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Biomedical subjects

E A Brown

Publications and source records attributed to E A Brown.

At least 19 recordsLinked to original sources
PubMed2006

Impact of new dialysis solutions on peritonitis rates.

Peritonitis remains a major cause of morbidity among patients on peritoneal dialysis (PD), yet there is little information about the effect of new biocompatible dialysis solutions on peritonitis rates and treatment. In our unit, information on each peritonitis episode is prospectively collected. Since 2003, bicarbonate/lactate dialysate has been gradually introduced for new patients and for patients experiencing abdominal pain with conventional lactate solutions. From 2002 to 2005, data from 121 episodes of peritonitis (71 automated PD and 50 continuous ambulatory PD) were analyzed; 107 episodes occurred in patients using standard lactate dialysate and 14 episodes in patients using bicarbonate/lactate solution. Patients using bicarbonate/lactate had a significantly lower peritonitis rate of 1 per 52.5 patient-months compared to those using standard lactate dialysate (1 per 26.9 patient-months) (P=0.0179). Response to treatment, however, was not affected by the type of dialysate; cure rates (71.4 and 69.1%, respectively) and recurrence rates (21.4 and 15.8%, respectively) were not significantly different. Catheter removal was required in three (21.4%) patients using bicarbonate/lactate and 23 (22.4%) patients using lactate solution. Use of biocompatible dialysate appears to reduce the peritonitis rate by 50%, although this has to be confirmed in a randomized study. The type of dialysate, on the other hand, does not affect response to treatment.

Bicarbonates↗
PubMed2004

An FPGA-based approach to high-speed simulation of conductance-based neuron models.

The constant requirement for greater performance in neural model simulation has created the need for high-speed simulation platforms. We present a generalized, scalable field programmable gate array (FPGA)-based architecture for fast computation of neural models and focus on the steps involved in implementing a single-compartment and a two-compartment neuron model. Based on timing tests, it is shown that FPGAs can outperform traditional desktop computers in simulating these fairly simple models and would most likely provide even larger performance gains over computers in simulating more complex models. The potential of this method for improving neural modeling and dynamic clamping is discussed. In particular, it is believed that this approach could greatly speed up simulations of both highly complex single neuron models and networks of neurons. Additionally, our design is particularly well suited to automated parameter searches for tuning model behavior and to real-time simulation.

Animals↗
PubMed2001

Initial treatment of peritoneal dialysis peritonitis without vancomycin with a once-daily cefazolin-based regimen.

To reduce the use of vancomycin, the current recommendations of the International Society of Peritoneal Dialysis (PD) for the initial treatment of peritonitis complicating PD are to administer intraperitoneal (IP) cefazolin or cephalothin in every PD fluid bag, together with once-daily gentamicin. In view of the inherent impracticalities of this regimen, we studied the efficacy of once-daily cefazolin (1.5 g) IP with gentamicin IP as initial treatment for primary (nonrecurrent) PD peritonitis. This regimen has been used in all episodes of peritonitis not associated with tunnel or exit-site infections or fluid leaks. Sixty-nine episodes in 61 patients were analyzed (44 patients, continuous ambulatory PD; 22 patients, automated PD; and 3 patients, hospital-based intermittent PD), of which 38 episodes (55%) were gram-positive infections, 6 episodes (9%) were gram-negative infections, and 18 episodes (26%) had negative culture results. Four patients died within 4 weeks of infection (none considered attributable to inadequate treatment of their peritonitis). Ten catheters (14.5%) required removal to clear the infection; 7 catheters were in patients with gram-negative infections. The relapse rate within 4 weeks of ceasing antibiotic therapy was 8.9%. Compared with the results of 40 episodes of peritonitis treated initially with our previous IP vancomycin and gentamicin regimen, successful treatment (no death, catheter removal, or recurrence) was achieved in 52 of 69 episodes in the cefazolin group (75.4%) versus 23 of 40 episodes in the vancomycin group (57.5%; P: = 0.058). In conclusion, once-daily IP cefazolin and gentamicin for the initial treatment of PD peritonitis is at least as effective as a vancomycin-based regimen and is well tolerated.

Adult↗
PubMed2001

Adequacy targets can be met in anuric patients by automated peritoneal dialysis: baseline data from EAPOS.

OBJECTIVE: Conventional continuous ambulatory peritoneal dialysis (CAPD) in patients without residual renal function and with high solute transport is associated with worse clinical outcomes. Automated peritoneal dialysis (APD) has the potential to improve both solute clearance and ultrafiltration in these circumstances, but its efficacy as a treatment modality is unknown. The European Automated Peritoneal Dialysis Outcomes Study (EAPOS) is a 2-year, prospective, European multicenter study designed to determine APD feasibility and clinical outcomes in anuric patients. The present article describes the baseline data for patients recruited into the study. DESIGN: All PD patients treated in the participating centers were screened for inclusion criteria [urinary output < 100 mL/24 h, or residual renal function (RRF) < 1 mL/min, or both]. After enrollment, changes were made to the dialysis prescription to achieve a weekly creatinine clearance above 60 L per 1.73 m2 and an ultrafiltration rate above 750 mL in 24 hours. SETTING: The study is being conducted in 26 dialysis centers in 13 European countries. BASELINE DATA COLLECTION: The information collected includes patient demographics, dialysis prescription, achieved weekly creatinine clearance, and 24-hour ultrafiltration (UF). RESULTS: The study enrolled 177 anuric patients. Median dialysis duration before enrollment was 22.5 months (range: 0-285 months). Mean solute transport measured as the dialysate-to-plasma ratio of creatinine (D/P(Cr)) was 0.74 +/- 0.12. Patients received APD for a median of 9.0 hours overnight (range: 7-12 hours) using a median of 11.0 L of fluid (range: 6-28.75 L). Median daytime volume was 4.0 L (range: 0.0-9.0 L). Tidal dialysis was used in 26 patients, and icodextrin in 86 patients. At baseline, before treatment optimization, the weekly mean total creatinine clearance was 65.2 +/- 14.4 L/1.73 m2, with 105 patients (60%) achieving the target of more than 60 L/1.73 m2. At baseline, 81% of patients with high transport, 69% with high-average transport, and 40% with low-average transport met the target. At baseline, 70% of patients with a body surface area (BSA) below 1.7 m2, 60% with a BSA of 1.7-2.0 m2, and 56% with a BSA above 2.0 m2 achieved 60 L/1.73 m2 weekly. Median UF was 1090 mL/24 h, and 75% of patients achieved the UF target of more than 750 mL/24 h. CONCLUSION: This baseline analysis of anuric patients recruited into the EAPOS study demonstrates that a high proportion of anuric patients on APD can achieve dialysis and ultrafiltration targets using a variety of regimes. This 2-year follow-up study aims to optimize APD prescription to reach predefined clearance and ultrafiltration targets, and to observe the resulting clinical outcomes.

Adult↗
PubMed2000

Semi-allogeneic cell hybrids stimulate HIV-1 envelope-specific cytotoxic T lymphocytes.

OBJECTIVE: The present study was designed to determine whether the HLA allogeneic T helper response stimulated by semi-allogeneic cell lines could be used as an in vitro model of immune-based therapy to stimulate HIV-specific cytotoxic T lymphocytes. DESIGN AND METHODS: Semi-allogeneic cell hybrids were obtained by the fusion of peripheral blood mononuclear cells from HIV-infected patients with the allogeneic beta2-microglobulin-deficient FO1-12 melanoma cell line. These hybrids were used as antigen presenting cells for HIV envelope peptide (env)-specific cytotoxic assays. RESULTS: The hybrid cell lines express HLA class I and II antigens from both parental cells, as well as the CD86 costimulatory molecule. HIV-specific cytotoxic T lymphocyte activity was obtained when patients' peripheral blood mononuclear cells were costimulated with env peptides plus semi-allogeneic hybrids, in contrast with stimulation with either env or hybrid cells alone. Thus, the semi-allogeneic hybrids enhanced HIV-specific killing of target cells. CONCLUSIONS: Irradiated, semi-allogeneic cell hybrids engineered for individual AIDS patients provide efficient and simultaneous co-recognition of HLA allogeneic determinants and viral antigenic determinants presented by self-HLA molecules on the same antigen presenting cells and results in the generation of enhanced HIV-specific cytotoxic T lymphocyte activity.

HIV Envelope Protein gp120↗
PubMed2000

Is lipoprotein(a)-cholesterol a better predictor of vascular disease events than total lipoprotein(a) mass? A nested case control study from the West of Scotland Coronary Prevention Study.

The clinical utility of a new assay for plasma lipoprotein(a)-cholesterol (Lp(a)-C) was assessed in parallel with our routine Lp(a) mass measurements in a nested-case control study of subjects within the placebo arm of the West of Scotland Coronary Prevention Study (WOSCOPS). A total of 238 control patients and 108 patients who had suffered a serious vascular event during the course of the WOSCOPS were examined. Lp(a) mass was assessed within 2 years of sampling by an ELISA method on baseline EDTA plasma samples which had been stored at -70 degrees C. Subsequently, the Lp(a) mass was re-measured by an immunoturbidimetric assay approximately 8 years after sampling. On the same stored aliquot the Lp(a)-C was measured. These analyses allowed us to assess whether the Lp(a)-C assay could provide any additional information over and above that which would be obtained from our Lp(a) mass assays. In addition the apo(a) isoform sizes of these subjects were measured using a high resolution immunoblotting system. The Lp(a)-C and Lp(a) mass measurements provided exactly the same information in the study, as they were equally non-discriminatory between cases and controls. The only difference between the two patient groups was the percentage of 'null' apo(a) alleles (control: 25.6% versus cases: 19.4%). We conclude that these results reinforce the concordance of the two assay systems and confirm that the Lp(a)-C assay provides no added information over and above that gained from traditional Lp(a) mass assays, which may be faster and less expensive.

Case-Control Studies↗
PubMed2000

Analytical performance of the Genzyme LipoPro Lp(a) kit for plasma lipoprotein(a)-cholesterol assay.

The analytical performance of a new assay for plasma lipoprotein(a)-cholesterol (Lp[a]-C) was compared with that of our existing Lp(a) protein assay. The Lp(a)-C assay utilises lectin affinity chromatography to isolate intact Lp(a) particles. The effect of apo(a) isoform size on this system was assessed and found to be negligible. Plasma Lp(a) concentrations measured by both assays were in excellent accord in 24 subjects with Lp(a) protein concentrations ranging from 1-65 mg/dL (r2 = 0.916). Linearity of the Lp(a)-C assay system was excellent (r2 = 0.997) and within-run precision was 6.9% at an Lp(a)-C concentration of 0.3 mmol/L. Between-calibration precision was checked and proved to be 7.9%. The lectin-binding reagent used in the assay bound different sized apo(a) isoforms equally, and the recovery of Lp(a) from the reagent was, on average, 64%. We conclude that the Lp(a)-C assay system performs well but that further information is required on what new information, if any, the assay provides over traditional Lp(a) protein measurements by enzyme-linked immunosorbent assay (ELISA) or immunoturbidimetry.

Biomarkers↗
PubMed1999

Predictors of plasma lipoprotein(a) concentration in the West of Scotland Coronary Prevention Study cohort.

An elevated plasma lipoprotein(a) (Lp(a)) concentration is an independent risk factor for coronary heart disease (CHD). Plasma Lp(a) levels are believed to be predominantly controlled by the APO(a) gene, which encodes the apo(a) glycoprotein moiety of the Lp(a) particle. However, other parameters in the lipoprotein profile as well as co-existing disease states or personal traits have been proposed as co-varieties. In order to examine these potential controlling factors in greater detail than previously possible, 1760 unrelated Caucasian subjects were studied, from which were identified 907 with a single expressing APO(a) allele. This strategy was followed to obviate the difficulty in dealing with the co-expression of different apo(a) isoforms and the resulting compound plasma Lp(a) level. After cube-root transformation of the plasma Lp(a) levels to normalise their distribution, a series of correlates were computed. There was no good correlation between Lp(a) concentration and any other measured lipid or lipoprotein in the lipid profile or with any other variable examined, with the important exception of the length of the expressed apo(a) isoform (r = -0.491, P = 0.0001). We conclude that in this population the plasma Lp(a) concentration is not predicted by the plasma lipid profile, alcohol intake, or smoking status but is predicted, albeit incompletely, by the length polymorphism of the APO(a) gene.

Age Distribution↗
PubMed1999

A double-blind study comparing idazoxan and bupropion in bipolar depressed patients.

BACKGROUND: There is a small body of evidence indicating that idazoxan, a potent and selective alpha-2 antagonist, may be effective in treating bipolar depressive disorder. The purpose of this prospective controlled study is to compare idazoxan to bupropion, an antidepressant which has been suggested to have some advantages over other antidepressants in treating bipolar depressed patients. METHODS: Bipolar I depressed patients were randomly assigned in this 6-week double-blind out-patient study to receive either idazoxan, titrated to 240 mg/day and placebo bupropion, or bupropion, titrated to 450 mg/day and placebo idazoxan. These doses were achieved after 2 weeks. Depression severity was assessed with the Hamilton Depression Rating Scale and possible psychosis with the Brief Psychiatric Rating Scale. Side effects, heart rate, weight, and orthostatic blood pressure were also monitored. RESULTS: Fourteen patients completed this study (seven in each group). Both idazoxan and bupropion demonstrated significant improvement over time with reductions in Hamilton scores of 50%. LIMITATIONS: Limitations of this study include lack of a placebo group and small sample size. CONCLUSION: In light of our preliminary findings suggesting the usefulness of idazoxan in bipolar depression, larger more rigorous studies are indicated.

Adrenergic alpha-Antagonists↗
PubMed1998

Laser-cured fibrinogen glue to repair bleb leaks in rabbits.

OBJECTIVE: To determine whether laser-cured fibrinogen glue can close bleb leaks in rabbits. METHODS: Full-thickness filtration surgery with intraoperative mitomycin and a sutured limbus-based conjunctival flap was performed in 1 eye each of 19 New Zealand albino rabbits. On the second postoperative day, a 2- to 3-mm hole was made in the bleb. In 9 rabbits, the hole was glued using fibrinogen glue with indocyanine green dye added. The glue was "cured" with a diode laser. Eyes that had been glued and developed a subsequent leak had the glue reapplied on the day the leak was detected. RESULTS: The glue remained on the conjunctiva for an average (mean+/-SD) of 1.9+/-1.8 days (range, 0-5 days). The last day of bleb leak for the rabbits with glued eyes was 1.6+/-2.4 days; for the control rabbits, it was 8.0+/-4.4 days (P=.001, Mann-Whitney U test). CONCLUSION: Laser-cured fibrinogen glue is effective in closing bleb leaks in rabbits.

Animals↗
PubMed1998

Patients surviving more than 10 years on haemodialysis. The natural history of the complications of treatment.

BACKGROUND: The purpose of this survey was to describe the natural history of complications in 52 long-surviving haemodialysis patients to obtain a clearer picture of the impact these patients have on the dialysis population. This is important as they are often no longer suitable for transplantation and therefore are destined to remain on dialysis for the rest of their lives. METHODS: The patients who survived for more than 10 years on haemodialysis alone were studied. Information was obtained from patients' records and from the renal unit computer. RESULTS: Mean age at start of dialysis was 43 years and mean duration of HD 14.5 years. Renal failure was most commonly due to polycystic kidney disease or glomerulonephritis. Sixty-two per cent of patients developed cardiovascular disease, 78% complained of joint pains, 72% had a parathyroidectomy, and 50% developed carpal-tunnel syndrome. Two hundred and forty-five episodes of infection were recorded, 41% related to vascular access acquired in hospital or on immunosuppression. Only three infections occurred which could be described as opportunistic. Twelve patients were hepatitis C positive. In the 37 patients who have died, cardiovascular disease was the most common cause of death. Compared to other patients who started on dialysis before 1986 but who had a successful transplant the survival of patients on haemodialysis is much worse. CONCLUSION: Long-term survival on renal replacement therapy is dependent on successful transplantation. Complications, morbidity, and mortality are high after 10 years of dialysis.

Adult↗
PubMed1998

A pharmacokinetic study of occupational and environmental benzene exposure with regard to gender.

Using physiologically-based pharmacokinetic (PBPK) modeling, occupational, personal, and environmental benzene exposure scenarios are simulated for adult men and women. This research identifies differences in internal exposure due to physiological and biochemical gender differences. Physiological and chemical-specific model parameters were obtained from other studies reported in the literature and medical texts for the subjects of interest. Women were found to have a higher blood/air partition coefficient and maximum velocity of metabolism for benzene than men (the two most sensitive parameters affecting gender-specific differences). Additionally, women generally have a higher body fat percentage than men. These factors influence the internal exposure incurred by the subjects and should be considered when conducting a risk assessment. Results demonstrated that physicochemical gender differences result in women metabolizing 23-26% more benzene than men when subject to the same exposure scenario even though benzene blood concentration levels are generally higher in men. These results suggest that women may be at significantly higher risk for certain effects of benzene exposure. Thus, exposure standards based on data from male subjects may not be protective for the female population.

Adult↗
PubMed1998

Impact of apo(a) length polymorphism and the control of plasma Lp(a) concentrations: evidence for a threshold effect.

Plasma lipoprotein(a) [Lp(a)] levels are believed to be controlled predominantly by the apolipoprotein(a) [APO(a)] gene, which encodes the apo(a) glycoprotein, a key constituent of the Lp(a) particle. Previously, it has been accepted that the plasma Lp(a) level is inversely proportional to apo(a) length. To examine this relationship in greater detail, 1500 unrelated, homogeneous (sex, race, age, plasma lipids) subjects were studied, from which 769 were identified with a single-expressing APO(a) allele. A bimodal frequency distribution of apo(a) isoforms was observed. As expected, there was a general inverse relationship between apo(a) isoform size and Lp(a) level. However, when groups with equivalent single-expressing apo(a) isoforms were studied, it was clear that although smaller isoforms were associated on average with higher levels, they were also associated with the greatest variability in level. After logarithmic transformation of Lp(a) data, the overall contribution of the apo(a) length polymorphism was calculated to be 38%. However, in subjects with apo(a) isoforms of </=20 kringle-4 (K-4) repeats, only 9% of the variability in Lp(a) concentration is explicable on the basis of the apo(a) length polymorphism. In those with apo(a) isoforms of >20 K-4 repeats, the corresponding contribution is 10%. We conclude that the contribution of the apo(a) isoform size to the control of plasma Lp(a) level is considerably lower than previously calculated, because the variability in plasma Lp(a) concentration is not uniform across the apo(a) size spectrum.

Alleles↗
PubMed1998

Mechanism for elevated plasma lipoprotein(a) concentrations in patients on dialysis: turnover studies.

Plasma concentrations of lipoprotein (a) [Lp(a)] are increased in patients on renal replacement therapy. Lipoprotein (a) is increasingly being recognized as an independent cardiovascular risk factor. In an effort to explore the mechanism for elevation of Lp(a) in patients on dialysis we have performed turnover studies of Lp(a) with radioactive iodine. Lp(a) was isolated from 1 patient on hemodialysis (HD) and 1 patient on continuous ambulatory peritoneal dialysis (CAPD); the protein was labeled with 125I and returned to each patient. Lipoprotein (a) was subsequently isolated from the patients over a 15-day period and the decay of the specific radioactivity of Lp(a) was used to determine the fractional catabolic rate (FCR), which was 0.27 (pool/day) for the HD patient and 0.28 (pool/day) for the CAPD patient. These rates are indistinguishable from those measured in 4 patients with hypercholesterolemia (0.29, SEM = 0.01) and in 4 other familial hypercholesterolemic patients (0.29, SEM = 0.02) studied previously using the same method by Knight et al. (7). We found no difference in the FCR of patients on dialysis when compared to patients with hyperlipidemia and normal renal function. Increased plasma concentration of Lp(a) in our patients on renal replacement therapy is not due to decreased catabolism, but is caused by increased synthesis.

Adult↗