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Biomedical subjects

S E Cole

Publications and source records attributed to S E Cole.

At least 19 recordsLinked to original sources
PubMed2003

Almonds vs complex carbohydrates in a weight reduction program.

OBJECTIVE: To evaluate the effect of an almond-enriched (high monounsaturated fat, MUFA) or complex carbohydrate-enriched (high carbohydrate) formula-based low-calorie diet (LCD) on anthropometric, body composition and metabolic parameters in a weight reduction program. DESIGN: A randomized, prospective 24-week trial in a free-living population evaluating two distinct macronutrient interventions on obesity and metabolic syndrome-related parameters during weight reduction. SUBJECTS: In total, 65 overweight and obese adults (age: 27-79 y, body mass index (BMI): 27-55 kg/m(2)). INTERVENTION: A formula-based LCD enriched with 84 g/day of almonds (almond-LCD; 39% total fat, 25% MUFA and 32% carbohydrate as percent of dietary energy) or self-selected complex carbohydrates (CHO-LCD; 18% total fat, 5% MUFA and 53% carbohydrate as percent of dietary energy) featuring equivalent calories and protein. MAIN OUTCOME MEASUREMENTS: Various anthropometric, body composition and metabolic parameters at baseline, during and after 24 weeks of dietary intervention. RESULTS: LCD supplementation with almonds, in contrast to complex carbohydrates, was associated with greater reductions in weight/BMI (-18 vs -11%), waist circumference (WC) (-14 vs -9%), fat mass (FM) (-30 vs -20%), total body water (-8 vs -1%) and systolic blood pressure (-11 vs 0%), P=0.0001-0.05. A 62% greater reduction in weight/BMI, 50% greater reduction in WC and 56% greater reduction in FM were observed in the almond-LCD as compared to the CHO-LCD intervention. Ketone levels increased only in the almond-LCD group (+260 vs 0%, P<0.02). High-density lipoprotein cholesterol (HDL-C) increased in the CHO-LCD group and decreased in the almond-LCD group (+15 vs -6%, P=0.05). Glucose, insulin, diastolic blood pressure, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and LDL-C to HDL-C ratio decreased significantly to a similar extent in both dietary interventions. Homeostasis model analysis of insulin resistance (HOMA-IR) decreased in both study groups over time (almond-LCD: -66% and CHO-LCD: -35%, P<0.0001). Among subjects with type 2 diabetes, diabetes medication reductions were sustained or further reduced in a greater proportion of almond-LCD as compared to CHO-LCD subjects (96 vs 50%, respectively) [correction]. CONCLUSION: Our findings suggest that an almond-enriched LCD improves a preponderance of the abnormalities associated with the metabolic syndrome. Both dietary interventions were effective in decreasing body weight beyond the weight loss observed during long-term pharmacological interventions; however, the almond-LCD group experienced a sustained and greater weight reduction for the duration of the 24-week intervention. Almond supplementation of a formula-based LCD is a novel alternative to self-selected complex carbohydrates and has a potential role in reducing the public health implications of obesity.

Adult↗
PubMed2002

Overexpression of S100beta in transgenic mice does not protect from serotonergic denervation induced by 5,7-dihydroxytryptamine.

Transgenic mice overexpressing S100beta were used to examine whether the chronic elevation of this protein alters the response to selective partial serotonergic lesions produced by bilateral intracerebroventricular injections of 5,7-dihydroxytryptamine (5,7-DHT). Basal levels of S100beta mRNA examined by in situ hybridization were two- to threefold higher throughout the brain in transgenic than in control mice, whereas 5-HT levels in forebrain were similar in both. After the 5,7-DHT-induced lesions, no differences were found in the S100beta mRNA levels in either normal or transgenic mice. At 5 and 60 days after the lesion, forebrain 5-HT levels were reduced by 56% and 35%, respectively, in control mice and by 51% and 35%, respectively, in the transgenic mice. Analysis of the 5-HT immunostaining showed a marked decrease of the immunoreactivity in various brain regions, which was comparable at the two intervals postlesion. One exception was the medial hypothalamus, where an almost complete disappearance of 5-HT immunoreactivity was observed in the medial region at 5 days after lesion, followed by a marked reinnervation 60 days later. These hypothalamic changes were seen in both controls and S100beta-overexpressing transgenic mice. Quantitative analysis of the density of 5-HT transporter sites using [(3)H]citalopram binding, a marker of serotonergic terminals, showed a marked decrease in different brain regions at both 5 and 60 days after 5,7-DHT injections. No difference in basal and postlesion levels of [(3)H]citalopram binding was seen between transgenic and control mice. In conclusion, this study demonstrates that constitutive overexpression of S100beta in transgenic mice does not modify serotonin levels during development, nor does it protect the serotonergic neurons from selective neurotoxicity or modify the serotonergic sprouting induced by partial lesion.

5,7-Dihydroxytryptamine↗
PubMed1999

High-resolution comparative physical mapping of mouse chromosome 10 in the region of homology with human chromosome 21.

Comparative mapping of human and mouse chromosomes can be used to predict locations of homologous loci between the species, provides the substrate to examine the process of chromosomal evolution, and facilitates the continuing development of mouse genetic models for human disorders. A YAC contig of the region of mouse Chromosome (Chr) 10 (MMU10) that demonstrates conserved linkage with the distal portion of human Chr 21 (HSA21) has been constructed. The contig contains all known genes mapped in both species, defines the proximal region of homology between MMU10 and HSA22, and contains the evolutionary junction between HSA21 and HSA22 on MMU10. It consists of 23 YACs and 2 PACs, and covers 3.2 Mb of MMU10. The average marker density for this region is 1 marker/69 kb. Nine of 22 expressed sequences are mapped here for the first time in mouse, and two are newly characterized expressed sequences. The contig also contains 12 simple sequence repeats (SSRs) and 16 YAC and PAC endclone markers. YAC fragmentation analysis was used to create a physical map for the proximal 2.2 Mb of the contig. Cloning of the corresponding region of HSA21 has proven difficult, and the mouse contig includes segments absent from previously described sequence ready maps of HSA21.

Animals↗
PubMed1999

Perfect conserved linkage across the entire mouse chromosome 10 region homologous to human chromosome 21.

The distal end of human Chromosome (HSA) 21 from PDXK to the telomere shows perfect conserved linkage with mouse Chromosome (MMU) 10. This region is bounded on the proximal side by a segment of homology to HSA22q11.2, and on the distal side by a region of homology with HSA19p13.1. A high-resolution PAC-based physical map is described that spans 2.8 Mb, including the entire 2.1 Mb from Pdxk to Prmt2 corresponding to HSA21. Thirty-four expressed sequences are mapped, three of which were not mapped previously in any species and nine more that are mapped in mouse for the first time. These genes confirm and extend the conserved linkage between MMU10 and HSA21. The ordered PACs and dense STS map provide a clone resource for biological experiments, for rapid and accurate mapping, and for genomic sequencing. The new genes identified here may be involved in Down syndrome (DS) or in several genetic diseases that map to this conserved region of HSA21.

Animals↗
PubMed1998

A cluster of keratin-associated proteins on mouse chromosome 10 in the region of conserved linkage with human chromosome 21.

A gene cluster of three to five high-cysteine keratin-associated proteins (KAPs) has been identified on mouse Chromosome 10 (MMU10) in the region of conserved linkage with human chromosome 21 (HSA21). One of these genes, Krtap12-1, has been sequenced in its entirety and shown to be an intronless gene encoding a predicted 130-amino-acid protein. Krtap12-1 is most closely related to two previously identified KAP4 genes, but variation in sequence and cysteine content suggests that it represents a new KAP family. Krtap12-1 is expressed in the skin of a 3-day-old mouse. The corresponding region of HSA21, between ITGB2 (integrin beta2) and PFKL (the liver isoform of phosphofructokinase), has proven refractory to cloning, and thus mapping of this region at high resolution has been problematic. Based on the KAP gene cluster position in mouse, evidence has been found for an orthologous human KAP cluster on HSA21q22.3, reinforcing the observation that comparative genomics can play an essential and practical role in determining mammalian genome organization.

Amino Acid Sequence↗
PubMed1998

Physical mapping of the evolutionary boundary between human chromosomes 21 and 22 on mouse chromosome 10.

Adjacent regions of mouse Chromosome 10 (MMU10) show conserved synteny with human chromosome 22 (HSA22) and the telomeric region of HSA21. Physical mapping on MMU10 using YAC fragmentation and PAC contig analyses demonstrates that Prmt2 has a position consistent with its human homolog, HRMT1L1, being telomeric to S100B on HSA21. This result establishes Prmt2 as the new proximal boundary of the region of conserved synteny between MMU10 and HSA21 and predicts that it is the most telomeric gene known on HSA21. Physical mapping refines the positions and order of HSA22 homologs Mmp11, Mif, and Ddt, demonstrates the orientation of S100b on the mouse chromosome, and localizes the junction of conserved synteny between HSA21 and HSA22 on MMU10. Comparative mapping in this region is important for defining gene structure and dosage imbalance in Down syndrome (DS), for developing animal models of DS, and for understanding processes of chromosome evolution.

Animals↗
PubMed1998

Unilateral asymptomatic carotid disease does not require surgery.

BACKGROUND AND PURPOSE: The efficacy of carotid endarterectomy (CEA) in symptomatic patients with > 70% stenosis is accepted. The stroke risk of asymptomatic patients may not justify surgical intervention. The aim of this study is to use natural history data from a single unit to identify asymptomatic patients who would benefit from CEA. METHODS: Five hundred and sixty-four patients attending for duplex ultrasound assessment of the internal carotid artery between 1986 and 1993 were retrospectively identified as focally asymptomatic with > 40% ipsilateral stenosis. Patients were traced using hospital records, family practitioner databases and the Office of Population of Census and Surveys. The number of strokes, transient ischaemic attacks and cause of death were determined. Exclusions were 15 (2.7%) asymptomatic occlusions and 49 patients (8.7%) who underwent surgery for asymptomatic disease. RESULTS: Thirteen patients (2.6%) were not traced, leaving 487 study patients. The average follow-up was 41 months (range, 1-120 months). Mean presentation age was 69 years (S.D. 8.9), and the male to female ratio was 3:2. One hundred and fifty-six (32%) patients died. Forty-three patients suffered strokes, of whom two had bilateral strokes. In total there were 16 (i/p) strokes, 25 (c/l) strokes and four strokes undetermined. The average yearly stroke rate was 2.74 per 100 person years and the (i/p) rate 1.02 per hundred person years. There was no effect of age, sex or degree of stenosis on stroke. The presence of bilateral disease did increase the risk of stroke (rel risk 2.35, p = 0.029) but not ipsilateral stroke (rel risk 1.6, p = 0.39). Patients with unilateral asymptomatic carotid disease had an all stroke rate of less than 5% in the first year after presentation and this was unaffected by degree of stenosis. In patients with bilateral disease the stroke rate in the first year after presentation increased with degree of stenosis to a stroke rate of 9.6 per 100 person years in patients with > 90% contralateral stenosis. CONCLUSIONS: This data suggests that CEA will not benefit patients with unilateral asymptomatic disease. Patients with bilateral disease warrant inclusion in clinical trials.

Aged↗
PubMed1997

Computerised audit of carotid endarterectomy: audit loopholes closed?

The number of carotid endarterectomies being performed in the UK is increasing. The role of carotid endarterectomy (CEA) in the prevention of stroke depends on the procedure being associated with as few operative strokes as possible. Good clinical practice, with minimum morbidity, depends upon the integration of recent advances. Continuing audit has been used to examine changes in surgical practice and in case mix. There was a combined death and permanent stroke rate of 3.6% after 333 CEAs in a 6-year period (1990-1995) compared with 4.4% in 203 CEAs in an earlier 5-year audit period (1985-1989). The impact of an increase in the number of operations performed after recovered strokes, those performed by trainees and the use of prosthetic patches on the results of CEA has been assessed. Specific areas to be targeted in future audits are identified.

Adult↗
PubMed1996

Risk prediction of outcome following carotid endarterectomy.

The quoted combined mortality and morbidity following carotid endarterectomy is about 5-7%. In an attempt to identify a subgroup of high risk patients, a review has been undertaken of 404 carotid endarterectomies performed between January 1985 and March 1994. The perioperative mortality rate was 2%, with 3.4% of patients experiencing transient neurological deficits and 4% permanent strokes. Multiple logistic regression analysis was used to estimate the influence on outcome of age, gender, indication for surgery, bilateral internal carotid artery disease, hypertension and smoking. No significant explanators were identified.

Adult↗
PubMed1995

Colour duplex in assessing the infrainguinal arteries in patients with claudication.

Non-invasive assessment of the lower-limb vasculature may avoid unnecessary arteriography. Colour duplex scanning of the femoral and popliteal arteries was performed in claudicants who were potential candidates for endoluminal therapy. This was compared with the findings of biplanar conventional arteriography and intra-arterial digital subtraction angiography. In 112 lower limbs duplex gave the following results compared with angiography: the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for occlusions (n = 48), stenoses (n = 31), atheromatous vessel (n = 21) and disease-free (n = 12) were all greater or equal to 94%. The lengths of the occlusions were accurately identified by duplex. Clinical examination and spectral analysis at the common femoral artery failed to identify two patients who had an iliac lesion. Colour duplex examination is the investigation of choice in assessing the major infrainguinal arteries in patients with claudication.

Adult↗
PubMed1995

Assessment of a mutation in the H5 domain of Girk2 as a candidate for the weaver mutation.

A mutation in the GIRK2 inwardly rectifying K+ channel was mapped recently to the region of mouse chromosome 16 containing the wv gene and shown to occur in mutant but not in wild-type mice. We demonstrate tight linkage of the Girk2 mutation to the wv phenotype and refine the localization of the weaver (wv) gene on recombinational and physical maps. This linkage between Girk2 and wv has existed since at least 1988 in descendants of the original mutation maintained in C57BL/6 animals. Girk2 is shown to be transcribed in brain before the first recognized manifestation of the wv phenotype and in cultures of granule cells (GCs) isolated from cerebellum at postnatal day 8. Wild-type GCs grown in this culture system display an important developmental property--the ability to extend neurites. However, no inwardly rectifying K+ current is detected in GCs cultured from either wv/wv or +/+ cerebellum under a variety of conditions that activate related channels in other tissues. This suggests that if the Girk2 mutation is responsible for the wv phenotype, it does not act by altering these electrical properties of developing GCs.

Animals↗
PubMed1994

Femoropopliteal angioplasty for severe limb ischaemia.

Fifty patients undergoing 51 percutaneous transluminal angioplasties of the femoropopliteal segment for severe limb ischaemia were reviewed regularly. They comprised 30 men and 20 women of median age 70 (range 56-85) years. There were two deaths within 30 days. At 2 years the cumulative patient survival rate was 60 per cent. Eleven angioplasties were technical failures, 25 failed in the first 6 months and 14 were successful at 6 months' follow-up; in addition one patient died from myocardial infarction within 30 days of technically successful angioplasty. Subsequent vascular procedures were successful in 11 limbs following failed angioplasty. The primary limb survival rate was 42 per cent at 2 years. There were eight major complications after angioplasty, requiring amputation in five instances. Of the 23 long occlusions (greater than 5 cm) that were recanalized and dilated, 22 procedures failed within 6 months. The run-off score and diabetic status did not predict outcome. In this group of patients angioplasty had a low durability. Dilatation of long occlusions is associated with high rates of reocclusion and, on the basis of these results, should not be performed.

Aged↗
PubMed1994

Magnetic resonance angiography or IADSA for diagnosis of carotid pseudo occlusion?

Accurate diagnosis of internal carotid artery (ICA) occlusion is essential in the investigation of carotid disease yet may be difficult using Duplex. Traditionally contrast arteriography has been used to confirm the diagnosis despite its cost and potential dangers. Twenty-one patients with 23 ICA occlusions were evaluated by a 3-dimensional time of flight magnetic resonance angiography (MRA) technique. The cervical carotids and circle of Willis were imaged during the MRA examination which lasted 30 minutes. Confirmatory conventional angiography was performed in all patients. Using angiography as the gold standard, all occlusions were correctly diagnosed by MRA and 22 of 23 occlusions correctly diagnosed by Duplex. There was good agreement between MRA and angiography for all 42 ICAs imaged (Kappa statistic 0.83). Diagnosis of internal carotid artery occlusion is critical as it determines the need for operation. In this situation MRA provides a useful non-invasive complement to Duplex. A combination of non-invasive studies may enable arteriography to be rejected with greater confidence in this high risk group.

Angiography, Digital Subtraction↗
PubMed1994

Angioplasty gives good results in critical lower limb ischaemia. A 5-year follow-up in patients with known ankle pressure and diabetic status having femoropopliteal dilations.

137 consecutive patients with known ankle pressures and diabetic status had attempted femoro-popliteal dilatation for lower limb ischaemia in an English provincial teaching hospital. All except one were followed until failure or death to assess survival and amputation rates. Non-diabetic patients with critical limb ischaemia had a 5 year survival rate of 62.2% (SE 17.1) compared to 50.5% (SE 7.0) for claudicants, with no significant difference on logrank testing. Diabetics had a relative risk of amputation of 11.2 compared to nondiabetics. Patients with pre-treatment ankle pressures of 50 mm or less had a relative risk of amputation of 2.6 compared to those with higher resting pressures. It is concluded that angioplasty should be the treatment of first choice in critical lower limb ischaemia whenever it is technically possible. Including patients with rest pain in the critical ischaemia group does not significantly affect cumulative patency rates.

Adult↗
PubMed1992

Duplex ultrasonography and pulse-generated run-off in selecting claudicants for femoropopliteal angioplasty.

Non-invasive assessment of lower limb vasculature may avoid unnecessary angiography in claudicants. Colour duplex ultrasonography of the femoral and popliteal arteries was performed to assess patency and the presence of any stenoses, and pulse-generated run-off (PGR) was used to assess the distal vasculature. In 65 legs colour duplex scanning was successful, compared with angiography, in identifying the site and type of disease in the femoropopliteal segment and 23 lesions were correctly identified as suitable for angioplasty. More patent distal vessels were demonstrated by PGR than by angiography; no vessels patent on angiography were missed by PGR. The estimated cost of diagnostic angiography was 330 pounds per test compared with 52 pounds for non-invasive assessment. By using duplex examination as a screening test, a potential saving of 8062 pounds could have been made in this series. Duplex ultrasonography offers a non-invasive and cost-effective alternative to diagnostic angiography for clinically suspected infrainguinal arterial disease presenting as claudication. PGR was not of clinical value in assessing suitability for angioplasty.

Aged↗
PubMed1992

The effect of diabetes mellitus on the outcome of angioplasty for lower limb ischaemia.

Angioplasty is an important tool in the armamentarium of the clinician dealing with atherosclerotic disease. Diabetic patients with occlusive disease pose special problems. Four hundred and twenty-five lesions were dilated in 370 patients. No difference in site was found when comparing the diabetic and non-diabetic groups (p less than 0.001), but a significant difference in indication for treatment was observed. Cumulative patency at 5 years for iliac lesions in non-diabetic patients was 61.2% and in diabetic patients was 35.6% (p less than 0.05), for superficial femoral and popliteal artery lesions in non-diabetic patients it was 49.7% and in diabetic patients it was 38.8% (NS). The need for subsequent surgical intervention (p less than 0.01) and risk of death (p less than 0.001) are both significantly greater in the diabetic group. This study shows that angioplasty is a technique that can be used with success in diabetic patients and if the indications for interventions are compared, diabetic patients do not worse.

Angioplasty, Balloon↗