Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in liver transplant patients presenting gastrointestinal disorders: a pilot study.

Gastrointestinal (GI) disorders are one of the main adverse events in patients treated by mycophenolic acid (MPA). The aim of this prospective study was to evaluate the effect of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) in liver transplant patients presenting GI side-effects Since January 2003, stable liver transplant patients receiving MMF and presenting GI disorders, without evidence of other origin than MMF were enrolled. Conversion was performed without a washout period at an equimolar daily dosage. Thirty-six patients were included after a median delay of 45 months after liver transplantation (LT) (16 women and 20 men, median age of 47 years). Diarrhoea was the main clinical symptom (n = 28, 77.7%). At the time of inclusion, patients were treated with MMF since 18 months (range 3-28) and GI disorders were known for 9 months (range 3-12). After a median follow-up of 12 months after conversion, GI disorders were resolved in 20 patients (55%), improved in 6 patients (17%) and not modified or worsened in 10 patients (28%). Our results strongly suggest that conversion from MMF to EC-MPS in liver transplant patients can improve gastrointestinal disorders in a majority of the patients, and therefore might be considered as the best therapeutic option.     

Leptin, lipid and lipid metabolism-related hormones in chronic renal failure in Arabia

SUMMARY: In patients with chronic renal failure (CRF), hyperleptinaemia has been widely reported, but the exact mechanisms leading to elevated leptin levels are unclear. Impaired renal clearance of leptin and the influence of other hormones may be important. In this study, we measured serum leptin levels in 150 patients on haemodialysis, peritoneal dialysis or in the predialysis phase of CRF. Furthermore, we measured plasma levels of insulin, growth hormone (GH) and insulin-like growth factor 1 (IGF-1), as well as plasma levels of triacylglycerols and total low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol. We observed significantly elevated levels of leptin, particularly in female patients, and leptin was shown to correlate significantly with insulin, total and LDL-cholesterol and log triacylglycerols. Leptin was inversely correlated with GH concentrations, but was not correlated with IGF-1 levels. Despite the multiple correlations established between leptin levels and other variables, only hyperinsulinaemia in CRF seems to be important as a determinator of leptin levels.     

Human placental glutathione transport mechanism

The placental transport mechanism of glutathione (GSH) was investigated using microvillous membrane vesicles prepared from human term placenta. Using (3H-glycine)-labeled-GSH, it was clarified that GSH in the extravesicular compartment of placental microvillous membranes was rapidly degraded by gamma-GTP (gamma-glutamyltranspeptidase) and resulting amino acid, and 3H-labeled-glycine was actively transported via a sodium cotransport system. AT-125 treated microvillous membrane vesicles almost entirely lost its gamma-GTP activity, and showed intact GSH transport. Using AT-125 treated microvillous membrane vesicles, it was revealed that GSH was transported across the microvillous membrane as an anion via a membrane potential-dependent mechanism. These results indicated that gamma-GTP which existed in microvillous membrane played a role in GSH metabolism and that intracellular GSH was translocated out of the syncythiotrophoblast cell into the maternal blood space via a specific carrier in microvillous membrane because the GSH concentration was higher in intracellular than extracellular and extracellular membrane potential was positively charged.     

Permanent access to the portal system for cellular transplantation using an implantable port device.

A novel application of the implantable Port-a-Cath (PAC) system is described in the context of cellular transplantation. A silicone catheter was inserted in a collateral branch of the portal vein and connected to a port device positioned subcutaneously on the left thoracic cage. This permanent vascular access allowed iterative intraportal infusions of allogenic hepatocytes without the need of repeated transhepatic catheterization of the portal vein. Using this technique, repeated infusions of cryopreserved and / or fresh hepatocytes were successfully carried out in 3 children with inborn errors of liver metabolism, with the aim of progressively providing a sufficient mass of transplanted liver cells to stabilize the metabolic condition of the patients. We suggest that this technique might also be valuable in pancreatic islet cell transplantation.     

Maternal orbital hematoma associated with labor

We examined two women with orbital hematomas that occurred during labor. Both women developed sudden diplopia, proptosis, and orbital pain. The location of the hematoma was confirmed by orbital echography and computed tomography. The patients were observed without surgical intervention. Neither patient developed clinical or echographic signs of compressive optic neuropathy. Clinical resolution occurred during the following two weeks. Serial standardized orbital echographic examinations documented resolution of the hematomas.     

The role of glutathione on placental amino acid transport (using microvillous membrane vesicles)

To elucidate the role of glutathione (GSH) on placental amino acid transport, we investigated L-lysine transport using microvillous membrane vesicles prepared from full term human placenta. 1. The transport of L-lysine into microvillous membrane vesicles was not affected by glutathione. 2. The transport of L-lysine into microvillous membrane vesicles was inhibited by inorganic mercury (Hg2+), and 0.1mM Hg2+ inhibited 34% of this transport and 1mM Hg2+ inhibited 50%. 3. The transport of L-lysine inhibited by Hg2+ was almost completely restored when glutathione was added simultaneously. These results indicated that glutathione defended the inhibitory action of inorganic mercury on L-lysine transport across microvillous membrane.     

Evaluation of nicotine,cotinine, thiocyanate,carboxyhemoglobin, and expired carbon monoxide as biochemical tobacco smoke uptake parameters

Summary In a cross-sectional study on 236 individuals in Japan (174 males, 62 females; 149 smokers, 87 non-smokers) plasma nicotine (pnic), cotinine (pcot) and thiocyanate (pSCN), urinary creatinine ratios of nicotine (unic), cotinine (ucot) and thiocyanate (uSCN) as well as carboxyhemoglobin (COHb) and expired carbon monoxide (COex) were determined. All tobacco smoke uptake parameters (TSUP) were significantly elevated in smokers as compared to non-smokers. The discriminant power (smokers vs non-smokers) rank in the following order: ucot pcot unic > pSCN COHb pnic > COex uSCN. All parameters except for pnic are significantly correlated with the self-reported number of cigarettes smoked per day. The reason for the poor correlation of pnic with daily cigarette consumption is the short half-life of pnic coupled with the arbitrary time of blood drawing in relation to the last time of smoking.Dr. Muranaka, the chief author of this paper, was the director of our hospital. He died suddenly on 18 April 1986. This article is therefore the last monument to be planned and achieved under the late Dr. Muranaka's direction.     

Foscarnet salvage therapy efficacy is associated with the presence of thymidine-associated mutations (TAMs) in HIV-infected patients

BACKGROUND: Salvage therapy based on foscarnet plus a thymidine analog is effective in patients with advanced-stage HIV disease and viruses harbouring multiple drug-resistance mutations. OBJECTIVE: To identify viral genetic determinants associated with the virological efficacy of foscarnet salvage therapy. STUDY DESIGN: Thirteen patients received foscarnet at a fixed dose of 80mg/kg twice daily for 14 days, in combination with zidovudine or stavudine. RESULTS: The baseline median HIV viral load and CD4 cell count were 5.10log(10)copies/ml and 23cells/mm(3), respectively. Following foscarnet therapy, viral load fell by a median of 1.84log(10)copies/ml (range: -0.29 to -2.82), and by at least 1log(10)copies/ml in 11 patients, all of whom harboured viruses with at least three thymidine-associated mutations (TAMs). The two patients with smaller declines in viral load (<0.50log(10)copies/ml) harboured viruses with only one or zero TAMs. CONCLUSIONS: These findings corroborate, in vivo, the impact of TAMs on HIV susceptibility to foscarnet. The virological response to foscarnet salvage therapy in multiclass-experienced patients may thus differ according to the number of TAMs.