Everolimus Rescue Treatment for Chronic Rejection After Pediatric Living Donor Liver Transplantation: 2 Case Reports.

Chronic rejection (CR) remains a challenging complication after liver transplantation. Everolimus, which is a mammalian target of rapamycin inhibitor, has an anti-fibrosis effect. We report here the effect of everolimus on CR. Case 1 was a 7-year-old girl who underwent living donor liver transplantation (LDLT) shortly after developing fulminant hepatitis at 10 months of age. Liver function tests (LFTs) did not improve after transplantation despite treatment with tacrolimus + mycophenolate mofetil (MMF). Antithymoglobulin (ATG) and steroid pulse therapy were also ineffective. The patient was diagnosed with CR, and everolimus was started with a target trough level of about 5 ng/mL. LFTs improved and pathological examination showed no progression of hepatic fibrosis. Case 2 was a 10-year-old girl with Alagille syndrome who underwent LDLT at 1 year of age. She had biopsy-proven acute cellular rejection with prolonged LFT abnormalities beginning 3 years after transplantation. She was treated with steroid pulse therapy, followed by MMF, tacrolimus, and prednisolone. Her condition did not improve, even after subsequent ATG administration. CR was suspected based on liver biopsy in the fourth postoperative year, and everolimus was introduced. The target trough level was around 5 ng/mL, but was reduced to 3 ng/mL due to stomatitis. Four years have passed since the initiation of everolimus, and LFTs are stable with no progression of liver biopsy fibrosis. We describe 2 cases in which everolimus was administered for CR. In both cases, LFTs improved and fibrosis did not progress, suggesting that everolimus is an effective treatment for CR after LDLT.

Pulmonary Arterial Pressure Management Based on Oral Medicine for Pediatric Living Donor Liver Transplant With Portopulmonary Hypertension.

Pediatric living donor liver transplantation (LDLT) in patients with advanced portopulmonary hypertension (PoPH) is associated with poor prognoses. Recently, novel oral medications, including endothelin receptor antagonists (ERAs), phosphodiesterase 5 (PDE5) inhibitors, and oral prostacyclin (PGI2) have been used to treat PoPH. Pediatric patients with PoPH who underwent LDLT from 2006 to 2016 were enrolled. Oral pulmonary hypertension (PH) medication was administered to control pulmonary arterial pressure (PAP). Four patients had PoPH. Their ages ranged from 6 to 16 years, and their original diseases were biliary atresia (n = 2), portal vein obstruction (n = 1), and intrahepatic portal systemic shunt (n = 1). For preoperative management, 2 patients received continuous intravenous PGI2 and 2 oral medications (an ERA alone or an ERA and a PDE5 inhibitor), and 2 received only oral drugs (an ERA and a PDE5 inhibitor). One patient managed only with intravenous PGI2 died. In the remaining 3 cases, intravenous PGI2 or NO was discontinued before the end of the first postoperative week. Postoperative medications were oral PGI2 alone (n = 1), an ERA alone (n = 1), or the combination of an ERA and a PDE5 inhibitor (n = 1). An ERA was the first-line therapy, and a PDE5 inhibitor was added if there was no effect. New oral PH medications were effective and safe for use in pediatric patients following LDLT. In particular, these new oral drugs prevent the need for central catheter access to infuse PGI2.

Sarcoidosis associated with psoriasis vulgaris.

We report a 70-year-old patient with sarcoidosis associated with psoriasis vulgaris. He had a nodule on the medial lower lid of his right eye. Oral corticosteroid for the sarcoid lesions and oral PUVA for psoriasis were employed. The cutaneous lesion disappeared within two months after starting the therapy. No relapse of sarcoidosis has been seen for eight years. The association of sarcoidosis with psoriasis has been previously reported; however, it is still unclear whether this association coincidental or meaningful.

[Studies on the conditions of blood sampling and storage for the liposome-based CH50 assay].

The CH50 values in the serum and plasma, especially those from chronic hepatitis caused by hepatitis C virus (HCV), are strongly affected and reduced through a process known as cold activation. We attempted to optimize the conditions of blood sampling and storage for the CH50 assay with a recently developed liposome-based assay kit. The bloods were obtained from HCV hepatitis patients as well as healthy donors. Regardless of the temperature (room temperature, 4 degrees C or 37 degrees C) at which samples were kept until the assay, higher values were always obtained in the serum than in the plasma. The plasma samples could either be heparinized or given any of the other anticoagulants, EDTA-2K and sodium citrate, at the time of sampling. We also attempted to optimize the temperature at which the fresh specimens were left during the period from sampling to assay and the temperatures to freeze them for storage and to thaw for assays. In the assays immediately after sampling, higher values were obtained when the specimens were left at 37 degrees C than at room temperature or 4 degrees C. To store at -80 degrees C rather than at -20 degrees C and to thaw rapidly at 37 degrees C rather than slowly at room temperature were found to be advantageous.

Vitamin A is involved in estrogen-induced cell proliferation but not in cytodifferentiation of the chicken oviduct.

We examined vitamin A-deficient chicks to determine whether vitamin A affects the estrogen-induced development of the chick oviduct. When oviduct development was stimulated for 5 days with the synthetic estrogen, diethylstilbestrol, the wet weight of the oviduct in vitamin A-deficient chicks was only half that in control chicks. The DNA content in this tissue showed that the decreased oviduct weight in the vitamin A-deficient chicks was caused by the decreased proliferation of oviduct cells. However, the estrogen-induced expression of the ovalbumin gene was not affected by the vitamin A deficiency, suggesting that estrogen-induced cytodifferentiation is not affected by vitamin A. To clarify the vitamin A action on estrogen-induced development in the oviduct, transcripts of nuclear estrogen receptor (ER) and all-trans-retinoic acid (RAR alpha, beta and gamma) receptors, which exert the effects of estrogen and vitamin A, were measured. The ER, RAR alpha and RAR beta genes, but not that of RAR gamma, were expressed during oviduct development, indicating that estrogen and vitamin A may control the expression of target genes through their cognate receptors. Thus, we have shown that vitamin A is involved in estrogen-induced cell proliferation but not in cytodifferentiation of the chicken oviduct.

Dissociation of the eyes in saccadic movement.

In horizontal saccades, abduction and adduction are not conjugate. Abduction starts shortly before adduction and reaches the turning point shortly after abduction. The duration in binocular recording is much shorter than in monocular recordings. The abducting eye has a tendency to move gradually on the new target. The adducting eye has, on the contrary, a tendency to overshoot. The characteristics of quick phases of horizontal optokinetic nystagmus, in which both eyes jump disconjugately to the new target, are similar to those of horizontal saccades. The main cause of this disparity may be a difference in neural mechanisms between abduction and adduction. Vertical saccades are not disconjugate.

Optokinetic nystagmus in artificial hemianopsy.

Optokinetic nystagmus in cases of artificial hemianopsy was studied. Hemianopsy was produced by using a combination of a projector, an erasing device and DC ENG. The effect of the condition of foveal vision in hemianopsy, whether reserved or involved, was discussed. When foveal vision was reserved, nystagmus during stimulation in cases of hemianopsy was essentially the same as in the normal eye. In cases of hemianopsy in which foveal vision was involved, there was a remarkable difference between the mystagmus induced by foveofugal stimulation and that induced by foveopetal stimulation. In the former case the nystagmus was very fine and irregular, in spite of the fact that the nystagmus was well induced (it was nearly the same as in the normal eye in the latter case). Foveal vision is very important for the formation of the slow component of optokinetic nystagmus. Foveopetal movement of the image on the peripheral retina is very important for the formation of the quick component. Foveofugal movement on the peripheral retinal has, on the contrary, only a small effect in attracting the eye.