Genetic analysis of radiation-associated rectal cancer

Genetic aberrations in radiation-associated colorectal cancer have not been studied in detail. We analyzed genetic aberrations in five rectal cancers that developed long after radiotherapy had been performed for cervical cancer. Microsatellite instability (MSI) in tumors was examined at five loci: D2S123, D3S966, TP53, DCC, and BAT26. Mutation of simple repeat sequences within the hMSH3, BAX, and transforming growth factor type II receptor (TGFRII) genes was examined by polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP). Mutation of p53 exons 5–8 was examined by PCR-SSP and direct sequencing. Mutations of the K-ras gene were analyzed by two-step PCR. No MSI was found in tumor specimens at any of the loci examined, and no mutations in the target genes were observed. K-ras mutation was detected in two carcinomas, but not in their irradiated normal mucosa, while p53 mutation was observed in another two carcinomas, but not in their irradiated normal mucosa. Our results suggest that the radiation-associated rectal carcinomas examined in this study did not develop through the mutator phenotype pathway; rather, tumorigenesis was probably mediated through the multistep carcinogenesis pathway.     

Renal osteodystrophy and vitamin D

Vitamin D deficiency is one of major pathogeneses of renal osteodystrophy (ROD). Vitamin D deficiency produces osteitis fibrosa via secondary hyperparathyroidism and osteomalacia via hypocalcemia. To prevent and treat ROD, vitamin D supplementation is an inevitable tool. Recent progresses of vitamin D therapy including development of new vitamin D analogues and direct injection to parathyroid gland will contribute to the successful treatment of ROD.     

An alpha-adrenergic blocker titrated by self-measured blood pressure recordings lowered blood pressure and microalbuminuria in patients with morning hypertension: the Japan Morning Surge-1 Study

BACKGROUND: The impact on microalbuminuria of strict treatment aimed at lowering of self-measured morning blood pressure using an adrenergic blockade is unclear. METHODS: We conducted an open-label multicenter trial, the Japan Morning Surge-1 Study, that enrolled 611 hypertensive patients, whose self-measured morning systolic blood pressure levels were more than 135 mmHg while taking antihypertensive drugs. These were randomly allocated to an experimental group, whose members received bedtime administration of 1-4 mg doxazosin (doxazosin group) or a control group whose members continued without any add-on medication (control group). The urinary albumin/creatinine ratio was investigated at the baseline and 6 months after the randomization. RESULTS: Both the morning and evening blood pressures and urinary albumin/creatinine ratio (-3.4 vs. 0.0 mg/gCr for urinary albumin/creatinine ratio; P < 0.001) were more markedly reduced in the doxazosin group than in the control group. This difference in the urinary albumin/creatinine ratio between the two groups was more marked in the patients with microalbuminuria (n = 238, -27.9 vs. -8.1 mg/gCr, P < 0.001). The reduction of urinary albumin/creatinine ratio was significantly associated with the use of doxazosin, and the change in all self-measured blood pressures (morning, evening, the average morning-evening), and these associations were independent of each other (P < 0.001). CONCLUSION: Adding a bedtime dose of an alpha-adrenergic blocker titrated by self-measured morning blood pressure in treated hypertensive patients with uncontrolled morning hypertension significantly reduced blood pressure and urinary albumin excretion rate, particularly in those with microalbuminuria.     

Clinical impact of selective spasm provocation tests: comparisons between acetylcholine and ergonovine in 1508 examinations

BACKGROUND: There are few reports regarding the concordance of coronary arterial response between acetylcholine (ACh) and ergonovine (ER) spasm provocation tests. OBJECTIVES: We attempted to perform selective spasm provocation tests to examine the incidence of provoked spasm in patients who had undergone first coronary angiography as much as possible and we compared the coronary arterial response and clinical usefulness between selective intracoronary injection of ACh and intracoronary administration of ER. METHODS: We performed 1508 selective spasm provocation tests, consisting of 873 ACh tests and 635 ER tests, from 1991 to 2002. We examined the frequency of provoked spasms of each agent retrospectively. ACh was injected in incremental doses of 20, 50 and 80 microg into the right coronary artery and 20, 50 and 100 microg into the left coronary artery. ER was administered as 10 microg/min over 4 min for a maximal dose of 40 microg in the right coronary artery and as 16 microg/min over 4 min for a total dose of 64 microg in the left coronary artery. Coronary spasm was defined as transient >99% luminal narrowing. RESULTS: Intracoronary ACh provoked spasms in 36.0% of patients and intracoronary ER induced spasms in 29.8% of patients. In patients with ischemic heart disease, the incidence of provoked spasms was not different between ACh tests (50.9%) and ER tests (43.8%). In contrast, the frequency of provoked spasms with ACh tests was significantly higher than that with ER tests (11.0% compared with 6.4%, P<0.05) in patients without ischemic heart disease. Moreover, ACh provoked more spasms in patients without fixed stenosis than ER (36.2% compared with 25.5%, P<0.01) and multiple spasms were frequently observed when performing ACh tests (40.0% compared with 27.0%, P<0.01). Major complications were observed in 1.4% of patients with ACh tests and in 0.2% of patients with ER tests. The need for intracoronary administration of isosorbide dinitrate to relieve coronary spasms during ER testing before performing another coronary artery test was more frequently observed in ACh tests (5.04% compared with 1.49%, P<0.01). However, no serious irreversible complications, such as death or acute myocardial infarction, were observed in this study. There was a significant difference in sex, history of smoking and hyperlipidemia between patients with and without spasms for both tests, whereas no difference in age or hypertension was observed in either test. CONCLUSION: Thus, both selective ACh and ER tests were useful as spasm provocation tests.     

Failure to find an association between CD14-159C/T polymorphism and asthma: a family-based association test and meta-analysis.

BACKGROUND: CD14 is an essential component of the receptor for lipopolysaccharide (LPS). LPS stimulates T-helper type 1 (Th1) cytokine expression, potentially suppressing Th2 immune responses involved in IgE-mediated allergic diseases. Previous studies have reported that -159C/T, a promoter polymorphism of CD14, is associated with total serum IgE levels and atopy, but other studies have shown conflicting results. METHODS: To examine possible associations of CD14 polymorphisms with asthma susceptibility, we performed transmission disequilibrium tests (TDTs) of 137 Japanese families identified through children with atopic asthma. RESULTS: We found no association between -159C/T polymorphism and asthma (p= 0.37). Quantitative TDT and ANOVA showed no association between the -159C/T genotype and total serum IgE levels. We also performed a meta-analysis of data from all available studies. Neither a fixed-effects model nor a random-effect model showed a significant odds ratio for the -159C/T polymorphism (p > 0.1). CONCLUSIONS: Our data indicate that CD14 does not contribute substantially to susceptibility to asthma. Further studies examining both genotypes and environmental factors will be necessary to elucidate the role of CD14 in the development of allergic diseases.     

Life threatening coronary artery spasm in childhood Kimura's disease

A 13 year old boy is described with hypereosinophilia associated with Kimura's disease, who showed repeated life threatening syncopal attacks during daily activities or at rest. Coronary arteriography demonstrated small aneurysms with irregular vessel walls of both coronary arteries, and the absence of organic stenotic lesions. Infusion of a minimal dose of ergonovine into the right coronary artery induced severe spasm of the vessel. Ventricular fibrillation recurred even after administration of nifedipine and isosorbide was started, but was completely inhibited by prednisolone.


Keywords: coronary vasospasm; hypereosinophilia; Kimura's disease; ventricular tachyarrhythmia     

Morphology and biochemistry of the lung from guinea pig after repeated injections of freund’s complete adjuvant

Guinea pigs received 5 daily injections of Freund’s complete adjuvant and the changes in the lung were investigated by light microscope and electron microscope. In the 20th week of experiment, fibrotic changes were found around the granulomata close to the surface of the lung. In addition the fraction of glycosaminoglycans was isolated from the lung and analyzed quantitatively. As a result, a decrease in quantity of hyaluronic acid and an increase in quantity of dermatan sulfate were observed.     

Intracranial Distribution of Intravenously Administered Gadolinium-based Contrast Agent over a Period of 24 Hours: Evaluation with 3D-real IR Imaging and MR Fingerprinting

Purpose:To evaluate the feasibility for the detection of slight contrast effects after intravenous administration of single dose gadolinium-based contrast agent (IV-SD-GBCA), the time course of the GBCA distribution up to 24 h was examined in various fluid spaces and brain parenchyma using 3D-real IR imaging and MR fingerprinting (MRF).Methods:Twenty-four patients with a suspicion of endolymphatic hydrops were scanned at pre-administration and at 10 min, 4 and 24 h post-IV-SD-GBCA. 3D-real IR images and MRF at the level of the internal auditory canal were obtained. The signal intensity on the 3D-real IR image of the cerebrospinal fluid (CSF) in the cerebellopontine angle cistern (CPA), Sylvian fissure (Syl), lateral ventricle (LV), and cochlear perilymph (CPL) was measured. The T₁ and T₂ values of cerebellar gray (GM) and white matter (WM) were measured using MRF. Each averaged value at the various time points was compared using an analysis of variance.Results:The signal intensity on the 3D-real IR image in each CSF region peaked at 4 h, and was decreased significantly by 24 h (P < 0.05). All patients had a maximum signal intensity at 4 h in the CPA, and Syl. The mean CPL signal intensity peaked at 4 h and decreased significantly by 24 h (P < 0.05). All patients but two had a maximum signal intensity at 4 h. Regarding the T₁ value in the cerebellar WM and GM, the T₁ value at 10 min post-IV-GBCA was significantly decreased compared to the pre-contrast scan, but no significant difference was observed at the other time points. There was no significant change in T₂ in the gray or white matter at any of the time points.Conclusion:Time course of GBCA after IV-SD-GBCA could be evaluated by 3D-real IR imaging in CSF spaces and in the brain by MRF.     

Initial report of bridge to recovery in a patient with DuraHeart LVAD

Continuous-flow left ventricular assist devices (LVADs) provide acceptable clinical results, but the long waiting period for heart transplantation leads to diverse complications. LVAD support can cause reverse left ventricular (LV) remodeling that results in the improvement of LV function and allows LVAD removal. We present a case of successful removal of a DuraHeart LVAD because of sufficient recovery of LV function. Before LVAD removal, we conducted an “LVAD weaning test” by decreasing pump speed and performing an additional normal saline infusion test. We consider that the LVAD weaning test can be used in place of the “pulsatile LVAD off test.”     

Effects of short-term administration of the CCK receptor antagonist,KSG-504, on regeneration of pancreatic acinar cells in acute pancreatitis in rats

Cholecystokinin (CCK) receptor antagonists have been reported on have an inhibitory effect on acute experimental pancreatitis, but their long-term administration is also reported to block pancreatic regeneration. We examined whether the short-term administration of KSG-504 )KSG), a synthetic CCK-A receptor antagonist, inhibited the regeneration of pancreatic acinar cells after ethionine-induced acute pancreatitis in rats. KSG (50 mg/kg), given 12 times by subcutaneous injection at 6-h intervals, prevented the reduction of protein, amylase, and trypsinogen levels, and the DNA content of the pancreas and facilitated the recovery of these values. Ornithine decarboxylase activity in pancreatic tissue and a 5-bromo-2′-deoxyuridine labeling study indicated that DNA synthesis was accelerated in rats treated with KSG. These findings suggest that the short-term administration of KSG inhibits the development of ethionine-induced acute pancreatitis and facilitates the regeneration of acinar cells.