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Biomedical subjects

E Peers

Publications and source records attributed to E Peers.

12 recordsLinked to original sources
PubMed1998

Reduction of the viral load of HIV-1 after the intraperitoneal administration of dextrin 2-sulphate in patients with AIDS.

OBJECTIVE: To determine the safety and efficacy of the sulphated polysaccharide, dextrin 2-sulphate, when delivered to the lymphatic circulation by the peritoneal route. DESIGN: An open Phase I/II dose-escalation clinical study in which six patients with AIDS were treated with seven courses of dextrin 2-sulphate each lasting 1 month. METHODS: During each course of treatment, the drug was administered daily for 28 days using an intraperitoneal catheter. Viral load was measured at frequent intervals using a plasma tissue culture infectious dose (TCID) assay, a cellular TCID assay, p24 antigenaemia, HIV-1 RNA and HIV-1 DNA. Plasma beta-chemokine levels were also measured. RESULTS: Dose escalation was completed without toxicity. A total of 7 patient-months of treatment were completed. With increasing doses of dextrin 2-sulphate, the infectious plasma viraemia, cellular viraemia and p24 antigenaemia all fell during the period of drug administration, but with no significant change in HIV-1 RNA. This was associated with increased plasma levels of macrophage inflammatory protein (MIP)-1alpha and MIP-1beta. Dextrin 2-sulphate accumulated in peritoneal macrophages and induced the release of MIP-1alpha and MIP-1beta from these cells in vitro. These beta-chemokines could have augmented the cell surface-mediated anti-HIV-1 effect of dextrin 2-sulphate in vivo by binding to and blocking the CC-chemokine receptor-5. A second fall in infectious plasma viraemia, cellular viraemia, p24 antigenaemia and HIV-1 RNA was seen at day 100 which was then sustained for several months. A clinical improvement in Kaposi's sarcoma was also seen. CONCLUSIONS: Our results suggest that the intraperitoneal administration of dextrin 2-sulphate can reduce the replication of HIV-1 in patients with AIDS. With increasing doses of dextrin 2-sulphate, the fall in viral load was seen during the period of drug administration and again 2 months after completing treatment.

AIDS-Related Opportunistic Infections↗
PubMed1998

Icodextrin provides long dwell peritoneal dialysis and maintenance of intraperitoneal volume.

Icodextrin 7.5% is an isosmolar solution for once-daily use in peritoneal dialysis for patients with end-stage renal failure (ESRF). It produces substantial ultrafiltration (UF), performing best over longer dwells of 8-12 h in continuous ambulatory peritoneal dialysis (CAPD) patients, and up to 16 h in automated peritoneal dialysis (APD) patients. Subsequent use in other clinical areas (ultrafiltration failure) and normal postmarketing clinical experience has established its tolerability and safety profiles; a small number of patients, including those with diabetes, have now received icodextrin for up to 6 years. Icodextrin's ability to maintain intraperitoneal volume over many hours has led to its undergoing development as an intraperitoneal drug delivery system for targeted regional delivery of anticancer drugs and lymphatic delivery of anti-HIV treatment. Isosmolar icodextrin 7.5% solution represents the first major advance in the treatment of ESRF by peritoneal dialysis since the development of CAPD using glucose-based solutions 20 years ago.

Dialysis Solutions↗
PubMed1997

Icodextrin instead of glucose during the daytime dwell in CCPD increases ultrafiltration and 24-h dialysate creatinine clearance.

BACKGROUND AND METHODS: Icodextrin 7.5% is an iso-osmolar, glucose polymer-containing peritoneal dialysis solution with an ultrafiltration potential similar to glucose 3.86%. We compared in an open, randomized, prospective study the ultrafiltration potential of icodextrin with that of glucose during the daytime dwell of 23 patients treated with automated peritoneal dialysis (CCPD). RESULTS: Daytime ultrafiltration volume and 24-h ultrafiltration volume increased significantly in icodextrin-treated patients (n = 11) at 3 and 6 months, allowing patients a less rigid fluid restriction or an adapted treatment schedule. This improved the patients' subjective well-being. Although ultrafiltration at 9 and 12 months also increased it did not reach statistical significance. Similar to the gain in ultrafiltration volume, 24-h dialysate creatinine clearance per 1.73 m2 (DCl/1.73 m2) and DCl/1.73 m2 per litre used dialysate (DCl/1.73 m2/l) increased in icodextrin-treated patients. DCl/1.73 m2/l per litre ultrafiltrate (DCl/1.73 m2/l/UF) did not increase. No side-effects of icodextrin were encountered, although serum disaccharide levels increased. CONCLUSION: Icodextrin enhances ultrafiltration during the daytime dwell in CCPD patients. As a result of an increased 24-h ultrafiltration volume, DCl/1.73 m2 and DCl/1.73 m2/l improve. DCl/1.73 m2/l/UF does not rise, which suggests that the increase in DCl/1.73 m2 and DCl/1.73 m2/l is caused by convective transport.

Creatinine↗
PubMed1994

A randomized multicenter clinical trial comparing isosmolar icodextrin with hyperosmolar glucose solutions in CAPD. MIDAS Study Group. Multicenter Investigation of Icodextrin in Ambulatory Peritoneal Dialysis.

The osmotic effectiveness of a large molecular weight glucose polymer fraction (Icodextrin) as a novel "colloid" osmotic agent in peritoneal dialysis was established, but the long-term safety remained undetermined. A randomized, controlled multicenter investigation of Icodextrin in ambulatory peritoneal dialysis (MIDAS) was undertaken to evaluate the long-term safety and efficacy by comparing daily overnight (8 to 12 hr dwell) use of isosmolar Icodextrin (282 mOsm/kg) with conventional 1.36% (346 mOsm/kg) and 3.86% (484 mOsm/kg) glucose exchanges over six months. Two hundred and nine patients were randomized from 11 centers, with 106 allocated to receive Icodextrin (D) and 103 to remain on glucose (control group; C); 138 patients completed the six month study (71 C, 67 D). All patients were divided into weak (1.36%) or strong (3.86%) subgroups based on their use of glucose solutions overnight during the pretreatment baseline period. The mean (+/- SEM) overnight ultrafiltration (UF) with D was 3.5 times greater than 1.36% glucose at eight hours [527 +/- 36 vs. 150 +/- 47 ml; 95% confidence interval (CI) for the difference +257 to +497 ml; P < 0.0001] and 5.5 times greater at 12 hours (561 +/- 44 vs. 101 +/- 48 ml, 95% CI for the difference +329 to +590; P < 0.0001) and no different from that of 3.86% glucose at eight hours (510 +/- 48 vs. 448 +/- 60 ml, 95% CI for the difference -102 to +226 ml; P = 0.44) and at 12 hours (552 +/- 44 vs. 414 +/- 78 ml, 95% CI for the difference -47 to +325 ml; P = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

A double-blind comparison of felodipine and hydrochlorothiazide added to metoprolol to control hypertension.

Seventy-six uncomplicated hypertensive patients treated in General Practice, whose seated diastolic blood pressure (Phase V) (dBP) remained greater than or equal to 95 mmHg after a minimum of 4 weeks treatment with metoprolol 50 mg b.i.d. as antihypertensive monotherapy, were randomized to receive the selective 'calcium antagonist' felodipine 5 mg b.i.d. or hydrochlorothiazide 12.5 mg b.i.d. in addition to metoprolol 50 mg b.i.d. The trial duration was 8 weeks, the dose of the felodipine or hydrochlorothiazide being doubled after 4 weeks if 'control' of BP (dBP less than 90 mmHg) was not achieved on the initial doses. Over the trial period of 8 weeks, felodipine reduced dBP from 102 to 85 mmHg and hydrochlorothiazide from 101 to 91 mmHg; the dBP reduction in the felodipine group was greater than that in the hydrochlorothiazide group (17 vs 9 mmHg) and the attained dBP lower in the felodipine group. About half of the patients in each group required the higher dose. Both regimes were effective and well tolerated. In the dosages used, felodipine was a slightly more effective antihypertensive drug than hydrochlorothiazide when added to metoprolol. There was no apparent difference in the tolerability of the two regimes.

Adult↗
PubMed1988

Felodipine, a new calcium antagonist, modifies exercise-induced asthma.

Recently, calcium antagonists have been reported to have a clinically beneficial effect in patients with asthma. Felodipine is a new calcium antagonist of the dihydropyridine group with a high selectivity for arteriolar smooth muscle; it is under clinical investigation for the treatment of hypertension. In this double-blind, randomized crossover trial in 9 patients, the effect of 10 mg felodipine in oral solution on exercise-induced asthma was compared with a placebo on separate days. The FEV1 was at least 80% of the predicted normal value, with variation between study days of less than 10%. Heart rate, blood pressure, and FEV1 were measured before and at 15 and 30 min after each treatment. The exercise test consisted of steady state running at submaximal work loads for 6 to 8 min and started at 30 min after treatments. FEV1 was measured at 1, 2, 5, 10, 15, and 30 min after the end of exercise. The predrug baseline FEV1 values were comparable on the 2 days of the study, and felodipine had no effect on the resting lung function. The mean percentage fall in FEV1 (SEM) after exercise with placebo was 27.0 (4.5)%, and with felodipine it was 13.5 (3.7)%. The difference between felodipine and placebo was statistically significant. While receiving felodipine, the resting heart rate was increased by 15%, with a tendency to lower systolic and diastolic blood pressures. The heart rate after exercise was higher during felodipine treatment than during placebo treatment. One patient receiving placebo and 7 receiving felodipine noted a transient headache. Two patients receiving felodipine also noticed lightheadedness after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Sizes of opioid receptor types in rat brain membranes.

The sizes of the receptors binding opiates and enkephalins in rat brain membranes were investigated by the radiation inactivation technique. By comparison with enzymes of known size added as internal standards, the mu and delta binding sites both gave a molecular weight of about 110000. Other opiate-binding components, which may include the kappa site, showed a much lower rate of inactivation when in reducing conditions, implying a subunit molecular weight of the order of 30000 for such a site.

Animals↗
PubMedDate not supplied

Specificity of the opioid affinity reagent, DALECK, in a set of isolated tissue assay systems.

The C-terminal chloromethyl ketone derivative of D-Ala2-Leu5-enkephalin (DALECK) has previously been shown to act as an affinity reagent at opioid receptors. The specificity of this derivative in its reversible interaction with functional opioid receptors has been examined here in a set of four field-stimulated isolated tissue preparations; the mouse, rat and rabbit vas deferens and the guinea pig ileum. Agonist potencies relative to selective reference agonists and Schild analysis were used to elucidate the overall activity of DALECK when interacting reversibly with opiate receptors under normal physiological conditions in the isolated tissue preparations. Under these conditions the ligand shows a very strong mu-selectivity. Data obtained in the guinea pig ileum suggest that DALECK is more potent than Tyr-D-Ala-Gly-N(CH3)Phe-Gly-ol (DAGO) when acting through mu-receptors. In contrast in the mouse vas deferens DALECK is at least 70-fold less potent than the delta-ligand D-Thr2-Leu5-enkephalin-Thr (DTLET). DALECK shows little interaction with kappa-receptors.

Amino Acid Chloromethyl Ketones↗
PubMedDate not supplied

Icodextrin: overview of clinical experience.

OBJECTIVE: To review all clinical studies and experience gained with icodextrin to date; primarily its use in peritoneal dialysis in patients with end-stage renal failure, but also its use as an intraperitoneal vehicle. DATA SOURCES: Peer-reviewed original research articles in the literature; abstracts from international scientific meetings; data generated from the compassionate use programme. STUDY SELECTION: All published studies to date are included, some 10-20 studies being included in this review. DATA EXTRACTION: Data have not been specifically extracted from studies; results have been described in the context of overall experience. RESULTS: Over ten years of clinical experience with icodextrin have now been accumulated, in both continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD). A small number of patients have received icodextrin for over five years, with no loss of effect. Icodextrin produces sustained ultrafiltration over long dwells while being iso-osmolar, by the process of colloid osmosis. CONCLUSIONS: Icodextrin represents the first viable alternative osmotic agent to glucose, for use in solutions for peritoneal dialysis. It also has a potential use as a vehicle solution for intraperitoneal drug delivery.

Dialysis Solutions↗