Peripheral blood mononuclear cells from patients with chronic renal failure release factors which suppress erythropoietin secretion in vitro

Decreased production of erythropoietin (Epo) as a result ofreduced renal mass is considered the main factor underlyingthe anaemia that is invariably associated with chronic renalfailure (CRF). Other mechanisms such as accumulation of inhibitorsof Epo also contribute. In this study we show that supernatantfrom peripheral blood mononuclear cells (PBMC) cultured frompatients with CRF inhibits Epo release by Hep G2 cells in vitro.Ten patients (5 male) with CRF (mean age 42 years, range 25–60)were studied. Five were approaching end-stage renal failureand five were maintained on haemodialysis (HD). Ten apparentlyhealthy volunteers were used as controls. Full blood countsand serum Epo (RIA) levels were determined and adherent PBMCwere cultured for 48 h with and without LPS. There was a significantrise in TNF- and IL1-ß levels measured in monocytesupernatant (MS) from patients and controls after LPS stimulation(P<0.05) and in IL-l levels in patients (P<0.05). IL-1ßlevels were higher in patients compared to controls both beforeand after stimulation with LPS (P<0.05). Hep G2 cells werecultured in 5% CO₂ and 20% O₂ and incubated with MS from patientsand controls for 24 h. Hep G2 harvest fluids were then analysedfor Epo levels, which were expressed as a function of totalcell protein (mU/mg). Epo production was inhibited by MS frompatients compared to controlsboth before and after stimulationwith LPS (P<0.0001). There was, however, no direct correlationbetween the degree of Epo suppression and concentrations ofMS TNF-, IL-l, and IL-ß. Inhibition byspecific polyclonalanti-TNF- antibodies and anti-IL-ß antibodies didnot abrogate the inhibition ofEpo release by Hep G2 cells. Theseresults demonstrate that although PBMC from patients with CRFproduce factors that inhibit Hep G2 cell secretion of Epo invitro, this effect does not appear to be directly related tothe proinflammatory cytokines TNF-, IL-l, and IL-ß.     

Measuring handicap: the London Handicap Scale, a new outcome measure for chronic disease.

OBJECTIVE--To develop a handicap measurement scale in a self completion questionnaire format, with scale weights allowing quantification of handicap at an interval level of measurement. DESIGN--Adaptation of the International Classification of Impairments, Disabilities and handicaps into a practical questionnaire incorporating the dimensions of handicap mobility, occupation, physical independence, social integration, orientation, and economic self sufficiency and scale weights derived from interviews with a general population sample, with the technique of conjoint analysis. SETTING--Two general practices in different areas of London. SUBJECTS--240 adults aged 55-74 years randomly selected from the practices, 101 (42%) of whom agreed to be interviewed, and 79 (78%) of whom completed the exercise. MAIN MEASURES--Rating of severity of handicap associated with 30 hypothetical health scenarios on a visual analogue scale, from which was derived a matrix of scale weights ("part utilities") relating to different levels of disadvantage on each dimension, with a formula for combining them into an overall handicap score. Severity scores measured directly for five scenarios not used to derive the scale weights were compared with those calculated from the formula to validate the model. RESULTS--The part utilities obtained conformed with the expected hierarchy for each dimension, confirming the validity of the method. The measured severities and those calculated from the formula for the five scenarios used to validate the model agreed closely (Pearson's r = 0.98, p = 0.0009; Kendall's tau = 1.00, p = 0.007). CONCLUSIONS--This interval level handicap measurement scale will be useful in assessing both specific therapies and health services, in clinical trials, in analyses of cost effectiveness, and in assessments of quality assurance.     

Activity of the morpholino anthracycline 3′-deamino-3′-morpholino-13-deoxo-10-hydroxycarminomycin (MX2) against human tumor colony-forming unitsin vitro

Summary In several preclinical systems, the morpholino anthracycline MX2 has greater antitumor activity than doxorubicin, is less cardiotoxic, and is effective against multidrug resistant cancer cells. We used a human tumor soft-agar cloning assay to test the cytotoxicity of MX2 against single cell suspensions from freshly obtained human tumors. Tumor cells were exposed to MX2 at 0.05 and 0.5 g/ml either for 1 hour (201 specimens; 77 [38%] assessable) or continuously (231 specimens; 91 [39%] assessable). Superior antitumor activity was observed with continuous exposure (19%in vitro response at 0.05 g/ml and 69% at 0.5 g/ml) than with 1-hour exposure (1.3% at 0.05 g/ml and 12% at 0.5 g/ml). Activity was seen against all types of cancer tested including renal (91%), melanoma (88%), ovarian (73%), breast (71%) and non-small-cell lung (67%) cancer at a MX2 concentration of 0.5 g/ml after continuous exposure. If appropriate plasma levels can be achieved in patients, MX2 could have significant clinical activity in patients with those tumors.     

Effects of two anaesthetic regimes, MS-222 and eugenol, on plasma biochemical profile in Barbus sharpeyi

For choosing an anaesthetic agent for a particular purpose, the different properties has been notified such as the convenience for use, safety for the fish, humans and the environment, effectiveness, physiological disturbances and its cost. Invariably, in any study with clove oil, it has been regarded as an effective and acceptable alternative to other anaesthetics. The aim of the present study was to investigate effects of two anaesthetic regimes, MS-222 and eugenol, on plasma biochemical parameters in Barbus sharpeyi. B. sharpeyi fingerlings (mean weight, 5?g?±?1; mean length, 6?cm?±?1) were exposed to MS-222 (100?ppm) and eugenol (40?ppm) for induction of anaesthesia. Blood samples were taken to verify the effects of these anaesthetics on plasma biochemical parameters may use as an indicator of stress at time 0 (designated for each tank at the time of exposure to anaesthetic agent), 0.5, 1, 2 and 24?h after exposure by caudal severance. Plasma biochemical parameters concentrations were not significantly affected in B. sharpeyi (p?<?0.05). These results were expected because the trials were conducted in short-term exposures. Ion balance appears to be altered only in long-term stressing condition. Based on the results of this study, eugenol appears to be a safe anesthetic for use in B. sharpeyi.