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Biomedical subjects

M Stewart

Publications and source records attributed to M Stewart.

At least 19 recordsLinked to original sources
PubMed2007

Indwelling trans-anastomotic rectal tubes in colorectal surgery: a survey of usage in UK and Ireland.

BACKGROUND: The use of rectal tubes in colorectal surgery appears to be a matter of individual choice, with little documented evidence to support their use. This study assesses the current practice of rectal tubes amongst consultant members of the Association of Coloproctology of Great Britain & Ireland (ACPGBI). METHODS: A piloted questionnaire was sent to practising ACPGBI consultant members listed in the 2003-04 directory. Statistical analysis was performed using SPSS software and Fishers exact test. RESULTS: Three hundred and thirty-nine replies were received from 579 posted questionnaires (response rate = 58.5%). Rectal tubes were used by 116 (35%) of responding surgeons. Rectal tubes were more commonly used by surgeons with less than 10 years practice as a consultant (P < 0.005). The main indications for tube placement were following ileo-anal or colonic pouch surgery (73%), after any anterior resection (36%) (rectal tubes were reserved for only low anterior resections by 16% of surgeons) and in the rectal stump after total or subtotal colectomy for acute colitis (11%). Twenty-three percent of these practising surgeons would use a rectal tube as an alternative to a diverting stoma, predominantly in selected patients following ileo-anal pouch surgery. A Foley catheter was the commonest type of tube used (70%) and this was usually placed above the anastomosis (80%). Rectal tubes were left in situ for a median of 5 days (range = 1-13 days). Three surgeons (2.6%) reported serious complications including tube perforation of the bowel or anastomosis. Several different mechanisms were suggested for the purpose and functioning of the rectal tube, the commonest being to decompress the rectum and/or pouch. CONCLUSION: Rectal tube placement is simple and safe and is used by a third of colorectal surgeons in UK and Ireland. Given their simplicity, the efficacy of rectal tubes in reducing local anastomotic complications requires further evaluation within the confines of a randomised controlled trial.

Catheterization↗
PubMed2006

Hemispheric differences in protein kinase C betaII levels in the rat amygdala: baseline asymmetry and lateralized changes associated with cue and context in a classical fear conditioning paradigm.

The amygdala is critically important for fear learning, and specific kinases have been implicated as contributors to the mechanisms that underlie learning. We examined levels of protein kinase C betaII (PKC betaII) in the left and right lateral and basolateral nuclei (LA/BLA) of the amygdala from animals that were classically fear conditioned with tones as cues and footshocks. Groups consisted of animals that received neither tones nor shocks, paired tones and shocks, or unpaired tones and shocks. At 1 h after conditioning, some animals from each group were used for biochemical measurements of PKC betaII levels and other animals were given probe trials to assess freezing behavior to cue and context. The levels of PKC betaII were greater in the left hemisphere in animals receiving neither tones nor shocks and animals receiving paired tones and shocks. PKC betaII levels were greater in the right hemisphere of animals receiving randomly presented tones and shocks. Freezing times to cue were long (>80% of probe trial time) in both the paired tone/shock and randomly unpaired tone/shock groups. Freezing times to context were long in the unpaired tone/shock group, but not the paired tone/shock group. Correlational analyses showed that freezing times to context, but not cue, precisely predicted the right/left relation of PKC betaII levels in the LA/BLA: the greater the time spent freezing to context, the greater the increase in right hemisphere PKC betaII levels. We conclude that fear conditioning causes hemisphere and input specific increases in PKC betaII in the rat LA/BLA.

Acoustic Stimulation↗
PubMed2006

Determinants of neuropsychological and behavioural outcomes in early childhood survivors of congenital heart disease.

AIMS: To evaluate the relative effect of cyanosis, surgical interventions and family processes on neuropsychological and behavioural outcomes in 4-year-old survivors of serious congenital heart disease (CHD). METHODS: 90 children with a range of cyanotic and acyanotic conditions, who underwent either corrective or palliative surgery, completed a neuropsychological and behavioural evaluation. Families of participants were also profiled by evaluation of maternal mental health, worry, social support, parenting style and family functioning. RESULTS: Compromised neuropsychological outcomes were associated with a combination of cyanotic conditions and open-heart surgery, but this was not exacerbated by having a complex, palliative, status. Both cyanotic and acyanotic conditions were associated with specific sensorimotor delays, regardless of method of the correction. Only children with complex conditions and palliative interventions seemed at risk of poor behavioural outcomes; indeed, children with cyanosis with complete repair showed favourable behavioural outcomes compared with controls. Multivariate analyses highlighted the sometimes greater relevance of family processes (eg parenting style, maternal mental health and worry), rather than disease or surgical factors, in predicting especially behavioural outcomes. CONCLUSIONS: The findings (1) suggest a more complex relationship between cyanosis, surgical methods of correction, neuropsychological and behavioural outcomes than previously charted, (2) highlight that family processes may be aetiologically more important than disease and surgical factors, and (3) indicate specific targets for secondary prevention programmes for this at-risk population.

Anxiety↗
PubMed2006

Endoscopic alternatives in managing anastomotic strictures of the colon and rectum.

BACKGROUND: The development of anastomotic strictures following colorectal surgery is a frequent problem, but commonly used treatments (e.g. dilatation or revisional surgery) are often ineffective. This study assessed the efficacy of self-expanding metallic stents (SEMS) and endoscopic transanal resection of strictures (ETARS) in managing high-grade benign colorectal anastomotic strictures after the failure of first-line therapies. METHODS: All patients with biopsy-proven benign anastomotic strictures (luminal diameter<7 mm) following colorectal surgery, seen in the period April 1995-October 2004, were treated with either SEMS or ETARS. RESULTS: In the study period, we treated 10 patients (7 men) of median age 71 years. Ten ETARS procedures were performed in six patients, with a mean operating time of 42 minutes and a median hospital stay of 1 day. Early complications of ETARS included: re- operation for bleeding, asymptomatic anastomotic perforation and technical failure in an acutely angulated stricture. SEMS were successfully inserted into five patients (including two with failed ETARS) without any early complications. Overall, nine patients have had satisfactory longterm outcomes (median follow-up, 29 months; range, 3-75 months). CONCLUSIONS: SEMS and ETARS are simple, safe and effective methods in treating high-grade anastomotic strictures.

Aged↗
PubMed2006

Structural basis for the nuclear protein import cycle.

Transport of macromolecules between the nuclear and cytoplasmic compartments through NPCs (nuclear pore complexes) is mediated by soluble transport factors that are commonly members of the importin-beta superfamily. In the nuclear protein import cycle, importin-beta binds cargo in the cytoplasm (usually via the importin-alpha adaptor) and transports it through NPCs with which it interacts transiently by way of NPC proteins ('nucleoporins') that contain distinctive FG (Phe-Gly) sequence repeats. In the nucleus, Ran-GTP binds to importin-beta, dissociating the import complex. The importin-beta-Ran-GTP complex recycles to the cytoplasm, whereas importin-alpha is recycled by the importin-beta family member CAS (cellular apoptosis susceptibility protein) complexed with Ran-GTP. Cytoplasmic RanGAP (Ran GTPase-activating protein) dissociates these complexes, freeing the importins for another import cycle. Crystallography and biochemical and cellular studies have enabled a molecular description of the transport cycle to be developed and tested using protein engineering and computer modelling. Importin-beta family members are elongated flexible molecules that adapt their shape to encircle their cargoes. Ran-GTP binds at three sites along importin-beta and CAS, locking the molecules into a rigid conformation that is unable to bind cargoes effectively. Interactions between transport factors and key nucleoporins (such as Nup1p, Nup2p and Nup50) accelerate the formation and dissolution of many of these complexes.

Animals↗
PubMed2006

Self-expanding metallic stents in the treatment of benign colorectal disease: indications and outcomes.

OBJECTIVE: The use of stents for benign colorectal obstruction is considered controversial because of a lack of data and perceived high failure and complication rates. The aim of this study was to evaluate the indications and outcomes following stent placement for benign colorectal disease in a UK district general hospital and to review the published literature. PATIENTS AND METHODS: Between 1997 and 2004, 11 of 90 attempted stent insertions were performed for benign colorectal disease (diverticular disease, 4; anastomotic strictures, 4; idiopathic rectal stricture, 1; rectal endometriosis, 1; caecal volvulus, 1). Complications and outcomes were analysed from a prospective database. RESULTS: Stent insertion was successful in nine patients. Early complications occurred in two patients (both with diverticular disease): one patient failed to decompress and needed a colostomy and laparotomy was performed in a second patient who developed peritonitis after five days although no stent perforation of the bowel was identified. Two patients were successfully decompressed and underwent subsequent elective surgery with full bowel preparation. Stent placement resulted in symptomatic improvement in three out of four patients with anastomotic strictures (allowing closure of defunctioning stomas) and in the one patient with an idiopathic rectal stricture. Stent migration occurred in two of these patients without recurrence of symptoms. Stent fracture occurred in one patient, who remained symptomatic. CONCLUSIONS: Self-expanding metallic stents are an effective treatment for benign colorectal obstructions, especially anastomotic strictures with long-term patency. Stents should be avoided in acute diverticular disease because of a higher incidence of complications.

Aged↗
PubMed2005

Drug resistance and neurotransmitter receptors of nematodes: recent studies on the mode of action of levamisole.

Here we review recent studies on the mode of action of the cholinergic anthelmintics (levamisole, pyrantel etc.). We also include material from studies on the free living nematode Caenorhabditis elegans. The initial notion that these drugs act on a single receptor population, while attractive, has proven to be an oversimplification. In both free living and parasitic nematodes there are multiple types of nicotinic acetylcholine receptor (nAChR) on the somatic musculature. Each type has different (sometimes subtly so) pharmacological properties. The implications of these findings are: (1) combinations of anthelmintic that preferentially activate a broad range of nAChR types would be predicted to be more effective; (2) in resistant isolates of parasite where a subtype has been lost, other cholinergic anthelmintics may remain effective. Not only are there multiple types of nAChR, but relatively recent research has shown these receptors can be modulated; it is possible to increase the response of a parasite to a fixed concentration of drug by altering the receptor properties (e.g. phosphorylation state). These findings offer a potential means of increasing efficacy of existing compounds as an alternative to the costly and time consuming development of new anthelmintic agents.

Adenosine Triphosphate↗
PubMed2005

The effects of stationary periods and external temperature and humidity on thermal stress conditions within sheep transport vehicles.

AIM: To identify the contributions of stationary periods and external climatic environments to thermal stress conditions for sheep on livestock transport vehicles during journeys in summer. METHODS: Two livestock transport vehicles carrying sheep, operating under commercial conditions in New Zealand, were monitored during February and March 2002. Temperature and humidity were logged in five pens inside each vehicle, as well as externally. From these data, the temperature-humidity index (THI) was calculated. Global positioning equipment was used to log the location of the vehicle and whether it was moving or stationary. Regression analysis was used to identify factors that made a significant contribution to the THI within the vehicle. Regression models included the effects of vehicle, journey, initial ambient temperature or THI, pen position and duration of each stationary period. RESULTS: The THI in the livestock pens generally increased when vehicles were stationary. The highest THI value (95) was recorded in a vehicle on an enclosed deck of a Cook Strait ferry. Ambient conditions, the initial THI of a pen, and duration of the stationary period were all significant contributors to increases in the THI. Some increases in the THI occurred in stationary vehicles despite ambient conditions being mild, suggesting that lack of airflow was a critical factor. During stationary periods, 34% of THI readings exceeded 75, and, on average, the THI increased by 0.16 for every minute of a stationary period. CONCLUSIONS: Increases in the THI that could be detrimental to the welfare of sheep could occur on stationary sheep transport vehicles at most daytime ambient temperatures during summer. For a given stocking density and vehicle design, the THI of a pen increased in proportion to the duration of the stationary period. Mild ambient conditions (<25 degrees C) provided some protection against excessive THI increases if the duration of the stop was limited, but drivers are best advised to park their vehicles where there is airflow, and to minimise the duration of stops where possible. Livestock transport vehicles during summer should not be placed on enclosed ferry decks where airflow is absent or minimal.

Animal Husbandry↗
PubMed2005

A prospective cohort study comparing hospital admission for gastro-enteritis with home management.

OBJECTIVES: To compare physical and psychological outcomes in children presenting at Accident and Emergency Departments (A&E), diagnosed with gastro-enteritis and admitted to hospital with those of a similar age, sex and severity of illness discharged home. The physical and psychological well-being of children in these two groups, in the month after the episode, were compared as was further use of health care services. DESIGN: A prospective cohort study. METHODS: A comparison of 116 children aged 1-6 years with gastro-enteritis, presenting at A&E over a 6 months period. Admitted children were compared with children discharged, of a similar age, sex and illness severity (triage score) with follow-up at 1 week and 1 month. Clinical history, psychosocial factors, investigations and outcomes were recorded at presentation and physical, psychological and family outcomes at 1 week and 1 month. RESULTS: Of 116 children, 112 (97%) completed the study (56 in each group). No differences were detected in psychosocial factors, socio-economic status, family factors, time of arrival at A&E or waiting times. Parental perception of illness was greater in the admitted group (P < 0.005), but was recorded after the decision on admission was made. At 1 week follow-up admitted children had increased separation anxiety compared with children who were discharged (P < 0.05), but this difference disappeared at 1 month. Clinical outcomes were the same for both groups, although admitted children had more investigations (91% vs. 39%). Parents were equally satisfied with their child's treatment, but one-third of children in both groups sought further consultation with a health professional in the following week. CONCLUSIONS: There is no statistically significant difference in socio-demographic data, time of arrival at A&E, waiting times, clinical and psychosocial outcomes in children with acute gastro-enteritis admitted to hospital compared with a group of children of similar age, gender and severity of illness managed at home. However, parents seek reassurance and follow-up of acutely ill children, even if the child is admitted to hospital, which has service and resource implications.

Child↗
PubMed2005

Colovesical fistula--is a surgical approach always justified?

OBJECTIVE: There is a tendency to over investigate patients with colovesical fistula and to advise surgical intervention as the sole course of action. Most patients are elderly and operative intervention often carries a high morbidity and mortality. PATIENTS AND METHODS: A retrospective study of 50 patients diagnosed with a colovesical fistula over a 12-year period was undertaken at our institution. The notes of all these patients were reviewed using a standardized proforma to look at the referral pattern, symtomatology, investigation, treatment and outcomes. RESULTS: Data analysis showed the median age of these patients to be 70 years with 92% having either pneumaturia or faecaluria or both as a symptom. There was no significant difference in disease-specific mortality in patients with benign colovesical fistula undergoing surgical intervention and patients treated conservatively. There was not a single documented case of septicaemia despite untreated colovesical fistula being present for a cumulative total of 3254 weeks. There was no statistically significant decline in the renal function due to the disease. CONCLUSION: We suggest that fewer investigations be performed for the diagnosis of colovesical fistula and conservative management offered to patients with benign pathology.

Adult↗
PubMed2005

Respiratory function monitoring during neonatal emergency transport.

This study reports for the first time the use of a respiratory function monitor in a prospective observational cohort of ventilated babies during transport. All 17 babies achieved target transcutaneous carbon dioxide tension within 15 minutes. Fifteen babies had improved ventilation with changes guided by the respiratory function monitor. The monitor was easy to use and useful.

Emergencies↗
PubMed2003

Vascular patterns in reactive lymphoid tissue and in non-Hodgkin's lymphoma.

The few studies published on angiogenesis in lymphoma have raised the question of whether or not microvessel density (MVD) is associated with more aggressive disease and have reported the observation that in follicular lymphomas, vessels are mature rather than immature. We investigated MVD and the vascular phenotype within follicular or diffuse large B-cell lymphomas, reactive nodes and tonsils. Vascular phenotype was defined by the expression or loss of reactivity to the antibody LH39 (detecting the LH39 laminin epitope of the basement membrane in mature vessels) and by detection of alpha V beta 3 (expressed on immature vessels). In reactive nodes and in follicular lymphomas, MVD was higher in the paracortex than in germinal centres or in neoplastic follicles. However, in neoplastic follicles an increase in alpha V beta 3-positive endothelium suggested the activation of an angiogenic pathway different from that present in the reactive follicles. In large B-cell lymphomas, MVD was higher than in reactive and neoplastic follicles but lower than in the reactive paracortex. The number of immature vessels (LH39 negative) and of alpha V beta 3-positive vessels was higher than in reactive lymph nodes and follicular lymphoma suggesting that a switch to a different angiogenic pathway has occurred. Finally, we have demonstrated that within reactive and neoplastic follicles vascular regression is occurring, perhaps constraining the growth of reactive follicles alongside other phenomena such as apoptosis. Vascular regression was previously believed to occur in adults only in ovarian and endometrial tissue. We conclude that different types of angiogenesis are present in follicular lymphomas and large B-cell lymphomas. This has implications for possible future therapies.

Basement Membrane↗
PubMed2003

Phase II study of the efficacy and safety of cisplatin-epinephrine injectable gel administered to patients with unresectable hepatocellular carcinoma.

PURPOSE: To study the efficacy and safety of percutaneous cisplatin-epinephrine (CDDP-EPI) injectable gel in patients with localized unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Eligible patients had histologically proven HCC, no prior treatment except for surgery, and no more than three tumors (each measured < or = 7 cm, total tumor volume < or = 200 cm(3)). They were treated percutaneously under ultrasound or computed tomography (CT) guidance, with up to 10 mL of CDDP-EPI gel (1 mL contains 4 mg of CDDP and 0.1 mg of EPI) per treatment and four treatments in 6 weeks to a maximum of eight treatments. The primary end points were tumor response, defined by change of percentage of tumor necrosis according to CT criteria, and safety. Survival parameters were secondary end points. RESULTS: From June 1997 to April 2000, 58 patients (median age, 65 years) entered the study. All patients were assessable for safety, and 51 were assessable for efficacy. The median number of treatments was four (range, one to eight treatments). Objective response rate was 53% (27 of 51 patients), including 16 complete and 11 partial responses. Of the 27 responders, 14 (52%) subsequently developed progressive disease, but in most of them (93%), a new tumor arose at untreated liver sites. Median survival was 27 months (range, 18.4 to 35.7 months). The 1-, 2-, and 3-year survival rates were 79%, 56%, and 14% respectively. The procedure was well tolerated with only minor side effects. CONCLUSION: Percutaneous local ablation with CDDP-EPI injectable gel can induce significant tumor necrosis and local control for localized unresectable HCC, and the treatment is well tolerated.

Adult↗
PubMed2003

The angiogenic receptor KDR is widely distributed in human tissues and tumours and relocates intracellularly on phosphorylation. An immunohistochemical study.

AIMS: Angiogenesis is an important factor in tumour growth and metastasis. Vascular endothelial growth factor receptor 2 (VEGFR-2) or KDR plays a crucial role in angiogenesis. The aim of this study was to raise and characterize antibodies against phosphorylated KDR which could be used for studies on human tissues to assess KDR activation and novel inhibitors of KDR activation in clinical trials. METHODS AND RESULTS: Three monoclonal antibodies and one rabbit polyclonal antiserum were produced. The specificity of the antibodies was confirmed by ELISA. One of the mouse antibodies and the rabbit polyclonal antiserum reacted with a 200-kDa band on a Western blot of human umbilical vein endothelial cell (HUVEC) lysates, the molecular weight of KDR. Immunohistochemical staining showed that phosphorylated KDR is present in a wide variety of normal tissues including liver, colon and placenta, and is not restricted to endothelium. It was also present in a number of human tumours including breast carcinomas, colonic carcinomas and non-Hodgkin's lymphomas. The pattern of staining was membranous, cytoplasmic and nuclear. CONCLUSIONS: This study has shown that phosphorylated KDR is present in a wide variety of tumour and tissue types and is not confined to endothelium.

Animals↗
PubMed2003

Long-range effects of retroviral insertion on c-myb: overexpression may be obscured by silencing during tumor growth in vitro.

The c-myb oncogene is a frequent target for retroviral activation in hemopoietic tumors of avian and mammalian species. While insertions can target the gene directly, numerous clusters of retroviral insertion sites have been identified which map close to c-myb and outside the transcription unit in T-lymphomas (Ahi-1, fit-1, and Mis-2) and monocytic and myeloid leukemias (Mml1, Mml2, Mml3, and Epi-1). Previous analyses showed no consistent effect of these insertions on c-myb expression, raising the possibility that other nearby genes were the true targets. In contrast, our analysis of four cell lines established from lymphomas bearing insertions at fit-1 (fti-1) (feline leukemia virus) and Ahi-1 (Moloney murine leukemia virus) shows that these display higher expression levels of c-myb RNA and protein compared to a panel of phenotypically similar cell lines lacking such insertions. An interesting feature of the cell lines with long-range c-myb insertions was that each also carried an activated Myc allele. The potential for oncogenic synergy between Myb and Myc in T-cell lymphoma was confirmed in transgenic mice overexpressing alleles of both genes in the T-cell compartment, lending further credence to the case for c-myb as the major target for long-range activation. In contrast, mapping and analysis of c-myb neighboring genes (HBS1 and FLJ20069) showed that the expression of these genes did not correlate well with the presence of proviral insertions. A possible explanation for the paradoxical behavior of c-myb was provided by one of the murine T-lymphoma lines bearing an insertion at Ahi-1 (p/m16i) that reproducibly down-regulated c-myb RNA and protein to very low levels or undetectable levels on prolonged culture. Our observations implicate c-myb as a key target of upstream and downstream retroviral insertions. However, overexpression may become dispensable during outgrowth in vitro, and perhaps during tumor progression in vivo, providing a potential rationale for the previously observed discordance between retroviral insertion and c-myb expression levels.

Animals↗
PubMed2003

Self-administration of epinephrine in children: a survey of current prescription practice and recommendations for improvement.

The prevalence of peanut allergy is increasing rapidly and many children are now prescribed self-injectable epinephrine as part of their management. We aimed to examine the current extent of self-injectable epinephrine dispensing to children in the Eastern Health and Social Services Board (EHSSB), Northern Ireland, including indications for prescription, investigations performed, information and training provided and actual usage. Dispensing records held by the EHSSB were examined for the period May to August 1998. All general practitioners prescribing 'Epipens' during this period were contacted and asked to identify the patient and provide contact details. Information was gathered using postal questionnaires sent to General Practitioners and parents. A total of 104 'Epipen' prescriptions were dispensed. Thirty-seven (36%) general practitioners responded to the initial questionnaire; of these 36 (35%) were suitable for analysis. Thirty-four parents were then contacted; 28 (82%) returned questionnaires were reviewed. The commonest indication for 'Epipen' prescription was peanut allergy (32 of 36 (89%) general practitioner responses; 25 of 28 (89%) parent responses). Twenty-six (72%) children had been seen by a specialist; all except one had either blood or skin tests. Six of the remaining eight children had no investigations. General practitioners reported 14 (39%) parents to have basic life support training, compared with six (21%) parents. Eighteen (64%) parents had been given written information regarding their child's allergy, nine (32%) had been referred to a dietician and seven (25%) children wore a medical warning bracelet. The Epipen had been used by three children; all three had multiple food allergies. This study has identified a great variability in the management of children with allergy including the need for specialist referral, further investigation, written allergy advice, referral to a dietician and formalised training in basic life support and administration of epinephrine. It suggests a lack of consensus amongst health care professionals as to the best practice in the management of potentially life threatening food allergy and indicates, at least, a need for better multidisciplinary communication.

Adolescent↗