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I Colquhoun

Publications and source records attributed to I Colquhoun.

17 recordsLinked to original sources
PubMed2004

Unintended effects and their detection in genetically modified crops.

The commercialisation of GM crops in Europe is practically non-existent at the present time. The European Commission has instigated changes to the regulatory process to address the concerns of consumers and member states and to pave the way for removing the current moratorium. With regard to the safety of GM crops and products, the current risk assessment process pays particular attention to potential adverse effects on human and animal health and the environment. This document deals with the concept of unintended effects in GM crops and products, i.e. effects that go beyond that of the original modification and that might impact primarily on health. The document first deals with the potential for unintended effects caused by the processes of transgene insertion (DNA rearrangements) and makes comparisons with genetic recombination events and DNA rearrangements in traditional breeding. The document then focuses on the potential value of evolving "profiling" or "omics" technologies as non-targeted, unbiased approaches, to detect unintended effects. These technologies include metabolomics (parallel analysis of a range of primary and secondary metabolites), proteomics (analysis of polypeptide complement) and transcriptomics (parallel analysis of gene expression). The technologies are described, together with their current limitations. Importantly, the significance of unintended effects on consumer health are discussed and conclusions and recommendations presented on the various approaches outlined.

Animals↗
PubMed2004

Comparison of survival following coronary artery bypass grafting vs. percutaneous coronary intervention in diabetic and non-diabetic patients: retrospective cohort study of 6320 procedures.

AIM: To determine whether mortality following percutaneous coronary intervention vs. coronary bypass grafting varies according to whether or not patients have diabetes. METHODS: We used the Scottish Coronary Revascularization Register to identify all patients undergoing revascularization in Scottish NHS hospitals since 1997. We excluded single-vessel disease, left main stem stenosis, and bypass grafting performed at the same time as other operations. We used death certificate data from the Registrar General to identify all subsequent deaths. RESULTS: Of the 6320 eligible procedures, 5042 (80%) were bypass grafts and 1278 (20%) angioplasties. Overall 831 (13%) patients had diabetes with no significant difference by procedure (13% vs. 12%). A total of 382 deaths occurred over a mean follow-up of 2.3 years. Diabetic patients had a poorer prognosis following both surgery (adjusted hazards ratio (HR) 1.43, 95% confidence interval (CI) 1.08, 1.89) and percutaneous intervention (adjusted HR 2.58, 95% CI 1.43, 4.63). Among non-diabetic patients, no significant differences in mortality were detected between the two procedures. Among diabetic patients, no significant difference was detected in those with two-vessel disease. In those with impaired left ventricular function and triple-vessel disease, angioplasty was associated with a significantly higher risk of death (adjusted HR 3.58, 95% CI 1.40, 9.19). CONCLUSIONS: This is the first study to demonstrate statistically significant results that support the BARI trial findings. Our study demonstrated a significant difference for triple-vessel disease but not two-vessel disease. The former may be due to incomplete revascularization using percutaneous intervention. Our results require corroboration from randomized trials.

Aged↗
PubMed1999

Post-translational modification of nisin. The involvement of NisB in the dehydration process.

The lantibiotic nisin is an antimicrobial peptide produced by Lactococcus lactis. As with all lantibiotics, nisin contains a number of dehydro-residues and thioether amino acids that introduce five lanthionine rings into the target peptide. These atypical amino acids are introduced by post-translational modification of a ribosomally synthesized precursor peptide. In certain cases, the serine residue, at position 33 of nisin, does not undergo dehydration to Dha33. With native nisin this partially processed form represents about 10% of the total peptide, whereas with the engineered variants, [Trp30]nisin A and [Lys27,Lys31]nisin A, the proportion of peptide that escapes full processing was found to be to approximately 50%. This feature of nisin biosynthesis was exploited in an investigation of the role of the NisB protein in pre-nisin maturation. Manipulation of the level of NisB was achieved by cloning and overexpressing the plasmid-encoded nisB gene in a range of different nisin-producing strains. The resulting fourfold increase in the level of NisB significantly increased the efficiency of the dehydration reaction at Ser33. The final secreted product of biosynthesis by these strains was the homogenous form of the fully processed nisin (or nisin variant) molecule. The results presented represent the first experimental evidence for the direct involvement of the NisB protein in the maturation process of nisin.

Amino Acid Sequence↗
PubMed1998

Phase I trial of temozolomide using an extended continuous oral schedule.

Temozolomide, a methylating imidazotetrazinone, has antitumor activity against gliomas, malignant melanoma, and mycosis fungoides and is presently administered as a 5-day oral schedule every 4 weeks. This Phase I study aimed to determine the maximum tolerated dose of temozolomide administered as a single oral daily dose for a continuous 6- or 7-week period, evaluate the plasma pharmacokinetics on this schedule, and compare total plasma exposure over 7 weeks with the conventional 5-day regimen. Twenty-four patients with varying tumor types (17 of 24 gliomas) received temozolomide. All had clinically evaluable, refractory disease; normal renal, hepatic, and bone marrow function; and WHO performance status < or = 2. Temozolomide was administered at 50 mg/m2/day, increasing by 25 mg/m2/day/cohort until at 100 mg/m2/day grade 4 myelotoxicity forced dose reductions to 85 mg/m2/day, then 75 mg/m2/day. At 75 mg/m2/day the regimen was extended to 7 weeks, allowing the future potential combination with irradiation for primary gliomas. Patient responses (standard Union International Contre Cancer criteria; for gliomas objective response) and toxicity were assessed. Temozolomide plasma pharmacokinetics were determined on day 1 and at the beginning of the final week of administration (n = 5). The most frequent toxicities were myelosuppression and grades 1 and 2 nausea and vomiting. Grade 4 leucopenia and thrombocytopenia occurred in one of four patients receiving 100 mg/m2/day temozolomide and in one of seven patients receiving 85 mg/m2/day. These hematological toxicities did not exceed grade 2 in 10 patients receiving 75 mg/m2/day temozolomide. One of 4 malignant melanoma patients and 7 of 17 glioma patients (41%) demonstrated tumor responses. The overall response rate for this prolonged schedule was 33% (objective response, 7 of 24 patients; partial response, 1 of 24 patients); also, 6 of 17 glioma patients maintained SD. Peak plasma temozolomide concentrations were obtained 30-90 min after oral administration. Elimination in plasma was best described by a monoexponential equation with an elimination half-life of 96 +/- 16 min. No plasma accumulation of temozolomide occurred. Toxicity was greatest in higher dose cohorts, with a resultant maximum tolerated dose of 85 mg/m2/day, whereas lower dose cohorts tolerated the schedule well. The area under the temozolomide plasma versus time curve was noncumulative between the first and last week of the schedule. Temozolomide administration of 75 mg/m2/day over a 7-week period permits a 2.1-fold greater drug exposure/4 weeks in comparison with the 5-day schedule of 200 mg/m2/day repeated every 28 days. The overall response rate was 33% (glioma patients, 41% and a further 25% SD). Temozolomide (75 mg/m2/day) for 7 weeks is the recommended starting dose for further assessment of this schedule.

Administration, Oral↗
PubMed1997

Multicentre CRC phase II trial of temozolomide in recurrent or progressive high-grade glioma.

PURPOSE: Patients with progressive or recurrent supratentorial high-grade gliomas were entered into a multicentre phase II trial to evaluate the efficacy and toxicity of temozolomide. METHODS: The treatment schedule was 150-200 mg/m2 per day orally for 5 days repeated every 28 days. Response evaluation was by a combination of neurological status evaluation (MRC scale) and imaging. RESULTS: Of 103 eligible patients enrolled, 11 (11%) achieved an objective response and a further 48 (47%) had stable disease. The median response duration was 4.6 months. Response rates were similar for anaplastic astrocytomas (grade III) and glioblastoma multiforme (grade IV) tumours. Predictable myelosuppression was the major toxicity. CONCLUSIONS: The observation of objective responses and tolerable side effects in this heterogeneous population of patients supports the further investigation of this agent in high-grade gliomas.

Adult↗
PubMed1996

The Charing Cross Hospital experience with temozolomide in patients with gliomas.

Temozolomide, a new oral cytotoxic agent, was given to 75 patients with malignant gliomas. The schedule used was for the first course 150 mg/m2 per day for 5 days (i.e. total dose 750 mg/m2), escalating, if no significant myelosuppression was noted on day 22, to 200 mg/m2 per day for 5 days (i.e. total dose 1000 mg/m2) for subsequent courses at 4-week intervals. There were 27 patients with primary disease treated with two courses of temozolomide prior to their radiotherapy and 8 (30%) fulfilled the criteria for an objective response. There were 48 patients whose disease recurred after their initial surgery and radiotherapy and 12 (25%) fulfilled the criteria for an objective response. This gave an overall objective response rate of 20 (27%) out of 75 patients. Temozolomide was generally well tolerated, with little subjective toxicity and predictable myelosuppression. However, the responses induced with this schedule were of short duration and had relatively little impact on overall survival. In conclusion, temozolomide given in this schedule has activity against high grade glioma. However, studies evaluating chemotherapy in primary brain tumours should include a quality-of-life/performance status evaluation in addition to CT or MRI scanning assessment.

Adult↗
PubMed1996

Effects of colestipol alone and in combination with simvastatin on apolipoprotein B metabolism.

The effects of colestipol therapy alone (20 g/d) or combined with simvastatin (20 mg/d) were examined in a group of eight male patients with primary moderate hypercholesterolemia (total cholesterol > or = 6.5 mmol/L [> or = 250 mg/dL]) who had undergone coronary artery bypass grafting more than 3 months previously. Colestipol therapy decreased total cholesterol by 14% (P < .001) and LDL cholesterol (LDL-C) by 23% (P < .001), while dual therapy decreased total cholesterol by 38% and LDL-C by 52% (both P < .001 versus baseline). No significant changes were observed in plasma triglyceride, VLDL cholesterol, or HDL cholesterol levels. VLDL subfraction turnovers were conducted at baseline and again on each regimen. ApoB kinetic parameters derived from a multicompartmental model suggested that colestipol therapy resulted in an expansion of the total VLDL apoB pool (36%, P < .05) that was largely due to a fall in the clearance rate of VLDL1 apoB (49%), while the LDL apoB pool decreased 23% as a result of diminished direct LDL input. The model used also revealed that addition of simvastatin to the resin therapy caused increases in the fractional transfer rates of VLDL2 to IDL and IDL to LDL together with a 37% increment in the LDL apoB fractional catabolic rate. Compared with baseline, combined therapy generated falls in both IDL (35%, P = .01) and LDL (37%, P < .04) apoB pools due to enhanced clearance of IDL (214%, P < .03) and reduced total input of LDL (39%, P < .003).

Adult↗
PubMed1995

Charing Cross CT protocol for endoscopic sinus surgery.

The Charing Cross computerized tomography protocol for imaging the paranasal sinuses uses 2 mm thick slices with table increments of 8 mm: 10 to 12 coronal and two axial images are produced. These provide the necessary information for diagnosis of chronic rhinosinusitis and safe endoscopic sinus surgery. The technique is quicker and cheaper than previously described protocols and exposes the lens of the eye to less radiation.

Chronic Disease↗
PubMed1993

Pneumatization of the uncinate process.

We report one case of extensive and two of partial pneumatization of the uncinate process from a consecutive series of 250 CT scans of the paranasal sinuses. The CT findings are illustrated and the literature reviewed.

Air↗
PubMed1992

Audiological, vestibular and radiological abnormalities in Kallman's syndrome.

Kallman's syndrome is a multifaceted congenital disorder with predominantly endocrine abnormalities. We have characterized the associated mixed hearing loss and identified consistent radiological evidence of abnormal temporal bone anatomy. Abnormal labyrinthine morphology is accompanied by a complete absence of response to vestibular stimulation with caloric or rotational chair testing. The endocrine abnormalities are correctable and Kallman's syndrome is a diagnosis worthy of consideration when assessing children with congenital hearing loss.

Adult↗
PubMed1992

The assessment of carotid and vertebral arteries: a comparison of CFM duplex ultrasound with intravenous digital subtraction angiography.

The use of duplex ultrasound with colour flow mapping is compared with that of intravenous digital subtraction angiography (IVDSA) in the investigation of carotid and vertebral artery disease. Ninety-nine carotid and vertebral arteries were examined independently by IVDSA and ultrasound for location and degree of disease in 30 men (mean age 58) and 20 women (mean age 53). For purposes of comparison the carotid tree was divided into six segments. In 46% of cases no disease was detected by either modality. In 36% of cases where disease was found, ultrasound found mild disease in arteries reported as normal by IVDSA. Both modalities detected the six cases of total occlusion found in the study. IVDSA underestimated five cases of major disease found by ultrasound at the bifurcation or in the bulb. Overall agreement in grading vessel segments was good, with 74.5% in complete agreement and 90.3% grading stenoses to within +/- 25% of the other modality. There was good qualitative agreement in the findings for vertebral arteries. In four patients conventional arteriography was also available for comparison.

Adult↗
PubMed1991

Radiological evidence of sinus infection in patients with multiple sclerosis.

The prevalence of radiological criteria of chronic sinus infection was compared in 42 cases of clinically definite or laboratory supported definite multiple sclerosis and 84 controls. No increase in relative risk of multiple sclerosis associated with the presence of chronic sinus infection was observed (odds ratio 1.2, 95% CI 0.5 to 3.1). The maxillary sinus was infected more often than the other paranasal sinuses but there was no difference in the distribution of infection within the sinuses between cases and controls. These results do not confirm an earlier report of an association between chronic sinus infection and multiple sclerosis.

Adolescent↗
PubMed1989

Severe segmental narrowing of the spinal cord: an unusual finding in congenital spastic paraparesis.

A three-year-old boy is reported who had congenital spastic paraparesis caused by severe segmental narrowing of the spinal cord. X-rays of the spine showed thoracolumbar scoliosis and anomalies of the thoracic vertebrae from T5 to T11. Myelography, with CT scanning, demonstrated severe narrowing of the T5 to T12 segments of the spinal cord, measuring only 1.5 mm at T10. This is believed to be the first report of this unusual anatomical finding in congenital spastic paraparesis. An early embryonic vascular insult is thought to be the most likely cause.

Child, Preschool↗
PubMed1981

A lack of essential fatty acids as a possible cause of hyperactivity in children.

The Hyperactive Children's Support Group (HCSG) in an organisation with over 70 branches in Britain devoted to helping such children and their families. We have carried out a detailed survey of the characteristics of many of our children and their families and have studied the literature in detail. We have come to the conclusion that many of these children have a deficiency of essential fatty acids (EFAs) either because they cannot metabolise linoleic acid normally, or because they cannot absorb EFAs normally from the gut, or because their EFA requirements are higher than normal. The main pieces of evidence are: 1. Most of the food constituents which cause trouble in these children are weak inhibitors of the conversion of EFAs to prostaglandins (PGs). 2. Boys are much more commonly effected than girls and males are known to have much higher requirements for EFAs than females. 3. A high proportion of our children have abnormal thirst and thirst is one of the cardinal signs of EFA deficiency. 4. Many of our children have eczema, allergies and asthma which some reports suggest can be alleviated by EFAs. 5. Many of our children are deficient in zinc which is required for conversion of EFAs to PGs. 6. Some of of our children are badly affected by wheat and milk which are known to give rise to exorphins in the gut which can block conversion of EFAs to PGE1. A preliminary study of EFA supplementation in a number of our children has given promising results. We hope that others with better facilities will be encouraged to test out this hypothesis.

Alprostadil↗