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Biomedical subjects

N Bilgin

Publications and source records attributed to N Bilgin.

192 records · Page 11Linked to original sources
PubMedDate not supplied

The pharmacokinetics of equoral versus neoral in stable renal transplant patients: a multinational multicenter study.

We studied the pharmacokinetics (PKs) of the new generic cyclosporine formulation, Equoral capsules, after the switch from original formulation Neoral capsules in stable renal transplant patients. The study was carried out in accordance with the basic principles defined in the US 21 CFR Part 312.20 and the principles of the Declaration of Helsinki. The study included clinically stable first renal transplant patients maintained on cyclosporine with no rejection episode during the past 6 months. Hematology, biochemistry, and urine chemistry were determined on day 7, and day 21. The patients were all switched to Neoral (lot number 416MFD0601) on day 0 when the first sparse sampling PK was performed. On day 14 a 12-hour PK profile included predose, 30 minutes; 1 hour; 1 hour 30 minutes; 2 hours; 3 hours; 4 hours; 5 hours; 6 hours; 8 hours; 10-hours and 12-hour samples. Cyclosporine levels were determined using a CYA kit (Abbott TDx). On day 15 the patients were switched from Neoral capsules to Equoral capsules (lot 5T111014) at an equivalent dosage (mg/mg). The second sparse sampling PK was performed on day 21 and a 12-hour PK was performed on day 28. On the morning of day 29 patients were switched from Equoral capsules to Neoral capsules at an equivalent dosage (mg/mg). Additional concentrations were measured on days -7, 18, and 35. Safety parameters were monitored at each visit. The pharmacokinetics of both formulations were equivalent. The mean AUC for Neoral and Equoral was 2856 and 2892, respectively. The ratios of LSM and the 90% confidence intervals for the in-transformed parameters (AUC o-t, AUC inf, and Cmax) of Equoral and Neoral SGC were 98% and 95%, respectively, suggesting that Equoral and Neoral SGC are bioequivalent.

Area Under Curve↗
PubMedDate not supplied

Immunosuppressive therapy and Kaposi's sarcoma after kidney transplantation.

Immunosuppressive therapy for organ transplant recipients is complicated by high rates of malignant diseases, one of which is Kaposi's sarcoma (KS). Between November 1975 and March 2003, 1425 patients underwent renal transplantation at our center, including the 1095 most recent procedures. Fifty-two malignancies were observed in 50 patients (4.7%), including 16 cases of KS. The 16 recipients comprised 6 men and 10 women of mean age 39 +/- 9 years (range 10 to 62 years). At the time of KS diagnosis, 14 recipients were receiving cyclosporine, azathioprine, and prednisolone, and the other 2 azathioprine and prednisolone. The mean time from transplantation to diagnosis was 24 +/- 15.2 months (range 8 to 74 months). One recipient showed a lymphoma concomitant with KS. Seven patients had lesions limited to the skin, 5 had the skin and gastrointestinal tract disease, and 4 had disseminated disease. After KS was confirmed, the first-line treatment was cyclosporine and azathioprine withdrawal with tapering of prednisolone. The tumors were managed by appropriate surgical and/or medical therapy. At the time of this presentation, 9 individuals are alive, 4 with normal renal function. Five patients lost their grafts due to chronic rejection. We found that the combination of immunosuppressive drug withdrawal and chemotherapy is effective in patients with limited disease, but the results are poor in cases of generalized disease.

Adult↗
PubMedDate not supplied

Health care professionals' knowledge of procedural issues in transplantation: the need for continuing education programs.

Organ transplantation is a multidisciplinary field that requires a good knowledge of the processes and excellent cooperation throughout the entire hospital. The aim of this study was to determine the level of knowledge of health care professionals (HCPs) at our transplantation center concerning general definitions and procedural issues related to transplantation. A questionnaire including nine items-five questions on general definitions and four on procedural issues-was distributed to 100 randomly selected HCPs. Four participants were excluded because they completed the questionnaire incorrectly; thus, there were 96 total respondents. The mean number (+/-SD) of correct answers overall was 5.78 +/- 1.36. Concerning general definitions, 11.5% of the respondents answered all of the questions correctly. However, the corresponding rate for the procedural questions was 3.1%. One percent of the respondents answered 1 or zero definition questions correctly, and 19.8% answered 1 or zero procedural questions correctly. The HCPs showed better knowledge of general issues related to transplantation than procedural issues. The results of this study suggest that the knowledge of HCPs in transplantation centers in Turkey is limited to the extent that their specialty is linked to transplantation. It is important that continuing medical education programs be instituted in organ procurement and transplantation centers in Turkey. These in-service training programs would enhance HCPs' understanding of and participation in procedures related to transplantation, and thus improve the total quality of the transplantation process.

Education, Continuing↗
PubMedDate not supplied

Problems in postoperative renal transplant recipients who present to the emergency unit: experience at one center.

When a renal recipient in Turkey develops a postoperative problem, consultation by the transplant team in the emergency unit is often the first step toward a solution. The main aim of this study was to identify the types of postoperative problems that cause renal transplantation patients to visit the emergency room. Gathering this information was believed to be an important step toward developing new management strategies for these problems, in line with the quality management systems used throughout our hospital network. We collated the physical signs in the 78 patients when they presented to the emergency room. The most common one was fever (26.9%) followed by nausea/vomiting, diarrhea, abdominal pain, dyspnea, skin lesions, headache, musculoskeletal trauma, hematuria/dysuria, epistaxis, psychological disorders, angina pectoris, hypertension, epilepsy, and rectal bleeding. Among the 78 patients, 45 (57.7%) were hospitalized and 33 (42.3%) were discharged with medical advice or drug treatment. Among the 45 hospitalized patients, 97.8% were initiated on medical treatment. Knowing the surgical and medical emergency issues prevalent in recipients enables the development of new procedures and algorithms, leading to more effective management and follow-up of renal transplant recipients.

Emergency Service, Hospital↗
PubMedDate not supplied

Tacrolimus conversion in kidney transplant recipients: analysis of 107 patients.

Early results of an alteration in immunosuppressive protocol of tacrolimus conversion at a mean follow-up of 16 (range 1 to 36) months are presented with a mean time after transplantation of 34 +/- 1.4 months (range 1 to 158 months). Chronic allograft nephropathy in 16 (17%) patients, nephrotoxicity related to cyclosporine in 27(23%) patients and steroids resistant acute rejection in 64 (58%) represented the indications for tacrolimus conversion. Before starting tacrolimus there were 1 acute rejection episode in 37 patients, 2 in 17 patients, and 3 in 10 patients. After the drug conversion, 1 acute rejection occurred in 18 and 2 acute rejection in 4 patients. Graft loss was seen in 16 (16%) patients after drug conversion. Tacrolimus was withdrawn due to diabetes mellitus (n = 9), epilepsy (n = 4), and severe Nocardia sepsis, lymphoma and Kaposi sarcoma (each in one patient). Decreases in serum creatinine and increases in blood glucose levels were significantly associated with the tacrolimus doses (P = 0.0004 and P = 0.0400, respectively). The increase in creatinine clearance values were closely related to higher tacrolimus levels. The target range with maximum efficacy and minimum toxicity seemed to be 10 to 15 ng/mL. Tacrolimus conversion can be successful in cases of rejection and nephrotoxicity, but dose-dependent blood glucose elevations require close observation in these patients.

Adolescent↗
PubMedDate not supplied

tRNA-ribosome interactions.

Direct measurements of the rates of dissociation of dipeptidyl-tRNA from the ribosome show that hyperaccurate SmP and SmD ribosomes have unstable A-site binding of peptidyl-tRNA, while P-site binding is extremely stable in relation to the wild type. Error-prone Ram ribosomes, on the other hand, have stable A-site and unstable P-site binding of peptidyl-tRNA. At least for these mutant ribosomes, we conclude that stabilization of peptidyl-tRNA in one site destabilizes binding in the other. Elongation factor Tu (EF-Tu) undergoes a dramatic structural transition from its GDP-bound form to its active GTP-bound form, in which it binds aa-tRNA (aminoacyl-tRNA) in ternary complex. The effects of substitution mutations at three sites in domain I of EF-Tu, Gln124, Leu120, and Tyr160, all of which point into the domain I-domain III interface in both the GTP and GDP conformations of EF-Tu, were examined. Mutations at each position cause large reductions in aa-tRNA binding. An attractive possibility is that the mutations alter the domain I-domain III interface such that the switching of EF-Tu between different conformations is altered, decreasing the probability of aa-tRNA binding. We have previously found that two GTPs are hydrolyzed per peptide bond on EF-Tu, the implication being that two molecules of EF-Tu may interact on the ribosome to catalyze the binding of a single aa-tRNA to the A-site. More recently we found that ribosomes programmed with mRNA constructs other than poly(U), including the sequence AUGUUUACG, invariably use two GTPs per peptide bond in EF-Tu function. Other experiments measuring the protection of aa-tRNA from deacylation or from RNAse A attack show that protection requires two molecules of EF-Tu, suggesting an extended ternary complex. To remove remaining ambiguities in the interpretion of these experiments, we are making direct molecular weight determinations with neutron scattering and sedimentation-diffusion techniques.

Bacterial Proteins↗