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.     

Large cell neuroendocrine carcinoma arising from the left main bronchus

A 67-year-old man was referred to our hospital for a detailed medical examination of a bronchial polyp that was detected during chest computed tomography. Bronchoscopic examination revealed a tumor that almost occluded the main left bronchus. Nd-YAG laser treatment and tumor removal with biopsy forceps were conducted. On the basis of the histopathological and immunohistochemical features, large cell neuroendocrine carcinoma (LCNEC), T2aN0M0, stage IB was diagnosed. After induction chemotherapy with a combination of cisplatin and etoposide, a sleeve resection of the left main bronchus with telescoping bronchial anastomosis was performed. LCNEC typically occurs in the peripheral lung field, but here, we report a rare case of LCNEC arising from the left main bronchus.     

QUANTITATIVE ANALYSIS OF LOW‐DOSE ASPIRIN‐ASSOCIATED SMALL BOWEL INJURY USING A CAPSULE ENDOSCOPY SCORING INDEX

Aim: The major limitation of capsule endoscopy (CE) has been the lack of a standardized and validated severity scale for mucosal injury. The aim of the present study was to verify the usefulness of quantifying small bowel mucosal changes associated with giving low‐dose aspirin (LDA) using a CE scoring index. Methods: The CE score for small bowel mucosal injury was investigated to evaluate the severity of mucosal injury. Healthy volunteers and patients suspected of having small bowel disease were recruited for this study. The short‐term LDA group (V + S‐LDA group) consisted of volunteers who took low‐dose aspirin for 14 days; this group was then compared with healthy volunteers who did not receive LDA treatment (V‐Control group). The long‐term LDA group (L‐LDA group) consisted of patients with at least a 3‐month history of daily LDA use; this group was compared with non‐users of LDA (P‐Control group). Results: The CE score was significantly higher in the V + S‐LDA group than in the V‐Control group. In the V‐Control group, almost all the subjects were categorized as exhibiting a ‘normal’ change. ‘Mild’ changes were observed significantly more frequently in the V + S‐LDA group than in the V‐Control group. The CE score was significantly higher in the L‐LDA group than in the P‐Control group. ‘Mild’ or ‘moderate or severe’ changes were observed significantly more frequently in the L‐LDA group than in the P‐Control group. Conclusion: The CE scoring system was useful for evaluating LDA‐associated small bowel mucosal disease activity and for objectively scoring the small bowel inflammatory disease state.     

Transnasal ultrathin endoscopy for placement of a long intestinal tube in patients with intestinal obstruction

BACKGROUND: The technical difficulties related to the insertion of a long intestinal tube into the jejunum under fluoroscopy present a considerable problem in patients with an intestinal obstruction. OBJECTIVE: To evaluate the usefulness of endoscopic long intestinal-tube placement with the ultrathin esophagogastroduodenoscope (UT-EGD). DESIGN: A prospective randomized clinical trial was conducted. PATIENTS: Twenty-eight consecutive patients who presented with an intestinal obstruction were included in the study. INTERVENTION: The UT-EGD was inserted nasally into at least the second portion of the duodenum or beyond. After a guidewire was introduced through the working channel, with fluoroscopic guidance, the UT-EGD itself was carefully removed with the guidewire left in place. Next, a hydrophilic intestinal tube was advanced over the guidewire into the jejunum, and then the guidewire was removed. MAIN OUTCOME MEASUREMENTS: Primary end points are the total procedure time, the radiation exposure time, and the rate of complications, all compared with the conventional method. RESULTS: The mean (+/-SD) total procedure time was 18.7 +/- 8.4 minutes for the UT-EGD method and 39.5 +/- 15.0 minutes for the conventional method, with a significant time difference between the 2 methods (P < .0005). The mean (+/-SD) radiation exposure time was also shorter with the UT-EGD method (11.1 +/- 6.0 minutes) than with the conventional method (30.3 +/- 13.7 minutes) (P < .0005). There were no complications, except for mild nasal bleeding with each method. CONCLUSIONS: The UT-EGD method has definite advantages in the placement of a long intestinal tube for patients with an intestinal obstruction in comparison with the conventional method.     

Successful treatment of chronic granulomatous disease with fludarabine-based reduced-intensity conditioning and unrelated bone marrow transplantation

Allogeneic hematopoietic stem-cell transplantation (HSCT) for chronic granulomatous disease (CGD) with a reduced-intensity conditioning regimen can be expected to lead to less therapy-related mortality and late-onset impairment, whereas it has also been reported to increase the risk of unsustained mixed donor chimerism and late rejection after transplantation. Herein, we report a 4-year-old boy with CGD who was successfully treated with unrelated bone marrow transplantation with a reduced-intensity conditioning regimen (RIC). Fludarabine-based RIC, 4 Gy of total body irradiation, 120 mg/kg of cyclophosphamide, and 125 mg/m² of fludarabine, was adopted for transplantation, followed with 8.9 × 10⁸/kg mononucleated donor cells infused without T-cell depletion. Although hematopoietic engraftment was rapidly obtained by day +17, he developed unstable donor chimerism. After tacrolimus withdrawal, the patient showed grade III acute graft-versus-host disease (GVHD), and subsequently reached full donor chimerism by day +61. Twelve months post-transplant, the patient has remained well with stable and durable engraftment, 100% donor chimerism, and normal superoxide production, without the requirement of donor lymphocyte infusions (DLI).     

Histiocytic sarcoma of the spleen: case report of asymptomatic onset of thrombocytopenia and complex imaging features

Histiocytic sarcoma of the spleen, in which the malignant cells display morphologic and immunophenotypic features similar to those of mature tissue histiocytes, is a rare but potentially lethal condition that can remain asymptomatic or only mildly symptomatic for a long period of time. We studied a case of histiocytic sarcoma of the spleen in an 82-year-old woman with prolonged chronic thrombocytopenia that was non-responsive to steroid therapy. Ultrasonography, computed tomography, and magnetic resonance imaging showed a characteristically enlarged spleen and liver. Palliative irradiation therapy was clinically effective; however, disease progression proved lethal. Autopsy revealed the proliferation of tumor cells within the splenic sinus and the liver sinusoids, which displayed extreme hemophagocytosis and strong expression of the histiocytic markers CD68 (KP1 and PG-M1) and CD163. The postmortem diagnosis showed histiocytic sarcoma of the spleen with liver infiltration. This and previous reports indicate that early detection (facilitated by imaging and clinical features) and management may improve patient prognosis and survival. Histiocytic sarcoma of the spleen should be considered as a differential diagnosis in therapeutically unresponsive patients with chronic thrombocytopenia.     

Growth process of small pancreatic carcinoma： A case report with imaging observation for 22 months

This report describes serial observations of the growth process of a small invasive ductal carcinoma （IDC） of the pancreas from imaging studies. Histopathological studies showed IDC with macroscopic retention cysts proximal to an intraductal papillary-mucinous adenoma with mild atypia of the branch duct type in the pancreatic body, with no relation between the two lesions. IDC was demonstrated as an extremely low-echoic mass resembling a cyst with an unclear margin on the initial endoscopic ultrasonography. We misinterpreted the lowechoic mass as a benign intraductal mucinous-papillary neoplasm （IPMN） based on findings of other imaging studies, and the patient was followed-up. The mass increased from 7 mm to 13 mm in diameter over 22 mo, and remained smaller than 10 mm in diameter for about 420 d. The tumor volume doubling time was 252 d. The Ki67 labeling index was 15.9%, similar to that described in previous reports. Hence, IDC may grow slowly while remaining small.     

Flow cytometric analysis of de novo acute lymphoblastic leukemia in childhood: report from the Japanese Pediatric Leukemia/Lymphoma Study Group

Although the antigen expression patterns of childhood acute lymphoblastic leukemia (ALL) are well known, little attention has been given to standardizing the diagnostic and classification criteria. We retrospectively analyzed the flow cytometric data from a large study of antigen expression in 1,774 children with newly diagnosed ALL in JPLSG. T- and B-lineage ALL accounted for 13 and 87% of childhood ALL cases, respectively. Cytoplasmic CD3 and CD7 antigens were positive in all T-ALL cases. More than 80% of T-ALL cases expressed CD2, CD5 and TdT. In B-lineage ALL, the frequencies of early pre-B, pre-B, transitional pre-B and B-ALL were 81, 15.5, 0.6 and 2.9%, respectively. More than 90% of early pre-B ALL cases expressed CD19, CD79a, CD22, CD10 and TdT. CD34 was expressed in three-fourths of early pre-B ALL cases. The frequencies of TdT and CD34 expression were lower in pre-B ALL than in early pre-B ALL. B-ALL showed less frequent expression of CD22, CD10, CD34 and TdT than other B-lineage ALL cases. Expression of CD13 and CD33, aberrant myeloid antigens, was significantly more frequently associated with B-lineage ALL than with T-ALL. Based on this retrospective study of antigen expression in 1,774 de novo childhood ALL cases in JPLSG, we propose standardized clinical guidelines for the immunophenotypic criteria for diagnosis and classification of pediatric ALL.     

Dietary fish oil does not prevent doxorubicin-induced cardiomyopathy in rats

BACKGROUND: Dietary fish oil potentiates the susceptibility of cellular membranes to lipid peroxidation, although it is also known to have beneficial effects on the development of cardiovascular diseases. OBJECTIVE: The effects of dietary fish oil against doxorubicin-induced cardiomyopathy, in which free radicals and lipid peroxidation are involved, were investigated in rats. ANIMALS AND METHODS: Sprague-Dawley rats (100 g) were fed a standard diet or a high fish oil diet (containing 10% fish oil) throughout the experimental period. Four weeks after starting each diet, experimental rats were treated with doxorubicin (cumulative dose 15 mg/kg) or vehicle (0.28 M dextrose solution). After three weeks of doxorubicin treatment, the cardiac performance, myocardial lipid peroxidation and myocardial vitamin E level were assessed. RESULTS: Compared with control rats, doxorubicin-treated rats showed a significantly increased mortality rate (P<0.05), and significantly decreased systolic blood pressure and left ventricular fractional shortening (P<0.01). The myocardial thiobarbituric acid-reactive substance level was significantly higher in doxorubicin-treated rats than in control rats (P<0.01), while the myocardial vitamin E level was significantly lower (P<0.05). Dietary fish oil enhanced the myocardial lipid peroxidation caused by doxorubicin, which was associated with a further decrease in myocardial vitamin E level. As a result, the rats treated with both doxorubicin and the high fish oil diet showed the highest mortality rate and the lowest cardiac performance of all the experimental groups. CONCLUSIONS: Dietary fish oil may reduce antioxidant defences and accelerate susceptibility of the myocardium to lipid peroxidation in rats under doxorubicin treatment. This may partly explain why dietary fish oil does not prevent doxorubicin-induced cardiomyopathy.     

Quinapril prevents restenosis after coronary stenting in patients with angiotensin-converting enzyme D allele.

Restenosis after coronary artery stent implantation is attributed chiefly to intimal hyperplasia, which is prevented experimentally by angiotensin-converting enzyme (ACE) inhibitors. Therefore, the present study investigated whether the effect of quinapril, a tissue-specific ACE inhibitor, on the prevention of coronary restenosis differs according to ACE polymorphism. One hundred consecutive patients with successful stent implantation were randomly assigned to quinapril and control groups. Both follow-up angiography and ACE polymorphism analysis were obtained from 92 patients (control, 46; quinapril treatment, 46). The prevalence of risk factors did not differ statistically according to quinapril treatment or ACE genotypes. There was no statistically significant difference in the occurrence of restenosis 6 months after stenting between the groups. Quantitative coronary angiography revealed that quinapril treatment resulted in significantly higher minimal lumen diameter and significantly lower percent diameter stenosis (22.9 +/- 22.6 vs 37.1 +/- 19.7% in the control group, p < 0.05) in patients with the D allele although there was no difference in those with the II genotype. In addition, intravascular ultrasound revealed that quinapril treatment significantly prevented the loss of minimal lumen cross-sectional area and the increase in percent area stenosis (34.5 +/- 14.0 vs 53.3 +/- 16.4% in the control group, p < 0.05) in patients with the D allele compared to those with the II genotype. These results suggest that the administration of ACE inhibitors for the attenuation of lumen loss after coronary stent implantation is best for subjects with the D allele of the ACE genotype.