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Recurrent aphthous ulceration (RAU) is considered to be an acute inflammatory disease of unknown pathogenesis. Apoptosis may represent an important event in the control of inflammation.The aim of this study was to investigate apoptosis process in RAU using immunohistochemistry.We studied the expression and location of p53, bcl-2 and bax in ulcerated lesions clinically diagnosed as RAU (n = 12) and compared it with that of oral clinically normal mucosa (n = 6) and of other inflammatory chronic disease such as oral fibrous inflammatory hyperplasia (FIH; n = 18).Significant statistically differences (n0.05) in p53 expression were noticed in RAU when compared with normal mucosa. No significant statistically differences (P0.05) were noticed between FIH and RAU. Bcl-2 and bax did not show remarkable differences between groups.Taken together, the data suggest that RAU induces p53 immunoexpression. Therefore, the protein might be related to the aetiopathogenesis of the ulcerated oral lesions.

The pathogenic role of hyperlipidemia in long-standing nephrotic syndrome (NS) is known to be responsible for both the progression of glomerulosclerosis and tubulointerstitial injury, especially in focal segmental glomerulosclerosis (FGS).Aggressive lipid lowering treatment by low density lipoprotein (LDL) apheresis (LDL-A) using a dextran sulfate cellulose column to treat patients with steroid-resistant or frequently recurrent severe NS was performed first without fixing the protocol in eight patients with FGS and one with minimal change nephrotic syndrome (MCNS). The period of NS before LDL-A, number and average intervals of LDL-A until the end of the therapy, and the prognosis were investigated. Next, a multicenter study with a fixed protocol of LDL-A treatment was designed in combination with steroid therapy for treatment twice a week for three weeks and weekly for six weeks, and was performed in 17 patients with FGS. The effects on the state of NS in addition to the change of urinary eicosanoid metabolites and remission rates were evaluated.In the preliminary study, along with a rapid improvement of hyperlipidemia, a high incidence of remission was achieved by LDL-A performed at relatively short intervals. In the multicenter study with a fixed protocol, there was a significant decrease of urinary protein (P0.001) and increase of serum albumin (P0.02) as well as a decrease of thromboxane B2 (TXB2) excretion (P0.05) after the treatment. Urinary excretion of TXB2 was significantly reduced after LDL-A (P0.05). The rate of entering into complete or incomplete remission was 71% with a relatively short duration of nephrotic-range proteinuria using the LDL-A therapy in comparison with steroid therapy alone.The rapid improvement of hypercholesterolemia with LDL-A treatment may provide a new approach for a high rate of improvement in the degree of NS in steroid-resistant NS of FGS and MCNS.

From 1981 to 1996, 48 consecutive patients, aged range 1 to 72 years, underwent surgical treatment for infective endocarditis. The infection was in the aortic valve in 10 patients, the mitral valve in 17, the aortic and mitral valves in 7, mixed aortic, mitral and tricuspid valves in one, the tricuspid valve in 9, the pulmonary valve in 3, and the other in 2, thirty-seven patients had native valve endocarditis (NVE) of which 22 cases were in the active stage. Seven cases had active prosthetic valve endocarditis (PVE) and 4 had VSD patch infection. The overall hospital mortality rate was 14.6% (7/48). The hospital mortality rate of NVE was 2.7% (1/37) and that of active NVE was 4.5% (1/22). That of PVE was 71.4% (5/7) and one of 4 cases with VSD patch infection was lost, so the mortality rate of the prosthetic material infection was 54.5% (6/11). Only 1 patient required reoperation for persistent infection. There were 2 late deaths caused by noncardiac disease. Thirty-nine of the total IE patients are now survived. These data demonstrate excellent results in patient with NVE undergoing the surgical treatment at the early phase, and support the premise that patients with active PVE should have also early surgical intervention.

We report a 46-year-old woman who has been suffered from myasthenia gravis and underwent thymomectomy in December 1988. Her myasthenic symptoms improved by treatment with corticosteroid and azathioprine; the latter drug was administrated for more than one year. She noticed weight gain of 10 kg and edema in both legs and feet, which developed acutely in August 1994. Laboratory data showed that she suffered from nephrotic syndrome with a large amount of proteinuria (15 g/day). Renal biopsy revealed that biopsied glomeruli showed early stage of membranous nephropathy associated with acute tubular necrosis. Although therapeutic trials of steroid pulses could not eliminate proteinuria, substitution of cyclophosphamide for azathioprine brought marked improvement of the nephrotic syndrome with disappearance of the urinary protein excretion within 10 days. From reports of similar cases with myasthenia gravis in Japan and in Europe, therapeutic usage of azathioprine in patients with myasthenia gravis associated with thymoma should be cautious for appearance of nephrotic syndrome when azathioprine is continued for more than one year.

The clinical significance of the chordae tendinae regarding postoperative left ventricular performance was evaluated in 148 patients with mitral regurgitation or mitral stenosis who underwent either mitral valve replacement using St. Jude Medical valve with complete chordal preservation, or with conventional mitral valve replacement, or valve repair. Mitral valve replacement preserving the autologous chordae tendinae (n = 28) or replacing them with Gore-Tex sutures (n = 16) was performed in 44 patients, 24 with mitral regurgitation and 20 with mitral stenosis. Their hemodynamic parameters were compared to those of patients who underwent conventional mitral valve replacement involving 25 with mitral regurgitation and 28 with mitral stenosis, or who underwent valve repair in 24 with mitral regurgitation, or commissurotomy in 27 patients with mitral stenosis. The LV performance was analyzed by cineangiography in the early (mean 1.2 months), and by multiple gated blood scintigraphy (MUGA), or echocardiography (UCG) in the late postoperative periods (mean 5.4 years) in the three groups of patients. In the mitral regurgitation group, the LV ejection fraction (EF) was unchanged in the chordal preserved group, but it was decreased in the conventional replacement and repair groups. The LV contractility index was better in the chordal preserved than in the conventional group. Both the LVEF by MUGA, and LV fractional shortening (FS) by UCG were significantly higher after chordal preservation or repair than after conventional valve replacement. The chordal preserved group exhibited superior LV performance than the conventional group, especially in those with mitral regurgitation and depressed preoperative left ventricular function (EF0.50). There were no significant difference between the three groups in patients with mitral stenosis. The results support the concept that maintenance of continuity between the mitral annulus and the papillary muscle has a beneficial effect on postoperative left ventricular performance, especially in patients with mitral regurgitation and depressed preoperative left ventricular function, but had no major effect in patients with mitral stenosis.

We report a rare case of coronary artery perforation by a guide wire for percutaneous transluminal coronary angioplasty (PTCA) complicating with postinfarction cardiac rupture (oozing type). The patient had acute myocardial infarction on the extensive anterior wall and developed cardiac rupture followed by serious cardiac tamponade during the emergency PTCA several hours after tissue plasminogen activator (t-PA) given intravenously. The meandering left anterior descending artery (LAD) was found injured by a PTCA guide wire apart from a small oozing-type cardiac rupture near the apex. We repaired urgently the perforated LAD as well as the ruptured left ventricle. It is thus suggested that coronary artery perforation by a PTCA guide wire may occur on meandering coronary arteries and develop a serious hemorrhagic complication, particularly after thrombolytic therapy.

From July 1979 to February 1995, 126 patients, including 4 reoperations, aged between 6 months and 77 years underwent mitral valve repair for mitral regurgitation. The patients were divided in two groups, 46 patients aged less than 16 years in pediatric age group and the other 80 patients in a dult group. The methods consisted of asymmetric annuloplasty (Kay-Reed method) in 98 patient, Carpentier-Edwards ring annuloplasty in 14, quadrangular resection of the posterior leaflet with annuloplasty in 9, and chordal and leaflet repair in 5. There was no hospital nor late death in pediatric age group. Three hospital deaths and one late death were in adult group. Follow-up was 96% complete and totaled 812.1 patient years. Reoperations underwent in 3 pediatric patients and 9 adults. At 15 years' follow-up, freedom from reoperation was 91.5 +/- 4.7% in pediatric age group and 67.1 +/- 12.7% in adults. Freedom from event was 63.5 +/- 12.1% in adult group. These results suggest that mitral repair with Kay-Reed method in pediatric age group is favorable for long-term. In contrast, indications for mitral reconstraction with other methods including ring annuloplasty should be extended for aged patients with severely dilated annuls and degenerated leaflets.

From April 1979 to October 1993, 126 adult patients underwent reoperative cardiac valve surgery. Patients were divided into two groups: 53 patients who underwent surgery before January 1990 (group 1) and 73 patients who underwent surgery after January 1990 (group 2). After January 1990, a clinical strategy for reducing homologous blood transfusions was implemented, including the use of predonation of autologous blood in the operating room, reduced heparin doses, an elevated threshold of indication for blood transfusion, and autotransfusion of shed, drained blood after surgery. In group 1, 44 patients (93.0%) received an average of 3785 +/- 1251 ml of homologous blood transfusions. In group 2, only 26 patients (35.6%) needed homologous blood transfusions and had a smaller amount (2985 +/- 1521 ml) on average. Furthermore, only seven patients needed fresh blood transfusion in group 2.

Bacteriological and clinical studies were carried out on staggered intensive chemotherapy regimen for methicillin-resistant Staphylococcus aureus (MRSA) infections combined with Gram-negative opportunistic pathogens as polymicrobial infections. The regimen consisted of administering ceftazidime (CAZ) 30 minutes after infusion of arbekacin (ABK) and a bolus injection of fosfomycin (FOM). The combination of these drugs strongly inhibited the growth of MRSA and Pseudomonas aeruginosa. By this combination treatment, both of MRSA and P. aeruginosa in mixed culture became more susceptible to killing by macrophages. We evaluated the clinical efficacy and safety of combination of ABK, FOM and CAZ in the treatment of 15 patients with MRSA infections. The total efficacy rate was 80.0% and the bacterial eradication rate of MRSA was 60.0%. It is considered that staggered intensive chemotherapy with ABK, FOM and CAZ is useful for such polymicrobial infections involving MRSA.

Deep hypothermic circulatory arrest (DHCA) was introduced as an adjunct for operations involving aortic arch lesions in 1970's and has since been widely used. Profound hypothermia protects the brain and other vital organs by reducing metabolic rate. We initiated the use of continuous retrograde cerebral perfusion (CRCP) via the superior vena cava during DHCA in 1987. We studied 15 patients who required DHCA and CRCP during repair or replacement of the aortic arch. CRCP times ranged from 11 to 78 (mean +/- S.D.; 37.3 +/- 21) minutes, and minimal nasopharyngeal temperatures ranged from 13.7 to 25 (17.7 +/- 2.6) degrees C. Two patients died one month postoperatively due to preoperative disease. Three patients, who were in shock preoperatively due to cardiac tamponade, developed acute renal failure postoperatively. The remaining patients were weaned from the respirator by the 2nd postoperative day. No patient had CRCP-related complications. During CRCP, the partial pressure of oxygen (PO2), saturation of oxygen (SO2), and oxygen content significantly decreased (p0.001), and the partial pressure of carbon dioxide (PCO2) and CO2 content significantly increased (p0.001) between retrogradely perfused blood and blood draining from the arch vessels. These results most probably reflected that the aerobic metabolism of the brain was maintained by CRCP while the central nervous system was maintained in a hypothermic state, with oxygen and substrate availability, wash-out of metabolites, and buffering capacity and oncotic pressure of the blood maintained. This technique offers the potentials of sufficient metabolic support to the brain during DHCA and prolonged safe time limits of DHCA.

We report two cases with chronic severe mitral regurgitation and atrial fibrillation in whom left atrial thrombus was detected by transesophageal echocardiography after excellent mitral valvuloplasty. The reason why thrombus developed after valvuloplasty is that preoperative severe mitral regurgitation made the left atrial blood less stagnant than it was after surgery. Thus, even when mitral valvuloplasty achieves excellent results in patients with severe chronic mitral regurgitation and atrial fibrillation, anticoagulation and left atrial appendage ligation should also be considered.

The in vitro production of granulocyte/macrophage colony stimulating factor (GM-CSF) by mononuclear cells from the peripheral blood of patients with bronchial asthma (BA) was examined by enzyme-linked immunosorbent assay (ELISA). In 3 of 12 cases studied, mononuclear cells from BA patients produced GM-CSF without stimulation. And in 5 of 12 cases studied, mononuclear cells from BA patients produced GM-CSF in response to IL-2. Mononuclear cells from patients with other diseases (n = 13) and healthy volunteers (n = 6) did not release any detectable (or = 7.5 pg/ml) GM-CSF. The culture media of mononuclear cells from BA patients showed activities for stimulating the proliferation and survival of eosinophils, and these activities were partially inhibited by anti-GM-CSF antibodies. GM-CSF production by mononuclear cells from BA patients treated with prednisolone was lower than that of mononuclear cells from untreated BA patients. And prednisolone showed a reduction in the GM-CSF production from mononuclear cells in response to IL-2. These results suggest that GM-CSF production by mononuclear cells may play a role in the pathogenesis of BA.

The postoperative regional left ventricular motion of 22 patients with a diagnosis of mitral regurgitation, and who underwent mitral valve replacement with preservation of chordae tendineae, were retrospectively analyzed by cineangiography in the early postoperative period and by multiple-gated cardiac blood pool scintigraphy in the mid-to-late postoperative period. The operation consisted of the division of the anterior leaflet into anterior and posterior segments, the shifting and reattachment of the divided segments to the mitral ring of the respective commissural areas, and the use of a low-profile bileaflet prosthetic valve. Control groups consisted of 28 patients with mitral regurgitation who underwent mitral valve replacement with a conventional technique and 16 patients who underwent mitral valve repair. Compared with the conventional mitral valve replacement group, the radial shortening of the left ventricle of the chordae-preserved mitral valve replacement group was greater at the apical septal, inferoapical, anterobasal, and anterolateral portions, whereas the radial shortening of the repair group was greater than that of the chordae-preserved group only at the inferolateral portion. The ejection fraction of the whole left ventricle was statistically greater in the chordae-preserved group, and also regional ejection fraction of the chordae-preserved mitral valve replacement group was greater at the apical septal, inferoapical, inferolateral, anterobasal, and anterolateral portions than that of the conventional mitral valve replacement group at these portions. On the other hand, the postoperative regional and global motion was identical to that of the mitral valve repair group except at the inferolateral portion. The result of this study supports a concept that maintenance of continuity between the mitral anulus and the papillary muscle has a beneficial effect on postoperative left ventricular performance.

We conducted a multiple-center joint study on the effects of recombinant human erythropoietin (rEPO) for predialysis patients. rEPO was intravenously administered to 42 predialysis patients (13 males and 29 females) with hematocrit (Ht) levels of less than 30%. The subjects were divided into group A (28 cases) in which rEPO was administered twice a week, and group B (14 cases) with rEPO administration once a week. The initial administration dosage was 6000IU/week. The Ht levels were 22.6 +/- 3.3% for group A and 23.2 +/- 2.7% for group B before the administration of rEPO, and increased to 31.0 +/- 4.0% and 27.7 +/- 3.7% respectively twelve weeks after initiating administration. The levels of effective improvement on anemia included 'markedly effective' in 17 cases (80.9%) and 'effective' in 2 cases (9.5%) in group A, and 'markedly effective' in 5 cases (41.7%) and 'effective' in 3 cases (25.0%) in group B. No significant change was seen in serum creatinine (Cr) levels during the study period. In the evaluation of renal function by reciprocal serum creatinine (1/Cr), a consistent tendency was not recognized; thus, suggesting that the rEPO administration had no effect on the renal function. No variation of blood pressure was seen. As far as side effects were concerned, headache and heavy headedness were recognized in four cases. There were, however, no cases in which the severity of the side effects dictated the discontinuation of the rEPO administration. In conclusion, rEPO was judged to be a safe and effective treatment for the anemia of predialysis patients.

A 64-year-old man underwent CABG. 18000 unit of bovine lung heparin was used during operation for extracorporeal circulation and small amount of heparin was injected until the 5th postoperative day to keep intravenous line patent. His postoperative course was uneventful until the 10th postoperative day when marked ecchymosis developed on his eyelid. Laboratory data showed marked thrombocytopenia (1.3 x 10(4)/microliters) and disseminated intravascular coagulation. The diagnosis of heparin-induced thrombocytopenia (HIT) was confirmed by platelet aggregation test with heparin. Gabexate mesilate and platelet-concentrates were administered and platelet count returned to normal within a week. HIT usually occurs during administration of heparin. In this case, it occurred 5 days after we stopped heparin. Delayed onset of HIT might be related to delayed metabolism of heparin due to postoperative fluid shift.

Between 1987 to 1990, six patients underwent replacement of the ascending aorta and aortic valve with a composite graft which was not wrapped with aneurysmal aortic wall; annuloaortic ectasia in 4, aortitis with acute onset of aortic regurgitation in 1, and acute aortic dissection with aortic regurgitation in 1. In 2 patients, "open aortic anastomosis" under deep hypothermic systemic circulatory arrest and retrograde cerebral perfusion was utilized for distal anastomosis of the graft to the resected aortic arch. Three patients required no transfusion. One patient with annuloaortic ectasia and severely dilated left ventricle died from ventricular fibrillation in ICU. One patient with aortitis died from stroke due to occlusion of bilateral carotid arteries 3 years postoperatively. The other 4 patients are alive and favorable. It is our belief that this technique still maintains simplicity and facilitates the secured anastomosis and minimized bleeding.

A case of delayed hemolytic transfusion reaction (DHTR) caused by blood transfusions after open heart surgery was reported in a 61-year-old woman. She had undergone mitral annuloplasty 8 years before. She underwent the 2nd mitral and tricuspid annuloplasty for recurrent mitral and tricuspid regurgitation in 1988. After the reoperation, she developed severe hemolytic anemia with fever. The anti-Jka antibody was detected in her serum by the blood antibody screening test. She was diagnosed to have a DHTR. She was treated conservatively and recovered.

Reported is a case of non-functioning malignant pheochromocytoma. The patient had an occupational history of asbestos exposure and pleural plaque was seen in the chest X-rays. The tumor appeared from right adrenal gland and its size was 12 x 15 cm, which was measured by CT scanning. This determined to be non functioning because catecholamines in the serum and VMA in the urine were within normal limits. A metastasis of this tumor was seen in the lung, the liver, and the bone. So far as is known, this is the first case of asbestos exposure complicated with malignant pheochromocytoma that has been reported in the Japanese literature.

Recently we replaced the ascending aorta and aortic arch in 8 patients with aneurysm or dissection, using profound hypothermic circulatory arrest with retrograde cerebral perfusion. There were no operative deaths. Open aortic anastomosis facilitated repair of the aortic arch without clamping the arch tributaries, and embolism due to particulate debris from clamping of the arch vessels was eliminated. Retrograde cerebral perfusion during profound hypothermic circulatory arrest is a simplified technique that may protect the brain. This method offers advantages over previously described methods, particularly in obviating dissection of the arch tributaries and the clamping thereof, and in protecting the central nervous system.

We report a case of 47-year-old woman with an isolated deficiency of adrenocorticotropic hormone. She was admitted complaining of fatigue and frequent loss of consciousness. The patient developed severe hyponatremia (100 mEq/l) after five days of the admission. Her plasma renin activity and plasma aldosterone concentration were low though she was dehydrated. After the treatment of dehydration, plasma osmolality was low but high plasma antidiuretic hormone (ADH) level sustained. Both high urinary sodium excretion and low urinary aldosterone excretion still remained after one month of replacement therapy with prednisolone. But, glomerular filtration rate and a response of urinary volume to acute water loading were normalized. These results suggested that severe hyponatremia of the patient was caused by an inappropriate secretion of ADH and suppression of renin-aldosterone system. We consider the suppression of renin-aldosterone system was partially independent of an inappropriate secretion of ADH.

The efficacy, safety, and pharmacokinetics of carvedilol were investigated in an open trial performed on six patients with hypertension and chronic renal failure requiring hemodialysis. The plasma level of unchanged carvedilol after a single dose of 10 mg reached a peak 1-5 h after administration both on days with and without hemodialysis. The drug was gradually metabolized thereafter and had almost disappeared from the plasma after 24 h. Blood pressure was lowered by carvedilol both on days with and without hemodialysis. No carvedilol passed through the dialysis membrane. During the 4-week administration period of carvedilol at 10 mg/day, assessment of plasma samples taken just prior to early morning administration demonstrated no drug accumulation. Blood pressure was well controlled during the administration period. Tolerance to the antihypertensive effect was not observed. Heart rate was not significantly changed at any time. There were no side effects in any of the patients during the trial, and laboratory parameters remained unchanged. These results indicate that carvedilol is a safe and effective antihypertensive agent for use in patients on chronic hemodialysis.

A total of 20 patients underwent mitral valve replacement (MVR) with preservation of the papillary muscles (PM) and chordae tendineae (CT) with the object of maintaining left ventricular contractility and decreasing the risk of left ventricular rupture after surgery. The patients comprised of 8 males and 12 females whose ages ranged from 33 to 67 years. In 8 patients, the posterior leaflet was left in place and in 12, the CT to the anterior leaflet were also preserved by excision of the central portion and reattachment of the rest of the leaflet to the appropriate commissural regions. St. Jude Medical valves were exclusively employed as a substitute. Reasons for MVR were isolated MR in 12 cases, MRs in 5 and MSr in 3. There were one operative, one hospital and one late death respectively. Postoperative C.I. increased from 2.65 +/- 0.48 to 3.8 +/- 0.75 ml/min./M2 and LVEF increased from 55.1 +/- 11.4 to 63.4 +/- 13.4%. The area method showed marked improvement of segmental wall motion in anterolateral regions. Chordal shortening also disclosed improvement in long axis. Preservation of papillary muscles and chordae tendineae during MVR has been found to have a beneficial effect on postoperative left ventricular contractility.

The percentage and absolute numbers of thymos-dependent (T) and thymos-independent (B) peripheral blood lymphocytes, the in vitro response of lymphocytes to phytohemagglutinin (PHA), and the sensitization with 2,4dinitrochlorobenzene (DNCB) was studied in 26 patients with hyperthyroidism due to Graves' disease. The results showed a normal percentage of both T and B cells and increased absoluted numbers of total lymphocytes in patients compared with 30 healthy controls. The in vitro response to PHA was normal in most patients with the exception of 5 of them who showed an impaired response. All patients developed a reaction of delayed hypersensitivity to DNCB. Our study indicated that there is no general abnormality in cell-mediated immunity in Graves' disease.

Cell-mediated immunity (CMI) was evaluated in 82 patients with non-lymphoid tumors by in vivo and in vitro methods. These included skin test with ubiquitous antigens, 2,4 dinitrochlorobenzene (DNCB) sensitization, determination of T and B peripheral blood lymphocytes, and lymphocyte response to phytohemagglutinin (PHA). The patients were divided into two groups: those with localized and those with disseminated disease (LD and DD). The patients with LD showed no significant differences in CMI when compared with normal controls. The patients with DD showed various defects in CMI when compared with controls and patients with LD. There were significant differences in the response to DNCB, and streptokinase-streptodornase (SK-SD) was the most discriminative of the skin-test antigens. The response to PHA was greatly depressed in patients with DD, whether in the presence of autologous or homologous plasma; in some patients a factor inhibiting to blastogenesis was detected in the serum. In patients with DD, a T-cell lymphopenia was observed. These data showed a correlation between immunocompetence and clinical stage.