Intraoperative angiographic assessment of graft patency during extracranial-intracranial bypass procedures

The use of intraoperative angiography to monitor graft patency was retrospectively reviewed in extracranial-intracranial bypass procedures. Forty-two patients underwent 43 extracranial-intracranial bypass procedures with the use of intraoperative angiography. Superficial temporal artery (STA)-middle cerebral artery (MCA) bypass was performed in 41 patients (42 procedures) with ischemic cerebrovascular diseases, and vertebral artery-MCA bypass using radial artery graft for intentional ligation of the common carotid artery in one patient with nasopharyngeal carcinoma. Intraoperative angiography provided high-quality subtraction images in every case. There were no complications due to angiography. Graft occlusion was observed intraoperatively in three cases, but an additional procedure reopened the occluded graft in all three cases. Graft patency rate was 100% after surgery. Outcome was excellent in 40 patients and good in one patient who underwent STA-MCA bypass. Intraoperative angiography provides useful information regarding graft patency during bypass surgery. Intraoperative assessment prior to wound closure allows for the recognition and correction of technical failure and decreases the risk of postoperative complications.     

Hepatocyte growth factor and transforming growth factor β1 contribute to regeneration of small-for-size liver graft immediately after transplantation

Although the ability of the liver to regenerate to a predetermined size after resection made adult-to-adult living donor liver transplantation (LDLT) possible, there is little information regarding the growth regulatory mechanism for a small-for-size graft. Forty-one cases of LDLT were divided into two groups by graft volume to standard liver volume ratio (GV/SLV); small graft group (Group S, GV/SLV<40%, n=16) and non-small graft group (Group NS, GV/SLV>40%, n=25). The regeneration rate (GV at 1 week/harvested GV) and serum levels of hepatocyte growth factor (HGF), transforming growth factor- (TGF-) and transforming growth factor-1 (TGF-1) were compared between two groups. The regeneration rates in Group S were significantly higher than that of Group NS (217±12% and 178±10%, respectively, P<0.01). The serum HGF levels of Group S were significantly higher than those of Group NS on POD 1. The TGF-1 levels of Group S were significantly higher than those of Group NS on POD 3 and 5. The TGF- levels were not different at any time points studied. These results indicate that a small-for-size graft retains the capacity to regenerate faster by modulation of expression pattern of HGF and TGF-1 immediately after LDLT. After the acceleration of the regenerative response by HGF, subsequent elevation of TGF-1 synergistically controls graft size, regulating uncontrolled proliferation of hepatocytes.     

Transient dysfunction of the retinal ganglion cells after laser in situ keratomileusis

PURPOSE: To evaluate the influence of high intraocular pressure(IOP) on the retinal ganglion cell function induced by suction during laser in situ keratomileusis(LASIK) using Frequency Doubling Technology(FDT). METHODS: Twenty-seven eyes of 15 patients were studied. Threshold values of 19 targeted areas, mean deviation(MD), and pattern standard deviation (PSD) were measured before LASIK, and 2 hours, 1 day, and 1 week after LASIK. These parameters obtained by N-30 program of FDT were compared between before and after LASIK. RESULTS: Significant decrease of MD and threshold value in all areas was recognized at 2 hours, but MD and threshold value in 6 of the 19 areas showed significant increase at 24 hours. Significant increase of PSD value at 2 hours was recognized. After 7 days, there were no significant differences in any parameters between before and after LASIK. CONCLUSION: These results indicated that a transient dysfunction of the magnocellular pathway might be induced by high IOP during LASIK procedure.     

Design and synthesis of the potent,orally available,brain-penetrable arylpyrazole class of neuropeptide Y5 receptor antagonists

Novel arylpyrazole derivatives were synthesized and evaluated as neuropeptide Y (NPY) Y5 receptor antagonists. Compound (-)-7, which features a novel chiral 2,3-dihydro-1H-cyclopenta[a]naphthalene moiety, showed good binding affinity and antagonistic activity for the Y5 receptor. After intracerebroventricular administration in SD rats, (-)-7 significantly inhibited food intake that was induced by the centrally administered Y5-preferring agonist, bovine pancreatic polypeptide, but had only a negligible effect on NPY-induced feeding.     

Effect of the addition of a beta-blocker on left ventricular remodeling and prognosis in patients with dilated cardiomyopathy treated with angiotensin-converting enzyme inhibitor

To examine the effect of the addition of a beta-blocker in the treatment of chronic heart failure due to dilated cardiomyopathy, we compared the change of left ventricular remodeling and the prognosis between patients treated with angiotensin-converting enzyme inhibitors and patients who had beta-blockers added to angiotensin-converting enzyme inhibitors. Fifty-seven patients were treated with an angiotensin-converting enzyme inhibitor in addition to combination therapy with furosemide, spironolactone and digoxin. In 60 patients, a beta-blocker was administered in addition to combination therapy with furosemide, spironolactone, digoxin and an angiotensin-converting enzyme inhibitor. Changes of left ventricular dimensions at end-diastole and end-systole, fractional shortening, cardiac events and death were examined during the follow-up periods. The mean follow-up periods were 4.9 +/- 4.1 years in the angiotensin-converting enzyme inhibitor group and 3.9 +/- 2.5 years in the beta-blocker group, respectively. Baseline hemodynamic characteristics showed no significant differences between the two groups. After the treatment, the heart rate significantly decreased in both groups and the systolic blood pressure increased in the beta-blocker group. Both left ventricular dimensions at end-diastole and end-systole significantly decreased in both groups. Fractional shortening increased from 17.0 +/- 7.6 to 19.8 +/- 8.9% (p = 0.017) in the angiotensin-converting enzyme inhibitor group and from 16.6 +/- 7.2 to 24.7 +/- 8.0% (p < 0.0001) in the beta-blocker group, respectively. Changes of left ventricular dimensions at end-diastole and at end-systole, and fractional shortening were all greater in the beta-blocker group than in the angiotensin-converting enzyme inhibitor group. The event-free rate and the cumulative survival rate during the follow-up periods were markedly better in the beta-blocker group than in the angiotensin-converting enzyme inhibitor group (p = 0.0019 and p = 0.0099, respectively). These results indicate that the suppression of left ventricular remodeling and the improvement of prognosis in patients with dilated cardiomyopathy are markedly stronger in the beta-blocker group than in the angiotensin-converting enzyme inhibitor group. Thus, beta-blocker should be added to patients with dilated cardiomyopathy treated with an angiotensin-converting enzyme inhibitor.     

Synthesis and antioxidative activity of 6-hydroxypyridoxine

An attempt to synthesize 6-hydroxypyridoxine (OPN), hydroxylation on C-6 of pyridoxine (PN) by hydroxyl radical (OH*). was conducted. Application of two well-known OH* generating reactions, i.e. the Fenton reaction and the Fe2+-EDTA/ascorbate reaction, were unsuccessful, as large amounts of by-products were formed. Although generation of OH* by autoxidation of ascorbic acid in the absence of metal ions was slow, by-products were formed in small quantities, and OPN was easily obtained in colorless crystals. Its structure was confirmed by spectral analyses. OPN was comparable to polyphenols such as (+)-catechin, rutin and gallic acid in the antioxidative activity against linoleic acid peroxidation, and was an effective DPPH radical scavenger, though the DPPH radical-scavenging activity of OPN was somewhat lower than that of the polyphenols. PN was relatively inactive under the conditions used here, indicating that the introduction of a hydroxyl group on C-6 of PN greatly enhanced both activities.     

Use of human liver S9 in the Ames test: assay of three procarcinogens using human S9 derived from multiple donors

The purpose of the present study was to examine the inter-individual variation in the mutagenicity of chemicals using a variety of human S9 fractions. For this purpose, three procarcinogens, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), benzo[a]pyrene (BP), and dimethylnitrosamine (DMN), were selected for the Ames test and their mutagenicity was examined using human liver S9 fractions prepared from 18 different donors and one pooled liver S9 fraction prepared from 15 different donors. In addition, rat S9 fraction prepared from male rats pretreated with phenobarbital and 5,6-benzoflavone (PB/BF) was used as reference in order to examine the mutagenic differences between human and rat (PB/BF) S9 fractions. The data demonstrate a large inter-individual diversity in the mutagenic response to procarcinogens. The mutagenicity of IQ and BP in the presence of a human liver S9 fraction (lot HLS-014) was equal to that observed in the presence of rat (PB/BF) S9 fraction. The mutagenicity of IQ and BP in the presence of a pooled human liver S9 fraction was lower (90 and 95%, respectively) than that observed in the presence of rat (PB/BF) S9. On the contrary, the mutagenicity of DMN in the presence of either a selected human liver S9 fraction (lot HLS-014) or pooled fraction was 8-fold higher than that found in the presence of rat (PB/BF) S9 fraction. Human liver S9 fraction (lot HLS-014) had one of the highest cytochrome P450 enzyme activities among the 18 different donors and higher than the pooled human liver S9 fraction. These results suggest that the use of both selected human liver S9 fractions with high metabolic activity (e.g., lot HLS-014 as used in this study) and a pooled S9 fraction with moderate metabolic activity could be used as a means to evaluate the inter-individual variability in mutagenic response to chemicals and to confirm positive responses from studies completed with rodent S9.     

Increased plasma concentrations of the mature form of adrenomedullin during cardiac surgery and hepatosplanchnic hypoperfusion

Adrenomedullin is a potent vasodilatory peptide. Plasma adrenomedullin (AM) concentrations increase during and after cardiopulmonary bypass (CPB). However, the cause of this increase and its site of production have not been identified. We investigated the role of the hepatosplanchnic and cerebral circulations in the increase of plasma AM and investigated whether tissue hypoxygenation is a cause of the AM increase seen during CPB. We measured plasma total AM (AM-T) and the biologically active form of AM, mature AM (AM-m), in seven patients undergoing CPB. Both plasma AM-T and AM-m concentrations increased significantly 60 min after weaning from CPB. At this time point, arterial AM-T and AM-m concentrations were 18-fold and 10-fold larger, respectively, than baseline values measured after the induction of anesthesia. The plasma AM-m concentration and the ratio of AM-m/AM-T in blood from the hepatic vein were significantly larger than those from the radial artery or jugular bulb. The AM-m/AM-T ratio decreased during CPB, suggesting that production of the intermediate form of AM, AM-glycine, is more than that of AM-m. The oxygen tension of the hepatic venous blood (PhvO2) was significantly less during CPB. Plasma AM-m concentrations sampled from the hepatic vein showed a significant negative correlation with PhvO2 at 10 min (r = 0.824; P < 0.02) and 60 min (r = 0.828; P < 0.02) after the onset of CPB. These data suggest that the hepatosplanchnic circulation is an important source of AM-m during CPB. Furthermore, hypoxygenation of the hepatosplanchnic region may be an important cause of this AM-m increase.     

Modified Daggett's technique for early repair of postinfarct posterior ventricular septal rupture

A surgical modification for safe early repair of posterior septal rupture is described. This technique is based on the method described by Daggett, but adds one internal patch, plus the application of fibrin glue between the internal and external patch for minimizing bleeding. This modification is a simple and reliable one for repairing posterior ventricular septal rupture.