IL-8 in cerebrospinal fluid from children with acute encephalopathy is higher than in that from children with febrile seizure.

We identify possible differences in the cytokine/chemokine profiles in cerebrospinal fluid (CSF) from children with encephalopathy and febrile seizure. Interleukin (IL)-1beta, 2, 4, 5, 6, 7, 8, 10, 12, 13, 17, interferon-gamma, tumour necrosis factor-alpha, granulocyte colony-stimulating factor, granulocyte monocyte colony-stimulating factor, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1beta were measured simultaneously in CSF supernatants from children with encephalopathy (n = 8), febrile seizure (n = 16) and fever without neurological complications (n = 8). IL-8 in CSF from children with encephalopathy was significantly elevated compared to that in CSF from children with febrile seizure and fever without neurological complications. IL-8 in CSF was also higher than serum IL-8, suggesting that increased IL-8 was generated from glia cells or astrocytes, not by leakage from serum. Increased IL-8 in CSF in encephalopathy may protect against severe brain damage.

[Reoperation due to failure of a Freestyle bioprosthesis].

We report re-do aortic valve and ascending aorta replacements by using the valve-on-valve technique for primary tissue failure of a Freestyle bioprosthesis. A 74-year-old male, who had had a 25 mm Freestyle bioprosthetic valve implanted by the sub-coronary method 5 years previously for aortic valve regurgitation due to congenital bicuspid valve, was referred to our hospital for dyspnea and palpitation. He presented with heart failure secondary to aortic regurgitation due to primary tissue failure, and computed tomography demonstrated an enlarged ascending aorta (5 cm in diameter). The operative findings revealed that the Freestyle bioprosthetic valve had a leaflet tear at the left coronary cusp. We replaced the degenerated Freestyle bioprosthesis with a 19 mm Mosaic aortic bioprosthesis by using the valve-on-valve technique, and ascending aorta replacement was performed simultaneously. This technique can be useful for re-do surgery for degenerated stentless valves to avoid potential risks of complete excision of the bioprosthesis.

[Multiple acute aortic dissection; report of a case].

A 60-year-old woman has been followed under the diagnosis of De Bakey type Illb acute aortic dissection. She developed sudden backache, and the diagnosis based on the emergent computed tomography (CT) was De Bakey type I dissection. At the operation, previous De Bakey type Illb dissection was far from the new dissection observed in the ascending aorta and arch aorta. We replaced the ascending aorta and aortic arch with woven Dacron graft (arch first technique) under retrograde cerebral perfusion. Since the residual dissection (De Bakey type III) in the multiple aortic dissection has tendency to dilate fast, intensive follow-up of the patient would be necessary.

Biological monitoring of metabolites of sarin and its by-products in human urine samples.

More than 20,000 passengers of Tokyo underground trains were intoxicated with warfare toxic chemicals. Most of the patients examined had marked miosis and decreased serum cholinesterase activity. Transient increase of serum CPK activity after 3 days of the exposure was the another sign. We intensively analyzed the metabolites in the urine of 4 patients. The following analytic results indicated the exposure to sarin as well as contaminated compounds such as diisopropyl methylphosphonate (DIMP), ethyl methylphosphonate fluoridate (EMPF, or ethylsarin), diethyl methylphosphonate (DEMP), and ethyl isopropyl methylphosphonate (EIMP). (1) Isopropanol (IPA) and ethanol (EtOH) were detected of large quantities in the urine samples, and were thought to be derived from sarin and the sarin counterpart, EMPF, DIMP, DEMP and EIMP. (2) Monoalkyl methylphosphonic acids (isopropyl methylphosphonic acid (IMPA) and ethyl methylphosphonic acid (EMPA) also were excreted in large amounts with taking the similar excretion pattern of IPA and EtOH. (3) The metabolite only derived from sarin and ethylsarin is F anions whose integral output in the urine was less than the equimolar level of the excreted (IMPA + EMPA + IPA + EtOH). (4) Other corroborative findings were low lethality: of more than 5,510 patients treated, 11 were acutely dead. (5) Nine exposed males had higher sister chromatid exchange (SCE) rate (5.00 +/- 1.48/cell) than the control (3.81 +/- 0.697/cell), because dialkyl methylphosphonates seemed to have alkylating activity and producing DNA adducts. The SCE rate also increased after the in vitro exposure of lymphocytes to dialkyl methylphosphonates.

An Interlaboratory Validation Study of the Improved Transformation Assay Employing Balb/c 3T3 Cells: Results of a Collaborative Study on the Two-stage Cell Transformation Assay by the Non-genotoxic Carcinogen Study Group.

The Non-genotoxic Carcinogen Study Group of the Environmental Mutagen Society of Japan organised the first step of an interlaboratory validation study on an improved cell transformation assay employing Balb/c 3T3 A31-1-1 cells. Nineteen laboratories participated in this study. The modified transformation assay was evaluated for its responsiveness, its interlaboratory reproducibility and its transferability. In this study, a mixture of Dulbecco's modified Eagle's medium and nutrient mixture F12, supplemented with insulin-transferrin-ethanolamine-sodium selenite and 2% fetal bovine serum (FBS) was used during the period of expression of transformed foci, intead of the usual minimum essential medium with 10% FBS. 20-Methylcholanthrene (MCA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) were selected as a prototype initiator and a tumour promoter, respectively. Two series of experiments were conducted. In the first series, the transformation activity of MCA was examined at various concentrations. In the absence of the promoting treatment with TPA, exposure to MCA only weakly induced transformed foci. In the presence of 0.1µg/ml TPA, all laboratories observed significant dose-dependent increases in the number of transformed foci with increasing MCA concentrations. In the second series of experiments, various concentrations of TPA were tested. In the absence of initiating treatment with MCA, exposure to TPA weakly induced transformed foci in about half of the laboratories. In the presence of 0.2µg/ml MCA, all the laboratories observed significant dose-dependent increases in the number of transformed foci with increasing TPA concentrations. The results from this study support the usefulness of this modified two-stage transformation assay with Balb/c 3T3 cells.

[Magnetic resonance imaging in diffuse brain injury].

Forty cases diagnosed as diffuse brain injury (DBI) were studied by magnetic resonance imaging (MRI) performed within 3 days after injury. These cases were divided into two groups, which were the concussion group and diffuse axonal injury (DAI) group established by Gennarelli. There were no findings on computerized tomography (CT) in the concussion group except for two cases which had a brain edema or subarachnoid hemorrhage. But on MRI, high intensity areas on T2 weighted imaging were demonstrated in the cerebral white matter in this group. Many lesions in this group were thought to be edemas of the cerebral white matter, because of the fact that, on serial MRI, they were isointense. In mild types of DAI, the lesions on MRI were located only in the cerebral white matter, whereas, in the severe types of DAI, lesions were located in the basal ganglia, the corpus callosum, the dorsal part of the brain stem as well as in the cerebral white matter. As for CT findings, parenchymal lesions were not visualized especially in mild DAI. Our results suggested that the lesions in cerebral concussion were edemas in cerebral white matter. In mild DAI they were non-hemorrhagic contusion; and in severe DAI they were hemorrhagic contusions in the cerebral white matter, the basal ganglia, the corpus callosum or the dorsal part of the brain stem.

[Clinical study of intracranial pressure and auditory brain stem response in the cases of diffuse axonal injury].

The course of intracranial pressure (ICP) and the finding of auditory brain stem response (ABR) was discussed in the cases diagnosed as diffuse axonal injury (DAI) established by Gennarelli. ICP was measured in twenty-six cases which were divided into three groups according to the course of ICP: Group (1), in which ICP remained below 20 mmHg (group I, 9 cases). Group (2), in which ICP rose above 20 mmHg but was controlled by therapy (group II, 8 cases). Group (3), in which ICP rose above 20 mmHg and could not be controlled by any therapies (group III, 9 cases). Glasgow outcome scale 3 months after the injury in the cases of group I and II was severe disability (SD) and/or persistent vegetative state (PVS), but all of the cases in group III died. The findings of serial ABR were divided into 3 groups. These were group A (2 cases) which showed normal record, group B (5 cases) which showed elongation of latencies between the first and fifth waves, and group C (5 cases) in which there was no response in ABR. GOS in group A or B was SD and/or PVS, but all of the cases in group C were shown to be dead in GOS. Our studies suggest that the level of ICP in DAI is rather higher than that published in previous reports, and the continuous measurements of ICP and serial records of ABR are useful for evaluating the outcome of DAI.

[Continuous intracarotid infusion of mannitol in severe head injury].

The clinical significance of continuous intracarotid infusion of a small dose of mannitol (ICI of mannitol) was discussed. Eighteen patients suffering from severe head injury with Glasgow coma scale (GCS) less than 6 were treated by ICI of mannitol for the improvement of raised intracranial pressure (ICP). In all of these 18 cases, conventional venous administration of mannitol could not be carried out, because of the unstable vital signs due to hypovolemic shock such as multiple trauma or disturbance of serum sodium and potassium levels. This method requires that a 20% mannitol solution be directly and continuously administered to the bilateral common carotid artery. The ICP 6 hours after the beginning of ICI of mannitol was significantly lower than the ICP just before the treatment. The total amount of excretion of the sodium and potassium through the urine every hour decreased significantly after this method was used. It was also noticed that this method was very suitable for stabilizing the vital signs in cases which had unstable vital signs such as hypovolemic shock. These findings suggested that ICI of mannitol has an advantage over the conventional venous administration of mannitol in cases which had to have correction of serum electrolyte or which had unstable vital signs.

[Ten cases of transverse aortic arch replacement using antlers graft technique].

Ten cases of total arch replacement were performed using the antlers graft technique. The patients consisted of 6 men and 4 women ranging in age from 34 to 76 years (mean: 62.1 years). These cases included 7 cases of Stanford type A acute aortic dissection and 3 cases of fusiform aneurysm of the aortic arch. During surgery we formed a composite graft (antlers graft) by attaching 10, 12 and 24 mm side branches to a 10 mm woven graft and under hypothermic circulatory arrest with retrograde cerebral perfusion (RCP), we first of all remodeled the neck vessels and re-established antegrade cerebral perfusion. We then remodeled the arch using another 24 mm graft and concluded surgery by anastmosing this graft to the antlers graft. Eighteen cases using the conventional technique, in which anastmosis is performed from the distal arch, needed 77 minutes on average for RCP. However, the antlers graft technique required only 46.2 minutes. Although 1 case each of cerebral complications was observed during both techniques, the antlers graft technique shortened the time required for emergence from the general anesthesia (4 hours vs 11.4 hours), the length of the stay in the ICU (6.0 days vs 7.3 days) and the total hospital stay (45.8 days vs 60.3 days), compared to the conventional technique.

[Replacement of subtotal aorta in a 2-stage operation; report of a case].

A non-Marfan patient with a chronic type B dissecting aorta suffered acute retrograde dissection during his follow-up period so a subtotal aortic replacement was performed in a scheduled 2-stage operation. During the first operation, this patient underwent replacement of the ascending aorta and aortic arch under continuous retrograde cerebral perfusion (CRCP). In the second operation 3 weeks after the first surgery, replacement of the thoracoabdominal aorta was performed using spinal cord protection under hypothermia. The intercostal arteries were remodeled into a cobra head shape a few pairs at a time. The patient progressed well after the procedures with a mean artery pressure maintained at over 90 mmHg using norepinephrine. We recommended stage surgery, which is safer than current techniques, for entire aortic replacement in centers and hospitals with limited experience of grafting procedure.

[Successful repair of the left ventricular wall rupture after mitral valve replacement of an octogenarian; report of a case].

The left ventricular wall rupture is not only a rare complication after mitral valve replacement, but also a high mortality disease. We have encountered a case of this complication after removal of the extracorporeal circulation in an octogenarian female after mitral valve replacement with Carpentier-Edwards (25 mm). It could be successfully repaired from outside the heart on the cardiopulmonary bypass without second cardiac arrest. Repair from inside the heart using extracorporeal circulation and cardioplesia is generally recommended because of the accuracy. However, second cardiac arrest might be a risk of postoperative complications in octogenarians. Hence, prevention is the most important. And operative strategy for the repair is also important in these patients.

[A surgical treatment of transverse arch aneurysm: use of ballooned venous cannula for maintenance of lower half body perfusion].

At present, open distal anastomosis method is widely used for the treatment of aneurysm of the transverse aortic arch during replacement, because anastomosis can be performed under direct vision. However, no established procedure is available for maintaining lower half body perfusion while this procedure is being performed, and various procedures have been employed, e.g. temporary circulatory arrest, low flow perfusion from the femoral artery by use of an occlusion catheter, or retrograde systemic perfusion. Spinal cord injury, MNMS, rhabdomyolysis and other complications cannot be completely prevented even by the use of these procedures. From this point of view, we have been using a ballooned venous cannula to be inserted in to the descending aorta while performing open distal anastomosis in order to prevent these complications. This procedure has the advantage of permitting the surgeon to perform the operation without clamping of the artery, hence without the cessation of the systemic circulation of blood, and we believe that this method will prove effective in the surgical treatment of transverse aortic arch aneurysm.

[Unstable angina pectoris associated with systemic lupus erythematosus and arterio-sclerotic obstruction in whom hemophagocytic syndrome appeared after emergent operation; report of a case].

A 45-year-patient who suffered from old myocardial infarction (OMI) associated with systemic lupus erythematosus (SLE) and arterio-sclerotic obstruction (ASO) had unstable angina. Emergent coronary artery bypass grafting (CABG) was performed using saphenous vein graft because the left inter mammary artery was possible to be the collateral source for ASO. A high grade fever occurred without return of SLE 9 days after the operation. Pancytopenia simultaneously occurred. Hemophagocytic syndrome was diagnosed by the bone marrow examination. Pulse therapy with steroids was given and it was remarkably effected. Hemophagocytic syndrome has high mortality. However, it is difficult to distinguish from the other disease with high fever and bone marrow suppression in early period. Therefore, bone marrow examination was required to diagnose and to start the appropriate therapy as soon as possible.

[Novel method for lower-half body perfusion at circulatory arrest].

It is generally accepted that patients with thoracic aortic aneurysma (TAA) require surgical reconstruction in the open distal anastomosis method. However, the optimal treatment of those with TAA remains controversial, as some of the postoperative complications are spinal-cord injury, rhabdomyolysis, MNMS and so forth caused by ischemia of lower-half body. Therefore the new Y connector with a one-way valve is useful for open distal anastomosis to avoid ischemia of the lower-half body. Through the branch of the Y connector between the femoral artery cannula and the arterial line, the occlusion balloon catheter is inserted and inflated at the descending aorta for perfusion of lower-half body. This procedure is safer and faster to perform than the conventional methodology in which a puncture is inserted, and a balloon catheter may be used only on the side of blood supply, thus making it possible to minimize the aggression of the patient.

[Extraction of infected pacemaker electrode using catheter and snare].

A 85-year-old man had undergone implantation of a transvenous pacemaker system in 1982. Nine years later the generator was explanted and he was underwent implantation of a new generator and electrode. After one year of the second operation, infection of the old electrode had been noted and it was not cured in spite of partial explantation of the infected electrode and appropriate antibiotic therapy. We decided to remove the infected electrode and succeeded in extraction using catheter and snare. The patient's recovery was uneventful. We suggest catheter and snare is useful for explantation of chronic transvenous pacemaker electrodes.

[Successful treatment of aortic prosthetic valve endocarditis and aortic root abscess by Bentall procedure].

A 53-year-old woman had undergone aortic valve replacement in 1990. Three years later, aortic prosthetic valve endocarditis and aortic root abscess had been noted. Debridement of all apparently infected tissue created left ventricular-aortic discontinuity, but the orifice of the coronary arteries were intact. We decided to reconstruct the left ventricular outflow tract and aortic root by Bentall procedure. Composite graft was made with 26 mm gelseal tube graft and a 23 mm SJM prosthetic valve, and the coronary ostia were sutured into the side of the graft. The patient's recovery was uneventful, and the aortography revealed no aortic regurgitation. We suggest that Bentall procedure using gelseal tube graft is useful to reconstruct the left ventrivular-aortic discontinuity if the coronary ostia were intact.

[Successful treatment by Konno's operation for congenital aortic stenosis associated with hypoplastic valve ring].

A 47-year-old woman with congenital aortic stenosis associated with hypoplastic aortic valve ring underwent aortic valve replacement by Konno method. We have to be careful preventing residual VSD because the left ventricular muscle was weak in the aged with congenital aortic stenosis. In early postoperative period, we also have to do a careful treatment in case by Konno's operation, particularly in the patient of advanced age. However, she made a satisfactory recovery with adequate size of aortic valve replacement.

[Replacement of the aortic root with woven and knitted Dacron composite graft].

Some of the patients with annuloaortic ectasia or Stanford type A require aortic root replacement. If conventional Bentall procedure is employed in such cases, aortic root will become a cylindrical shape totally lacking sinus of Valsalva because the procedure utilizes a straight tube. The sinuses of Valsalva support an important role in opening and closing the valvar leaflets, and opening of the coronary arteries, together with the interleaflet triangles and the sinutubular junction. In this study, we performed aortic root replacement with composite graft which consisted of two types of graft including 30 mm Knitted Dacron Graft (Gelsoft) with different dilation rates and 30 mm Woven Dacron Graft (Hemashield) as well as bioprosthesis (27 mm Carpentier-Edwards), in order to reconstruct sinus of Valsalva. Post-operative angiography revealed an excellent diastolic coronary flow, as evidenced by proximal Knitted graft of 37 mm in diameter, distal Woven graft of 30.3 mm in diameter and Doppler flow DSVR (Diastolic/Systolic Velocity Ration) of 2.2 measured at the left coronary orifice. Since it is difficult to obtain homograft at present, this procedure would be worth trying during aortic root replacement.

[Thoracic aneurysm repair using circulatory arrest or retrograde cerebral perfusion].

Ascending aortic and transverse arch aneurysm repair requires some brain protection. At our hospital, profound hypothermia, circulatory arrest and retrograde cerebral perfusion have been used. Thirty patients for whom we used such brain protection techniques were studied with regard to incidence of stroke. Of these 30 patients, 7 underwent circulatory arrest with median arrest time was 31 minutes (range, 25 to 42 minutes), and 23 underwent retrograde cerebral perfusion with median perfusion time was 59 minutes (range, 24 to 123 minutes). The overall 30-day mortality rate was 16.6% (5 of 30 patients); these patients were all aortic dissection cases, and had exhibited signs of vital organs ischemia before the operation. Of the twenty-five patients who survived the operation, incidence of stroke was observed in 2 patients. One was a saccular transverse arch aneurysm, who underwent 71 minutes retrograde cerebral perfusion; debris was the cause of stroke in this case. The other was a Stanford type A aortic dissection, who underwent 32 minutes perfusion; malperfusion caused stroke in this case. Stroke did not occur in any of the 3 patients who underwent retrograde cerebral perfusion for more than 100 minutes. These results suggest that a uniform and constant cooling of the entire brain is important for brain protection. To this end, transapical aortic cannulation is effective to prevent malperfusion. It is also suggested that retrograde cerebral perfusion time can be up to 100 minutes, a longer duration hitherto accepted.

[An experience with St. Jude medical prosthetic 19A-HP which resulted in restricted opening at an early stage after operation].

St. Jude medical hemodynamic plus series is positively used for aortic valve replacement (AVR) of small orifice because it can increase the orifice area by 26% compared with conventional prosthetic valves of the same size. We performed AVR with SJM 19A-HP on a patient having aortic stenosis with regurgitation using horizontal mattress suturing technique. The aortic orifice size was 18.9 mm at the preoperative measurement. The course after the operation was uneventful until 9 days after the operation when cinefluoroscopy revealed symmetrical restriction of opening of valve leaflets. We are now monitoring the clinical course at the patient has not developed any symptoms though the LV-Ao pressures gradient is 60 mmHg by Doppler echocardiography. As the restriction of valve leaflet opening was symmetrical, it is not likely that an excess of the ligature or remnant caused the restriction; structural problems of St. Jude medical prosthesis appear to be a more reasonable explanation. Since the orifice ring of this prosthesis is not reinforced, longitudinal forces applied to the hinge may alter the shape of the ring, thus restricting the movement of valve leaflets. In the present case, forced insertion of 19A-HP instead of more desirable 17-HP is considered to have caused longitudinal forces acting on the hinge.