Ventriculography Using ECG-Gated Multiple Diastolic Injection of Contrast Material in Pediatric Angiocardiography

In pediatric patients, the lower body weight limits the volume of contrast medium. Conventionally, angiocardiography is carried out with a single large bolus injection of contrast material. Angiocardiograms are used in pediatric patients with complex congenital heart diseases. In patients with complex congenital heart disease, especially with MAPCA, the volume of contrast medium used may be excessive. This would allow further injection to provide additional information. To reduce contrast medium used in the angiocardiogram in pediatric patients, we decided to use electrocardiogram (ECG)-gated multiple diastolic injection (EMDI). Three small boluses were injected during the diastolic phase of three consecutive cardiac cycles using a commercially-available power injector. Seventy-eight ventriculograms (47 left ventriculograms and 31 right ventriculograms) using EMDI were carried out on 53 patients with congenital heart disease. Total contrast medium volume with EMDI ventriculograms (mean [±SD] per body weight: 0.72 [±0.25] ml/kg) was significantly smaller than with conventional injection (1.01 [±0.36] ml/kg) (p <0.001). The grades of ventriculograms with EMDI tended to be slightly better than those with conventional injection (statistically not significant, p = 0.478). No short-run type premature ventricular contraction (PVC)s or intramural injection occurred in the ventriculograms with EMDI. PVCs tended to be less frequent in the ventriculograms with EMDI than in those with conventional injection (statistically not significant, p = 0.131). EMDI may be worthwhile in reducing ventricular ectopy when checking ventricular function by angiography, since hemodynamic conditions are less affected by small quantities of contrast medium and only during the filling phase of the ventricles. In conclusion, EMDI may be a useful method for reducing complications of ventriculography in pediatric angiocardiography.     

Dissemination of the phage-associated novel superantigen gene speL in recent invasive and noninvasive Streptococcus pyogenes M3/T3 isolates in Japan

In Japan, more than 10% of streptococcal toxic shock-like syndrome (TSLS) cases have been caused by Streptococcus pyogenes M3/T3 isolates since the first reported TSLS case in 1992. Most M3/T3 isolates from TSLS or severe invasive infection cases during 1992 to 2001 and those from noninvasive cases during this period are indistinguishable in pulsed-field gel electropherograms. The longest fragments of these recent isolates were 300 kb in size, whereas those of isolates recovered during or before 1973 were 260 kb in size. These 260- and 300-kb fragments hybridized to each other, suggesting the acquisition of an about 40-kb fragment by the recent isolates. The whole part of the acquired fragment was cloned from the first Japanese TSLS isolate, NIH1, and its nucleotide sequence was determined. The 41,796-bp fragment is temperate phage phiNIH1.1, containing a new superantigen gene speL near its right attachment site. The C-terminal part of the deduced amino acid sequence of speL has 48 and 46% similarity with well-characterized erythrogenic toxin SpeC and the most potent superantigen, SmeZ-2, respectively. None of 10 T3 isolates recovered during or before 1973 has speL, whereas all of 18 M3/T3 isolates recovered during or after 1992 and, surprisingly, Streptococcus equi subsp. equi ATCC 9527 do have this gene. Though plaques could not be obtained from phiNIH1.1, its DNA became detectable from the phage particle fraction upon mitomycin C induction, showing that this phage is not defective. A horizontal transfer of the phage carrying speL may explain the observed change in M3/T3 S. pyogenes isolates in Japan.     

Diagnostic implications of circulating oxidized low density lipoprotein levels as a biochemical risk marker of coronary artery disease

OBJECTIVES: To examine the diagnostic performance of circulating oxidized low density lipoprotein levels as a biochemical risk marker of coronary heart disease. DESIGN AND METHODS: 361 patients with coronary artery disease and 710 healthy volunteers as normal controls were examined. Receiver-operating characteristics curve analysis in addition to statistical analysis (univariate, multivariate) were done to determine the usefulness of the assay. RESULTS: Patients with coronary artery disease showed significantly elevated circulating oxidized low density lipoprotein levels. Males less than 70 years of age showed a significant association between oxidized low density lipoprotein levels and coronary artery disease. Receiver-operating characteristics curve analysis showed superior performance (e.g., sensitivity, specificity) of oxidized low density lipoprotein as a diagnostic marker of coronary artery disease as compared against other lipid markers (total cholesterol, triglyceride, high density lipoprotein, lipoprotein (a), and total cholesterol to high density lipoprotein ratio) with optimal performance in younger males. CONCLUSIONS: Oxidized low density lipoprotein levels may be a promising biochemical risk marker of atherosclerotic disease, especially in young males.     

Internalization of antibodies by endothelial cells via fibronectin implicating a novel mechanism in lupus nephritis

BACKGROUND: One of the crucial events in lupus nephritis is the glomerular deposition of immunoglobulins (Igs), of which pathogenic properties have been proposed mostly to be either type IIor type III allergic reactions. Some of IgG3-producing hybridoma clones established from an MRL/MpTn-gld/gld (MRL/gld) lupus mouse generate wire loop-like lesions in glomeruli resembling lupus nephritis when injected into SCID mice. These clones are useful for analyzing the mechanisms of glomerular deposition of antibodies in lupus nephritis at the monoclonal level. METHODS: Glomerular lesions of SCID mice injected with the hybridoma clones, 17H8a or 1G3 as control were analyzed by light and electron microscopy. Interaction of the antibodies with human glomerular endothelial cells (HGECs) and human umbilical vein endothelial cells (HUVECs) in vitro was studied by fluorescence microscopy, electron microscopy, and flow cytometry. RESULTS: Both antibodies did not show any antigen specificity for mouse glomeruli. The glomerular lesions generated by 17H8a, but not by 1G3, contained electron-dense deposits not only in subendothelial regions but also in the cytoplasm of endothelial cells, suggesting internalization of the 17H8a antibodies by endothelial cells. In cell culture studies, internalization of only 17H8a antibodies by HGECs and HUVECs was observed, but the antibodies did not have antigen specificity for both types of endothelial cells. The internalization by HUVECs was mediated by actin polymerization, and it was inhibited by RGDS (Arg-Gly-Asp-Ser) tetrapeptide, antihuman fibronectin and antihuman integrin beta1 monoclonal antibodies. CONCLUSION: The interaction between particular antibodies and endothelial cell surface integrins via fibronectin may be involved in their subsequent internalization by endothelial cells leading to antibody deposition in glomeruli. This may be one of the mechanisms of glomerular injury in lupus nephritis.     

Relationship between aortic-to-radial arterial pressure gradient after cardiopulmonary bypass and changes in arterial elasticity

BACKGROUND: An aortic-to-radial arterial pressure gradient may develop during and after cardiopulmonary bypass (CPB). The mechanisms of this pressure gradient remain controversial. To clarify the cause of the pressure gradient after CPB, the authors investigated the relationship between the pressure gradient and changes in the pulse wave velocity (PWV) before and after CPB. METHODS: The pressure gradient from the aorta to the radial artery and a change in PWV were measured with a wire (0.37 mm in diameter) tipped with a miniature pressure transducer in 12 patients undergoing cardiac surgery. The pressure distributions and waveforms were measured and recorded with electrocardiograph. The PWV was calculated by measuring the propagation time between the R wave of the electrocardiograph and the rising point of the arterial pressure waveform at 10-cm intervals. RESULTS: After CPB, 7 of 12 patients demonstrated a marked pressure gradient. In these patients, the pressure distribution showed a gradual decrease toward the periphery without a precipitous step-down in pressure at any one specific anatomic location. The PWV decreased as the intraarterial pressure decreased from the aorta to the radial artery, and the relative arterial elasticity decreased linearly toward the periphery. CONCLUSIONS: The results showed that the decrease in PWV implies a decrease in arterial elasticity, and the decrease in the arterial elasticity correlated with the decrease in intraarterial pressure. These findings demonstrated that a radial artery pressure lower than the aortic pressure after CPB may be due to the decrease in arterial elasticity.     

Possible mechanism of dexamethasone therapy for prostate cancer: suppression of circulating level of interleukin-6

BACKGROUND: Glucocorticoids may have favorable effects on prostate cancer patients showing clinical and/or biochemical failure after androgen ablation. The efficacy and mechanisms of dexamethasone therapy as possible alternative endocrine therapy were investigated. METHODS: Twenty five patients with prostate cancer treated by androgen ablation and showing a steady increase in serum prostate specific antigen (PSA) were treated with low-dose dexamethasone. RESULTS: Of 25 patients, 11 demonstrated 50% or more decline of serum PSA and 9 showed improvement of pain on dexamethasone therapy. Of 8 patients who responded to dexamethasone therapy, 5 had 80% or more decrease in serum interleukin-6 (IL-6). In contrast, none of 8 non-responders showed remarkable IL-6 suppression. Response of PSA was not correlated to the changes in serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, or androstendione. CONCLUSIONS: Significant suppression of serum IL-6, probably through inhibition of androgen-independent activation of androgen receptor, may be one of the mechanisms for the effect of dexamethasone therapy in prostate cancer patients with progressive disease.     

Renoprotective effect of triple therapy with low-dose angiotensin receptor blocker,low-dose diuretic and Ca-antagonist in hypertensive type 2 diabetic patients with overt nephropathy

Combination therapy with angiotensin receptor antagonist(ARB) plus angiotensin converting enzyme inhibitor(ACE-I) (ARB/ACE-I) was efficacious in reducing proteinuria in patients with progressive renal disease. However, this therapy may be associated with the worsening of anemia and hyperkalemia. The present study addressed whether or not triple therapy with low-dose ARB, low-dose diuretic (D) and calcium channel blocker(CCB) (ARB/D/CCB) is as effective as therapy with low-dose ARB/ACE-I in retarding the progression of overt diabetic nephropathy. In the triple therapy, the patients were initially subjected to monotherapy with CCB for 24 weeks. Low-dose ARB and low-dose D were added to the treatment for an additional 24-week period. In parallel, patients undergoing double therapy were initially treated with low-dose ACE-I alone for 24 weeks, and then low-dose ARB was added for an additional 24-week period. The results were as follows: 1) In the triple therapy, blood pressure was reduced by 9 mmHg in systole and 5 mmHg in diastole (not significant) compared to monotherapy with CCB. There was a significant decline in proteinuria (3.3 +/- 1.2 g/day in the CCB-treated period vs. 2.1 +/- 1.0 g/day in the ARB/D/CCB-treated period, n = 12, p = 0.0143). Furthermore, a significant improvement in the slope of reciprocal serum creatinine concentration(1/Cr) was found in response to triple therapy(1/Cr: -0.0118 +/- 0.0009 in the CCB-treated vs. -0.0035 +/- 0.0028(I/mg/dl/month) in the ARB/D/CCB-treated period, n = 12, p < 0.001). There was neither a worsening of anemia nor an increase in the serum potassium(K) concentration. 2) In the double therapy, blood pressure was reduced by 12 mmHg in systole(p = 0.0079, n = 11) and 6 mmHg in diastole(n = 11, p = 0.0037) compared to the monotherapy with ACE-I. A significant improvement in the slope of 1/Cr was found in the double therapy(1/Cr: -0.0095 +/- 0.0052 in the ACE-I treated period vs. -0.0029 +/- 0.0028(I/mg/dl/month) in the ARB/ACE-I, n = 11, p < 0.001). In addition, there was a substantial reduction in hematocrit and increase in serum K concentration. The present result suggests that triple therapy consisting of ARB/D/CCB is as efficacious as double therapy with ARB/ACE-I in protecting the kidney from the progression in patients with diabetic overt nephropathy. The former may be expected to have less adverse effects.