The additive effect ofα-difluoromethylornithine (DFMO) and radiation therapy on a rat glioma model

Summary The effects of -difluoromethylornithine (DFMO), radiation and the therapy of their combination were investigated in rats bearing G-XII glioma. DFMO treatment as well as radiation therapy prolonged the survival period when compared to the results in non-treated control rats. The combination therapy showed a greater effect on the survival rate than the single therapies, the effect being additive. The concentration of putrescine, spermidine, andN ¹-acetylspermidine in tumor tissues was lowered by DFMO, while that of spermine was slightly elevated. Radiation decreased the concentration of all the polyamines, putrescine, spermidine, spermine andN ¹-acetylspermidine. The concomitant treatment with DFMO and radiation further decreased the concentrations of putrescine andN ¹-acetylspermidine in tumor tissues. The survival period of glioma-bearing rats is inversely correlated with the tissue levels of putrescine plusN ¹-acetylspermidine.Abbreviations DFMO -difluoromethylornithine - BrdUrd bromodeoxyuridine     

Familial Crohn's disease with systemic lupus erythematosus

We describe a young Japanese woman who was diagnosed with Crohn's disease affecting the ileum, transverse colon, and rectum, as confirmed by barium studies, colonoscopy, and histopathological examination. Her father and sister also had Crohn's disease. After a 4-yr course of sulfasalazine and elemental diet therapy, she was readmitted for perianal abscess associated with the presence of pancytopenia, microhematuria with granular cast, hypocomplementemia, and high titers of autoimmune antibodies (anti-ANA and anti-dsDNA antibodies). Based on these features, a diagnosis of systemic lupus erythematosus (SLE) was made. Despite the rarity of such combination (Crohn's disease with SLE), patients with Crohn's disease who develop such clinical findings might need evaluation for SLE.     

Effect of H. pylori on COX-2 expression in gastric remnant after distal gastrectomy

BACKGROUND/AIMS: Helicobacter pylori infection is known to induce gastritis, oxidative stress, and cyclooxygenase (COX)-2 expression in the gastric mucosa. However, the effect of H. pylori infection on remnant gastritis has not been studied. We investigated whether the severity of remnant gastritis and COX-2 expression were affected by H. pylori infection after distal gastrectomy. METHODOLOGY: The study included 97 patients with gastric cancer who underwent curative distal gastrectomy with lymphadenectomy in our department between May 1999 and April 2001. All patients underwent endoscopic examination 2 weeks before and 12 weeks after surgery. The presence of H. pylori infection was determined by urease activity, hematoxylin-eosin staining, and immunochemical staining. Histologic remnant gastritis was graded based on the degree of neutrophil infiltration using the updated Sydney System. COX-2 expression was estimated immunohistochemically. RESULTS: Both the degree of neutrophil infiltration and the level of COX-2 expression were significantly higher in patients with than without H. pylori (p<0.05). There was a significant correlation between the degree of neutrophil infiltration and the degree of COX-2 expression (p<0.001). CONCLUSIONS: H. pylori eradication may become a treatment for preventing both remnant gastritis as well as remnant gastric carcinoma after distal gastrectomy.     

Bone mineral density in Japanese prostate cancer patients under androgen-deprivation therapy

Androgen-deprivation therapy (ADT) of patients with prostate cancer (PCa) is known to reduce bone mineral density (BMD). However, the most studies examined Caucasian or black patients and the effects of ADT on the bone metabolism of East Asians are unclear. Therefore, we performed a cross-sectional study to elucidate the influence of ADT on bone metabolism in Japanese patients. In total, 101 native Japanese patients with PCa were enrolled. They consisted of 58 ADT-treated and 43 hormone-naive patients. The BMD in the lumbar spine, total hip, and femoral neck was measured by dual energy X-ray absorptiometry and expressed in s.d. units relative to young adult men (T-score) or age-matched men (Z-score). Serum levels of bone metabolism markers were also measured. The BMDs at the three sites revealed that 2.3% (1/43) and 8.6% (5/58) of the hormone-naive and ADT-treated PCa patients had osteoporosis respectively, but this difference failed to achieve statistical significance (P=0.294). The two groups also did not differ significantly in their Z-scores of the three sites, and univariate and multivariate analyses indicated that ADT was not a significant risk factor for decreased BMD. In addition, a significant correlation between the duration of ADT and BMD was not observed for all three sites measured. However, the ADT-treated patients had significantly higher serum levels of N-terminal telopeptide of type I collagen (NTx) than the hormone-naive patients (P=0.017). To our knowledge, this is the first study to demonstrate the low prevalence of osteoporosis in both ADT-treated and hormone-naive Japanese PCa patients. Moreover, ADT did not significantly increase the prevalence of osteoporosis in this Japanese population.     

Herpes simplex encephalitis and subsequent cytomegalovirus encephalitis after chemoradiotherapy for central nervous system lymphoma: a case report and literature review

Neurological complications during the treatment of hematological malignancies have a wide range of causes. Treatment-related leukoencephalopathy has been recognized as a major complication of combined chemotherapy and radiotherapy for central nervous system (CNS) lymphoma, and can complicate the diagnosis of CNS infection. Herein, we present a patient with diffuse large B-cell lymphoma who developed herpes simplex encephalitis (HSE) and subsequent cytomegalovirus encephalitis after chemoradiotherapy for CNS relapse. Although cerebrospinal fluid examination (CSF) showed no significant pleocytosis, brain magnetic resonance imaging and polymerase chain reaction analysis of the CSF were useful in the diagnosis. With a review of the literature on the association between HSE and radiotherapy for CNS malignancies, our case suggests that an awareness of viral encephalitis is important in the differential diagnosis of acute neurologic disturbance during chemoradiotherapy for CNS lymphoma.     

Differential effects of central fructose and glucose on hypothalamic malonyl-CoA and food intake

The American diet, especially that of adolescents, contains highly palatable foods of high-energy content and large amounts of high-fructose sweeteners. These factors are believed to contribute to the obesity epidemic and insulin resistance. Previous investigations revealed that the central metabolism of glucose suppresses food intake mediated by the hypothalamic AMP-kinase/malonyl–CoA signaling system. Unlike glucose, centrally administered fructose increases food intake. Evidence presented herein indicates that the more rapid initial steps of central fructose metabolism deplete hypothalamic ATP level, whereas the slower regulated steps of glucose metabolism elevate hypothalamic ATP level. Consistent with effects on the [ATP]/[AMP] ratio, fructose increases phosphorylation/activation of hypothalamic AMP kinase causing phosphorylation/inactivation of acetyl–CoA carboxylase, whereas glucose has the inverse effects. The changes provoked by central fructose administration reduce hypothalamic malonyl–CoA level and thereby increase food intake. These findings explain the paradoxical fructose effect on food intake and lend credence to the malonyl–CoA hypothesis.     

Metastatic gastrinoma to the liver 20 years after primary resection

Gastrinoma is a rare endocrine tumor that is frequently associated with liver metastasis. The liver metastasis is usually seen simultaneously or soon after a primary operation. A 47-year-old woman who had had a total gastrectomy 20 years earlier developed liver metastasis. An interval of this length between surgery and metastasis is extremely rare. The total gastrectomy prevented the patient from developing the usual symptoms of hypergastrinemia that would have enabled early diagnosis of the metastasis. Laboratory examinations on admission revealed a high serum gastrin concentration (1500 pg/ml). Computed tomography showed an irregularly enhanced mass lesion with an uneven, low-density central area in the right anterior inferior segment of the liver. An extended right hepatectomy was performed. Intraoperative ultrasonography showed no abnormalities in the remnant pancreas. Examination of the cut surface of the specimen revealed a yellow, firm, elastic tumor, 55 mm in diameter. The interior of the tumor appeared necrotic. Histopathologically, the tumor was composed of cells with hyperchromatic, dysplastic nuclei arranged in a trabecular pattern with nest formation. Gastrin staining was positive. A histologic diagnosis of metastatic gastrinoma was made. The patient's gastrin concentration returned to normal and she was well at 2-year follow-up. Received: August 19, 1999 / Accepted: January 28, 2000     

Numerical chromosomal abnormality in gastric MALT lymphoma and diffuse large B-cell lymphoma

Background: We investigated numerical chromosomal abnormalities, using the fluorescence in situ hybridization (FISH) method, in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBL). We also compared the histopathological findings, including the presence or absence of Helicobacter pylori infection, with the analytical results. Methods: Sixteen patients who underwent operation for malignant gastric lymphoma in our department were divided into three groups: patients with low-grade gastric MALT lymphoma (l-MALT; n = 5), those with high-grade gastric MALT lymphoma (h-MALT; n = 8), and those with DLBL (n = 3). Numerical abnormalities of chromosomes 8, 9, 12, and 17 were investigated by the FISH method, and the presence or absence of H. pylori infection was microscopically examined. Results: Numerical abnormality was observed in chromosome 12 in 11 patients (68.8%), in chromosome 8 in 10 (62.5%), and in chromosome 17 in 5 (31.3%), showing a high frequency. H. pylori infection was detected in 80% and 50% of patients with l-MALT and h-MALT, respectively, but no H. pylori infection was observed in patients with DLBL. Conclusions: A new biological characteristic of gastric MALT lymphoma was obtained, i.e., a high frequency of numerical abnormalities of chromosomes 12, 8, and 17. There was no correlation between the numerical chromosomal abnormalities and the clinicopathological findings. Received: September 5, 2001 / Accepted: February 22, 2002 Acknowledgments. We sincerely appreciate the instruction and cooperation provided by Mr. A. Furuhata, Mr. S. Nakamura, and the staff, Department of Collaborative Pathology, Juntendo University, Tokyo, Japan. Reprint requests to: I. Watanobe     

A case of pyomyositis following influenza virus infection

A 45-year-old man visited the first hospital complained of high fever on January 2003. He was diagnosed as having Influenza virus type A infection and prescribed of Oseltamivir. He was afebrile next day, but severe myalgia of neck, shoulder, lumbar region and right femoral region was appeared. His illness was considered as polymyalgia rheumatica and started of oral steroid therapy. His symptom was deteriorated and transferred to our hospital. Echography, Ga scintigraphy, computed tomography and magnetic resonance imaging revealed the multiple abscesses and the diagnosis of pyomyositis was made. Pyomyositis following Influenza virus infection must be considered as a differential diagnosis of myalgia after Influenza virus infection.