[Atheromatous aorta: clinical pitfall in cardiovascular surgery].

A highly atheromatous aorta has been reported to bring about devastating complications such as endorgan ischemia with or without aortic manipulation. One of the complications has been perioperative stroke known that almost the halves suffered have been dead even in recent era. The other of the devastating complications has been called cholesterol crystal embolization or blue toe syndrome, meaning scattered embolization by small cholesterol crystals towards splanchnic organs or lower extremities respectively, which has also known to be critical. Nowadays, new devices have encouraged cardiovascular clinician to have a plan for a safe cardiovascular intervention including aortic manipulation even with highly atheromatous aorta. Before the manipulation, modern powerful modalities such as transesophageal echocardiography, epiaortic ultrasonography and computed tomography (CT), have already become common based on many evidences. During operation, evolving techniques and technologies such as off-pump coronary artery bypass grafting (OPCAB) and axillary artery cannulation both of which are aorta non-touch techniques, which are technically demanding, has proved to reduce perioperative stroke recently even though severe complications still occur in lower percentages.

[Is emergency aortic root replacement combined with arch replacement safe?].

BACKGROUND: Aortic root replacement (ARR) combined with aortic arch replacement (AAR) is an invasive procedure even in elective cases. Nevertheless, such combined operations are often mandatory in acute type A aortic dissection. We examined whether emergency operation might have further incremental risks compared with elective surgery in this type of operations. METHODS: Forty-six cases of ARR combined with AAR were divided into 2 groups, the emergency (EM) group and the elective (EL) group. The EM group consisted of 10 cases of acute type A aortic dissection, whereas the EL group of 36:23 of chronic aortic dissection and 13 of true aneurysm. RESULTS: There were no statistical differences between the 2 groups in the durations of aortic crossclamp, selective cerebral perfusion and cardiopulmonary bypass. The incidences in the EM and EL groups were as follows:in-hospital death; 0 vs 3( 8%), respiratory failure; 4 (40%) vs 14 (39%), renal failure; 0 vs 6 (17%), IABP requirement; 1 (10%) vs 3 (8%), and cerebral infarction; 0 vs 1 (3%), respectively. CONCLUSION: Early surgical results of emergency ARR combined with AAR were almost equal to those in elective surgery.

A serine elastase inhibitor reduces inflammation and fibrosis and preserves cardiac function after experimentally-induced murine myocarditis.

In viral myocarditis, inflammation and destruction of cardiac myocytes leads to fibrosis, causing progressive impairment in cardiac function. Here we show the etiologic importance of serine elastase activity in the pathophysiology of acute viral myocarditis and the therapeutic efficacy of an elastase inhibitor. In DBA/2 mice inoculated with the encephalomyocarditis virus, a more than 150% increase in myocardial serine elastase activity is observed. This is suppressed by a selective serine elastase inhibitor, ZD0892, which is biologically effective after oral administration. Mice treated with this compound had little evidence of microvascular constriction and obstruction associated with myocarditis-induced ischemia reperfusion injury, much less inflammation and necrosis, only mild fibrosis and myocardial collagen deposition, and normal ventricular function, compared with the infected nontreated group.

[Aortic root surgery in patients with previous aortic root or valve operations].

OBJECTIVES: To assess the operative indication, risk factors, procedures, and outcomes of aortic root surgery in patients with previous aortic root or valve surgery. PATIENTS AND METHODS: Between 1995 and 2007, aortic root surgery was performed in 137 patients. Thirty-five of those, who had previous root replacement, root remodeling or aortic valve surgery, were evaluated retrospectively. RESULTS: Indications for redo surgery included lesions at coronary artery reconstruction site after root procedures, aneurysmal formation or dissection of sinus Valsalva after aortic valve procedures, and prosthetic material infection. Two cases with prior graft infection died of sepsis, and one case with extended aortic dissection died of esophageal bleeding. Hospital mortalities were, hence, 8.6% in redo cases, which was comparable to 5.0% in primary root surgery cases. Multivariate risk factor analysis of root surgery revealed that preceding infective aortic root lesion was the only significant independent risk factor for postoperative mortality, whereas redo procedure per se was not a significant risk. CONCLUSIONS: Redo aortic root surgery can be performed with a reasonably low operative risk. Graft infection in patients with previous aortic root surgery remains a challenging lesion.

Efficacy of perfusion cooling of the epidural space and cerebrospinal fluid drainage during repair of extent I and II thoracoabdominal aneurysm.

AIM: The aim of this study was to evaluate spinal cord injury and mortality resulting from repair of extent I and II thoracoabdominal aneurysm. The authors compared patients operated under mild hypothermia with or without epidural perfusion cooling (EPC) and cerebrospinal fluid drainage (CSFD). METHODS: From 1988 to 2007, 116 patients underwent replacement of the thoracoabdominal aorta; the procedure was performed in 38 patients with the aid of mild hypothermia alone (group A), and in 78 patients with the aid of EPC, mild hypothermia and CSFD (group B). Two catheters for epidural perfusion cooling were inserted in group B, in which one catheter was inserted into the epidural space to infuse chilled saline, and the other was inserted into the subdural space to drain the cerebrospinal fluid and to measure temperature and pressure. There were no significant differences in mean age, etiology of aortic disease, and aneurysm extent between the two groups. RESULTS: There were no significant differences in cardiopulmonary bypass time, the lowest nasopharyngeal temperature and operation time between the two study groups. The incidence of spinal cord injury in group A (16.2%) was significantly higher than in group B (3.8%, P=0.03). Hospital mortality in groups A and B was 10.5% and 2.6%, respectively (P=0.08). There was no significant difference in postoperative complications between the two study groups. CONCLUSION: The combination of EPC and CSFD was effective in lowering the incidence of postoperative spinal cord injury in the repair of extent I and II thoracoabdominal aortic aneurysm.

Functional results of intersphincteric resection for low rectal cancer.

BACKGROUND: Intersphincteric resection (ISR) is the ultimate sphincter-preserving operation for very low rectal cancer. The aim of this study was to assess defaecatory function after ISR in relation to the degree of resection of the internal anal sphincter. METHODS: Between 2001 and 2003, 35 consecutive patients with low rectal cancer had curative ISR, categorized as total, subtotal or partial resection of the internal anal sphincter. Defaecatory function was assessed in terms of frequency of bowel movements and continence. Sphincter function was evaluated by manometric study and anorectal sensation testing before surgery and 3, 6 and 12 months afterwards. RESULTS: Defaecatory function was satisfactory after ISR; 34 of 35 patients were grossly continent. The maximum resting anal canal pressure fell after all three procedures. Patients who had total ISR had reduced anal canal sensation at 3 months, but this had improved by 12 months after surgery. CONCLUSION: These functional results suggest that ISR should be considered as an alternative to abdominoperineal resection for low rectal cancer. However, as the outcome for continence is worse after total ISR than subtotal or partial ISR, the indication for total ISR should strictly take into account the preoperative sphincter function.

Evi9 encodes a novel zinc finger protein that physically interacts with BCL6, a known human B-cell proto-oncogene product.

Evi9 is a common site of retroviral integration in BXH2 murine myeloid leukemias. Here we show that Evi9 encodes a novel zinc finger protein with three tissue-specific isoforms: Evi9a (773 amino acids [aa]) contains two C(2)H(2)-type zinc finger motifs, a proline-rich region, and an acidic domain; Evi9b (486 aa) lacks the first zinc finger motif and part of the proline-rich region; Evi9c (239 aa) lacks all but the first zinc finger motif. Proviral integration sites are located in the first intron of the gene and lead to increased gene expression. Evi9a and Evi9c, but not Evi9b, show transforming activity for NIH 3T3 cells, suggesting that Evi9 is a dominantly acting proto-oncogene. Immunolocalization studies show that Evi9c is restricted to the cytoplasm whereas Evi9a and Evi9b are located in the nucleus, where they form a speckled localization pattern identical to that observed for BCL6, a human B-cell proto-oncogene product. Coimmunoprecipitation and glutathione S-transferase pull-down experiments show that Evi9a and Evi9b, but not Evi9c, physically interact with BCL6, while deletion mutagenesis localized the interaction domains in or near the second zinc finger and POZ domains of Evi9 and BCL6, respectively. These results suggest that Evi9 is a leukemia disease gene that functions, in part, through its interaction with BCL6.

Anti-prolactin (PRL) autoantibody-binding sites (epitopes) on PRL molecule in macroprolactinemia.

Macroprolactinemia, in which serum prolactin (PRL) mainly consists of PRL with a molecular mass greater than 100 kDa, has been demonstrated to be associated with hyperprolactinemia. We previously reported that anti-PRL autoantibody is the major cause of macroprolactinemia. In this study, the autoantibody-binding sites (epitopes) on the PRL molecule were examined using deletion mutant PRL. The sera from 159 patients with hyperprolactinemia were screened for macroprolactinemia using the polyethylene glycol method and 18 patients (11%) were diagnosed with macroprolactinemia. The sera from these patients were incubated with glutathione S-transferase-human prolactin (hPRL) fragment fusion proteins immobilized on glutathione sepharose and the amounts of bound immunoglobulin G (IgG) were measured using ELISA. IgG was bound to full-length hPRL1-199 in significantly greater amounts in sera from 14 of 18 patients with macroprolactinemia than in controls. hPRL, but not PRL of other species such as bovine, porcine, rat, or human GH, dose-dependently displaced the binding, suggesting that these patients had hPRL-specific autoantibodies. Deletion of 34 amino acid residues from N-and/or C-terminals significantly reduced the binding and N- or C-terminal fragment alone showed partial but significant binding, suggesting that the major epitopes recognized by anti-PRL autoantibodies are located in both N- and C-terminal residues of the PRL molecule.

[Emergent coronary artery bypass grafting using percutaneous cardiopulmonary support in a patient with a quadricuspid aortic valve; report of a case].

A 63-year-old man was admitted to our hospital for acute myocardial infarction. A cardiac catheter study showed 3 vessels coronary disease. He was treated by percutaneous coronary intervention for a left anterior descending arterial (LAD) lesion. Unfortunately, cardiac tamponade following stenting for LAD was complicated. A percutaneous cardiopulmonary support system was commenced along with an emergent coronary artery bypass grafting to the LAD and obtuse marginal branch. A quadricuspid aortic valve was discovered by an aortotomy and identified as Hurwitz-Roberts classification type b. Blood from the left coronary main trunk had already stopped. Intraaortic balloon pumping was instituted while weaning from the cardiopulmonary bypass. The patient's postoperative course was uneventful and all bypass grafts were sufficient. He was well 1 year after the operation.

Abnormal Ca2+ release from cardiac sarcoplasmic reticulum in tachycardia-induced heart failure.

OBJECTIVE: In heart failure, little information is available as to the Ca2+ release function of sarcoplasmic reticulum (SR), which plays a major role in cardiac contractile function. Here, we assessed the rapid kinetics of drug-induced Ca2+ release from cardiac SR in combination with a measurement of ryanodine binding in heart failure. METHODS: The SR vesicles were isolated from dog left ventricular (LV) muscles (normal (N), n = 10; pacing induced heart failure (HF), n = 10). The time course of SR Ca2+ release was continuously monitored by a stopped-flow apparatus using arsenazoIII as a Ca2+ indicator, and Ca2+ uptake and [3H]ryanodine binding assays were done using a filtration method. RESULTS: The amount of Ca2+ uptake was reduced in HF to 55% of N (P < 0.05). Even the more marked and earlier appeared decrease was seen in the rate constant and the initial rate of polylysine (PL; a specific release trigger)-induced Ca2+ release (P < 0.05). However, the PL concentration dependency of the initial rate shifted towards lower concentrations of PL in HF than in N ([PL] at half maximum stimulation = 0.13 vs. 0.35 microM). The [3H]ryanodine binding assay revealed a lower Bmax (pmol/mg) in HF than in N (0.91 +/- 0.19 vs. 2.64 +/- 0.59, P < 0.05), but no difference in Kd (nM) (0.95 +/- 0.29 vs. 0.90 +/- 0.11, P = n.s.). The [PL] dependency on the enhancement of [3H]ryanodine binding again showed a shift towards lower [PL] in HF than in N. CONCLUSIONS: In pacing-induced heart failure, the Ca2+ releasing function of SR is disturbed, which may result in an intra-cellular Ca2+ transient that was slowed down.

Herpes virus type 8-negative primary effusion lymphoma associated with PAX-5 gene rearrangement and hepatitis C virus: a case report and review of the literature.

At present, there is no case report of HHV8- primary effusion lymphoma (PEL) with t(9;14)(p13;q32) involving both PAX-5 and immunoglobulin heavy chain gene rearrangement, which is a rare translocation in B-cell non-Hodgkin's lymphoma, in an HIV- patient. We examined an HIV-seronegative 63-year-old Japanese man with hepatitis C virus-associated liver cirrhosis and hepatocellular carcinoma manifesting peritoneal lymphomatous effusion without tumor mass at any body site. The lymphoma cells were examined twice by light microscopy, immunohistochemistry, three-color flow cytometry, cytogenetics, and molecular analyses. The nuclear morphology of lymphoma cells was similar to that of large noncleaved cells, although the lymphoma cell size was a little smaller that of the usual large-cell lymphoma. Immunophenotyping of lymphoma cells in the ascitic fluid revealed a mature peripheral B-cell phenotype (CD5- CD10- CD19+ CD20+ CD22+ Ig G+ lambda+). Cytogenetics showed a clonal population: 45,X,-Y, der(2) t(2;6)(q31;p21.3), t(4;8)(q21;q11.2), der(6) t(2;6)(q31;p21.3) add(6)(q15), t(9;14)(p13;q32.3) [10]/47, idem, +der(6) t(2;6), +16[10]. Southern blot analysis revealed rearranged fragments with a probe for immunoglobulin heavy chain, some of which were a size similar to those with a PAX-5 gene probe. Polymorphism, not rearrangement, of the c-MYC gene, was also found. HHV8 and the Epstein-Barr virus were not detected by polymerase chain reaction. This case is the first report of an HHV8- PEL with t(9;14) involving a PAX-5 gene rearrangement in an HIV-seronegative patient. This primary effusion lymphoma manifested spontaneous regression without any therapy. These findings suggest that there may be an additional subcategory of primary effusion lymphoma that is not associated with HHV8 nor c-MYC(R) but is pathogenetically associated with the PAX-5 gene or hepatitis C virus.

Hemodynamic alteration by fetal surgery accelerates myocyte proliferation in fetal guinea pig hearts.

BACKGROUND: Fetal heart development occurs by hyperplasia as myocytes lose the capacity to proliferate at birth. This potential for cell division may have application in altering fetal growth patterns in congenital cardiac malformations, but it is not known whether the proliferative activity can be modified by intrauterine surgical manipulation. The purpose of this study was to determine whether hemodynamic alteration by fetal surgery influences myocyte proliferation and myocardial development. METHODS: Six pregnant guinea pigs of 50 to 52 days of gestation (term, 65 days) underwent hysterotomy, and the fetal ascending aorta was banded and narrowed by 50% (AoB). Cesarean section was performed near term, and the heart was assessed for myocyte proliferative activity (Ki-67 monoclonal antibody), apoptosis, and morphologic features. RESULTS: The heart to body weight ratio (1.02% +/- 0.12% versus 0.42% +/- 0.02%, p < 0.01) and left ventricular posterior wall thickness (1.89 +/- 0.25 mm versus 1.31 +/- 0.19 mm, p < 0.01) were significantly higher in the AoB group. The percentage of Ki-67 positive cells was increased in AoB group (29.5% +/- 4.4% versus 15.3% +/- 1.3% in right ventricle, 35.8% +/- 5.1% versus 13.1% +/- 1.7% in interventricular septum, and 39.8% +/- 3.2% versus 12.0% +/- 2.0% in left ventricle (p < 0.01). The apoptotic cell to myocyte ratio was less than 1/1000 in both groups. CONCLUSIONS: Fetal hemodynamic alteration by aortic banding accelerates myocardial cellular proliferation without affecting apoptosis, suggesting that in utero cardiac interventions have a greater influence on myocardial development compared with postnatal intervention.

Serum growth hormone-binding protein, insulin-like growth factor-I, and growth hormone in patients with liver cirrhosis.

We determined serum growth hormone-binding protein (GHBP), insulin-like growth factor-I (IGF-I), and growth hormone (GH) levels in patients with cirrhosis and in age-matched control subjects, and investigated their relationships. Serum GHBP levels in cirrhotic patients (14.6% +/- 3.9%) (means +/- SD) were significantly lower than those in normal subjects (20.4% +/- 4.7%). GHBP levels had positive correlations with cholinesterase (r = .58, P less than .001) and Normotest (r = .66, P less than .001), both of which represent liver function in cirrhotic patients. Basal GH levels in cirrhotic patients (range, 0.35 to 13.0 micrograms/L; median, 3.9 micrograms/L) were significantly higher than those in normal subjects (0.015 to 6.0 micrograms/L; 0.19 microgram/L). GHBP levels in cirrhotic patients correlated positively with IGF-I levels (r = .39, P less than .01), and negatively with GH levels (r = -.33, P less than .01). These results may indicate that the serum GHBP level reflects the number of hepatic GH receptors, and that the high basal GH level observed in cirrhotic patients is, at least in part, attributable to decreased clearance of GH by these receptors.

Intraoperative TEE during mitral valve repair: does it predict early and late postoperative mitral valve dysfunction?

BACKGROUND: Intraoperative transesophageal echocardiography (TEE) using color Doppler flow mapping can accurately measure residual mitral regurgitation (MR), but it is unknown to what extent such measurements correlate with those obtained with postoperative transthoracic echocardiography (TTE). METHODS: We used intraoperative TEE (based on direct planimetry of the maximal regurgitant jet area) to measure residual MR in 42 patients who underwent mitral valve reconstruction for MR and compared these measurements with those obtained with early and late postoperative TTE. RESULTS: Residual MR as measured by intraoperative TEE correlated significantly with values obtained with both early (r = 0.66; p < 0.0001) and late (r = 0.71; p < 0.0001) postoperative TTE. Forty patients with no or trivial MR (< or =2 cm2) as measured by intraoperative TEE also had no or trivial MR as measured by early (probability of 87.5%) and late (probability of 80.0%) postoperative TEE. Of the 40 patients, 6 had clinically insignificant mild MR (< or =4 cm2) when measured by late postoperative TTE. Two other patients in whom intraoperative TEE showed mild MR developed moderate regurgitation about 3 months later. CONCLUSIONS: Intraoperative TEE correlates with early and late postoperative TTE in measurement of residual MR, suggesting it can reliably predict early and late postoperative mitral valve dysfunction.

Flavonoid glucuronides from Helicteres isora.

Five flavonoid glucuronides were obtained from the fruit of Helicteres isora, three of which were previously unknown compounds: isoscutellarein 4'-methyl ether 8-O-beta-D-glucuronide 6"-n-butyl ester. isoscutellarein 4'-methyl ether 8-O-beta-D-glucuronide 2", 4"-disulfate and isoscutellarein 8-O-beta-D-glucuronide 2",4"-disulfate. The structures were determined on the basis of spectroscopy and hydrolysis experiments.

Severe hemolysis due to artificial chordae displacement.

Hemolytic anemia is a well-recognized complication of mechanical heart valve prosthesis but, as yet, has not been reported after mitral valve repair with chordal replacement. We report a case of severe hemolytic anemia after mitral valve repair with chordal replacement and Carpentier-Edwards annuloplasty ring insertion. Progressive prolapse of the anterior leaflet due to the artificial chordae being too long caused recurrent regurgitation which was responsible for the hemolysis. The patient also had idiopathic thrombocytopenic purpura, but successful second mitral valve repair was performed after high-dose gamma-globulin therapy.

Experimental branch pulmonary artery stenosis angioplasty using a novel cutting balloon.

To determined the safety and efficacy of a bladed balloon in the treatment of branch pulmonary artery stenosis, a model of left pulmonary artery stenosis was surgically created in two-week-old pigs. Seven pigs underwent angioplasty, five with the bladed balloon and two with conventional balloons. Overall, acute results showed a fall in the peak systolic pressure gradients from 8.3 +/- 2.3 mmHg to 3.2 +/- 3.1 mmHg and an increase in the minimum stenotic diameters from 4.5 +/- 2mm to 5.6 +/- mm. Acute pathological examination after cutting angioplasty showed regular luminal cuts that healed completely by four to six weeks in chronically surviving animals. Two of three surviving animals had persistent vessel enlargement at follow-up with one showing little overall change. Cutting balloons are effective in branch pulmonary artery angioplasty and may have clinical applications.

Fetal cardiac intervention and surgery.

Fetal echocardiography has changed our understanding of congenital heart disease by allowing us to diagnose and observe the malformed human heart within weeks of primary morphogenesis. Serial echocardiographic studies have shown that some complex heart malformations result from relatively simple primary lesions that occur early during heart development and may be amenable to an in utero intervention aimed at altering abnormal growth patterns. Although fetal cardiac intervention or surgery does not presently exist as a realistic therapeutic option in the management of critical congenital heart disease, progress in several areas of investigation give merit to the concept and future potential of in utero cardiac repair.

Lymphoid cell infiltration into Epstein-Barr virus-positive nasopharyngeal carcinomas.

OBJECTIVES: A pilot study was designed to analyze lymphoid cell infiltration in Epstein-Barr virus-positive (EBV+) nasopharyngeal carcinomas (NPCs) and to determine whether this pattern of infiltration is consistent with non-EBV+ head and neck carcinomas or with solid EBV+ tumors in other locations. STUDY DESIGN: We performed a retrospective analysis of archived NPCs and oral cavity carcinomas. METHODS: Immunohistochemical staining of the archive material for various markers (CD3, CD8, UCHL-1, S-100, and intercellular adhesion molecule) was performed. Polymerase chain reaction techniques to establish the presence of the EBV genome were used. Cells in different locations were counted under a light microscope by 2 of the authors. RESULTS: The infiltration pattern of NPCs was different from that of oral cavity carcinomas. Stromal infiltration was significantly denser in oral cavity carcinomas. Tumor nest infiltration was more pronounced in NPCs. The pattern of infiltration was comparable with what has been described for other solid EBV+ tumors. CONCLUSIONS: The immune response to NPCs is likely to be strongly influenced by the presence of the EBV genome. The pattern of infiltration is similar to that of other non-head and neck EBV+ solid tumors and different from that of EBV- head and neck carcinomas.

pH paradox and neonatal heart.

BACKGROUND: To evaluate the functional status of the Na+/H+ exchanger in the neonatal heart. METHODS: On the Langendorff system, isolated neonatal rabbit hearts were arrested by using cardioplegia with or without a specific Na+/H+ exchanger blocker, 5-(N,N dimethyl) amiloride (DMA) (20 microM). Ischemic period was 40 minutes at 37 degrees C or 120 minutes at 20 degrees C before 30 minutes of reperfusion at 37 degrees C. When DMA was added to the cardioplegia solution, it was also added to the reperfusate for the first 5 minutes of reperfusion (20 microM). RESULTS: Postischemic developed pressure was 50.3+/-7.1 mmHg in the DMA group versus 25.9+/-6 mmHg in the control group (p<0.05) at 37 degrees C and 74.8+/-14.6 mmHg in the DMA group versus 60.6+/-11.5 mmHg in the control group (p<0.05) at 20 degrees C. Postischeimic diastolic pressure was 40.4+/-3.3 mmHg in the DMA group versus 28.4+/-7 mmHg in the control group (p<0.05) at 37 degrees C and 9.6+/-3.1 mmHg in the DMA group versus 15+/-3.7 in the control group (p<0.05) at 20 degrees C. Creatine kinase washout was 296+/-97 IU/L in the DMA group versus 1253+/-537 IU/L in the control group (p<0.05) at 37 degrees C and 370+/-156 IU/L in the DMA group versus 524+/-104 IU/L in the control group (p<0.05) at 20 degrees C. CONCLUSIONS: 1) The Na+/H+ exchanger is active in the neonatal heart. 2) The Na+/H+ exchanger plays a key-role in the pathogenesis of reperfusion injury of the neonatal myocardium. 3) This exchanger is sensitive even for low H+ transmembrane gradients and even under hypothermic conditions.