Quantitative assessment of PTPN11 or RAS mutations at the neonatal period and during the clinical course in patients with juvenile myelomonocytic leukaemia

To evaluate minimal residual disease (MRD) after chemotherapy and haematopoietic stem cell transplantation in juvenile myelomonocytic leukaemia (JMML), a locked nucleic acid‐allele specific quantitative polymerase chain reaction (LNA‐AS‐qPCR) was developed for 13 patients (four types of PTPN11 mutation and four types of RAS mutation). The post‐transplant MRD detected by LNA‐AS‐qPCR analysis was well correlated with chimerism assessed by short tandem repeat PCR analysis. Non‐intensive chemotherapy exerted no substantial reduction of the tumour burden in three patients. There was no significant difference in the quantity of RAS mutant DNA after spontaneous haematological improvement in 4 patients with NRAS or KRAS 34G > A during a 2‐ to 5‐year follow‐up. PTPN11, NRAS, or KRAS mutant DNA was detected from Guthrie card dried blood in five of seven patients (who were aged <2 years at diagnosis) at a level of 1·0–6·5 × 10^?1 of the values at diagnosis. Accordingly, these five patients might have already reached a subclinical status at birth. Considering the negative correlation between mutant DNA level in neonatal blood spots and age at diagnosis, JMML patients with a larger tumour burden at birth appeared to show earlier onset.     

Greater development of 1,2-dimethylhydrazine-induced colon cancer in a rat model of type 2 diabetes mellitus

Several clinical cohort and case-control studies have suggested a link between diabetes and colon cancer. Otsuka Long-Evans Tokushima Fat (OLETF) rats spontaneously develop type 2 diabetes mellitus and Long-Evans Tokushima Otsuka (LETO) rats are non-diabetic. The relationship between type 2 diabetes mellitus and colon cancer was examined in these rats. The carcinogen 1,2-dimethylhydrazine was administered subcutaneously once weekly for 10 weeks, and the animals were killed and necropsied in week 29. All OLETF rats and 80% of the LETO rats developed cancer. The number of colon cancers per rat was significantly greater in the diabetic than in the non-diabetic rats. Although the tumours tended to be larger in diabetic rats, the difference was not statistically significant. No significant differences were observed in the depth of invasion or histological type of cancer in the two groups. Type 2 diabetes mellitus may enhance the generation and growth of colon cancer.     

A Family with Hemoglobin Hirosaki

A 48-year-old man had a 30-year history of hemolytic anemia of undetermined cause. Spherocytes were not observed, osmotic fragility was normal, and red cell enzyme activities were normal. His brother and daughter also had hemolytic anemia. The brother had previously undergone splenectomy, and the anemia had been ameliorated. In the proband and daughter, no abnormal hemoglobin was apparent in the results of isoelectric focusing and DEAE anion-exchange high-performance liquid chromatography analyses. On evaluation with the isopropanol test, unstable hemoglobin was not observed in the proband but was detected in the daughter. There was also a decreased ratio of 3 globin/3 globin chain production. Analysis of the 32 gene demonstrated the presence of a mutation (alpha43 [CE1] Phe --> Leu), hemoglobin Hirosaki.     

Staging of Early Colorectal Cancers: Magnifying Colonoscopy versus Endoscopic Ultrasonography for Estimation of Depth of Invasion

BACKGROUND AND AIMS: Preoperative estimation of depth of invasion in early colorectal cancers (CRCs) is essential for patient management. This study was conducted to compare the diagnostic accuracies of magnifying colonoscopy and endoscopic ultrasonography (EUS) for estimating the depth of invasion of early CRCs. SUBJECTS AND METHODS: A total of 438 early CRCs were removed endoscopically or surgically from July 1993 through March 1999 at our hospital. Before removal, 102 lesions were evaluated with both magnifying colonoscopy and EUS and were included in this analysis. The diagnostic accuracy of each method, referring to the histology of the resected specimens, was evaluated. RESULTS: The overall diagnostic accuracies were 87% (89/102) for magnifying colonoscopy and 75% (76/102) for EUS (P = 0.0985). Subgroup analysis was also done for polypoid and non-polypoid lesions. For polypoid lesions, the overall diagnostic accuracies of magnifying colonoscopy and EUS were 88% (60/68) and 72% (49/68), (P = 0.0785), and for non-polypoid lesions, they were 85% (29/34) and 79% (27/34), (P = 0.7169). CONCLUSION: Although, there is a substantial difference in the overall diagnostic accuracies, it is not statistically significant. Therefore, we conclude that magnifying colonoscopy is at least as accurate as EUS for preoperative staging of early CRCs.     

Follicular lymphoma in Osaka,Japan: histological features and chronological change

Follicular lymphoma (FL) is defined as a neoplastic proliferation of follicle center cells with varying follicular areas. To learn the time trend of FL in the Osaka area, an adult T-cell leukemia/lymphoma (ATL) nonendemic area of Japan, we examined the frequency of FL among all non-Hodgkin's lymphomas (NHLs) during the period 1964 to 1987 (n = 1,000) and 1999 to 2001 (n = 659).The frequency of FL with varying follicular areas increased from 1964-1987 to 1999-2001.There was a significant difference in frequency of total cases of FL (14.2% versus 18.8%) (P < .05) and FL with no to 25% follicular area (2.3% versus 5.0%) (P < .01). According to the Berard criteria, cytologic grade of FL was defined by counting the number of centroblasts (CB) in 10 neoplastic follicles as follow: < or = 5 CB per high power field (HPF), grade 1; 6-15 CB, grade 2; >15 CB, grade 3. Immunohistochemical staining with monoclonal antibodies for bcl-2 and CD10 was performed. There was an inverse correlation between follicular area and cytological grade (P < .0001) and bcl-2 expression and cytological grade (P < .01). That is, the larger the follicular area in cases with a lower cytological grade, the stronger was bcl-2 expression in a lower cytological grade. There was a significant correlation between follicular area and stage of disease (P < .05). That is, the follicular area was larger in cases in an advanced stage. This study showed the increase in frequency of FL in Osaka, Japan. Change of lifestyle in Japan may be one of the causative factors for the increase.     

Effect of adiponectin on murine colitis induced by dextran sulfate sodium

BACKGROUND & AIMS: Adiponectin, an adipose tissue-derived hormone, exhibits anti-inflammatory properties and has various biological functions, such as increasing insulin sensitivity, reducing hypertension, and suppressing atherosclerosis, liver fibrosis, and tumor growth. The aim of the present study was to determine the effect of adiponectin on intestinal inflammation. METHODS: We investigated the effect of adiponectin on dextran sulfate sodium (DSS)-induced colitis by using adiponectin-knockout (APN-KO) mice and an adenovirus-mediated adiponectin expression system. We also examined the contribution of adiponectin deficiency to trinitrobenzene sulfonic acid (TNBS)-induced colitis. In vitro, we examined the effect of adiponectin on intestinal epithelial cells. RESULTS: After administration of 0.5% DSS for 15 days, APN-KO mice developed much more severe colitis compared with wild-type mice. The messenger RNA expression levels of chemokines were significantly higher in the colonic tissues of DSS-treated APN-KO mice compared with wild-type mice, accompanied by increased cellular infiltration, including macrophages. Adenovirus-mediated supplementation of adiponectin significantly attenuated the severity of colitis, but there were no differences in the severity of TNBS-induced colitis between the 2 groups. Adiponectin receptors were expressed in intestinal epithelial cells, and adiponectin inhibited lipopolysaccharide-induced interleukin-8 production in intestinal epithelial cells. CONCLUSIONS: Adiponectin is protective against DSS-induced murine colitis, probably due to the inhibition of chemokine production in intestinal epithelial cells and the following inflammatory responses, including infiltration of macrophages and release of proinflammatory cytokines.     

Continuous hemodiafiltration in pediatric critical care patients

Continuous hemodiafiltration (CHDF) is an essential procedure in critical care. However, application of this therapy to pediatric patients is associated with several problems derived from their smaller body size and weight compared with adults. We have successfully conducted CHDF in pediatric patients including newborns by taking such problems into consideration and carefully coping with them. The present study consisted of 60 pediatric patients treated with CHDF. Clinical efficacy and safety of CHDF in pediatric patients were assessed in these patients by reviewing patient clinical records. The 60 patients treated with CHDF included 27 males and 33 females. Their body weight ranged from 700 g to 53.0 kg. The mean CHDF duration was 6.80 +/- 6.94 days. Blood access was provided in a veno-venous mode in 42 patients, and an arterio-venous mode in 18 patients. Of the 60 pediatric patients receiving CHDF, 31 patients survived without serious complications, achieving a survival rate of 51.7%. Successful CHDF in pediatric patients was achieved by careful and exact execution of the following countermeasures to overcome problems specific to application of this therapy to pediatric patients: minimization of the priming volume; use of colloid solutions or whole blood as priming solution; maintaining secure blood access; selection of an appropriate anticoagulant; temperature control of both the patient's body and components of the hemofiltration circuit. In pediatric critical care, CHDF is safely applicable to the critically ill and expected to produce a wide spectrum of clinical efficacy just as in adults.     

Chronic lung abscess with Pasteurella multocida infection

We report a patient with chronic lung abscess due to Pasteurella multocida infection that may be caused by the contact with cows in his workplace. Despite its apparent rarity, chronic abscess due to P. multocida should be considered in the differential diagnosis of solitary pulmonary masses. This case report suggests that P. multocida infection can be potentially caused from saliva of cows as well as dogs or cats.