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Biomedical subjects

C Brattström

Publications and source records attributed to C Brattström.

At least 37 records · Page 2Linked to original sources
PubMed1997

Determination of rapamycin in whole blood by HPLC.

Sirolimus (rapamycin, RAPA) is a natural fermentation product (macrolide antibiotic) that has demonstrated potent immunosuppressive activity. A reverse-phase high-performance liquid chromatographic (HPLC) method is described for analysis of the drug in whole blood. The samples are purified by using liquid-liquid extraction with butyl chloride/diethyl ether combined with reversed-phase solid-phase extraction. RAPA and internal standard were traced by UV-detection at 278 nm. Linear calibration curves with correlation coefficients > 0.999 were obtained (range, 1-50 ng/ml). Minimum detectable concentration was approximately 0.4 ng/ml and recovery approximately 45% for both RAPA and internal standard. Coefficient of variation (day to day) was 9.8% at 5 ng/ml (n = 6) and 5.6% at 40 ng/ml (n = 6). The chromatography requires < 10 min per sample. The assay has proved to be free of interference peaks from cyclosporine or tacrolimus. The method has been used to determine the whole blood concentrations in samples from healthy volunteers and renal transplant recipients receiving single and multiple doses of oral rapamycin.

Chromatography, High Pressure Liquid↗
PubMed1997

Kinetics and dynamics of single oral doses of sirolimus in sixteen renal transplant recipients.

Sirolimus is a new immunosuppressive drug that has been evaluated in animal experiments. The current study was conducted on humans with reformulated sirolimus in doses from 3 mg/m2 to 15 mg/m2. Sixteen renal transplant recipients were included in this phase I study to determine the safety, tolerance, and preliminary pharmacokinetics of increasing single doses of orally administered sirolimus. All 16 patients had stable renal graft function after a renal transplant at least 6 months before the study. Basal immunosuppression consisted of cyclosporine and prednisolone (n = 10) or cyclosporine, azathioprine, and prednisolone (n = 6). Four groups (I, 3 mg/m2; II, 5 mg/m2; III, 10 mg/m2; IV, 15 mg/m2) of four patients were assigned randomly to receive sirolimus (n = 3) or placebo (n = 1). Among the 12 patients who received sirolimus, five had mild transient study events such as headache, nausea, mild dizziness, hypoglycemia, epistaxis, and decrease in platelets. No serious adverse events occurred and no nephrotoxic effects could be related to the single dose administration of sirolimus. The only study event that was judged as probably related to sirolimus was the single case of thrombocytopenia. The other events were evaluated as possibly related. Thrombocytopenia occurred at the highest dose level (15 mg/m2 sirolimus). In two of the patients in the placebo group, slight elevations of liver enzymes and serum amylase were seen. Blood and plasma sirolimus concentrations were analyzed by an electrospray-high performance liquid/mass spectrophotometric (ESP-HPLC/MS) method Sirolimus showed an extensive red blood cell distribution with a mean blood/ plasma ratio of 49.1. The elimination half-life ranged from 43.8 to 86.5 hours (mean 56.9 hours). The Cmax and the area under the concentration versus time curves (AUC) correlated reasonably with doses from 3 to 15 mg/m2. The oral dose clearance ranged from 42 to 339 ml/h.kg. No clinically significant differences were seen in the trough concentrations of cyclosporine or the AUCs before and after the administration of sirolimus. Administration of single oral doses of sirolimus from 3 to 15 mg/m2 was safe and well tolerated in stable renal transplant recipients. Thrombocytopenia may be the dose-limiting toxicity. Additional phase II and phase III clinical trials will define the immunosuppressive efficacy of sirolimus.

Administration, Oral↗
PubMed1996

Improved results with a simplified technique for pancreaticoduodenal transplantation with enteric exocrine drainage.

A simplified technique for pancreaticoduodenal transplantation with enteric exocrine drainage is described. The whole-organ pancreaticoduodenal transplant is placed intraperitoneally with vascular anastomosis to the right common iliac artery and the caval vein, respectively. The graft duodenum is anastomosed side-to-side to the most proximal part of the donor jejunum. No Roux-en-Y loop or pancreatic duct catheter is used to protect the anastomosis with this technique. Nevertheless, excellent results have been obtained, with no graft losses occurring due to leakage or infection. With this technique, the 1-yr patient and graft survival rates in uremic recipients of simultaneous renal and pancreas transplants are 100% and 87%, respectively.

Anastomosis, Surgical↗
PubMed1993

Detection of CMV-matrix pp65 antigen in leucocytes by immunofluorescence as a marker of CMV disease.

The finding that active cytomegalovirus (CMV) infection is associated with an increased mortality after organ transplantation and the introduction of successful antiviral treatment render more urgent the development of rapid and accurate diagnostic methods. Rapid immunodiagnosis of active CMV infection was investigated by means of immunofluorescence staining of leucocytes by monoclonal antibodies. Monoclonals directed against the matrix protein, pp65, and ClonabR monoclonal antibody, which has been claimed to be directed against immediate early antigens, were used. All monoclonal antibodies directed against the matrix protein reacted equally well in staining of polymorphonuclear cells. Monoclonals described by Gerna et al. [1991] and by Pereira et al. [1982] also reacted more clearly with mononuclear cells. One hundred fifty heparinized blood samples were collected monthly from 82 patients within 3 months after transplantation. In addition, 132 EDTA blood samples were tested in connection with suspected CMV infection. The latter approach gave a better agreement between antigen detection and virus isolation. There was a relationship between active CMV infection and the finding of antigen-positive leucocytes (P = 0.002, Fisher's exact test) found within 1 month of one another. When the number of antigen-positive cells was taken into account, a relationship to severe CMV disease was detected (P < 0.001, Fisher's exact test). The antigen test was positive at an early stage during the development of severe CMV disease. This rapid method is useful for following the disease process of CMV and in determining when to initiate antiviral treatment.

Antibodies, Monoclonal↗