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Biomedical subjects

C McCollum

Publications and source records attributed to C McCollum.

At least 19 recordsLinked to original sources

Prosodic structure and wh-questions.

This study examines the influence of wh-gaps on the prosodic contour of spoken utterances. A previous study (Nagel, Shapiro, & Nawy, 1994) claimed that the phonological representation of a sentence containing a filler-gap dependency explicitly encodes the location of the syntactic gap. In support of this hypothesis, Nagel et al. presented evidence that the word immediately preceding a gap is lengthened and that there is a reliable increase in pitch excursion across the gap location. Our study challenges Nagel et al.'s claim. We argue that their materials confounded the presence/ absence of a gap with other factors that are known to affect intonational phrasing independently. We show that, when these factors are separated, the evidence that syntactic gaps are explicitly encoded in the phonological representation of a sentence disappears.

Adult↗

Heparin-bonded Dacron or polytetrafluoroethylene for femoropopliteal bypass grafting: a multicenter trial.

BACKGROUND: Dacron (polyester fiber) was largely abandoned for femoropopliteal bypass grafts 30 years ago because saphenous vein achieved better patencies. However, in patients taking aspirin, patency in above-knee femoropopliteal bypass grafts has recently been shown to be equivalent to that with saphenous vein. We compared heparin-bonded Dacron (HBD) and polytetrafluoroethylene (PTFE) in a randomized multicenter trial including below-knee popliteal or tibioperoneal trunk bypass graft where the long saphenous vein was absent or inadequate. METHODS: Over 28 months, 209 patients undergoing femoropopliteal bypass grafts (180 above-knee, 29 below-knee) were randomized to HBD (n = 106) or PTFE (n = 103). Each patient was given aspirin (300 mg/d) before surgery, and this continued unless the patient had intolerance to the aspirin. RESULTS: The mean follow-up was 42 months (range, 28-55). Fifteen (7.1%) patients died with patent grafts, and three (1.4%) infected grafts were removed. Patency (measured with Kaplan-Meier survival analysis) at 1, 2, and 3 years for HBD was 70%, 63%, and 55% compared with 56%, 46%, and 42%, respectively, for PTFE (P =.044). A total of 67 secondary interventions were performed on 48 thrombosed grafts; long-term patency was achieved in only three. Risk factors for arterial disease did not significantly influence patency. Amputations have been performed in 23 patients, six after HBD and 17 after PTFE bypass grafts (P =.015). CONCLUSIONS: HBD achieved better patency than PTFE, which carried a high risk of subsequent amputation.

Adult↗

Stroke in young adults: the role of paradoxical embolism.

Stroke in young adults may be devastating and frequently no cause can be found. However, there is ample literature to suggest an association between cryptogenic stroke in young people and paradoxical embolisation via a venous to arterial circulation shunt (v-aCS), commonly due to patent foramen ovale (PFO). Although paradoxical embolisation is assumed to be a rare event, this review suggests that it is an important or even dominant cause of stroke in young people and that a transcranial Doppler (TCD) technique may be the investigation of choice to identify v-aCS.

Adult↗

In vitro cloning of complex mixtures of DNA on microbeads: physical separation of differentially expressed cDNAs.

We describe a method for cloning nucleic acid molecules onto the surfaces of 5-micrometer microbeads rather than in biological hosts. A unique tag sequence is attached to each molecule, and the tagged library is amplified. Unique tagging of the molecules is achieved by sampling a small fraction (1%) of a very large repertoire of tag sequences. The resulting library is hybridized to microbeads that each carry approximately 10(6) strands complementary to one of the tags. About 10(5) copies of each molecule are collected on each microbead. Because such clones are segregated on microbeads, they can be operated on simultaneously and then assayed separately. To demonstrate the utility of this approach, we show how to label and extract microbeads bearing clones differentially expressed between two libraries by using a fluorescence-activated cell sorter (FACS). Because no prior information about the cloned molecules is required, this process is obviously useful where sequence databases are incomplete or nonexistent. More importantly, the process also permits the isolation of clones that are expressed only in given tissues or that are differentially expressed between normal and diseased states. Such clones then may be spotted on much more cost-effective, tissue- or disease-directed, low-density planar microarrays.

Cloning, Molecular↗

Regional variation in incidence and case fatality of myocardial infarction among young women in England, Scotland and Wales.

OBJECTIVES: To examine the regional variation in incidence and case fatality of myocardial infarction among young women. DESIGN: Cross sectional survey, using population based incidence data. SETTING: England, Scotland and Wales. SUBJECTS: Subjects were women aged 16-44 with a diagnosis of myocardial infarction between 1 October 1993 and 15 October 1995. OUTCOME MEASURES: Incidence of myocardial infarction per 100,000 women years, with case fatality as a percentage of total cases. RESULTS: Incidence of myocardial infarction rose steeply from age 33 upwards, (maximum = 20.2 cases per 100,000 women years at age 44). The adjusted incidence rate for myocardial infarction was 3.7 (95% CI 3.2, 4.2) times greater in Scotland than in southern England. In contrast, case fatality was significantly lower in Scotland: 18.5% (95% CI 13.1%, 25.0%), compared with 31.0% (95% CI 25.9%, 36.0%) in southern England. CONCLUSIONS: The incidence of myocardial infarction varied widely within the United Kingdom. Case fatality variation may reflect differences in ambulance response, or in diagnostic acumen, within the regions.

Adolescent↗

Oral contraceptives and myocardial infarction: results of the MICA case-control study.

OBJECTIVES: To determine the association between myocardial infarction and use of different types of oral contraception in young women. DESIGN: Community based case-control study. Data from interviews and general practice records. SETTING: England, Scotland, and Wales. PARTICIPANTS: Cases (n=448) were recruited from women aged between 16 and 44 who had suffered an incident myocardial infarction between 1 October 1993 and 16 October 1995. Controls (n=1728) were women without a diagnosis of myocardial infarction matched for age and general practice. MAIN OUTCOME MEASURES: Odds ratios for myocardial infarction in current users of all combined oral contraceptives stratified by their progestagen content compared with non-users; current users of third generation versus second generation oral contraceptives. RESULTS: The adjusted odds ratio for myocardial infarction was 1.40 (95% confidence interval 0.78 to 2. 52) for all combined oral contraceptive users, 1.10 (0.52 to 2.30) for second generation users, and 1.96 (0.87 to 4.39) for third generation users. Subgroup analysis by progestagen content did not show any significant difference from 1, and there was no effect of duration of use. The adjusted odds ratio for third generation users versus second generation users was 1.78 (0.66 to 4.83). 87% of cases were not exposed to an oral contraceptive, and 88% had clinical cardiovascular risk factors or were smokers, or both. Smoking was strongly associated with myocardial infarction: adjusted odds ratio 12.5 (7.29 to 21.5) for smoking 20 or more cigarettes a day. CONCLUSIONS: There was no significant association between the use of oral contraceptives and myocardial infarction. The modest and non-significant point estimates for this association have wide confidence intervals. There was no significant difference between second and third generation products.

Adolescent↗

Soluble intercelluar adhesion molecule-1, E-selectin, vascular cell adhesion molecule-1 and von Willebrand factor in stroke.

We investigated the role of endothelial cell and leukocyte adhesion in the pathophysiology of acute stroke. The immunocytochemical expression of adhesion molecules in brain tissue from six patients who died following acute ischaemic stroke showed weak endothelial expression of intercellular adhesion molecule-1 (ICAM-1), but intense expression of vascular cell adhesion molecule-1 (VCAM-1) by astrocytes and endothelial cells from the infarcted, but not the non-infarcted areas. We also measured soluble adhesion molecules E-selectin, ICAM-1, VCAM-1 and von Willebrand factor (all by enzyme-linked immunosorbent assay) in 21 patients after an acute ischaemic stroke (ictus < 12 h), and again 3 months later. Blood levels in the stroke patients were compared with 82 healthy controls and 22 subjects with carotid atherosclerosis. Compared with healthy controls, both patient groups had raised levels of von Willebrand factor (P < 0.02) but the level of soluble VCAM-1 was raised only in patients with acute stroke (P < 0.02). Levels of von Willebrand factor and soluble VCAM-1 in the stroke patients were still high at 3 months follow-up. We suggest that there might be changes in adhesion molecule expression and release in the acute and chronic stages of ischaemic stroke, where blood levels are related to immunocytochemical findings on infarcted brain. These changes may perhaps be part of the complex pathophysiological responses to infarction and repair of brain tissue following stroke.

Aged↗

Risk of myocardial infarction in young female smokers.

OBJECTIVES: To determine the extent of risk of myocardial infarction from cigarette smoking in young women, and to examine the relation of smoking with other putative risk factors. DESIGN: Community based case control study. SETTING: England, Scotland, and Wales. PATIENTS: Women (n = 448) between 16 and 44 years old with a diagnosis of incident myocardial infarction between 1 October 1993 and 16 October 1995. Controls (n = 1728) were age and general practice matched women without a diagnosis of myocardial infarction. OUTCOMES MEASURES: Odds ratios for risk of myocardial infarction associated with smoking and other risk factors. RESULTS: Odds ratios for myocardial infarction in smokers versus non-smokers showed a strong dose response, from 2.47 (95% confidence interval (CI) 1.12 to 5.45) in smokers of 1-5 cigarettes per day to 74.6 (95% CI 33.0 to 169) in smokers of >/= 40 cigarettes per day. There was no interaction of smoking with use of oral contraceptives, but there were additive risks with other clinical risk factors such as hypertension and diabetes. It is estimated that if all women aged 16-44 years were able to stop smoking, 400 cases of myocardial infarction per annum (of whom 112 would die) would be prevented. CONCLUSIONS: In young women the risk of myocardial infarction from smoking was considerable, and heavy smokers with other risk factors were especially at risk.

Adolescent↗

Tension-free mesh hernia repair: recovery and recurrence after one year.

The outcome of 200 consecutive patients with inguinal hernias repaired by the tension-free mesh technique at a specialist clinic was assessed one year after operation. There were no recurrences and no major complications. The wound infection rate was 1%. Less than 10% of patients had only minor complaints and 99% of patients were satisfied or very satisfied with the operation and its outcome. Low recurrence rates after one year imply low long-term recurrence and testify to the benefits of a specialist approach.

Adolescent↗

Calcification in atherosclerotic plaque of human carotid arteries: associations with mast cells and macrophages.

Calcification has been examined in 250 samples of atherosclerotic lesions (types II to VI) of human carotid arteries using von Kossa and haematoxylin staining. Early calcification described as 'stippling' was first noted in stage III specimens, with intermediate and solid calcifications becoming increasingly prominent within advanced plaques, especially stages Vb and VI. Although the relative frequencies of stippling, intermediate and large calcified deposits varied between plaques of the same stage, the prevalent sites of calcification were recognized as the deeper regions of the intima and the atheroma. Immunolocalization and histochemical techniques were used to identify the associations of mast cells (MCs), macrophages, smooth muscle cells (SMCs), and elastin with the different stages of calcification. Early, dispersed stippling was commonly associated with local accumulations of macrophages (HAM56 and CD68-positive), MCs and extracellular MC tryptase, the presence of immunoreactive elastin, but the relative absence of SMCs. Intermediate stages of calcification described as 'morula' deposits were also associated with local increases in the numbers of macrophages and MCs. Larger calcified deposits, even within the same plaque specimen, showed no regular pattern of cellular or elastin associations. However, in the vast majority of specimens, macrophages represented the predominant cell type associated with different phases of calcification. By contrast, the calcification less frequently observed in the media beneath advanced plaques was commonly associated with SMCs and elastin; only rarely were macrophages or MCs present. These studies are the first to demonstrate that macrophages, MCs, and extracellular tryptase frequently occupy micro-environmental loci showing the first stages of calcification within the atherosclerotic plaque; similar associations with more advanced mineral deposits are discussed in relation to plaque rupture.

Aged↗

Observations on bone formation and remodelling in advanced atherosclerotic lesions of human carotid arteries.

Immunolocalisation and histochemical techniques were used to examine mineralised bone deposits within late stage atherosclerotic plaques of human carotid arteries. These specimens showed characteristic features of osteogenesis. Large calcifications were often observed in close association with or integrated within mineralised bone. Smooth muscle cells (alpha-actin positive) were often located around osteoid-like matrix, together with focal accumulations of macrophages (CD68 and HAM56 positive). Local accumulations of mast cells (tryptase positive) were consistently observed in close association with the bone. Multinucleated giant cells in close apposition with mineralised bone demonstrated typical osteoclastic morphology, and were positively stained for acid phosphatase and the macrophage marker CD68. Thus, all the normal features of bone formation and resorption were observed in this microcosm of osteogenesis within atherosclerotic plaque; the term 'osteosome' seems appropriate for the structure. These osteosomes have numerous advantages for experimental studies of the various osteogenic factors responsible for bone metabolism, especially following short-term tissue culture. This ex vivo technique was used to demonstrate the distribution and the multiple cellular sources of bone morphogenetic protein 6.

Acid Phosphatase↗

von Willebrand factor, fibrinogen and other plasma proteins as determinants of plasma viscosity.

Plasma viscosity and fibrinogen are risk factors for cardiovascular disease and on rheological grounds, it is widely believed that the latter is a major determinant of the former. However, other plasma constituents may also be important determinants of plasma viscosity. Our aim was to determine whether or not levels of von Willebrand factor contributed to plasma viscosity. We measured plasma viscosity, fibrinogen, von Willebrand factor, immunoglobulins G, A and M, total, HDL- and LDL-cholesterol, triglycerides and albumin in 95 patients with peripheral arterial disease and in 120 healthy controls. A stepwise multivariate analysis was performed to determine the major influences of plasma viscosity. We also measured fibrinogen, von Willebrand factor, immunoglobulins G, A and M, total, HDL- and LDL-cholesterol, triglycerides, albumin and viscosity in 32 smokers as they successfully progressed to being non-smokers. The level of von Willebrand factor was an independent influence on plasma viscosity in the controls (P < 0.05), patients (P < 0.01) and in the combined group (P < 0.001). von Willebrand factor, fibrinogen and plasma viscosity, but not the immunoglobulins, lipoproteins or albumin, fell (P < 0.05) in smokers as they became non-smokers. We find that von Willebrand factor contributes to plasma viscosity, hence a reduction in levels of von Willebrand factor should result in a reduction in viscosity. These data may have implications for the pathogenesis of cardiovascular disease.

Adult↗

Mast cell distribution, activation, and phenotype in atherosclerotic lesions of human carotid arteries.

Immunohistochemical staining for mast cell tryptase and chymase was used to examine the distribution, activation, and tryptase/chymase phenotype of mast cells (MCs) in 250 samples of atherosclerotic lesions (type I to VI) of human carotid arteries. Dual immunolocalization and histochemical techniques were used to identify the associations of MCs with macrophages, smooth muscle cells, and extracellular matrix components. Whereas normal carotid arteries contained very few MCs within the intima, atherosclerotic lesions showed increased MC numbers with variable focal accumulations. MCs were identifiable from the earliest stages of atherosclerosis, and especially at the shoulder regions of the fully formed atheroma. They were observed in close association with macrophages (HAM56 positive) and extracellular lipid, as well as at sites of foam cell formation. MCs and diffuse tryptase staining were also evident within sites of new calcification and around small calcified deposits. Extensive MC activation/degranulation, as judged by diffuse extracellular tryptase staining, was a common feature of the advanced atherosclerotic plaques complicated by fissure, haemorrhage, and thrombus formation. Moreover, such sites of extracellular MC tryptase were often associated with localized oedema and disruption of the stromal matrix. MCs which contained both tryptase and chymase (the MCTC phenotype) represented approximately 80-95 per cent of all MCs. These studies are the first to demonstrate significant numbers and focal accumulations of MCs in all developmental stages of atherosclerotic carotid arteries. Since MCs contain or express a variety of potent mediators, their release could profoundly influence the development and pathological complications of atherosclerotic plaques.

Aged↗

Single-layer and multilayer bandaging in the treatment of venous leg ulcers.

This study compares levels of compression achieved in the application of both multilayer compression bandage systems and single-layer bandages by practitioners who are experienced with levels achieved by those who are inexperienced. Nineteen practitioners experienced in compression bandaging (13 nurses, six doctors) and 18 inexperienced (12 nurses, six doctors) participated in the study. Both experienced and inexperienced practitioners achieved a pressure of 40 mmHg more consistently when applying multilayer compression bandage systems than in the application of single-layer bandages. Compression bandaging experience does not result in significantly better sub-bandage pressure when using a multilayer system. Inexperienced practitioners are more likely to apply dangerously high levels of pressure with single-layer bandages than with a multilayer system. Single-layer compression bandages should be applied only by those health-care professionals with extensive experience of applying compression bandages.

Bandages↗