Detection of stunned myocardium in post-reperfusion cases of acute myocardial infarction

OBJECTIVE: This study was designed to evaluate the correlation between improvements in serial images obtained by SPECT imaging with Tc-99m MIBI (MIBI) and I-123 BMIPP (BMIPP) and the recovery of cardiac function in acute myocardial infarction (AMI) patients after reperfusion therapy. METHODS: Twenty five patients who were admitted to the emergency room within 24 hours after the onset of the first event of AMI were enrolled in this study. The culprit coronary arteries were identified by CAG and were treated with direct percutaneous transluminal coronary angiography (PTCA), followed by stent implantation. To determine risk areas, initial image at the onset was acquired by the freeze method, in which MIBI was injected before the treatment and the image was collected after the reperfusion therapy. After the reperfusion treatment was completed, MIBI SPECT images at rest were performed on days 7 and 60. Both early and late images, including gated SPECT images were acquired after 30-60 minutes and 6 hours post injection, respectively. In addition, BMIPP SPECT images at rest were obtained 30 minutes after injection of 148 MBq BMIPP on days 7 and 60 (BMIPP image). The obtained image was divided into 48 segments and percent uptake of each segment was calculated. The number of abnormal areas (NAA) was defined as the segment with a % uptake less than 60% of normal uptake, and the change of NAA over time was evaluated. RESULTS: The NAA on the MIBI-early image significantly improved between thepre image and the day 7 image (p < 0.001), but no similar improvement was observed between day 7 and day 60. On the other hand, the NAA of the MIBI-delayed image did not significantly improve up to day 7, but a slight improvement was observed on days 7 and 60 (p < 0.05). A significant improvement in the NAA of the BMIPP image was observed between day 7 and day 60, as shown in the delayed image (p < 0.05). An excellent correlation on the NAA between the MIBI-delayed image and the BMIPP image was observed with r = 0.983 (p < 0.001) at day 7 and r = 0.984 (p < 0.001) at day 60 resulting in a consistent diagnosis. Analysis of the myocardial function by means of gated SPECT indicated that the wall motion significantly improved as the myocardial perfusion improved up to day 7 and thereafter a steady improvement was observed up to day 60. The improvement in the NAA in MIBI-delayed images in the subacute phase (day 7) and in the chronic phase (day 60) as well as BMIPP images showed excellent correlation with the improvement in RWM and RWT (MIBI-delayed image: r = 0.550 (RWM), r = 0.647 (RWT)), (BMIPP image: r = 0.536 (RWM), r = 0.565 (RWT)). CONCLUSION: We conclude that insufficient ATP production caused by mitochondrial dysfunction in stunned myocardium is closely related to MIBI delayed and BMIPP image Furthermore, MIBI delayed imaging as well as BMIPP imaging will provide a clue to the state of stunned myocardium after reperfusion therapy in patients with AMI.     

Oral chemolysis of uric acid stones

Oral chemolysis of uric acid stones was performed retrospectively. Twenty-one patients with upper urinary uric acid stones were given alkaline citrate (Uralyt-U) orally. In the case of hyperuicemia, allopirinol was combined. In 11 out of 15 patients (73.3%) treated with oral chemolysis alone, stones were dissolved. In 4 out of 6 cases (66.7%) combined with extracorporeal shock-wave lithotripsy, administration of alkaline citrate shortened the period to be stone-free. In conclusion, we successfully treated 15 out of 21 cases (71.4%) with the administration of alkaline citrate.     

A case report: renal arteriovenous malformation associated with horseshoe kidney detected by hemorrhage due to injury

A case report of a patient with renal arteriovenous malformation associated with horseshoe kidney detected by hemorrhage due to injury. A 71-year-old man was injured in a traffic accident and conveyed to our hospital. The computed tomographic scan showed renal injury of the horseshoe kidney with retroperitonial hemorrhage. We treated him conservatively, but he complained of abdominal fullness and went into hemorrhagic shock. So, we performed arterial angiography. It showed a right renal arteriovenous malformation from which leakage of contrast medium was detected. Hemostasis was possible by embolization of the abnormal artery. He has not had any recurrence of renal arteriovenous malformation. To our knowledge, this case is the third report of renal arteriovenous malformation associated with horseshoe kidney in Japan.     

Diagnosis of the autonomic nervous function during sedation by peripheral blood flow and psychogenic perspiration

BACKGROUND: Pain induces a variety of physiological responses, many of which are mediated by the sympathetic nervous system. Among these are a reduction in peripheral blood flow and evaporative cutaneous water loss (sweating). We therefore tested the hypothesis that adequate sedation obliterates the normal pain-induced reduction in peripheral blood flow and an increase in evaporative water loss. METHODS: We studied eight volunteers. Two different painful stimuli were randomly applied: 1) electrical pulp stimulation (200 microamperes) and 2) electrical pain stimulation on the right upper thigh (80 mA). Conscious sedating was controlled by propofol infusion titrated to a Bispectral Index near 80, or near 60. RESULTS: At each stimulation, peripheral blood flow detected by laser Doppler decreased without any relation to the level of consciousness (by Bispectral Index). On the other hand, although the psychogenic perspiration rate increased significantly at alert level, during BIS 80 or 60 level, the increase was not significant. CONCLUSION: Peripheral blood flow reacts most to pain stimulation during intravenous sedation.     

The restriction of all minerals in the diet enhancing paraquat toxicity is regarded primarily as the shortage of Mg

This study compares the effect of the restriction of Mg with that of all-minerals in the diet on the toxicity of paraquat. To compare the severity of the toxicity, several biological values were examined; kininogen in plasma, thiobarbituric acid reactive substances in liver, Ca level in kidney, and Mg levels in liver and kidney. Osteogenic disorder Shionogi rats that cannot synthesize vitamin C like humans did not display paraquat symptoms after receiving minute amounts of paraquat dichloride, i.e. 125 ppm in the diet for 8 days, and those biological values remained the same as those of the control. Rats fed with Mg at half of the recommended amounts also did not show any changes in those levels. The dosage of 125 ppm paraquat under the restriction of Mg, however, induced paraquat intoxication and increased those levels greatly. This result arises a question whether the intoxication is due to the imbalance of Ca and Mg or due to the shortage of Mg itself, because imbalance of Ca and Mg sometimes induces more serious effects than the shortage of Mg itself. Therefore, we fed rats an all-mineral restricted diet where the balance of Ca and Mg was maintained. The dosage of paraquat under all-mineral restriction, however, induced much more serious intoxication than that under Mg restriction. In conclusion, the shortage of Mg itself seems to be responsible for the induction of paraquat intoxication.     

Use of candesartan cilexetil decreases proteinuria in renal transplant patients with chronic allograft dysfunction

BACKGROUND: Posttransplant proteinuria and hypertension are difficult to treat after renal transplantation. Therefore, we examined whether candesartan cilexetil is effective in reducing urinary protein excretion or in controlling hypertension in patients with renal allograft dysfunction. METHODS: Sixty-two renal transplant recipients with proteinuria were enrolled in this study. They underwent kidney transplantation under cyclosporine or tacrolimus immunosuppression between February 1983 and December 1998. Causes of proteinuria were chronic rejection in 28, glomerulonephritis in 16, cyclosporine or tacrolimus nephrotoxicity in 9, and unknown in 9 recipients. The dose of candesartan cilexetil ranged from 4 to 12 mg/day. Eleven patients with proteinuria who had not been treated with candesartan cilexetil constituted a matched control population. RESULTS: Hypertension was well controlled by administration of candesartan cilexetil. Both systolic blood pressure and diastolic blood pressure significantly decreased from 141.7+/-14.8 mm Hg to 118.7+/-11.9 mm Hg and 121.2+/-11.6 mm Hg, and from 89.0+/-13.0 mm Hg to 72.0+/-10.4 mm Hg and 74.9+/-9.4 mm Hg, at 2 months and 1 year after administration, respectively. Urinary protein excretion was reduced from 0.93+/-1.2 g/day to 0.34+/-0.7 g/day and 0.43+/-1.2 g/day at 2 months and 1 year after administration, respectively. The levels of creatinine clearance were 55.7+/-28.9 mL/min before treatment, 50.9+/-24.8 mL/min at 2 months, and 52.6+/-24.8 mL/min at 1 year after treatment, respectively. There was no clinically significant difference between them. Regarding the calcineurin inhibitor levels, there was no significant difference between the levels before and 1 year after treatment. There was a significant difference in all examinations (systolic blood pressure, diastolic blood pressure, proteinuria, and renal function) between the patients with and without candesartan at 1 year after treatment. No significant adverse effects occurred. CONCLUSIONS: Candesartan cilexetil can effectively control hypertension and proteinuria without deterioration in renal allograft function. These data suggest that treatment with candesartan cilexetil may be useful for maintaining long-term renal allograft function.     

Hepatocyte growth factor prevents chronic allograft dysfunction in liver-transplanted rats

BACKGROUND: Hepatocyte growth factor (HGF) is a growth factor with multiple biologic properties, including mitogenic, morphogenic, anti-apoptotic, and antifibrogenic activities. Long-term administration of the deletion variant of HGF (dHGF) might contribute to the prevention of chronic liver allograft dysfunction, which is attributed to immunologic and nonimmunologic reactions. METHODS: Low-dose tacrolimus was administered to rat-liver recipients after transplantation. Effects of dHGF on transplanted livers treated with low-dose tacrolimus were investigated. RESULTS: Rats receiving liver transplants treated with only low-dose tacrolimus administration showed chronic allograft dysfunction. Treatment with dHGF prolonged the survival time of rats that received liver allografts and suppressed fibrosis of liver allograft. Treatment with dHGF also suppressed the expression levels of interleukin (IL)-1beta, caspase-1, and transforming growth factor (TGF)-beta mRNAs in liver allografts. CONCLUSIONS: The findings indicate that dHGF may prevent chronic liver-allograft dysfunction and thus may become a novel treatment for chronic liver-allograft dysfunction.     

The sensitivity of lung cancer cell lines to the EGFR-selective tyrosine kinase inhibitor ZD1839 ('Iressa') is not related to the expression of EGFR or HER-2 or to K-ras gene status

ZD1839 ('Iressa') is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that inhibits EGFR signaling. Emerging evidence indicates that ZD1839 has clinical potential in lung cancer, but very little is known about the molecular characteristics of lung cancers that may determine sensitivity to ZD1839. We examined a panel of 19 lung cancer cell lines to investigate possible association between ZD1839 sensitivity and histological type, expression level and constitutive phosphorylation of EGFR and K-ras gene status. Our results indicate that neither expression level nor constitutive activation status of EGFR seems to predict sensitivity to ZD1839. In addition, ZD1839 sensitivity was not associated with expression of human epidermal growth factor receptor-2 (HER-2), another member of this tyrosine kinase receptor family nor with co-expression of EGFR and HER-2. Finally, no correlation was found between the presence of activating mutations of the K-ras gene, an important downstream mediator of the EGFR-transduced signals and the relative resistance to ZD1839. These findings warrant future study to clarify how ZD1839 inhibits lung cancer cell growth and to find a useful marker for prediction of sensitivity to this novel and promising agent for the treatment of lung cancers.     

Lack of initiation activity in rat liver of low doses of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline

It has been generally accepted that genotoxic carcinogens have no threshold in exerting their potential for cancer induction. However, the non-threshold theory can be challenged for cancer risk assessment in humans. Here we examined low dose carcinogenicity of a food-derived, genotoxic hepatocarcinogen, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), using an in vivo medium-term bioassay to detect initiating activity for rat hepatocarcinogenesis. With MeIQx initiation at various doses followed by administration of phenobarbital, a well known hepatopromoter, no induction of glutathione S-transferase placental form-positive foci, assessed as preneoplastic lesions, was noted at doses of 0.001-1 ppm. The results imply a no-observed effect level for hepatocarcinogenicity with this genotoxic agent.