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Biomedical subjects

O Konno

Publications and source records attributed to O Konno.

At least 19 recordsLinked to original sources
PubMed2006

The role of plasmapheresis therapy for perioperative management in ABO-incompatible adult living donor liver transplantation.

BACKGROUND: Although living donor liver transplantation (LDLT) was established as a treatment for end-stage liver disease in Japan, the indication for LDLT across an ABO-incompatible barrier remains controversial. The purpose of this study was to elucidate the role of plasmapheresis in incompatible LDLT. METHODS: Eleven adult patients (seven men and four women) who underwent incompatible LDLT were enrolled in this study. Of these three patients had hepatocellular carcinoma, three chronic hepatitis C, one Wilson's disease, one autoimmune hepatitis, one chronic hepatitis B, one hemochromatosis, and one fulminant hepatic failure. The immunosuppressive regimen consisted of tacrolimus, prednisolone, mycophenolate mofetil (or cyclophosphamide), and prostaglandin E1 in all patients. Multiple plasmapheresis was performed perioperatively to reduce the recipient's antibody titers against the donor's blood type. RESULTS: Plasmapheresis was useful for the reduction of the recipient's antibody titers to x 16 or lower before and after transplantation. There was no difference in transplant outcome between the 11 patients with incompatible blood group and 30 patients with identical or compatible blood groups. DISCUSSION: Major postoperative complications such as intrahepatic biliary complications and hepatic necrosis may occur in incompatible transplantation. Several investigators suggested that anti-immunoglobulin (Ig) M and anti-IgG antibody titers sustained these complications. The antibody titers must be decreased sufficiently with plasmapheresis. An elevation of anti-ABO titers after transplantation may be a predictive risk factor for increased mortality and morbidity. In order to perform LDLT in a safer manner, plasmapheresis is an indispensable treatment to improve the outcome of ABO-incompatible cases.

ABO Blood-Group System↗
PubMed2005

Optimal dose and target trough level in cyclosporine and tacrolimus conversion in renal transplantation as evaluated by lymphocyte drug sensitivity and pharmacokinetic parameters.

We evaluated the relative clinical potency of cyclosporine (CyA) and tacrolimus (Tac) using pharmacodynamic and pharmacokinetic parameters of the drug to obtain the most suitable converting dose and target trough level. The relative pharmacodynamic potency was examined by the mean ratio of drug concentrations giving 50% inhibition of blastogenesis of lymphocytes (IC50) in 66 chronic renal failure patients. The relative potency estimated from clinical pharmacokinetic parameters was examined by the mean ratio of each pharmacokinetic parameter value of CyA versus Tac. The pharmacokinetic parameters were estimated by 12-hour monitoring of drug blood concentrations in seven CyA patients and seven Tac patients. The mean IC50 ratio of CyA and Tac (CyA/Tac of IC50) was 25.1. The mean area under the concentration-time curve (AUC) ratio (CyA/Tac of AUC) was 25.5, the mean trough level (C(min)) ratio (CyA/Tac of C(min)) was 13.2, and the mean dose per body weight ratio was 25.2. The relative potency estimated from AUC that is the most reliable pharmacokinetic parameter for the estimation of clinical efficacy of calcineurin inhibitors appeared to agree with the relative pharmacodynamic potency estimated from IC50. The data suggest that TAC 25-fold more potent than CyA, which represents a suitable converting dose ratio, and that target trough level of CyA is about 13-fold greater than Tac based on CyA/Tac of C(min). We conclude that these relative values may be useful to estimate the suitable dose and target trough levels to convert between CyA and Tac.

Area Under Curve↗
PubMed2005

Evaluation of appropriate blood level in continuous intravenous infusion from trough concentrations after oral administration based on area under trough level in tacrolimus and cyclosporine therapy.

The target blood concentrations of tacrolimus (TAC) and cyclosporine (CYA) during continuous intravenous infusion (C(ss)) have been determined based on clinical experience. However, it is desirable that C(ss) should be set so that the AUC after intravenous infusion is equal to the AUC after oral administration (AUC(po)). Accordingly, we performed 12-hour monitoring of blood concentrations to calculate C(ss) from the blood trough levels (C(TL)) on 15 kidney recipients administered TAC and 12 recipients administered CYA (Neoral). We used an area under the trough level (AUTL) as a new pharmacokinetic parameter. The C(ss) was evaluated from C(TL), AUC(po), and AUTL was calculated to be C(ss) = C(TL) x (AUC(po)/AUTL). In addition, AUTL/AUC(po) ratio and blood peak/trough level ratio (C(max)/C(min)) were examined to compare pharmacokinetics of TAC and CYA. The formula for TAC was C(ss) = C(TL) x 1.40 and that for CYA, C(ss) = C(TL) x 2.55. The calculated target C(ss) of TAC was 1.40 times that of C(TL), which was similar to the present clinical C(TL). In contrast, the calculated target C(ss) of CYA was 2.55 times the C(TL), and therefore an extremely high C(ss) was necessary to obtain a sufficient AUC that will be available after oral administration. Consequently, intravenous administration of CYA twice a day was considered to be more appropriate to obtain sufficient CYA pharmacokinetics, rather than a continuous intravenous administration. We conclude that the formula, C(ss) = C(TL) x (AUC(po)/AUTL) was useful to calculate the target blood concentration of calcineurin inhibitors when changing from continuous intravenous infusion to oral administration of these drugs.

Administration, Oral↗
PubMed2005

Pharmacokinetic differences between morning and evening administration of cyclosporine and tacrolimus therapy.

We performed 24-hour monitoring of cyclosporine (NEO) and tacrolimus (TAC) blood concentrations, evaluating pharmacokinetic parameters and characterizing circadian variations. The monitoring was performed in 10 instances on nine patients administered NEO and 12 out of 11 patients administered TAC. All cases were administered equally divided doses of drugs twice daily orally. Blood samples were taken before and 1, 2, 3, 4, 6, and 12 hours after NEO or TAC administration in the morning and evening. The pharmacokinetic parameters were compared between morning and evening administrations of both drugs. AUC0-12, AUC0-4, C(max), C2, and C(max)/C(min) of NEO and TAC were significantly lower during the evening compared with morning administrations. C(min) values were significantly higher in the evening. T(max) of NEO was longer in evening, although there was not a significant difference; T(max) of TAC was significantly longer in the evening. We found that NEO and TAC administrations in the evening resulted in reduced bioavailability and delayed absorption when compared with drug administrations in the morning. It was thought that the difference in bioavailability between morning and evening administrations was smaller with TAC, because TAC shows lower peak levels and a flatter blood concentration curve than NEO. C(min) was higher after evening administration than morning because of delayed absorption, though the bioavailability of both drugs decreased in the evening. These results suggest that we have to appreciate apparently high trough levels.

Administration, Oral↗
PubMed2004

Successful case of adult ABO-incompatible liver transplantation: beneficial effects of intrahepatic artery infusion therapy: a case report.

BACKGROUND: In Japan ABO-incompatible liver transplantation has been done on >100 occasions up to 2003. However, <30% are cases involving adults. The difficultly of ABO-incompatible liver transplantation is associated with the high frequency of humoral rejection and local disseminated intravascular coagulation (DIC), leading to many postoperative complications. We report a successful case of adult ABO-incompatible liver transplantation with the use of an intrahepatic artery infusion. METHODS: A 36-year-old man with Wilson disease, underwent living donor liver transplantation from an ABO-incompatible donor. The immunosuppressive therapy included multiple perioperative plasmaphereses, splenectomy, and treatment with tacrolimus, methylprednisolone, and cyclophosphamide. The dose and blood level of tacrolimus were the same as in ABO-compatible cases. In addition to these therapies, we administered an intrahepatic arterial infusion with prostaglandin (PG) E1 alone. RESULTS: After perioperative plasmapheresis and cyclophosphamide, antidonor blood group antibody titers remained undiluted and without vascular complications throughout the postoperative course, but there was a tendency for bleeding that continued for 10 days after transplantation. On postoperative day 10, a reexploration was performed for intraabdominal bleeding. During another operation on postoperative day 59 a biloma was found and drained. The patient has now survived for 120 days after transplantation with normal liver function. CONCLUSIONS: Beneficial effect of intrahepatic artery infusion with PGE1 seems to be useful in adult ABO-incompatible liver transplantation.

ABO Blood-Group System↗
PubMed2002

[Right atrial lipoma with calcification in ascending aorta; report of a case].

A 67-year-old male was diagnosed to have a right atrial tumor by echocardiography incidentally. Computed tomography (CT) indicated a mass which showed very low radiodensity and magnetic resonance imaging (MRI) [T1-weighted] showed the high signal intensity of tumor. We could predict the mass as lipoma. Tumor removal was performed under cardio-pulmonary bypass and under ventricular fibrillation because of the calcification in ascending aorta. Microscopically the tumor was consisted of mature adipose tissue. The postoperative course was uneventful. Cardiac lipomas are rare tumors. CT and MRI are better investigations for preoperative diagnosis. After surgical excision the prognosis is excellent.

Aged↗
PubMed1995

[Respiratory failure after surgery for esophageal cancer and hypercoagulability].

Operation of esophageal cancer accompanies a big surgical stress and postoperative pulmonary complications such as respiratory failure are observed at high frequencies. On the other hand, when a big stress is added to a body, a state of hypercoagulation in which blood coagulation mechanism is abnormally enhanced appears and this state is closely related to organ failures but has many unknown points. So, we examined 39 patients given excision of esophageal cancer with respect to occurrence of postoperative respiratory failures, participation of coagulopathy in aggravation and their degrees before and after the operation to find out the relationship between postoperative respiratory failure and the state of hypercoagulation. We gave a diagnosis of respiratory failure to the patients whose respiratory index exceeded 1.5 on the day after operation but did not show atelectasis or hydrothorax. As a result, respiratory failures were observed in 7 out of 39 cases (17.9%). When a risk score (RS) of postoperative respiratory failure was determined using multivalent analysis (quantification type II) with preoperative factors such as age and function of heart, lung, liver, and kidney as well as preoperative blood coagulation factors, RS = 2.87 (antithrombin-III (AT-III) less than 75%) +1.89 (age over 70 years) +1.78 (respiratory index over 0.15) +1.44 (serum albumin less than 3.0 mg/dl) +1.28 (cardiac index less than 3.0 l/min/m2) was obtained and a drop in preoperative AT-III was considered a risk for occurrence of post operative respiratory failure. In contrast, referring changes in postoperative value of blood coagulation factors, a distinct rise in fibrinogen (FBG) appeared in early stage after operation in the respiratory failure group compared to the control group (p < 0.01). Moreover, recovery in AT-III of blood coagulation factors and in plasminogen and antiplasmin of fibrinolytic factors was delayed (p < 0.05) indicating promotion of postoperative hypercoagulation state and delay in recovery of coagulation-fibrinolysis factors. However, participation of platelet factors was absent.

Age Factors↗
PubMed1993

[Evaluation of factors aggravating and delaying recovery from postoperative hypercoagulable state in patients operated on for esophageal cancer].

When a living body is invaded to a high degree, a hypercoagulable state develops. The radical operation for esophageal cancer is known as a very high risk operation. The purpose of this study is to evaluate in detail the postoperative changes in platelet, coagulation and fibrinolytic systems, in 34 patients operated on for esophageal cancer, and to clarify the factors contributing to both the aggravation and delay of recovery from the postoperative hypercoagulable state. Operating time and blood loss during surgery were factors aggravating the postoperative hypercoagulable state. The mechanism of coagulation progressed significantly in those patients requiring 500 minutes or more operating time and having a blood loss of 600 ml or more during surgery. Age was seen as an important factor delaying recovery, as the recovery of the coagulative parameters was delayed significantly in patients aged 70 or above. Hepatic function was the most important of post operative organ functions. Renal, cardiac and respiratory functions were unrelated to the postoperative hypercoagulable state.

Blood Coagulation↗
PubMed1993

[Postoperative arrhythmia after operation of esophageal cancer].

The postoperative arrhythmias (exclusive of sinus tachycardia) was reviewed in 77 patients (male: 69, female: 8, mean age: 63.9 years) who underwent esophagectomy for esophageal carcinoma. The results were as follows: 1. The incidence of postoperative arrhythmias in all patients but seven who had preoperative chronic atrial fibrillation (af) or pacemaker rhythm was 47.1%, and af was observed most frequently (45.5%). Postoperative arrhythmias occurred in patients with abnormal preoperative electrocardiographic findings more often than in those with normal preoperative electrocardiographic findings (53% vs 41%). The incidence of postoperative arrhythmias in aged patients (> or = 66 years old) was significantly higher than that in younger patients (< or = 65 years old) (64% vs 35%, p < 0.05). Other risk factors for postoperative arrhythmias were sex and history of hypertension. 2. Postoperative arrhythmias occurred more often in patients who underwent blunt dissection of the thoracic esophagus and reconstruction using the whole stomach via the posterior mediastinal route than in those who underwent esophagectomy with right thoracotomy and reconstruction using the gastric tube via the poststernal route (60.0% vs 45.0%). 3. Most supraventricular premature contractions and ventricular premature contractions occurred immediately after surgery or on the first postoperative day, and af often occurred during the first postoperative night or the second postoperative day. 4. For treatment, various antiarrhythmic agents were administered according to the patient's condition. Glucose-insulin-kalium therapy was especially effective (63%). None of the arrhythmias was fatal.

Aged↗