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Biomedical subjects

D Saltissi

Publications and source records attributed to D Saltissi.

At least 19 recordsLinked to original sources
PubMed2005

Dosing strategy for enoxaparin in patients with renal impairment presenting with acute coronary syndromes.

BACKGROUND: Phase III clinical studies have confirmed that enoxaparin is superior to standard heparin in reducing the rate of recurrent ischaemic events in patients with non-ST elevation acute coronary syndromes. Patients with moderate to severe renal impairment were, however, excluded from these studies. Due to the hydrophilic disposition of enoxaparin, accumulation is likely in patients with renal dysfunction, thereby increasing the risk of haemorrhagic complications if standard weight adjusted treatment doses are used. Arbitrary dose reduction has been reported to increase the risk of ischaemic events, presumably due to inadequate enoxaparin concentrations. AIM: The aims of this study were to investigate the influence of glomerular filtration rate (GFR) on the pharmacokinetics of subcutaneously administered enoxaparin, and to develop a practical dosing algorithm in renal impairment that can easily be used at the bedside. METHODS: Thirty-eight patients, median age 78 years (range 44-87), mean GFR 32 ml min(-1) (range 16-117) and mean weight 69 kg (range 32-95), presenting with acute coronary syndrome were recruited into the study. Approximately 10 anti-Xa concentrations were taken per patient over their period of therapy. A population pharmacokinetic model was developed using non linear mixed effects modelling techniques, utilizing the software NONMEM. Stochastic simulations were performed to identify the most suitable dosing regimen. RESULTS: Three hundred and thirteen anti-Xa concentrations were collected. A two compartment, first order input model was identified as the best baseline model. Covariates found to improve model fitting were GFR as a linear function on clearance (CL) and weight as a linear function on the central volume compartment (Vc). The fraction of drug excreted unchanged (Fu) was estimated at 71%. CL and Vc from the final covariate model were estimated as; CL (l h(-1)) = 0.681 per 4.8 l hr(-1) (GFR) + 0.229 Vc (l) = 5.22 per 80 kg (total body weight) CONCLUSIONS: Clearance of enoxaparin was predictably related to GFR estimated using the Cockroft and Gault equation, with ideal body weight used as the size descriptor. According to our model no dosage adjustment from the standard 1.0 mg kg(-1) 12 hourly is required for the first 48 h of treatment. Maintenance doses thereafter can be calculated using standard proportional adjustments based on Fu equal to 0.71.

Administration, Cutaneous↗
PubMed2001

Effect of lipid-lowering dietary recommendations on the nutritional intake and lipid profiles of chronic peritoneal dialysis and hemodialysis patients.

Patients with end-stage renal failure are a high-risk group for atherosclerotic cardiovascular disease and commonly have dyslipidemia as a major factor. Dietary manipulation is the recommended first line of therapy for reducing lipid levels in people with normal renal function; however, complex dietary requirements of dialysis-treated patients with end-stage renal failure impose significant constraints. In this study, we evaluated the effect of trying to comply with established lipid-lowering recommendations superimposed on our normally prescribed dialysis diet over 14 weeks in stable subjects treated with either hemodialysis (HD) or chronic peritoneal dialysis (PD). Of 306 dialysis patients screened, 75 subjects were enrolled; 8 subjects did not complete the study. In the remainder, HD subjects (n = 41) decreased saturated fat intakes by 18% overall and cholesterol intakes by 16%. This was associated with a decrease in total cholesterol levels from 232 +/- 8 to 209 +/- 4 mg/dL (mean +/- SEM; P = 0.007) and low-density lipoprotein cholesterol levels from 147 +/- 4 to 131 +/- 4 mg/dL (P = 0.009). However, energy intakes decreased by almost 10%. There were no statistically significant changes in PD patients (n = 26). Only 24.4% of HD (10 of 41 patients) and 15.4% of PD patients (4 of 26 patients) normalized their lipid levels. Considerable problems were encountered in maintaining compliance with the modified dialysis diets. This study shows that if adhered to, properly constructed dialysis diets are close to optimal lipid-lowering recommendations. Further dietary manipulation is difficult, leads to little benefit in the majority, and is accompanied by added problems of adherence. We conclude that the vast majority of dyslipidemic patients with end-stage renal failure require pharmacological therapy.

Body Mass Index↗
PubMed1999

A double-blind placebo controlled trial of simvastatin for the treatment of dyslipidaemia in renal allograft recipients.

BACKGROUND: With current techniques, renal failure patients are now able to regain near-normal health following renal transplantation. However, the development of premature cardiovascular disease is a major problem. Dyslipidaemia may be an important contributor to this. The use of lipid lowering agents in renal allograft recipients has been limited by potential interaction of these agents with the now widely used immunosuppressive agent, cyclosporine. AIM: This study was designed to investigate efficacy and safety of simvastatin in subjects taking either cyclosporine or azothioprine post renal transplantation. METHODS: Fifty-one subjects (32 females, 19 males -- mean age 51 +/- 12.5 yr) who were at least 1 yr post transplant, had creatinine < or = 2.5 mmol/L and a total cholesterol > or = 6 mmol/L were enrolled in a prospective, double-blind, placebo-controlled study. After an initial 10-wk dietary period, the last 4 wk on placebo, subjects were randomised to receive either 5 mg simvastatin/d for 6 wk followed by 10 mg simvastatin/d for 6 wk, or matching placebo. After this 12-wk double-blind phase, there was an open-label phase when all subjects were treated with 10 mg simvastatin/d for a period of 36 wk. RESULTS: Compared to placebo, 5 mg simvastatin/d significantly decreased total cholesterol by 20% (p < 0.01), low-density lipoprotein cholesterol (LDL cholesterol) by 29% (p < 0.01), and Apolipoprotein B (ApoB) by 26% (p < 0.01). Increasing simvastatin to 10 mg/d did not lead to further significant changes. But high-density lipoprotein cholesterol (HDL cholesterol) increased by 9% (p < 0.01) and Apolipoprotein A1 (ApoA1) by 7% (p < 0.01) only on 10 mg simvastatin/d. During the open-label phase, subjects previously randomised to placebo achieved similar significant changes to their lipoprotein profile. The benefits achieved from simvastatin were maintained to the end of the study. There were three withdrawals from the study, all from the simvastatin/ cyclosporine group. Two subjects had musculoskeletal pain and 1 had abdominal pain. Minor adverse events were similar in both the simvastatin- and placebo-treated groups. CONCLUSION: Low-dose simvastatin is an effective and well-tolerated agent in the treatment of dyslipidaemia in renal allograft recipients.

Adolescent↗
PubMed1999

Comparison of low-molecular-weight heparin (enoxaparin sodium) and standard unfractionated heparin for haemodialysis anticoagulation.

BACKGROUND: Low-molecular-weight heparin (LMWH) has been suggested as providing safe, efficient, convenient and possibly more cost-effective anticoagulation for haemodialysis (HD) than unfractionated heparin, with fewer side-effects and possible benefits on uraemic dyslipidaemia. METHODS: In this prospective, randomized, cross-over study we compared the safety, clinical efficacy and cost effectiveness of Clexane (enoxaparin sodium; Rhône-Poulenc Rorer) with unfractionated heparin in 36 chronic HD patients. They were randomly assigned to either Clexane (1 mg/kg body weight, equivalent to 100 IU) or standard heparin, and followed prospectively for 12 weeks (36 dialyses) before crossing over to the alternate therapy for a further 12 weeks. Heparin anticoagulation was monitored using activated coagulation times. RESULTS: Dialysis with Clexane resulted in less frequent minor fibrin/clot formation in the dialyser and lines than with heparin (P<0.001), but was accompanied by increased frequency of minor haemorrhage between dialyses (P<0.001). Clexane dose reduction (to a mean of 0.69 mg/kg) eliminated excess minor haemorrhage without increasing clotting frequencies. Mean vascular compression times were similar in both groups. Over 24 weeks, no changes in standard serum lipid profiles were observed. CONCLUSIONS: This study suggests that a single-dose protocol of Clexane is an effective and very convenient alternative to sodium heparin, but currently direct costs are about 16% more. We recommend an initial dose of 0.70 mg/kg.

Adult↗
PubMed1998

Goodpasture's syndrome associated with multiple sclerosis.

Multiple sclerosis (MS) has been reported to occur in association with other autoimmune diseases. Here we report the case of a woman with primary progressive MS who developed and died of Goodpasture's syndrome associated with anti-glomerular basement membrane antibodies. Of interest she had the human leukocyte antigen haplotype (DRB1*1501-DQA1*0102-DQB1*0602) most frequently associated with these two diseases; however, it is likely that other genes, particularly those involved with immunoregulation, also contributed to her susceptibility to these diseases. The association of MS and autoimmune renal disease may be more common than currently recognized.

Adult↗
PubMed1998

Comparative response to single or divided doses of parenteral iron for functional iron deficiency in hemodialysis patients receiving erythropoietin (EPO).

EPO treatment rapidly corrects anemia in patients with end-stage renal failure treated with hemodialysis, as long as sufficient iron is available. Absolute and relative (to demand) iron deficiency blunts the erythropoietic response and parenteral iron is frequently required during the course of therapy to restore EPO efficacy. Since the optimum time course of iron administration to restore EPO response in the short term is unknown, we compared three protocols of i.v. iron dextran administration in apparent functionally iron-deficient HD patients on oral iron therapy (hemoglobin < 10.0 g/dl plus ferritin < 100 micrograms/l and/or transferrin saturation < 20%). Intravenous iron (Imferon; Fisons Pty Ltd.) was given either as a single 600 mg dose (n = 15, Group I) or in divided doses of 100 mg administered on 6 successive dialyses (n = 14, Group II) or weekly for 6 weeks (n = 14, Group III). Response was monitored for 8 weeks. No adverse effects were observed. Collectively, mean hemoglobin increased (p < 0.01) by 0.4-0.5 g/dl plateauing at 4 weeks (between group comparison, p = 0.92). Mean ferritin concentrations changed with time (p < 0.01), peaking at 2 weeks in Groups I and II and at 4 weeks in Group III. Mean transferrin saturation levels also increased during the study (p < 0.001). The between group comparisons for the trends in iron indices were significant (p < 0.01 and 0.05 respectively). As there were no clinically significant differences in hemoglobin response at 4 weeks, single dose iron infusion would seem to be the most expedient in the short term, however frequent small doses are similarly effective.

Aged↗
PubMed1997

Oxidation of low density lipoprotein in hemodialysis patients: effect of dialysis and comparison with matched controls.

End stage renal failure is associated with lipoprotein abnormalities and a high prevalence of premature atherosclerosis. Oxidative modification of low density lipoprotein (LDL) may be promoted by hemodialysis increasing its atherogenicity. The oxidative status of LDL was therefore examined in female subjects before and after routine hemodialysis (HD; n = 10) and compared with women of similar age without significant renal disease (n = 19). There were no significant differences between the groups in the LDL fatty acid composition, or in the content of reactive amino acid groups (lysine) before or after exposure to Cu2+. The kinetics of LDL oxidation by Cu2+ showed no significant differences between the groups with respect to the lag time, the level of conjugated dienes before and after oxidation, or the maximal rate of oxidation during the propagation phase. No acute effects of HD were demonstrated. The present study provides no evidence that circulating LDL isolated from HD patients is more extensively modified or more susceptible to oxidation in vitro than gender-matched controls without renal failure.

Aged↗
PubMed1997

Simplified sizing of low-density lipoprotein using polyacrylamide gradient gel electrophoresis of plasma.

Low-density lipoprotein (LDL) particles can be separated into subfractions according to size by non-denaturing polyacrylamide gradient gel electrophoresis. Established research methods require specialised equipment and are frequently unsuited to the clinical laboratory. In this study, we utilised a colour flat bed scanner in conjunction with shareware image analysis software to compare LDL particle diameters of isolated LDL with LDL in whole plasma. LDL was isolated by ultracentrifugation and electrophoresed on 3-13% gels (Gradipore; Sydney, Australia) for 2400 Volt-hours in parallel with plasma and molecular size standards. Coomassie Blue-stained gels were scanned in reflexive mode using a colour flat-bed scanner and Adobe Photoshop 3.0 software. Density traces of each lane were obtained using NIH Image software (public domain, USA). LDL particle diameters were determined from calibration curves of the log of molecular diameter of standards against migration distance. There was a good correlation between LDL particle diameters obtained using isolated LDL and whole plasma (r = 0.87, P < 0.001; n = 22). However, the group means (+/- S.D.) (24.7 +/- 0.6 and 24.8 +/- 0.5 nm respectively) were statistically different on the paired t-test (P < 0.05). It is unclear whether this numerically small difference is due to alterations in LDL during the longer preparative procedures for LDL, or to matrix effects during electrophoresis of plasma samples. In conclusion, plasma samples stained with Coomassie Blue and scanned with a colour flat bed scanner can conveniently be used for LDL particle sizing by non-denaturing polyacrylamide gradient gel electrophoresis.

Adult↗
PubMed1992

Effect of dialyzer reprocessing with Renalin on serum beta-2-microglobulin and complement activation in hemodialysis patients.

The peracetic acid-based sterilant Renalin is increasingly being used for reprocessing hemodialyzers. In order to evaluate the effects of reprocessing on beta 2-microglobulin (beta 2M) kinetics and complement activation in chronic hemodialysis patients, we compared 4 dialyzer membranes on 1st, 2nd and 4th use of the membrane. Dialysis with new cuprammonium rayon dialyzers (0.8 m2) for 4 h resulted in a nonsignificant increase in serum beta 2M concentrations of 10.7% (corrected for changes in extracellular volume) and significant generation of the complement component C3a des Arg. On reuse, minimal changes in serum beta 2M levels were noted and complement activation was absent. Dialysis with new cellulose acetate (CA, 1.5 m2), polyacrylonitrile (AN69 HF, 1.6 m2) or polymethylmethacrylate (PMMA, 1.6 m2) membranes resulted in significant decreases in serum beta 2M levels (19.5, 31.7 and 50.8%, respectively). Reprocessing had negligible effects on the removal of beta 2M by CA and AN69, but by the 4th use halved the effectiveness of PMMA. Reprocessing reduced the significant generation of C3a des Arg observed with new CA and PMMA membranes. We conclude that, except for PMMA, Renalin reprocessing has minor effects on the ability of the membranes to remove beta 2M and improves the biocompatibility of all membranes studied.

Acetic Acid↗
PubMed1987

Survival of sub-optimal cadaver renal grafts with prolonged cold ischaemic times using cyclosporin.

Between September 1983 and December 1985, 33 cadaver kidneys with prolonged ischaemic times (mean 47.3 +/- 11.0 h), and frequently in problematic conditions, were received from Europe and transplanted into adults (16 male, 12 female, mean age 34 +/- 11 years) and children (2 male, 3 female, mean age 8.8 +/- 4.0 years), using cyclosporin (CsA) and steroid immunosuppression. Six patients have died (three with functioning grafts) and 12 grafts have been lost. Eighteen grafts remain functioning, with a mean survival of 27 months. The 1 year actuarial patient and graft survivals were 82% and 69% respectively. The mean time to cessation of haemodialysis was 17 +/- 10 days, and to stable graft function was 28 +/- 11 days. At 3 months (27 patients) mean serum creatinine was 191 +/- 88 mumol/l (2.16 +/- 1.0 mg/dl), with a mean CsA dose of 6.7 +/- 2.2 mg/kg per day. There was an association between the immediate post-transplant renographic perfusion index and the serum creatinine at 3 months (r = 0.52, P less than 0.01). At no stage did the serum creatinine correlate with CsA dose or length of ischaemic time. These results demonstrate that despite suboptimal conditions, prolonged cold ischaemic times, and periods of oliguria, cadaver kidney transplants may be managed successfully with CsA and low-dose steroids.

Actuarial Analysis↗
PubMed1985

Association of secondary hyperparathyroidism with red cell survival in chronic haemodialysis patients.

51Cr red cell mass (RCM), 51Cr red cell survival (RCS) and plasma parathyroid hormone (PTH) levels were measured in 27 stable chronic haemodialysis patients with a variable degree of clinical secondary hyperparathyroidism. Included were five patients who had had total parathyroidectomy. The results showed a strong negative correlation between PTH and RCS (r = -0.67, P less than 0.001) and a positive correlation between RCS and RCM (r = +0.53, P less than 0.005). However, the negative correlation between PTH and RCM was weak (r = -0.45, P less than 0.02). When the 13 patients with normal PTH levels (mean 0.18 +/- 0.12 microgram/l) were compared with the 14 patients with raised levels (mean 1.35 +/- 0.71 micrograms/l), there was a marked difference in RCS (P less than 0.005) but no difference in RCM.

Adult↗
PubMed1984

The hematological response to continuous ambulatory peritoneal dialysis.

Over the first three months of continuous ambulatory peritoneal dialysis (CAPD) the level of hemoglobin (Hb) rises significantly in most patients. To elucidate this further we studied the hematological response over 3 months of 8, previously non-transfused new patients treated with CAPD. Mean Hb rose by +2.78 g/dl (P less than 0.02). Mean RCM rose by 284 ml (37.7%) (P less than 0.05) and 3.7 ml/kg (29.6%) (P less than 0.05). PV fell relative to BW only, by -8.6 ml/kg (P less than 0.05). There was no significant change in serum vitamin B12 or folate concentrations or evidence of hemolysis. Plasma ferritin fell in all patients, but hematological changes of iron deficiency appeared in only one. Bio-assayable erythropoietin (EPO) levels were generally in the normal range, but inappropriately low for the degree of anemia. EPO did not change significantly apart from in two patients, one with polycystic disease. These results indicate that over the initial 3 months of therapy the majority of CAPD patients have a rise in Hb, due mainly to a rise in RCM, unrelated to changes in serum EPO level.

Adult↗