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Biomedical subjects

M J McCarthy

Publications and source records attributed to M J McCarthy.

At least 37 records · Page 2Linked to original sources
PubMed1998

Bilateral infrainguinal vein grafts and the incidence of vein graft stenosis.

OBJECTIVES: To elucidate the incidence of significant vein graft stenosis in patients who have undergone bilateral infrainguinal vein grafts. MATERIALS: Between 1987 and 1996, 22 patients were identified from our vascular studies database as having undergone bilateral infrainguinal vein bypass grafting. METHODS: Data was obtained from the vascular studies database and by case note review. All patients had been part of a vein graft surveillance programme. RESULTS: Of the 22 patients with bilateral vein grafts, eight were excluded from further analysis because one or more of their grafts failed within 30 postoperative days. In the remaining 14 patients (28 vein grafts) there were 15 primary vein graft stenoses. Six patients (43%) had bilateral vein graft stenoses, which is significantly higher (p = 0.0008) than the predicted value of 9%, for developing bilateral vein graft stenoses. For those patients who developed a vein graft stenosis in their first grafted limb (9/14), 67% (6/14) subsequently developed a vein graft stenosis in their second grafted limb. CONCLUSION: Patients who develop vein graft stenosis in one limb are at a greater risk of developing a contralateral vein graft stenosis if that limb is grafted. This may well be due to individual vein morphology or unidentified systemic factors that play a role in the aetiology of vein graft stenosis.

Aged↗
PubMed1998

At what peak velocity ratio value should duplex-detected infrainguinal vein graft stenoses be revised?

OBJECTIVES: To determine the peak velocity ratio (PVR) threshold at which to intervene and correct duplex detected vein graft stenoses. DESIGN: Prospective study. MATERIALS: Infrainguinal vein grafts in patients attending the vascular studies for routine postoperative surveillance. METHODS: Colour duplex detected stenotic vein graft lesions with a peak velocity ratio (PVR) between 2.0 and 2.9 were identified and monitored by serial duplex scans performed monthly for 3 months and then at 3-monthly intervals thereafter. At the end of the study period, the outcome of these lesions were analysed. RESULTS: Thirty-eight lesions were identified from 32 grafts. Of these lesions, sixteen (42%) resolved, 11 (29%) remained stable and 11 (29%) progressed to a PVR of > or = 3.0 and underwent angioplasty. There were no occlusions in any of the grafts during the period of study. CONCLUSIONS: Colour duplex detected vein graft stenoses with a PVR of less than 3.0 can be treated expectantly if grafts with stenoses with a PVR 2.0-2.9 are scanned every month for at least 3 months after detection.

Angioplasty, Balloon↗
PubMed1998

Carotid endarterectomy without angiography does not compromise operative outcome.

OBJECTIVES: Carotid angiography is associated with a 2% risk of stroke and, since the advent of colour-duplex ultrasound, its role in the assessment of patients with carotid disease has been the subject of debate. The aim of this study was to evaluate a policy of adopting routine duplex supplemented by selective angiography on operative outcome over a 5-year period. METHODS: A prospective audit of the results of carotid endarterectomy without routine angiography from January 1992 to December 1996. Angiography was performed only if the ultrasonography was concerned about the distal or proximal extent of disease or to assess subocclusion. RESULTS: During the study period, 494 carotid endarterectomies were performed but only 35 patients underwent carotid angiography. The indications for angiography were subocclusion/string sign in 22 patients, to assess the limits of proximal or distal disease in 12 and abnormal anatomy in one. During the 5-year study period the overall perioperative death and/or stroke rate was 4.2%. By 1997, the perioperative stroke rate had fallen to 1.3%. In no case in this series was the operation abandoned due to unexpected findings. CONCLUSION: Although concerns exist about the precise duplex criteria for diagnosing a severe stenosis, this study has shown that a policy of selective angiography does not compromise patient safety or operability and avoids the unnecessary mortality, morbidity and costs associated with routine angiography.

Angiography↗
PubMed1998

Prediction of resectability of pancreatic malignancy by computed tomography.

BACKGROUND: The accuracy of computed tomography (CT) in predicting resectability of pancreatic malignancy has been questioned recently and alternative methods have been recommended. METHODS: To determine the accuracy of CT for predicting resectability and its influence on survival, a standard protocol for performing CT and reporting the results was developed and then compared retrospectively with the ability of one surgeon to perform a resection during 1989-1994. Postoperative survival was determined. RESULTS: Of 88 consecutive patients 35 (40 per cent) had CT-resectable disease and 53 (60 per cent) had CT-irresectable disease. Twenty-one patients were excluded because of advanced disease or poor performance status. Of the remaining 67 patients, 47 (70 per cent) had pancreatic ductal adenocarcinoma and 20 (30 per cent) had ampullary adenocarcinoma, of whom 32 had a resection, 32 had a palliative bypass and three had only a staging laparoscopy. The sensitivity and specificity for computed tomographic prediction of resectability were 72 and 80 per cent respectively. The positive predictive value was 77 per cent and the negative predictive value 76 per cent. There were seven false-positive and nine false-negative findings. Survival was more dependent on whether or not resection was performed than on computed tomographic predictability of resection. CONCLUSION: CT was reasonably accurate in predicting resectability but cannot be relied on entirely, requiring an improvement in staging methods for pancreatic malignancy.

Adenocarcinoma↗
PubMed1998

Lower limb surveillance following autologous vein bypass should be life long.

BACKGROUND: The aim of the study was to investigate whether infrainguinal vein graft surveillance can be stopped at 1 year without prejudicing graft or leg survival. METHODS: Data were collected prospectively on 351 infrainguinal vein bypass grafts (326 patients) that had been entered into a vein graft surveillance programme between 1988 and 1997. RESULTS: Some 104 grafts (30 per cent) developed significant new vein graft stenoses, 95 (91 per cent) of which occurred within 12 months. After 1 year, the risk of developing a significant graft stenosis was 3 per cent per year. Sixty-nine grafted limbs (20 per cent) developed new arterial inflow or run-off stenoses that required intervention, but only 37 (54 per cent) occurred within the first year, after which the risk was 9 per cent per year. The overall risk of developing a new vein graft or arterial stenosis after 1 year was 10 per cent per year. CONCLUSION: The incidence of vein graft stenosis decreases significantly 1 year after operation but there is still at risk of developing potentially graft-threatening arterial stenoses. Legs that have undergone infrainguinal vein bypass grafting should continue to be monitored in a surveillance programme for life.

Adolescent↗
PubMed1998

The setting up and implementation of a venous thromboembolism prophylaxis policy in clinical hospital practice.

Clinical management policies are meant to lead to the delivery of better health care. However, as we demonstrate in this review, having an oral or written venous thromboembolism prophylaxis policy does not necessarily lead to the majority of general surgical inpatients receiving the appropriate prophylaxis. We discovered, through prospective clinical audit, that for a clinical policy to be effective in delivering the appropriate health care, it must be repeatedly scrutinized and implemented in the correct manner. Only after several rounds of the audit cycle were we able to achieve the deliverance of venous thromboembolism prophylaxis to the majority of general surgical patients on our unit. This has wider implications, not just for the implementation of a venous thromboembolism prophylaxis policy, but also for all clinical management policies, and illustrates the importance of clinical audit in clinical practice.

Guideline Adherence↗
PubMed1997

Activated phosphatidylinositol 3-kinase and Akt kinase promote survival of superior cervical neurons.

The signaling pathways that mediate the ability of NGF to support survival of dependent neurons are not yet completely clear. However previous work has shown that the c-Jun pathway is activated after NGF withdrawal, and blocking this pathway blocks neuronal cell death. In this paper we show that over-expression in sympathetic neurons of phosphatidylinositol (PI) 3-kinase or its downstream effector Akt kinase blocks cell death after NGF withdrawal, in spite of the fact that the c-Jun pathway is activated. Yet, neither the PI 3-kinase inhibitor LY294002 nor a dominant negative PI 3-kinase cause sympathetic neurons to die if they are maintained in NGF. Thus, although NGF may regulate multiple pathways involved in neuronal survival, stimulation of the PI 3-kinase pathway is sufficient to allow cells to survive in the absence of this factor.

Animals↗
PubMed1997

Kinetics of repair of UV-induced DNA damage in repair-proficient and -deficient cells as determined by quantitative polymerase chain reaction.

Advances in methodologies to monitor gene-specific repair in human cells have facilitated a detailed understanding of the complexity of the nucleotide excision repair system. One of these procedures, quantitative polymerase chain reaction (QPCR), holds significant promise for dissecting the fine structure of the repair of UV-induced DNA damage. This assay was used to study the repair of UV photoproducts in both actively transcribed and nontranscribed genes from human cells that were capable of (1) repair of both cyclobutane pyrimidine dimers and 6-4 photoproducts; (2) removal of neither dimers nor 6-4 photoproducts; (3) strong preferential repair of 6-4 photoproducts relative to dimers; and (4) severely depressed rates of 6-4 photoproducts and dimers. Detailed kinetic analyses revealed that repair of both active and inactive genes can be studied with a very fine degree of precision and that the repair status of the cells can easily be detected by use of the procedures described.

Cell Cycle↗
PubMed1997

Bax promotes neuronal cell death and is downregulated during the development of the nervous system.

The Bcl-2 and Bcl-x proteins suppress programmed cell death, whereas Bax promotes apoptosis. We investigated the pattern of expression of Bcl-2, Bax and Bcl-x during neuronal differentiation and development. All three proteins were widely expressed in neonatal rats but, in the adult, Bax levels were 20- to 140-fold lower in the cerebral cortex, cerebellum and heart muscle, whereas Bcl-x was not downregulated in any of the tissues examined. In the cerebral cortex and cerebellum, the decrease in Bax levels occurred after the period of developmental cell death. Further, microinjection of a Bax expression vector into cultured sympathetic neurons, which depend on nerve growth factor for survival, induced apoptosis in the presence of survival factor and increased the rate of cell death after nerve growth factor withdrawal. This effect could be blocked by co-injection of an expression vector for Bcl-xL or for the baculovirus p35 protein, an inhibitor of caspases (ICE-like proteases). These results suggest that, during development, the sensitivity of neurons to signals that induce apoptosis may be regulated by modulating Bax levels and that Bax-induced death requires caspase activity.

Aging↗
PubMed1997

Involvement of caspases in sympathetic neuron apoptosis.

In order to study the involvement of caspases in neuronal cell death, we have examined the effects of the viral caspase inhibitor p35 and peptide caspase inhibitors on sympathetic neurons isolated from the superior cervical ganglion (SCG). In these neurons, apoptosis can be induced by the withdrawal of nerve growth factor (NGF) and also by the addition of the kinase inhibitor staurosporine. p35 has been shown to be a broad spectrum inhibitor of the caspase family and promotes the survival of SCG neurons withdrawn from NGF. We show that p35 is also protective when apoptosis is induced by staurosporine. In addition, p35 inhibits a number of the morphological features associated with apoptosis, such as nuclear condensation, TUNEL labelling, and externalisation of phosphatidylserine. The tri-peptide caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp (O-methyl)-fluoromethylketone (zVAD-fmk) was effective at inhibiting NGF withdrawal-induced and staurosporine-induced apoptosis of SCG neurons. Two other peptide inhibitors, acetyl-Tyr-Val-Ala-Asp-aldehyde (Ac-YVAD-CHO) and acetyl-Asp-Glu-Ala-Asp-aldehyde (Ac-DEVD-CHO), also inhibited apoptosis induced by both means when microinjected into SCG neurons but peptides derived from the caspase cleavage site in p35 were not protective. We present data to suggest that apoptosis induced by separate death stimuli can result either in the activation of distinct caspases or in differences in the time of activation of the family members.

Animals↗
PubMed1997

Surgical audit: the junior doctors' viewpoint.

Clinical audit is now an integral part of surgical practice. The Royal College of Surgeons of England has stated that all members of the clinical team should participate in the clinical audit. Junior surgical doctors from the West Midlands Region were interviewed, using a questionnaire, to investigate their attitudes towards audit. Sixty-eight junior doctors were interviewed from six hospitals. Sixty-one (90%) felt that audit was necessary in routine surgical practice, 21 (31%) had presented data at audit meetings and only three (4%) were allocated study periods to prepare for their audit topics. In those hospitals in which all elective work was cancelled, there was a higher attendance rate at audit meetings by junior doctors. Many junior doctors felt that they lacked direction from senior colleagues and had not received any formal training in clinical audit. Clinical audit should become part of undergraduate and postgraduate medical training and junior doctors need to take a more active role in clinical audit.

Attitude of Health Personnel↗
PubMed1996

A modified quantitative polymerase chain reaction assay for measuring gene-specific repair of UV photoproducts in human cells.

Methods for measuring the induction and repair of ultraviolet (UV) induced modifications in short DNA fragments are essential for the study of gene-specific DNA repair. Measurements in genomic fragments of 14 kilobases (kb) or larger can be obtained using the enzyme-sensitive site (ESS) assay introduced by Hanawalt and Bohr (Bohr et al., 1985). More recently, several assays based on variations of the polymerase chain reaction (PCR) technique have been developed which have increased sensitivity (Govan et al., 1990; Kalinowski et al., 1992; Jennerwein and Eastman, 1991), even nucleotide resolution (Pfeifer et al., 1993). However, examination of these reports indicates that the PCR based DNA repair assays lack precision (Govan et al., 1990; Kalinowski et al., 1992; Tornaletti and Pfeifer, 1994; Jennerwein and Eastman, 1991). We report here, the development of a highly precise QPCR DNA repair assay. The assay was used to measure the induction and repair of UV photoproducts in a 2.7 kb genomic fragment containing the human growth hormone (hGH) gene in SL89 (wild-type) fibroblasts. The assay was exceedingly reproducible with an overall coefficient of variation from the mean of about 2.5%. This level of precision enabled the apparent simultaneous resolution of cyclobutane dimer (CPD) and (6-4) photoproduct (6-4PP) induction and repair.

Base Sequence↗
PubMed1996

Applications of magnetic resonance imaging to food research.

Global food markets are changing in response to consumer demands for more processed foods and higher quality foods. Consumers find processed foods convenient, less prone to spoilage, more portable, nutritionally efficient, and more consistent in quality level than fresh foods. These demands have resulted in food producers working to develop new types of foods and reformulate standard types of foods. A typical type of reformulation would be a reduced-calorie food or an all-natural food product. The characterization of food processes and products is most often accomplished through the use of averaged measurements. An averaged measurement provides a characterization of the process or product with a single value of one variable measured at a specific time. For example, the average moisture content of a food during drying or the shear viscosity of an emulsion at one temperature and one shear rate. Averaged measurements are useful in characterizing a given process and are in many cases sufficient for process design or product development. However, these single point measurements do not provide significant information on the phenomena responsible for controlling product properties during processing or storage. More information on the physical and chemical processes controlling or influencing process performance and product quality should result in both improved production efficiency, improved product quality, and novel products. Magnetic resonance imaging provides new methods and approaches to investigate and quantify the attributes of products as they vary in time and location within the product. The attributes that can be quantified range from the composition of a material (moisture content, fat content), to physical structure and to derived characterizations like the shear-stress shear-rate relationship in fluids.

Food Technology↗
PubMed1996

Magnetic resonance imaging (MRI) of a cookie in comparison with time-lapse photographic analysis (TLPA) during baking process.

Magnetic Resonance Imaging (MRI) has been used to study the baking of a cookie. The structural and dynamic changes occurring during baking have been monitored, including changes in the internal moisture saturations and distribution. The images reveal the moisture distribution is initially uniform, and during baking a gradient in moisture develops from the interior to the edge. Changes in physical dimensions calculated from the data are consistent with those obtained from time-lapsed photography.

Cooking↗
PubMed1996

NMR applications in complex food systems.

The rheological and functional properties of food components are related to their molecular structure, morphology, and atomic mobilities. NMR provides a powerful tool for elucidating chemical structures, molecular conformations, and interactions of components in food systems. Quantitative analysis of sugars, fats, and other principal compounds in complex food systems was achieved by high-resolution liquid NMR. In addition to information available from liquid experiments, solids NMR experiments can reveal differences and changes in crystal packing of structures in food model systems. Interpretation of experimental results is enhanced by molecular modeling of key food compounds. Models for fat crystallization are carried out to enhance understanding of the molecular structures involved in the fat crystallization process. Recently, MRI has also shown significant impact on food science and technology. Some examples of NMR applications are given in this presentation.

Crystallization↗
PubMed1996

Morphological and biochemical changes in neurons: apoptosis versus mitosis.

Apoptosis and mitosis are often thought to share certain morphological similarities and therefore to be regulated by similar sets of enzymes. In this study, the Golgi apparatus and nuclear lamina were examined in PC12 cells and rat superior cervical ganglion neurons undergoing apoptosis in response to withdrawal of nerve growth factor or addition of staurosporine. We found that the Golgi apparatus disperses during apoptosis, without obvious degradation, in a manner similar to that occurring in mitosis. In contrast, the nuclear lamina did not become completely solubilized during apoptosis, as occurs in mitosis, but remained as a distinct structure around the nucleus, although some degradation of nuclear lamins was seen. To assess the integrity of the nuclear envelope, fluorescent probes were introduced into the cytoplasm of live and dying cells. High molecular weight tracers were still excluded from the nuclei of apoptotic cells, demonstrating the continued existence of a functional nuclear barrier. These data suggest, therefore, that cell death is unlikely to occur simply as a result of inappropriate activation of cell cycle enzymes.

Animals↗
PubMed1995

Tumors of the trachea.

Tumors of the trachea are rare and create signs and symptoms that mimic common upper airway diseases. A tracheal mass is not usually considered in the clinical differential diagnosis of an affected patient and is often overlooked on chest radiographs. The purpose of this article is to prompt earlier diagnosis and improve long-term survival of patients with a tracheal tumor through the presentation of the salient clinical, pathological, and radiological features of a variety of benign and malignant tracheal diseases.

Adolescent↗