Case of chronic-phase chronic myelogenous leukemia with an abdominal hematopoietic tumor of leukemic clone origin

We report a 59-year-old man with chronic myelogenous leukemia (CML) in chronic phase who presented with a large abdominal tumor. Biopsy revealed proliferation of granulocytic-, erythroid-, and megakaryocytic-lineage cells in a retroperitoneal lymph node. The BCR/ABL fusion gene was detected on a paraffin-embedded tissue section of the lymph node by double-color fluorescence in situ hybridization, indicating an extramedullary hematopoietic tumor of CML origin. This patient has achieved a complete cytogenetic response for 19 months with imatinib mesylate (STI571; Gleevec), in association with the regression of the tumor. However, the development of an extramedullary tumor in chronic-phase CML generally indicates a poor prognosis, because it commonly consists of blast proliferation and is followed by blast crisis in the marrow within a few months. This case, therefore, points to the importance of histological examination of extramedullary tumors in CML for evaluation of disease status and for therapeutic decisions.     

Uremic Toxins Enhance Statin-Induced Cytotoxicity in Differentiated Human Rhabdomyosarcoma Cells

The risk of myopathy and rhabdomyolysis is considerably increased in statin users with end-stage renal failure (ESRF). Uremic toxins, which accumulate in patients with ESRF, exert cytotoxic effects that are mediated by various mechanisms. Therefore, accumulation of uremic toxins might increase statin-induced cytotoxicity. The purpose of this study was to determine the effect of four uremic toxins—hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionate, indole-3-acetic acid, and 3-indoxyl sulfate—on statin-induced myopathy. Differentiated rhabdomyosarcoma cells were pre-treated with the uremic toxins for seven days, and then the cells were treated with pravastatin or simvastatin. Cell viability and apoptosis were assessed by viability assays and flow cytometry. Pre-treatment with uremic toxins increased statin- but not cisplatin-induced cytotoxicity (p < 0.05 vs. untreated). In addition, the pre-treatment increased statin-induced apoptosis, which is one of the cytotoxic factors (p < 0.05 vs. untreated). However, mevalonate, farnesol, and geranylgeraniol reversed the effects of uremic toxins and lowered statin-induced cytotoxicity (p < 0.05 vs. untreated). These results demonstrate that uremic toxins enhance statin-induced apoptosis and cytotoxicity. The mechanism underlying this effect might be associated with small G-protein geranylgeranylation. In conclusion, the increased severity of statin-induced rhabdomyolysis in patients with ESRF is likely due to the accumulation of uremic toxins.     

Elevated Von Willebrand factor propeptide for the diagnosis of thrombotic microangiopathy and for predicting a poor outcome

Thrombotic microangiopathy (TMA) is associated with vascular endothelial cell injury and is sometimes linked with poor outcome. Von Willebrand factor (VWF) propeptide (VWFpp) is considered to be a marker of vascular endothelial cell injury. The plasma levels of VWF, VWFpp, and thrombomodulin (TM) were evaluated for their use in the diagnosis of TMA in 75 patients with TMA. There were 30 TMA patients with marked decreases in ADAMTS13 (TMA/ADAMTS13) and 45 without the decrease (TMA/other). The plasma levels of TM, VWF, and VWFpp values were significantly high in patients with TMA, especially TMA/other group. The plasma levels of TM and VWFpp were significantly high in non-survivor with TMA. In the TMA/other group, the plasma levels of VWFpp were negatively correlated with ADAMTS13 activity. The plasma levels of TM correlated with the renal function, but the plasma levels of VWFpp did not. A ROC analysis indicated that VWFpp and TM were useful markers for the prediction of a poor outcome. These findings suggest that VWFpp is an useful marker for the diagnosis of TMA and for the prediction of poor outcome.     

Successful treatment of radiation-induced brain necrosis by hyperbaric oxygen therapy

We describe a 68-year-old man who underwent hyperbaric oxygen (HBO) therapy to manage radiation necrosis of the brain, which developed after two treatments with stereotactic radiosurgery (SRS) to the same lesion. The necrosis was subsequently treated with steroids alone for 2 months; however, he progressed clinically and radiographically. Improvement again was noted with the reinstitution of HBO therapy. This case suggests that HBO therapy is an important therapeutic option in the treatment of brain radiation necrosis caused by SRS.     

Toxicity of dichloropropanols

A rare outbreak of acute hepatic damage in workers exposed to dichloropropanols was reported in 1992. As there are no detailed reports of dichloropropanols (DCPs) toxicity and its mechanism, we reviewed the toxicity of dichloropropanols using our results. 1) A marked elevation of serum AST and ALT with massive necrosis of the liver was noted in the 1/2 x, the 1 x and 2 x LD50 (0.149 mg/kg) of 1, 3-dichloro-2-propanol(DC 2 P). Hepatic malondialdehyde level was significantly increased, and associated with a decrease in liver glutathione S-transferase activity and reduced glutathione content. It is suggested that the free radical is associated with DCPs. 2) A reduction of leukocytes, platelets and fibrinogen, and prolonged prothrombin time were observed in the 1 x LD50 of DC 2 P. 3) In the CA1 area of the hippocampus, inhibition of population spikes was reduced by the 1 x LD50 of DC 2 P. This research was completed with the assistance of several other papers concerning dichloropropanols toxicity.     

Acute decompression illness following hyperbaric exposure: clinical features of central nervous system involvement

Decompression illness (DCI) is a general term encompassing all pathological changes secondary to reduction of environmental pressure. This condition has two forms: decompression sickness (DCS) and arterial gas embolism (AGE) secondary to pulmonary barotrauma. Moreover, DCS is categorized as minor, such as limb and/or joint pains or skin rash (Type I), and serious, as in cardiopulmonary and/or central nervous system involvements (Type II). Cerebral and spinal injuries have been symptomatically classified into AGE and DCS. Brain scans of patients with AGE or DCS showed multiple cerebral infarctions in the terminal and/or border zones of the cerebral arteries. Brain involvements of patients in both AGE and DCS show no differences in neurological or neuro-radiological findings. From the neurological and radiological standpoint, it is therefore impossible to distinguish these two conditions. Despite established treatments for neurological DCI (both AGE and DCS), it is unclear whether US Navy treatment Table 6 is preferable to standard hyperbaric oxygen therapy such as 2.4 atmospheres pressure for 90 minutes. Japanese laws and regulations have peculiarities that permit air diving to 90 meters depth, but with explicit prohibition of the use of oxygen for decompression, albeit a limited use of mixed gas is permissible. Moreover, currently the health screening for hyperbaric workers does not include detailed examination of the cardiopulmonary or the central nervous system.     

Considerable multiple esophageal carcinoma. Implications of a new clinical entity

BACKGROUND/AIMS: The multiple occurrence of primary squamous cell carcinoma of the esophagus is often observed, and most such occurrences are double cancers. There have also been some cases with three or more intra-esophageal cancers, however, no detailed clinicopathologic study has yet been performed in the literature. METHODOLOGY: Two hundred and fifty patients of primary esophageal squamous cell carcinoma without preoperative treatment that underwent esophageal resection were re-evaluated by serial histopathologic investigations and we analyzed the data of ten patients with three or more intraesophageal cancers. RESULTS: The clinical and histopathologic characteristics were as follows; 1) all but one of the cases were male, 2) all patients had a history of both heavy smoking and drinking but only one case had a family history of esophageal cancers among their siblings, 3) the depth of invasion in the carcinomas was restricted to within the submucosal layer of the esophageal wall, which was defined as superficial esophageal carcinoma, almost all (90%) of the cases accompanied esophageal squamous epithelial dysplasia. CONCLUSIONS: Based on these prominent characteristics of considerable multiple intra-esophageal cancers, a new clinical entity of "esophageal field cancers" could thus be suggested.     

β2-Adrenergic Receptor Genotype-Related Changes in cAMP Levels in Peripheral Blood Mononuclear Cells After Multiple-Dose Oral Procaterol

Purpose. To evaluate the ₂-adrenergic receptor (₂AR) genotype frequency in the Japanese population and the relationship between ₂AR genotype at amino acid position 16 (₂AR-16) and desensitization to ₂-agonist ex vivo. Methods. The ₂AR genotypes at amino acid positions 16, 27, and 164 of 92 healthy Japanese subjects were determined by polymerase chain reaction-restriction fragment-length polymorphism. The relationship between the ₂AR-16 genotype and the desensitization to ₂-agonist was examined in 10 male subjects ex vivo. Procaterol tablet (HCl salt, 50g, Meptin®) was given orally for 5 days, and peripheral blood was obtained before and after 5 days of consecutive medications followed by the assessment of the intracellular cAMP levels in peripheral blood mononuclear cells after incubation with or without procaterol hydrochloride (0-1000 ng/mL). Results. Allele frequency was Arg16:Gly16 = 46%:54%, Gln27:Glu27 = 92%:8%, and Thr164:Ile164 = 100%:0%, respectively. The cAMP levels were increased by incubation with procaterol hydrochloride, and the increase was suppressed after 5 days of consecutive medications. The suppression was more significant in the homozygote for Gly16 than the homozygote for Arg16. Conclusions. The desensitization to ₂-agonist was associated more frequently with the mutation at ₂AR-16 (Gly16).