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Biomedical subjects

J Ahonen

Publications and source records attributed to J Ahonen.

At least 73 records · Page 4Linked to original sources
PubMed1996

Does delayed kidney graft function increase the risk of chronic rejection?

The impact of delayed graft function (DGF) on later renal graft loss due to chronic rejection was studied in a single center using uniform protocol for organ procurement and posttransplant patient care. DGF function was observed in 34% of 829 consecutive first cadaveric renal transplants in adults and in 47% of 169 retransplantations (P < 0.05). There were no significant differences in graft survival between groups with early graft function (EGF) and DGF, either in first transplantations or retransplantations. The half-life in EGF and DGF groups of first transplants was 12.3 years and 10.5 years, respectively, and of retransplantants was 8.0 years and 6.5 years, respectively. DGF was divided in three subgroups according to the day of onset. If graft function started during the first or second week after transplantation there were no significant differences in long-term graft survival rates compared with EGF. Only in retransplants, if graft function started later than 2 weeks postoperatively, were long-term graft survival rates significantly lower when compared with EGF and the difference persisted if other causes of graft loss except chronic rejection were censored.

Adolescent↗
PubMed1996

The effects of the systemic antimycotics, itraconazole and fluconazole, on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam.

We studied the interaction of azole antimycotics with intravenous (IV) and oral midazolam using a cross-over design in 12 volunteers, who ingested placebo, itraconazole, or fluconazole for 6 days. A 7.5-mg dose of midazolam was ingested on the first day, 0.05 mg/kg was administered IV on the fourth day, and 7.5 mg orally on the sixth day. Itraconazole reduced the clearance of IV midazolam by 69% and fluconazole reduced the clearance of IV midazolam by 51% (P < 0.001). A single dose of itraconazole and fluconazole increased the area under the oral midazolam concentration-time curve [AUC(0-infinity)] 3.5-fold (P < 0.001) and the peak concentration two-fold (P < 0.05) compared to placebo. On the sixth day the AUC(0-infinity) of oral midazolam was almost seven times greater with itraconazole (P < 0.001) and 3.6 times greater with fluconazole (P < 0.001) than without the antimycotics. The psychomotor effects of midazolam were also profoundly increased (P < 0.001). The psychomotor tests demonstrated only a weak interaction between the antimycotics and IV midazolam. When bolus doses of midazolam are given for short- time sedation, the effect of midazolam is not increased to a clinically significant degree by itraconazole and fluconazole, and it can be used in normal doses. However, the use of large doses of IV midazolam increases the risk of clinically significant interactions also after IV midazolam. Use of oral midazolam with itraconazole and fluconazole should be avoided.

Administration, Oral↗
PubMed1996

Effect of diltiazem on midazolam and alfentanil disposition in patients undergoing coronary artery bypass grafting.

BACKGROUND: Midazolam and alfentanil are desirable anesthetic adjuncts for cardiac anesthesia. They are metabolized by cytochrome P450 3A (CYP3A) enzymes. These isozymes are inhibited by concurrent medications, including the calcium channel antagonist diltiazem, which may have an effect on recovery from anesthesia. METHODS: Thirty patients having coronary artery bypass grafting were randomly assigned to receive either diltiazem (60 mg orally 2 h before induction of anesthesia and an infusion of 0.1 mg.kg-1.h-1 started at induction and continued for 23 h) or placebo in a double-blind study. Anesthesia was induced with 0.1 mg/kg midazolam, 50 micrograms/kg alfentanil, and 20 to 80 mg propofol and maintained with infusions of 1 microgram.kg-1.min-1 of both midazolam and alfentanil supplemented with isoflurane. Plasma midazolam and alfentanil concentrations and areas under the plasma concentration-time curves were determined. The terminal half-life and the time for the drug plasma level to decrease 50% after cessation of the infusion (t50) were calculated for midazolam and alfentanil. Separation from mechanical ventilation and tracheal extubation were performed according to the study protocol. RESULTS: Diltiazem increased the mean concentration-time curves (from end of anesthesia until 23 h) of midazolam by 24% (P < 0.05) and that of alfentanil by 40% (P < 0.05). The mean half-life of midazolam was 43% (P < 0.05) and that of alfentanil was 50% (P < 0.05) longer in patients receiving diltiazem. The mean t50 of alfentanil was 40% longer (P < 0.05) in patients receiving diltiazem, but the change in the mean t50 of midazolam (25%) was not statistically significant. In patients receiving diltiazem, tracheal extubation was performed on average 2.5 h later (P = 0.054) than in those receiving placebo. CONCLUSIONS: Diltiazem slows elimination of midazolam and alfentanil and may delay tracheal extubation after large doses of these anesthetic adjuncts. CYP3A-mediated drug interactions should be considered as confounders when recovery from anesthesia with midazolam and alfentanil infusions is assessed.

Adjuvants, Anesthesia↗
PubMed1996

Lack of effect of antimycotic itraconazole on the pharmacokinetics or pharmacodynamics of temazepam.

The azole antimycotics itraconazole and ketoconazole are potent and relatively nonspecific inhibitors of cytochrome P450 enzymes and have a potentially dangerous interaction with midazolam and triazolam. The possible interaction between itraconazole and a short-acting benzodiazepine, temazepam, was investigated in a double-blind, randomized crossover study. Ten healthy volunteers were given placebo or 200 mg itraconazole a day orally for 4 days. The challenge dose of 20 mg of temazepam was ingested on the fourth day, after which plasma samples were collected, and psychomotor performance tests were carried out for 24 h. Despite a statistically significant small increase of the area under the temazepam concentration-time curve, there was no clinically significant interaction, as determined by the psychomotor performance tests. The different metabolic pathways and the lack of significant firstpass metabolism of temazepam explain the great difference in the interaction potential of temazepam compared with midazolam and triazolam. Temazepam, unlike midazolam and triazolam, can be prescribed in usual doses for patients receiving itraconazole and other inhibitors of P450 3A4.

Adolescent↗
PubMed1996

The effect of the antimycotic itraconazole on the pharmacokinetics and pharmacodynamics of diazepam.

The azole antimycotic itraconazole is a potent and relatively unspecific inhibitor of cytochrome P450 enzymes and has a potentially dangerous interaction with midazolam and triazolam. The possible interaction between itraconazole and diazepam was investigated in a double-blind, randomized, cross-over study. Ten healthy volunteers were given orally placebo or itraconazole 200 mg a day for 4 days. The challenge dose of 5 mg of diazepam was ingested on the fourth day, after which plasma samples were collected and psychomotor performance tests were carried out for 42 h. Despite a statistically significant small increase in the area under the plasma diazepam concentration-time curve and the elimination half-life of diazepam, there was no clinically significant interaction as determined by the psychomotor performance tests. The lack of significant first-pass metabolism and the different metabolic pathways of diazepam explain the smaller interaction potential of diazepam compared with midazolam and triazolam. Diazepam, unlike midazolam and triazolam, can be prescribed in usual doses for patients receiving itraconazole and probably other inhibitors of P4503A4, at least when diazepam is used as single doses.

Adolescent↗
PubMed1996

Increased serum neutral endopeptidase activity in acute renal allograft rejection.

Neutral endopeptidase (EC 3.4.24.11; NEP), originally isolated from renal tubular brush border, is a cell surface peptidase identical to the CD10 antigen (or CALLA; common acute lymphoblastic leukemia antigen) in lymphoid cells. We studied the serum NEP levels daily after transplantation (Tx) in 19 renal allograft recipients. The NEP activity was determined with a two-step enzymatic assay utilizing a fluorogenic substrate (Suc-Ala-Ala-Phe-AMC; see text) and related to clinical signs of graft rejection, to signs of immunoactivation in transplant fine-needle aspiration biopsy (FNAB) specimens, to renal function, and to serum levels of C-reactive protein. The serum NEP levels remained normal (peak level 10.3 +/- 1.8 micrograms/l on days 6-9 after Tx, initial level after Tx 7.3 +/- 1.4 micrograms/1 on day 2; mean values +/- SEM) in patients who neither showed clinical signs of rejection nor had findings of immunoactivation in FNAB samples. On the contrary, the serum NEP levels rose clearly in patients developing acute rejection verified clinically and in FNAB samples (peak value 90.4 +/- 18.7 micrograms/l on days 6-9 post-Tx; p < 0.001 compared with patients without sings of immunoactivation) and even in patients having immunoactivation in FNAB without clinical evidence of rejection (108.2 +/- 22.4 micrograms/l, p < 0.001). Serum NEP peak appeared 2-3 days before clinical diagnosis of rejection and a positive findings in FNAB samples. Serum NEP increments did not correlate with changes in serum creatinine, delayed onset of renal excretory function, blood leukocyte count, C-reactive protein level, or infections. Thus, the serum NEP activity was shown to increase after renal allotransplantation associated with early phases of immunoactivation and development of acute graft rejection. Because of the limited number of patients studied, the clinical implications of these preliminary observations for kidney transplant monitoring clearly need confirmation in larger studies.

Adolescent↗
PubMed1996

Cyclosporine in severe interstitial cystitis.

PURPOSE: Cyclosporine is a widely used immunosuppressive drug in organ transplantation and recently it has been used in several autoimmune disorders with good results. Because interstitial cystitis may have an autoimmune etiology, we wished to determine whether cyclosporine has any effect on symptoms in patients with severe interstitial cystitis. MATERIALS AND METHODS: A total of 11 patients, who fulfilled the criteria for interstitial cystitis according to an international accrual form, received cyclosporine for 3 to 6 months at an initial dose of 2.5 to 5 mg./kg. daily and a maintenance dose of 1.5 to 3 mg./kg. daily. Blood pressure, serum creatinine and cyclosporine concentrations were monitored regularly. The patients completed frequency-volume charts at 2-week intervals. RESULTS: The frequency-volume charts showed favorable effects. Micturition frequency decreased (p<0.01), and mean and maximum voided volumes increased significantly (p<0.001 and p<0.01, respectively). Bladder pain decreased or disappeared in 10 patients, allowing for storage of large urine volumes. Serum creatinine did not change with the dosages used. Mild hypertension occurred in 2 patients and resolved after the cyclosporine dose was lowered. After cessation of treatment symptoms recurred in the majority of patients. CONCLUSIONS: The findings revive the concept of interstitial cystitis as an autoimmune disease.

Adult↗
PubMed1995

Effect of itraconazole and terbinafine on the pharmacokinetics and pharmacodynamics of midazolam in healthy volunteers.

Twelve healthy volunteers were given orally placebo, itraconazole 100 mg or terbinafine 250 mg for 4 days. Midazolam 7.5 mg was ingested on the fourth day, after which plasma samples were collected and psychomotor performance tests carried out for 17 h. Itraconazole increased the area under the midazolam concentration-time curve six-fold (P < 0.001), the peak concentration 2.5-fold (P < 0.001) and the elimination half-life two-fold (P < 0.001) compared with placebo and terbinafine pretreatments. The pharmacokinetic parameters did not differ between placebo and terbinafine phases. The higher concentrations of midazolam during the itraconazole phase were associated with increased effects. In contrast to itraconazole, terbinafine had no effect on midazolam pharmacokinetics and psychomotor performance tests were unchanged from placebo.

Administration, Oral↗
PubMed1994

X window system based user interface in radiology.

A teleradiology system was designed for image transfer between two hospitals. One of the main challenges of the work was the user interface, which was to be easy to operate and to learn, and was equipped with useful functions for image manipulation and diagnosing. The software tools used were the Unix operating system (HP-UX v.7.0), C programming language and the X Window System (or simply X). The graphical user interface (GUI) was based on OSF-Motif standard, and it was developed by using the HP-Interface Architect. Both OSF-Motif and HP-Interface Architect are based on X. The results of the development project were installed for clinical use in the Turku University Central Hospital. The work demonstrates, that the X Window System has useful and advantageous features for radiology department's computer network environment.

Computer Communication Networks↗
PubMed1994

Risk factors predicting chronic rejection of renal allografts.

Chronic rejection is clinically defined as a gradual but progressive impairment of renal allograft function in the absence of other specific causes. The risk factors predisposing to chronic rejection are incompletely known. In this prospective single-center project, logistic regression analysis was used to study the long-term outcome of 94 consecutive first renal allografts in relation to 10 potential risk factors. Whether serum lipid levels, histopathological changes or the mode of immunosuppressive therapy had a predictive value for chronic rejection was of special interest. The risk factors for renal allograft outcome were determined 2 years after the transplantation, when graft function was still normal, and the results were evaluated 2 years later. Occurrence of acute rejections, cold ischemia time, the high-density lipoprotein cholesterol level, and the high-density lipoprotein and total cholesterol ratio were not significant predictors of graft outcome. In a univariate analysis, triglyceride, total cholesterol, and low-density lipoprotein cholesterol level, and donor age were significantly related to graft outcome. In a logistic regression analysis, triple immunosuppressive therapy was better than any double-drug regimen in preventing the deterioration of renal allografts. Incipient histological changes in graft biopsy, quantitated as the "chronic allograft damage index," was the most important single predictor of chronic rejection. The effect of both the histological changes and low-density lipoprotein cholesterol on adverse graft outcome was level dependent.

Adult↗