Can t(8;21) oligoblastic leukemia be called a myelodysplastic syndrome?

The new World Health Organization (WHO) classification of hematologic malignancies has incorporated t(8;21) myelodysplastic syndromes (MDS) according to the French-American-British classification into the category of acute myeloid leukemia (AML) with t(8;21)(q22;q22), while our knowledge about clinicopathological features of t(8;21) oligoblastic leukemia is still limited. We present our experience with 12 patients meeting the FAB diagnostic criteria of MDS and having t(8;21), who were compared to 43 t(8;21) AML patients. The MDS and AML patients shared most hematomorphologic, immunophenotypic, and clinical features, whereas the differences lay along myeloid maturation. The MDS patients had higher percentages of circulating neutrophils and marrow myeloid cells beyond promyelocytes than the AML patients. The incidence of Auer rods in mature neutrophils in MDS was significantly higher than that in AML, and furthermore, the neutrophils in MDS more commonly contain t(8;21) than in AML. Our findings support the rationale for the WHO classification, and future studies on large patient populations should help clarify whether the spontaneous differentiation potential could be actively associated with a hematological manifestation of t(8;21) leukemias.     

Specific IgE for wheat in tear fluid of patients with allergic conjunctivitis

Context: Allergy to hydrolyzed wheat protein in facial soap has become a major social issue in Japan. It has been reported that the most frequent early symptoms of allergy to hydrolyzed wheat protein in soap are allergic conjunctivitis and rhinitis, while wheat-dependent exercise-induced anaphylaxis can be induced by long-term use.

Objective: We evaluated the relation between tear fluid levels of specific IgE for wheat and the features of allergic conjunctivitis.

Methods: A prospective, non-randomized, cross-sectional study was conducted in 103 patients with moderate to severe allergic conjunctivitis (allergic group) and 20 age- and sex-matched healthy control subjects (control group). Specific IgE for wheat was measured in tear fluid with an immunochromatography assay, and a skin prick test (SPT) was also performed. Symptoms (sneezing, rhinorrhea, nasal obstruction, ocular itching, and lacrimation) were assessed in each subject along with the activities of daily living (ADL) score and the total ocular symptom score for allergic conjunctivitis. A severity score (0, 1, 2, or 3) was assigned for various changes of the palpebral and bulbar conjunctiva, as well as for limbal and corneal lesions associated with allergic conjunctivitis.

Results: The IgE positive rate and specific IgE score were both higher in the allergic group than in the control group (71.8% versus 40.0% and 1.9?±?0.7 versus 1.4?±?0.5). A positive SPT for wheat was also more frequent in the allergic group than in the control group (6.8% versus 0.0%). Within the allergic group, patients with a positive SPT had higher specific IgE scores than patients with a negative SPT (3.3?±?0.5 versus 1.8?±?0.6, p?r?=?0.665), tearing (r?=?0.672), and the total ocular symptom score (r?=?0.204). Wheat IgE in tear fluid was also correlated with the severity of rhinitis symptoms, including sneezing (r?=?0.610), nose blowing (r?=?0.640), and nasal obstruction (r?=?0.677). Furthermore, the tear fluid wheat IgE score was correlated with five objective features of allergic conjunctivitis (p?Conclusions: These results suggest that wheat allergy may be involved in the development of allergic conjunctivitis.     

Interleukin‐8‐producing primary cardiac undifferentiated sarcoma in a child with sustained fever

We report the case of a 12‐year‐old boy with primary undifferentiated sarcoma of the left atrium. He had sustained fever during the clinical course and multiple lung and brain metastases. Chemotherapy and irradiation were ineffective; he died 41 days after hospitalization. On retrospective analysis, interleukin‐8 (IL‐8) was elevated; this was supported by immunohistochemistry and gene expression analysis of tumor samples. IL‐8 continued to increase with tumor progression accompanied by elevated neutrophil count and C‐reactive protein. IL‐8 is involved in malignant tumor proliferation, migration, and angiogenesis and may have been related to the clinical condition and prognosis in the present case.     

An unexpected cause of a febrile patient with huge splenomegaly

We report an unexpected cause of a febrile patient with huge splenomegaly. A 32-year-old patient with fever and huge splenomegaly was admitted to our hospital. Diagnostic splenectomy revealed that the enlarged spleen adhered strongly to the abdominal organs. Pathologically, the splenic parenchyma showed no malignant cells, and the soft tissue adjacent to the splenic hilum showed a proliferation of fibroblastic or myofibroblastic spindle cells with fibrosis and lymphoplasmacytic infiltration. These findings lead to a diagnosis of peritoneal fibrosis, and an administration of 50 mg/day of prednisolone alleviated all the symptoms. The differential diagnosis of huge splenomegaly with fever usually includes hematolymphoid malignancies and infectious diseases; however, our case was diagnosed as idiopathic retroperitoneal fibrosis. Our case suggests that when we see patients with fever and huge splenomegaly, differential diagnosis should include retroperitoneal fibrosis.     

Bioactivation of loxoprofen to a pharmacologically active metabolite and its disposition kinetics in human skin

Loxoprofen (LX) is a prodrug‐type non‐steroidal anti‐inflammatory drug which is used not only as an oral drug but also as a transdermal formulation. As a pharmacologically active metabolite, the trans‐alcohol form of LX (trans‐OH form) is generated after oral administration to humans. The objectives of this study were to evaluate the generation of the trans‐OH form in human in vitro skin and to identify the predominant enzyme for its generation. In the permeation and metabolism study using human in vitro skin, both the permeation of LX and the formation of the trans‐OH form increased in a time‐ and dose‐dependent manner after the application of LX gel to the skin. In addition, the characteristics of permeation and metabolism of both LX and the trans‐OH form were examined by a mathematical pharmacokinetic model. The K_m value was calculated to be 10.3 mm in the human in vitro skin. The predominant enzyme which generates the trans‐OH form in human whole skin was identified to be carbonyl reductase 1 (CBR1) by immunodepletion using the anti‐human CBR1 antibody. The results of the enzyme kinetic study using the recombinant human CBR1 protein demonstrated that the K_m and V_max values were 7.30 mm and 402 nmol/min/mg protein, respectively. In addition, it was found that no unknown metabolites were generated in the human in vitro skin. This is the first report in which LX is bioactivated to the trans‐OH form in human skin by CBR1. Copyright © 2015 John Wiley & Sons, Ltd.     

Ventilatory efficiency during ramp exercise in relation to age and sex in a healthy Japanese population

BackgroundThe current understanding of ventilator efficiency variables during ramp exercise testing in the normal Japanese population is insufficient, and the responses of tidal volume (VT) and minute ventilation (V?E) to the ramp exercise test in the normal Japanese population are not known.MethodsA total of 529 healthy Japanese subjects aged 20–78 years underwent cardiopulmonary exercise testing using a cycle ergometer with ramp protocols. VT and V?E at rest, at anaerobic threshold, and at peak exercise were determined. The slope of V?E versus carbon dioxide (V?CO₂) (V?E vs. V?CO₂ slope), minimum V?E/V?CO₂, and oxygen uptake efficiency slope (OUES) were determined.ResultsFor males and females in their 20 s, peak VT (VTpeak) was 2192 ± 376 and 1509 ± 260 mL (p < 0.001), peak V?E (V?Epeak) was 80.6 ± 18.7 and 57.7 ± 13.9 L/min (sex differences p < 0.001), the V?E vs. V?CO₂ slope was 24.4 ± 3.2 and 25.7 ± 3.2 (p = 0.035), the minimum V?E/V?CO₂ was 24.2 ± 2.3 and 27.0 ± 2.8 (p < 0.001), and the OUES was 2452 ± 519 and 1991 ± 315 (p < 0.001), respectively. VTpeak and V?Epeak decreased with age and increased with weight and height. The V?E vs. V?CO₂ slope and minimum V?E/V?CO₂ increased with age, while conversely, the OUES decreased with age.ConclusionsWe have established the normal range of VT and V?E responses, the V?E vs. V?CO₂ slope, the minimum V?E/V?CO₂, and the OUES for a healthy Japanese population. Some of these parameters were influenced by weight, height, sex, and age. These results provide useful reference values for interpreting the results of cardiopulmonary exercise testing in cardiac patients.     

Metabolic syndrome amplifies the age-associated increases in vascular thickness and stiffness

OBJECTIVES: We sought to evaluate whether the clustering of multiple components of the metabolic syndrome (MS) has a greater impact on these vascular parameters than individual components of MS. BACKGROUND: Intima-media thickness (IMT) and vascular stiffness have been shown to be independent predictors of adverse cardiovascular events. The MS is defined as the clustering of three or more of the cardiovascular risk factors of dysglycemia, hypertension, dyslipidemia, and obesity. METHODS: Carotid IMT and stiffness were derived via B-mode ultrasonography in 471 participants from the Baltimore Longitudinal Study on Aging, who were without clinical cardiovascular disease and not receiving antihypertensive therapy. RESULTS: The MS conferred a disproportionate increase in carotid IMT (+16%, p < 0.0001) and stiffness (+32%, p < 0.0001), compared with control subjects. Multiple regression models, which included age, gender, smoking, low-density lipoprotein, as well as each individual component of MS as continuous variables, showed that MS was an independent determinant of both IMT (p = 0.002) and stiffness (p = 0.012). The MS was associated with a greater prevalence of subjects whose values were in the highest quartiles of IMT, stiffness, or both. CONCLUSIONS: Even after taking into account each individual component of MS, the clustering of at least three of these components is independently associated with increased IMT and stiffness. This suggests that the components of MS interact to synergistically impact vascular thickness and stiffness. Future studies should examine whether the excess cardiovascular risk associated with MS is partly mediated through the amplified alterations in these vascular properties.     

The subserosal elastic lamina: An anatomic landmark for stratifying pT3 colorectal cancer

PURPOSE Approximately 50 percent of all patients with resected colorectal carcinoma have tumors with pT3 status; however, no subclassifications of the penetration depth have been proposed. The purpose of this study is to evaluate the significance of histologic invasion beyond subserosal elastic lamina by colorectal carcinoma for postoperative recurrence and long-term survival after resection.METHODS pT3 colorectal carcinomas located above the peritoneal reflection were retrospectively classified into two depth grades (subserosal elastic lamina classification). Namely, pT3-shallow is defined as tumors those are confined above the subserosal elastic lamina, and pT3-deep is defined as tumors those penetrate beyond it. Based on subserosal elastic lamina classification, the 325 consecutive patients who underwent resections were divided into two groups, and then the clinicopathologic features, incidence of postoperative recurrence, and survival rates were compared between the two groups.RESULTS The overall postoperative recurrence rate in the pT3-deep group (35.2 percent) was higher than that in the pT3-shallow group (20.8 percent). In detail, liver and peritoneal recurrence rates in the pT3-deep group (19.7 percent, 7.7 percent, respectively) were higher than those in the pT3-shallow group (9.4 percent, 2.0 percent, respectively). There was a strong difference (P < 0.0001) in overall survival rate between the pT3-deep group (5-year survival of 57.0 percent) and the pT3-shallow group (5-year survival of 78.6 percent). Multivariate analysis revealed that synchronous hematogenous metastasis (P < 0.0001), lymph node metastasis (P < 0.05), venous invasion (P < 0.01), and subserosal elastic lamina classification (P < 0.05) were the independent prognostic factors for postoperative survival.CONCLUSIONS The newly proposed subserosal elastic lamina classification is a useful subclassification to predict the prognosis of patients with resected pT3 colorectal carcinomas.Presented at the 101st Annual Congress of the Japan Surgical Society, Sendai, Miyagi, Japan, April 11 to 13, 2001.     

Clinical and Portal Hemodynamic Features in Cirrhotic Patients Having a Large Spontaneous Splenorenal and/or Gastrorenal Shunt

Clinical and portal hemodynamic features in 28 cirrhotic subjects with a large spontaneous spleno- and/or gastrorenal shunt were studied in comparison with 30 control cirrhotic cases without such collaterals. Forty-six percent of the former had chronic hepatic encephalopathy, but none of the latter was encephalopathic. These patients with large renal shunts were divided into those with and those without encephalopathy. Large esophageal varices were significantly less common in patients with a large shunt and encephalopathy compared with those who had a large shunt but no encephalopathy, and the control. But there was no significant difference of past variceal bleeding among these three groups. In all those with encephalopathy, part of superior mesenteric venous blood was shunting through these collaterals into the left renal vein or inferior vena cava, but the same was not demonstrable in patients with a large shunt and no encephalopathy and control cirrhotics. In the chronic encephalopathic, portal venous flow was estimated to be less than one-half of that in control cirrhotics, and the portion of superior mesenteric venous blood that was flowing hepatofugally through a large shunt into the left renal vein seemed about the same or greater than the portal venous flow. Thus, a large spontaneous spleno- and/or gastrorenal shunt might prevent development of large esophageal varices but not variceal hemorrhage and it increased a risk of chronic hepatic encephalopathy.     

Dedifferentiated liposarcoma of the spermatic cord with a hemangioendothelioma-like component: A case report and review of the literature

Atypical lipomatous tumor or well-differentiated liposarcoma/dedifferentiated liposarcoma (DDLPS) is the most frequent subtype of malignant adipocytic tumor. This tumor typically presents in late adult life, most commonly in the retroperitoneum, extremities, or spermatic cord. It has been reported that the dedifferentiated component consists mainly of high-grade sarcoma, including undifferentiated pleomorphic sarcoma, fibrosarcoma, and myxofibrosarcoma, and it has been recently reported that the dedifferentiated component can be also made up of a low-grade sarcomatous component. Therefore, the dedifferentiated areas exhibit a wide morphological spectrum that commonly includes fibroblastic/myofibroblastic and fibrohistiocytic tumors but very rarely includes vascular tumors. We present here the first reported case of DDLPS with a hemangioendothelioma-like component in the spermatic cord.