Liver transplantation: patients' experiences

The Dutch orthotopic liver transplant programme was evaluated recently. This article focuses on the physical functioning, the pattern of activities, the social functioning and the level of wellbeing of 31 transplant patients. Data were generated by means of questionnaires and interviews. The majority of the patients look upon themselves as 'healthy'. Their physical potential has greatly improved. Three-quarters of the patient group think they are able to go back to work. However, from the interviews it appears that one third of the patient group suffered from more or less serious psychological problems following transplantation.     

In vitro modulation of cisplatin cytotoxicity by sparsomycin inhibition of protein synthesis

Inhibition of protein synthesis can alter cellular responsiveness to the classical anticancer drugs. The in vitro response of Chinese hamster ovary (CHO) cells to cisplatin with or without sparsomycin (Sm) was studied with the use of [3H]leucine and [methyl-3H]thymidine incorporation and clonogenic assay. Pretreatment of exponentially growing CHO cells with 1 microgram Sm/ml for 3 or 5 hours decreased [3H]leucine incorporation by 20% and resulted in significant resistance to cisplatin (P = .005). Sm in a concentration of 10 micrograms/ml reduced [3H]leucine and [methyl-3H]thymidine incorporation after 3 hours by 92 and 84%, respectively, and resulted in potentiation of the cisplatin cytotoxicity (P = .004). This effect was the same in the case of nonproliferating cells (P = .005), while protection due to Sm (1 microgram/ml) was seen only during cell proliferation. Simultaneous incubation and postincubation with Sm proved to have much less or no potentiating effect on cisplatin. The mechanisms of both protection and potentiation are still not clear, but our data indicate that Sm is a promising drug for further studies on the modulation of the cancer cell response to classical anticancer drugs.     

Recombinant human interferon alpha increases oestrogen receptor expression in human breast cancer cells (ZR-75-1) and sensitizes them to the anti-proliferative effects of tamoxifen

Exposure of ZR-75-1 human breast cancer cells for 48 h to human recombinant interferon alpha (IFN alpha) resulted in increased expression of oestrogen receptors as measured in a whole cell binding assay. This effect was inversely proportional to dose being significant following treatment with 10-100 IU IFN ml-1 and was only observed at a low initial cell plating density. The extent of the increase in oestrogen receptor levels ranged from 1.2- to 7.2-fold following treatment with 10 IU IFN ml-1. No increase in progesterone receptor expression was observed under the same experimental conditions. Concentrations of IFN which increased oestrogen receptor levels had no effect on cell proliferation. IFN (500 IU ml-1) inhibited cell proliferation and the combination of this treatment with tamoxifen (2 microM) had a greater anti-proliferative effect than either drug alone although there was no evidence of synergism. However, a 5-day pretreatment of cells with IFN (10 IU ml-1) markedly sensitised them to the growth-inhibiting effect of a subsequent 6-day exposure to tamoxifen.     

Lipid-drug conjugate nanoparticles of the hydrophilic drug diminazene-cytotoxicity testing and mouse serum adsorption.

Sleeping sickness is a widely distributed disease in great parts of Africa. It is caused by Trypanosoma brucei gambiense and rhodiense, transmitted by the Tse-Tse fly. After a hemolymphatic stage, the parasites enter the central nervous system where they cannot be reached by hydrophilic drugs. To potentially deliver the hydrophilic antitrypanosomal drug diminazene diaceturate to the brain of infected mice, the drug was formulated as lipid-drug conjugate (LDC) nanoparticles (NP) by combination with stearic- (SA) and oleic acid (OA). To estimate the in vivo compatibility, the particles were incubated with human granulocytes. Because as potential delivery mechanism the absorption of specific serum proteins (ApoE, Apo AI and Apo AIV) was found to be responsible for the delivery of nanoparticles to the brain, demonstrated using PBCA nanoparticles coated with polysorbate 80 (LDL uptake mechanism) the nanoparticles were incubated with mouse serum and the adsorption pattern was determined using the 2-D PAGE technique. As a result of this study, the cytotoxic potential was shown to decrease when diminazene is part of the particle matrix compared to pure fatty acid nanoparticles and the mouse serum protein adsorption pattern differs from the samples studied earlier in human serum. Especially, the fact concerning Apo-E that could be detected when the particles were incubated in human serum is absent after the mouse serum incubation, potentially, is a critical point for the delivery via the LDL-uptake mechanism but the data demonstrate that LDC nanoparticles, with 33% (wt/wt) drug loading capacity possess the potential to act as a delivery system for hydrophilic drugs like diminazene diaceturate and that further studies have to demonstrate the usability as a brain delivery system.     

Effect of short daily home haemodialysis on quality of life, cognitive functioning and the electroencephalogram.

BACKGROUND: End-stage renal disease patients have a poor quality of life (QoL), suffer from impaired cognitive functioning, and their electroencephalogram (EEG) shows abnormalities. Conventional haemodialysis (CHD) only partially restores these disorders. Short daily haemodialysis (SDHD) has been reported to improve QoL, but effects on cognitive functioning and EEG have yet to be described. METHODS: Of the 13 patients (11 male, 2 female, age 45.5 +/- 8.1 years), 11 completed the Kidney Disease Quality of Life and Affect Balance Scale questionnaires, 10 underwent neuropsychological testing, and all 13 underwent EEG examination. For the neuropsychological assessments, nine patients (six male, three female, age 45.4 +/- 12.6) who remained on the CHD schedule, served as controls. The dialysis schedule of thrice-a-week for 4 h was changed in the experimental group to six times a week for 2 h (SDHD) over a period of 6 months and back to thrice a week for 4 h. RESULTS: When on SDHD, patients rated several dimensions of health-related QoL as being improved. After resuming CHD, one of these dimensions again decreased and several others worsened even lower than baseline. Cognitive functioning did not change when compared with control data. On the EEG, alpha peak frequency increased slightly when on SDHD but decreased significantly after resuming CHD. CONCLUSIONS: SDHD improves health-related QoL, but has no clear effects on cognitive functioning and EEG. Resumption of CHD after SDHD decreases aspects of QoL and EEG alpha peak frequency but has no effect on cognitive functioning.     

The Effect of Anti-Tuftsin Antibody on the Phagocytosis of Bacteria by Human Neutrophils

Tuftsin (Thr-Lys-Pro-Arg) is a naturally occurring tetrapeptide which stimulates most known functions of the polymorphonuclear and mononuclear phagocytic cell lines. Although tuftsin is a well characterized bioactive peptide, the exact physiological role tuftsin plays remains unclear. Specific mouse anti-tuftsin antiserum generated in our laboratory, is now available for phagocytosis inhibition studies. Monolayers of human neutrophils were prepared on glass coverslips from a few drops of finger prick blood obtained from a single healthy donor. The monolayers were treated with and without mouse anti-tuftsin antiserum at dilutions of 1:1000 or 1:2000. Exogenous tuftsin (1 μg/ml) was also added with and without antibody. Treated and untreated neutrophils were subsequently incubated with unopsonized Staphylococcus aureus. The proportion of cells accomplishing phagocytosis (phagocytic index) and the number of bacteria engulfed per cell (avidity index) were recorded. The results showed that exogenous tuftsin increased phagocytosis while the addition of mouse anti-tuftsin antiserum at a 1:1000 dilution inhibited phagocytosis both with and without exogenous tuftsin. This effect was diminished by the antiserum at the 1:2000 dilution. This study reaffirms that tuftsin plays an important physiological role in phagocytosis.