Does severe nutcracker phenomenon cause pediatric chronic fatigue?

BACKGROUND: In the past five years we experienced 9 fatigued disabled children who were intermittently or persistently absent from school. PATIENTS: They had been suspected to be burdened with psychosomatic disorders, having orthostatic hypotension, postural tachycardia, or other autonomic dysfunction symptoms. RESULTS: Investigating the cause of moderate orthostatic proteinuria in some of them, we found by chance severe typical nutcracker phenomenon (NC), which was present in all 9 children complaining of chronic fatigue. CONCLUSION: Their symptoms filled the criteria of chronic fatigue syndrome or idiopathic chronic fatigue (CFS/CF). An association between severe NC and autonomic dysfunction symptoms in children with CFS/CF has been presented.     

An angiogenesis inhibitor E7820 shows broad-spectrum tumor growth inhibition in a xenograft model: possible value of integrin alpha2 on platelets as a biological marker.

We reported previously that an angiogenesis inhibitor, E7820, inhibits in vitro tube formation of human umbilical vein endothelial cell through the suppression of integrin alpha2 expression. Here we describe the antiangiogenic and antitumor effects of E7820 in mice and discuss the feasibility of using platelet integrin alpha2 expression on platelets as a biological marker of the efficacy of E7820. Oral administration of E7820 significantly inhibited basic fibroblast growth factor-induced angiogenesis in Matrigel implants and human colon WiDr tumor-induced angiogenesis in a dorsal air sac model. Twice-daily treatment with E7820 clearly inhibited the s.c. tumor growth of seven tumor cell lines derived from human colon, breast, pancreas, and kidney, and completely suppressed the growth of human pancreatic KP-1 and human colon LoVo cell lines. Moreover, E7820 significantly inhibited the growth of KP-1 and human colon tumor Colo320DM cells orthotopically implanted in the pancreas and cecum, respectively. The efficacy of E7820 was comparable in the s.c. and orthotopic transplantation models. Immunohistochemical analyses using anti-CD31 antibody showed that E7820 significantly reduced microvessel density in orthotopically implanted KP-1 tumor. E7820 reduced integrin alpha2 expression on a megakaryocytic cell line, Dami cells, induced by phorbol 12-myristate 13-acetate treatment. It also decreased the expression level of integrin alpha2 on platelets withdrawn from mice bearing s.c. KP-1 tumor at a dosage close to that affording antitumor activity. These data demonstrate that E7820 showed a broad-spectrum antitumor effect in mice through inhibition of angiogenesis and indicate that the decrease of integrin alpha2 on platelets might serve as a biological marker for the antitumor efficacy of E7820.     

Glutathione S-transferase (GST) M1, T1 and N-acetyltransferase 2 (NAT2) polymorphisms and urothelial cancer risk with tobacco smoking.

The objective of this study was to examine the association between the genetic polymorphism of glutathione S-transferase (GST) M1, T1 and N-acetyltransferase 2 (NAT2) genes and urothelial cancer risk in relation to smoking status. In this study, 325 Japanese patients with urothelial transitional cell carcinoma and 325 healthy controls were compared for frequencies of GSTM1, T1 and NAT2 genotypes. The frequencies of GSTM1 null genotype and NAT2 slow genotype were significantly higher in the cases than in the controls (adjusted odds ratio (OR) 1.37, 95% confidence interval (CI) 1.01-1.87, adjusted OR 3.09, 95% CI 1.69-5.63, individually). Furthermore, the risk of GSTM1 null genotype and NAT2 slow genotype was higher among smokers (adjusted OR 1.48, 95% CI 1.01-2.15, adjusted OR 4.28, 95% CI 1.96-9.36, individually). The regression analysis of cancer risk as a function of the amount of smoking showed that the susceptibility of people who had GSTM1 null genotype increased from 45 pack-years, while the susceptibility of people with NAT2 intermediate or slow genotype increased rapidly from 25 pack-years, compared with non-smokers. A multiplicative interaction between NAT2 intermediate or slow genotype and pack-years of smoking was found (P<0.001), but GSTM1 null genotype was not (P=0.06). Our results indicate that the GSTM1 null genotype and NAT2 intermediate or slow genotype are associated with an increased risk of urothelial cancer in relation to smoking amounts. Furthermore, the interaction between NAT2 intermediate or slow genotype and pack-years of smoking has a strong impact on urothelial cancer.     

Exacerbation of renal failure due to hypothyroidism in a patient with ischemic nephropathy

A case of acute-on-chronic renal failure in a 70-year-old woman with ischemic nephropathy and primary hypothyroidism is presented. Her renal function became progressively worse as the level of serum creatinine increased from 283 to 628 micromol/l (3.2-7.1 mg/dl) within 8 months. Her thyroid function had been normal before the exacerbation of renal failure, but it was markedly reduced with a marked elevation of serum thyroid-stimulating hormone. Thyroid hormone replacement therapy resulted in rapid improvement of the renal function to 159 micromol/l (1.8 mg/dl) of serum creatinine. The development of primary hypothyroidism seemed to worsen the already impaired renal function in this case. We suggest the assessment of thyroid function in patients with unexplained deterioration of renal failure.     

Macrophage-derived transforming growth factor-beta1 induces hepatocellular injury via apoptosis in rat severe acute pancreatitis

BACKGROUND: The mechanism of acute pancreatitis-induced hepatocellular injury is unclear. We have observed hepatocyte apoptosis in rat acute necrotizing pancreatitis. These studies were designed to determine the mediator(s) responsible for hepatocyte apoptosis and to clarify the significance of macrophages as its source. METHODS: A rat sodium deoxycholate-induced pancreatitis model was used. Immunohistochemical studies for apoptosis-inducing mediators on hepatocytes were examined in the liver and on the peritoneal macrophages. The levels of transforming growth factor-beta1 (TGF-beta1) were also evaluated quantitatively with an enzyme-linked immunosorbent assay. Induction of apoptosis on the hepatocytes was evaluated by in situ nick-end labeling and tissue DNA fragmentation enzyme-linked immunosorbent assay. Finally, the effects of TGF-beta1 neutralization and macrophage depletion were examined. RESULTS: In the liver and the peritoneal macrophages, strong expression of TGF-beta1 was detected early in the course of pancreatitis. In sodium deoxycholate-induced pancreatitis, the levels of TGF-beta1 were also elevated in the plasma (9.2 +/- 0.8 ng/mL), in the pancreatitis-associated ascitic fluid (11.5 +/- 0.6 ng/mL), and in the liver homogenate (2.8 +/- 0.3 ng/g of liver tissue). Moreover, the amount of fragmented DNA of the liver with pancreatitis was 290% +/- 20% of that with a sham operation and serum alanine aminotransferase levels elevated to 248.2 +/- 67.0 IU/L. TGF-beta1 neutralization partly blocked the positive labeling on the nuclei of the hepatocytes, the elevation of the amounts of fragmented DNA (205% +/- 10% of sham operation), and the serum alanine aminotransferase level (144.2 +/- 14.9 IU/L). On the other hand, the macrophage depletion caused a marked decrease in the TGF-beta1 protein level in the plasma (4.8 +/- 1.2 ng/mL) or in the pancreatitis-associated ascitic fluid (8.0 +/- 1.0 ng/mL). Moreover, the macrophage depletion completely inhibited the elevation of the TGF-beta1 protein level in the liver homogenate (1.5 +/- 0.4 ng/g of liver tissue), and thereafter decreased the amounts of the positive labeling on the nuclei of the hepatocytes and decreased the amount of fragmented DNA (120% +/- 18% of sham operation) and the serum alanine aminotransferase elevation (119.2 +/- 24.2 IU/L). CONCLUSIONS: In a model of sodium deoxycholate-induced pancreatitis, macrophages are responsible for pancreatitis-induced hepatocellular injury by means of apoptosis, and macrophage-derived TGF-beta1 is one of the major factors inducing the hepatocyte apoptosis.     

Tumor lysis syndrome in widely metastatic small-cell lung cancer

Tumor lysis syndrome is a rare complication of nonhematologic malignancies that results from massive necrosis of neoplastic cells after chemotherapy. This syndrome consists of life-threatening metabolic derangements, including severe hyperphosphatemia, hyperkalemia, hyperuricemia, and hypocalcemia, and may result in renal failure and death if not recognized early and treated appropriately. We report a case of tumor lysis syndrome after induction chemotherapy in a patient with widely metastatic smallcell lung cancer. This case emphasizes the importance of awareness and early treatment of this syndrome.     

Role of Sialylglycoconjugate(s) in the Initial Phase of Metastasis of Liver-metastatic RAW117 Lymphoma Cells

To elucidate the early events of blood-borne metastasis under actual blood flow, real-time trafficking of RAW117 large cell lymphoma cells, namely parental RAW117-P and liver-metastatic RAW117-H10 cells, was investigated using positron emission tomography (PET). Both types of cells accumulated in the liver immediately after injection via the portal vein, and were eliminated from the liver time-dependently. The elimination rate of RAW117-H10 cells, however, was slower than that of RAW117-P cells, suggesting that RAW117-H10 cells interact more strongly with hepatic sinusoidal endothelium than the parental cells. This result correlated with the metastatic potential of these cells: RAW117-H10 cells metastasized in the liver to a greater extent than RAW117-P cells after injection via this route. To investigate the role of sialylglycoconjugates in the interaction of RAW117-H10 cells with the hepatic endothelium after injection via the portal vein, the trafficking of RAW117-H10 cells was examined after the cells had been treated with sialidase. The elimination rate of RAW117-H10 cells from liver was observed to be greatly accelerated by sialidase treatment. To elucidate what kind of sialylglycoconjugates is related to this phenomenon, we analyzed the distribution of sialyl Lewis A and sialyl Lewis X antigens of both sublines of RAW117 by using flow cytometry. RAW117-H10 cells were found to express a much higher level of sialyl Lewis A than RAW117-P cells, whereas the amount of sialyl Lewis X did not differ significantly. These findings suggest that some sialylglycoconjugates, perhaps sialyl Lewis A in particular, play an important role in the initial interaction of RAW117-H10 cells with the hepatic endothelium, leading to metastasis.     

Angiomyolipoma arising in the thigh

A 41-year-old man presented with an asymptomatic mass in the right medial thigh. Magnetic resonance imaging (MRI) revealed a well-demarcated, 10-cm mass in the right adductor muscles. The margins of the mass exhibited high signal intensity and the rest showed low or iso signal intensity on T1-weighted MR images. However, the high signal intensity was decreased on T2-weighted images with fat suppression. The central part of the tumor was of inhomogeneous high signal intensity on T2-weighted images; after Gd-DTPA injection it enhanced inhomogeneously on T1-weighted images with fat suppression. On dynamic computed tomography (CT) in the arterial phase, there were strongly enhancing spotty areas in the tumor. At surgery, a yellow-whitish tumor was resected and a pathological diagnosis of angiomyolipoma (AML) in the thigh was made. Received: 21 June 1999 Revision requested: 28 July 1999 Revision received: 13 December 1999 Accepted: 15 December 1999     

Coronary artery bypass grafting for a patient with bronchial asthma seceeded from cardiopulmonary bypass by additional bypass for spasm of radial artery graft: a case report

A 78-year-old male who had a bronchial asthma underwent coronary artery bypass grafting (CABG) using the left internal thoracic artery and the radial artery. The patient could not be weaned from the cardiopulmonary bypass because the radial artery which anastomosed to the obtuse marginal artery (OM) had a spasm after CABG. An additional bypass using a long saphenous vein to OM was carried out immediately. It brought a weaning from cardiopulmonary bypass. If the cardiac function after CABG is insufficient in patients with bronchial asthma, CABG must be re-done immediately, considering that they cause the arterial spasm more than patients without bronchial asthma.