinally, the younger cohort develops, while the elder cohort develops with non significance. 3) When the corresponding groups compared, it proves that neither the testing effect nor the time of measurement is significant in this design. 4) Consequently, the development or growth of running long jump is due to the net age effect, especially so in the younger cohort. We hope to expand the tri-factorial model by adding more data. Because there are evidences which support the application of this model to our area, and because the present approach would be of great value to the study of growth and development.古典的な発育・発達研究のデザインのうち,横断的な方法はDX＝f(A,C),縦断的な方法はDLO＝f(A,T)という関数式で表現されているが,KessenやSchaieの三要因モデルは心理学,社会心理学の領域にとり入れられ一定の成果をあげている。本稿では三要因モデルの拡張版としたNymegen Growth Studyのデザインがデータとは年令(A),コホート(C),測定時(T),テスト効果(L)の合成値(Go＝B＋A＋T＋C＋L)として表現できるものであることを紹介し,このミニマムなタイプをもちいて小学校男子児童の走り幅とびについて適用した事例を報告した。この適用事例の結果を要約すると,以下のようになる。1.春季の5年生と6年生の間には有意な年令効果(a)が認められた。2.春季と秋季の比較では,5年生に有意な年令効果が認められたが,6年生では認められなかった。3.テスト効果(L),測定時効果(t)には有意な効果は認められなかった。4.走り幅とびの時期は5年生の春季頃にピークが一つ存在し,これは正味の年令効果,生理機能の生物学的変化によるものと考えられる。一変数について少数標本を用い,ミニマムなデザインを示して適用を行なったが,デザインのタイプを拡大し,多変数・大標本を用いていく必要性が今後にのこされている