Intestinal transplantation in children under FK 506 immunosuppression

Intestinal transplantation, solitary (n = 3) or in combination with the liver (n = 7), was performed in 10 pediatric patients with intestinal failure. The liver was only replaced if there was liver failure and portal hypertension. Immunosuppression was based on FK 506. Two patients died, one of graft-versus-host disease and one of lymphoproliferative disease. One patient as still in the intensive care unit 1 month posttransplantation due to perioperative complications. The function of the intestinal grafts in the remaining patients is normal. All nutrition and medications including immunosuppression are being administered enterally. This series indicates that small bowel transplantation, alone or in combination with the liver, is feasible in pediatric patients.     

Evidence that SMS 201-995 enhances the immunosuppressive effect of FK506

Somatostatin (SS) was originally described as a growth hormone release inhibiting factor synthesised in the hypothalamus. Recently, SS and its receptor (SSTR) have been demonstrated in lymphoid tissues and seem to play a regulatory, largely inhibitory, role in immune responses. The aim of the present study was to check the immunosuppressive effect of a SS derived peptide, the octreotide (SMS 201-995) and to verify whether this molecule acted synergistically with FK506. An immunosuppressive effect of SMS was observed on the proliferation of rat spleen cells induced in vitro, either by polyclonal mitogens such as PHA or by alloantigens. With PHA stimulation, 10(-14) M SMS significantly enhanced the immunosuppressive action of 0.00001 microg/ml FK506. The addition of SMS in MLR (10(-11)-10(-9)M) increased the antiproliferative effect of both 0.0001 microg/ml and 0.00001 microg/ml FK506. In consideration of the extremely low concentration of both drugs that was required to obtain a good immunosuppression in vitro, we verified the association of FK506 and SMS in vivo in an allogeneic skin graft model that used Lewis (Lew) rats as donors and Brown Norway (BN) rats as recipients. BN treated with 0.1 mg/kg FK506 and 0.5-10 microg/kg SMS showed a significant increase in mean skin allograft survival time when compared to either a monotherapy or control group. None of the animals died or showed signs of drug-related toxicity. In conclusion, a combined therapy of SMS and FK506, administered at lower dosages than those that are considered therapeutic, led to an effective immunosuppression without any undesirable side effects.     

Protective effect of FK506 on ischemia/reperfusion-induced myocardial damage in canine heart

We investigated the cardioprotective effect of FK506, a newly developed immunosuppressive agent, on ischemia-reperfusion-induced myocardial damage and the inhibitory effect of FK506 on superoxide radical formation by neutrophils. Open-chest anesthetized dogs were divided into two groups: group 1, 2-h occlusion of the coronary artery followed by 1-h reperfusion; and group 2, 2-h occlusion followed by 1-h reperfusion with preadministration of FK506 (0.5 mg/kg). After reperfusion, heart mitochondria were prepared from the normal and reperfused areas and mitochondrial function and mitochondrial GSH (the reduced form of glutathione) and GSSG (the oxidized form of glutathione) concentrations were measured. In addition, neutrophils were collected from normal healthy dogs, and the inhibitory effect of FK506 on superoxide radical formation by neutrophils was also investigated. One-hour reperfusion after 2-h coronary occlusion induced significant mitochondrial dysfunction associated with a marked depletion of mitochondrial GSH concentration. FK506 reduced mitochondrial dysfunction, depletion of mitochondrial GSH concentration, and development of reperfusion arrhythmias. FK506 also reduced stimulant-induced superoxide radical formation by normal neutrophils dose dependently. Radical scavenging activity decreased in association with reperfusion, and FK506 reduced superoxide radical formation by neutrophils, which might contribute to lessening ischemia-reperfusion damage.     

A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group

BACKGROUND: Tacrolimus (FK506), a macrolide molecule that potently inhibits the expression of interleukin 2 by T lymphocytes, represents a potential major advance in the management of rejection following solid-organ transplantation. This randomized, open-label study compared the efficacy and safety of tacrolimus-based versus cyclosporine-based immunosuppression in patients receiving cadaveric kidney transplants. METHODS: A total of 412 patients were randomized to tacrolimus (n=205) or cyclosporine (n=207) after cadaveric renal transplantation and were followed for 1 year for patient and graft survival and the incidence of acute rejection. RESULTS: One-year patient survival rates were 95.6% for tacrolimus and 96.6% for cyclosporine (P=0.576). Corresponding 1-year graft survival rates were 91.2% and 87.9% (P=0.289). There was a significant reduction in the incidence of biopsy-confirmed acute rejection in the tacrolimus group (30.7%) compared with the cyclosporine group (46.4%, P=0.001), which was confirmed by blinded review, and in the use of antilymphocyte therapy for rejection (10.7% and 25.1%, respectively; P<0.001). Impaired renal function, gastrointestinal disorders, and neurological complications were commonly reported in both treatment groups, but tremor and paresthesia were more frequent in the tacrolimus group. The incidence of posttransplant diabetes mellitus was 19.9% in the tacrolimus group and 4.0% in the cyclosporine group (P<0.001), and was reversible in some patients. CONCLUSIONS: Tacrolimus is more effective than cyclosporine in preventing acute rejection in cadaveric renal allograft recipients, and significantly reduces the use of antilymphocyte antibody preparations. Tacrolimus was associated with a higher incidence of neurologic events, which were rarely treatment limiting, and with posttransplant diabetes mellitus, which was reversible in some patients.     

Cholesterol control: long-term benefit of pancreas-kidney transplantation with FK 506 immunosuppression

The present study investigated the relationship between the sex ratio of dream characters and the person's waking-life pattern of social contacts. Results partly confirm the continuity between waking and dreaming.