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Biomedical subjects

C McCollum

Publications and source records attributed to C McCollum.

At least 55 records · Page 3Linked to original sources

Free radicals, antioxidants, and endothelial cell damage after percutaneous transluminal coronary angioplasty.

BACKGROUND: Oxygen-derived free radicals (ODFRs) and subsequent lipid peroxidation may be responsible for myocardial damage associated with ischaemia/reperfusion after percutaneous transluminal coronary angioplasty (PTCA). These potentially cytotoxic ODFRs are likely to be generated in the plasma, where the primary target organ or cell may be the endothelium. Some of these toxic effects may be limited by the action of antioxidant enzymes such as glutathione peroxidase (GPx). The aim of this study was to determine whether there was evidence of ODFR-mediated damage to the endothelium after PTCA and to examine the roles of lipid peroxides and GPx. METHODS: Serial samples of plasma were obtained at the time of catheter insertion, at the time of balloon inflation, 10 min after inflation, and 60 min after inflation, from 16 patients undergoing PTCA. We measured levels of von Willebrand factor (vWf, a specific product of the endothelium and a marker of damage), thiobarbituric acid reactive substances (TBARS, an indirect measure of the activity of ODFRs in peroxidizing lipoproteins), and the antioxidant GPx. RESULTS: There was a simultaneous peak in the levels of TBARS (P = 0.0096) with a fall in the levels of GPx (P = 0.004) 10 min after balloon deflation. Sixty min after balloon deflation, GPx levels were still reduced (P = 0.005) but there was a rise in levels of vWf (P = 0.038). CONCLUSIONS: Our interpretation of these data is that an early peak in ODFR activity associated with PTCA causes an endothelial injury 1 h after inflation. This may be related to the reduced ability of GPx to scavenge ODFRs.

Adult↗

Dialkylformamidine protected deoxyadenosine phosphoramidites in oligonucleotide synthesis.

A series of dialkylformamidine protected deoxyadenosine phosphoramidites were prepared for automated, solid-support DNA synthesis. The set of Abz, Gdmf, Cbz, T phosphoramidites gave high purity and high yield oligonucleotides, with rapid and complete deprotection at 65 degrees C in one hour. Different times and temperatures of exposure to concentrated ammonium hydroxide were examined to establish the optimum conditions for deprotection of oligonucleotides.

Amidines↗

Chemical synthesis of RNA using fast oligonucleotide deprotection chemistry.

The exocyclic amine protecting groups in oligonucleotide synthesis which require 8-16 hours at 55 degrees C for deprotection in ammonia have been replaced with more labile base protecting groups (dimethylformamidine for adenine and guanine and isobutyryl for cytosine). Using these fast oligonucleotide deprotecting groups which require 2-3 hours at 55 degrees C for complete deprotection, a new set of cyanoethyl phosphoramidite ribonucleoside monomers and supports has been developed. Ribozymes and substrate RNAs which were synthesized with these phosphoramidites were assayed and were found to have full catalytic (biological) activity.

Base Sequence↗

Fluorescent dye phosphoramidite labelling of oligonucleotides.

A series of fluorescein phosphoramidites (FAM) have been synthesized for use on automated DNA synthesizers. After coupling of the FAM reagents to the 5' hydroxyl of the oligonucleotide on the DNA synthesizer, the excess reagent is removed by washing the solid support. The dye, and its linkage to the oligonucleotide, are stable during the conditions of DNA synthesis and cleavage/deprotection conditions. Purification is attained with the OPC (Oligonucleotide Purification Cartridge), a polystyrene based affinity matrix, which selectively retains hydrophobic oligonucleotide conjugates. Analysis by MicroGel capillary electrophoresis effectively separates fluorescent dye labelled oligonucleotides from unlabelled products.

Base Sequence↗

PTFE or HUV for femoro-popliteal bypass: a multi-centre trial.

Despite wide clinical experience the choice between human umbilical vein (HUV) or polytetrafluoroethylene (PTFE) when the saphenous vein is inadequate remains unclear. In a multi-centre trial of 801 femoro-popliteal bypasses, autogenous vein could not be used in 252 (31%), of which 191 were randomised to either HUV or PTFE and started on aspirin 300 mg plus dipyridamole 150 mg (ASA + DPM) twice daily. Graft patency measured objectively by independent trial coordinators was expressed on an "intention to treat" basis by life table and analysed statistically by log rank and confidence intervals (95% CI). Overall, 101 grafts failed and cumulative patency was 53% (45-61%) at 3 years compared with 60% (55-65%) in 549 vein grafts. Prosthetic bypass patency above knee was 65% (55-75%); markedly better than 35% (23-47%) below knee (p less than 0.001) and comparable with 62% (55-69%) in 217 above knee saphenous vein grafts. Most failures occurred early at a rate of 52/1000 patient-months in the first 3 months (43/1000 for vein) falling to 21/1000 by 6 to 12 months and around 10/1000 subsequently. Randomisation produced comparable groups of 87 HUV and 104 PTFE grafts. Cumulative primary patency for HUV was 68, 63 and 57% at 1, 2 and 3 years, respectively compared with 61, 56 and 48% for PTFE with wide confidence intervals for the difference at 3 years (-20 to 38%, p = 0.27).(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial Occlusive Diseases↗

Antiplatelet drugs in femoropopliteal vein bypasses: a multicenter trial.

To evaluate the influence of antiplatelet drugs on patency in femoropopliteal vein bypasses, 48 vascular surgeons recruited 549 patients to a randomized double-blind trial of aspirin (300 mg) + dipyridamole (150 mg) or placebo twice daily starting 2 days before surgery and continuing indefinitely. Graft occlusion measured objectively by independent coordinators and cardiovascular events (myocardial infarction or stroke) were studied, expressed by life table, and analyzed statistically by log rank and confidence intervals (95% CI). Randomization achieved comparable groups with 60% of grafts inserted for rest pain or gangrene. Operative complications on aspirin plus dipyridamole included 18 reoperations for bleeding and 12 hematomas compared with 9 and 14, respectively, on placebo (NS). Most of the 172 graft failures occurred early with failure rates of 43/1000 patient-months in the first 3 months, reducing to 17/1000 at 6 to 12 months, and under 10/1000 in subsequent years. Cumulative graft patency on placebo was 72%, 62%, and 60% at 1, 2, and 3 years, respectively, compared with 78%, 70%, and 61% on aspirin plus dipyridamole. The difference in patency of 6.1% (95% CI, -3% to 15.5%) at 1 year and 8.0% (95% CI, -5% to 21%) at 2 years failed to achieve significance (p = 0.43). On mean follow-up of 34 months, 53 (132/1000 patient-years) cardiovascular events (myocardial infarction or cerebrovascular accident) occurred in patients on placebo compared with only 35 (73/1000) on aspirin plus dipyridamole, a significant difference of 59/1000 (p = 0.004). Antiplatelet therapy had little influence on femoropopliteal vein patency, but subsequent myocardial infarction and stroke was reduced in these patients with peripheral vascular disease.

Aspirin↗

Clinical trial of calcium alginate haemostatic swabs.

The influence of a new haemostatic material on surgical bleeding was evaluated in 100 patients who were prospectively randomized to either normal surgical gauze or calcium alginate swabs used throughout cholecystectomy (n = 40), simple mastectomy (n = 18) or inguinal hernia repair (n = 42). Overall, median (range) blood loss was 91 (3-329) ml for gauze and was significantly reduced by calcium alginate swabs to 72 (2-181) ml (P less than 0.05). Unexpectedly, operation times were also shortened from 45 (17-95) min for gauze to 35 (13-70) min with calcium alginate swabs (P less than 0.02). This reduction in blood loss and operating time was greatest for mastectomy, was still statistically significant for cholecystectomy, but was unimportant in inguinal hernia repair. Calcium alginate haemostatic swabs may become routine in major surgery, particularly where blood loss leads to the need for transfusion.

Alginates↗

The influence of smoking and plasma factors on prosthetic graft patency.

The effects of smoking and plasma risk factors on the patency of prosthetic femoro-popliteal bypass grafts were investigated in 93 patients entered into a multicentre trial of prosthetic graft materials (70 patients had patent grafts and 23 patients had occluded grafts 2 years after surgery). The smoking markers thiocyanate and fibrinogen were significantly higher in patients with occluded grafts, whereas LDL-cholesterol was significantly higher in patients with patent grafts 2 years after bypass. Based on smoking markers, graft patency in smokers was 57% at 2 years by life table, compared to 78% in non-smokers. P less than 0.05. Fibrinogen was an important variable, predicting graft occlusion with graft patency in patients with below median fibrinogen levels, being 84% at 2 years by life table compared to 51% in those with above median fibrinogen levels, P less than 0.025. Although increased levels of LDL-cholesterol have been associated with accelerated atherosclerosis, patients with above median levels of LDL-cholesterol had improved graft patency (83%) at 2 years compared to patency in patients with below median LDL-cholesterol (60%), P less than 0.05. The plasma risk factors associated with the failure of prosthetic grafts are similar to those associated with the failure of saphenous vein grafts, indicating that higher fibrinogen levels and smoking may contribute to an hypercoagulable state. Greater efforts are needed to stop patients smoking after vascular reconstruction.

Aged↗

New reagents and solid support for automated oligonucleotide synthesis.

The optimal system for the rapid, efficient, convenient, and economical synthesis and purification of synthetic oligonucleotides has been advancing. By recognizing the very rapid reaction kinetics and taking advantage of an efficient, low volume delivery system, cycle times have decreased to about 5.5 minutes, without compromising synthesis performance. A new set of base protecting groups for cyanoethylphosphoramidite nucleoside monomers have been developed, which decreases the post-synthesis time requirements. A particular form of polystyrene has also been developed as a solid support for automated oligonucleotide synthesis. Typical sequencing or PCR primers (20mers) now require less than 2 hours for synthesis and 2 hours for cleavage and deprotection.

Indicators and Reagents↗

The influence of prostaglandin E1 on systemic and pulmonary haemodynamics after aortic surgery.

The influence of a peroperative prostaglandin E1 (PGE1) infusion on systemic and pulmonary haemodynamics in a porcine model of aortic surgery was studied. Twenty-four pigs were randomised to PGE1 (100 ng/kg/min) or 0.9% Saline as placebo. Haemaccel was then infused to maintain a central venous pressure (CVP) of greater than 4 less than 6 mmHg and pulmonary artery wedge pressure (PAWP) of greater than 3 less than 5 mmHg. Standardised aortic surgery consisted of midline laparotomy, small bowel exteriorisation, 1.5 h aortic clamping and 1 h shock before resuscitation. Serial measurements of blood pressure (BP), cardiac output (CO), pulmonary vascular resistance (PVR), pulmonary shunt (A-V shunt), and arterial PO2 (PaO2) were recorded during and three days after surgery. Volume loading with Haemaccel prevented a significant fall in initial BP on PGE1 at 95.1 +/- 48 mmHg compared to 102 +/- 4.9 mmHg in control animals with similar CO in the two groups. Following release of the aortic clamp all animals became profoundly hypotensive with BP falling to 74.6 +/- 3.0 and 68.7 +/- 3.2 mmHg for PGE1 and placebo respectively, but CO was protected in those animals receiving PGE1 at 1.92 +/- 0.04 compared to 1.67 +/- 0.1 L/min/m2 on placebo and remained significantly higher following resuscitation and three days later (P less than 0.05). PGE1 also reduced the marked rise in pulmonary vascular resistance to 922 +/- 84 dynes-s/cm5/m2 during shock in control animals to only 555 +/- 30 (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗

Pinch skin grafting or porcine dermis in venous ulcers: a randomised clinical trial.

Chronic venous ulcers are common, and even with effective compression or elevation large ulcers may take months to heal. Pinch skin grafting may allow healing from epithelial islands throughout the surface area of the ulcer, and a prospective randomised trial was therefore conducted comparing this treatment with porcine dermis dressings. Most patients were treated as outpatients, 25 ulcers being randomised to treatment with pinch skin grafts and 28 to treatment with porcine dermis. Though the groups were well matched, the mean healing rate in the first week was 15 cm2 for pinch skin grafts compared with 3.5 cm2 with porcine dermis (p less than 0.02). By life table analysis 64% of ulcers treated by pinch grafts were healed at six weeks and 74% by 12 weeks compared with 29% and 46% of ulcers, respectively, treated with porcine dermis dressings (chi2 = 4.1; p less than 0.05). All ulcers that failed to heal within 12 weeks included an area posterior to the medial malleolus, where local compression may have been inadequate. Pinch skin grafting improves the rate of healing in large venous ulcers and is a simple technique that may be performed as an outpatient procedure under local anaesthesia.

Bandages↗

Indium-111-labelled leucocytes in the diagnosis of abdominal abscess.

The extensive morbidity and mortality of intra-abdominal abscess is mainly due to the delay in a diagnosis. The diagnostic accuracy of 111In-labelled mixed leucocytes with gamma imaging has been investigated in 100 consecutive patients including 34 following surgery and 36 with inflammatory bowel disease. White cell scans were performed 24 h following injection of autologous 111In-labelled leucocytes and were compared with clinical outcome where abscess was only diagnosed when pus either discharged or was drained at operation. Gamma images detected 28 of the 30 abscesses with no false positives giving 93 per cent sensitivity and 100 per cent specificity. Loculi of pus were identified in 11 of the 36 patients with inflammatory bowel disease with no errors in interpretation. Inflammation was reported in 15 of the remaining 25 patients with known but not necessarily active inflammatory bowel disease. 111In-labelled leucocyte imaging provides a rapid, safe and precise method for detecting intra-abdominal abscess even in the presence of inflammatory bowel disease.

Abscess↗