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Biomedical subjects

T Hunt

Publications and source records attributed to T Hunt.

At least 19 recordsLinked to original sources
PubMed2005

Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations.

The nuclear-encoded Krebs cycle enzymes, fumarate hydratase (FH) and succinate dehydrogenase (SDHB, -C and -D), act as tumour suppressors. Germline mutations in FH predispose individuals to leiomyomas and renal cell cancer (HLRCC), whereas mutations in SDH cause paragangliomas and phaeochromocytomas (HPGL). In this study, we have shown that FH-deficient cells and tumours accumulate fumarate and, to a lesser extent, succinate. SDH-deficient tumours principally accumulate succinate. In situ analyses showed that these tumours also have over-expression of hypoxia-inducible factor 1alpha (HIF1alpha), activation of HIF1alphatargets (such as vascular endothelial growth factor) and high microvessel density. We found no evidence of increased reactive oxygen species in our cells. Our data provide in vivo evidence to support the hypothesis that increased succinate and/or fumarate causes stabilization of HIF1alpha a plausible mechanism, inhibition of HIF prolyl hydroxylases, has previously been suggested by in vitro studies. The basic mechanism of tumorigenesis in HPGL and HLRCC is likely to be pseudo-hypoxic drive, just as it is in von Hippel-Lindau syndrome.

Carcinoma, Renal Cell↗
PubMed2005

Sequential cohort study of Dacron patch closure following carotid endarterectomy.

BACKGROUND: Carotid endarterectomy reduces the risk of stroke and death in patients with severe carotid artery stenosis. This study examined whether the technique used to close the arteriotomy influenced the rate of perioperative transient ischaemic attack (TIA), stroke or death. METHODS: A cohort of 236 patients undergoing carotid endarterectomy at a single centre was studied; 117 patients had primary closure of the arteriotomy and 119 patients in a sequential series had closure with a Dacron patch. A standard endarterectomy with completion intraoperative duplex imaging and digital subtraction angiography was used throughout. RESULTS: Patch closure was associated with a significant reduction in the 30-day combined death, stroke and TIA rate: 10.3 per cent for primary closure versus 2.5 per cent for patch closure (P = 0.017). The risk of any cerebral event (stroke or TIA) was also significantly reduced (7.7 versus 1.7 per cent; P = 0.033). Residual stenosis on completion angiography was more common after primary closure (24.6 versus 7.4 per cent; P = 0.003). CONCLUSION: Dacron patch closure had a higher technical success rate on completion imaging and was associated with a significant reduction in the risk of perioperative stroke, TIA and death.

Adult↗
PubMed2004

Sacral fractures with neurological injury: is early decompression beneficial?

During a 6-year period, 177 patients with a displaced sacral fracture were treated at our level-one trauma centre. At the initial presentation, 13 patients demonstrated a neurological deficit as a result of their sacral fracture. Six patients underwent surgical decompression, and seven patients were managed without surgical decompression. All patients were re-assessed at an average follow-up of 27.1 (range 12-84) months using the modified SOFCOT Index and the SF-36. Patients undergoing surgical decompression had a significantly better neurological improvement as measured by the modified SOFCOT Index (p=0.014). Moreover, patients undergoing surgical decompression had a significantly better physical function than the patients that were managed without surgical decompression, as measured by the SF-36 (p=0.044). We therefore believe that patients undergoing surgical decompression achieve better neurological improvement and better functional results.

Adolescent↗
PubMed2004

Porcine small intestine submucosa as a flexor tendon graft.

An attractive strategy for tendon tissue engineering is the use of natural extracellular matrices as scaffold materials. One matrix that has been shown to promote healing and regeneration of neotissue in various applications is porcine-derived small intestinal submucosa. It was the objective of this study to investigate small intestinal submucosa for intrasynovial flexor tendon grafting in a canine model. We hypothesized that at 6 weeks small intestinal submucosa grafts would undergo host cell infiltration, neovascularization, and replacement by host neotendon. We also hypothesized that small intestinal submucosa grafts would be incorporated by the host without extensive adhesions to surrounding tissues and therefore maintain normal digit function. An intrasynovial tendon autograft was used as a gold standard. At 6 weeks the intrasynovial tendon autografts remained viable, contained normal numbers of cells along their length, and had minimal peritendinous adhesions. Four of six autografts had normal function as determined by rotation of the distal interphalangeal joint. Also at 6 weeks, the small intestinal submucosa grafts had host cell infiltration, neovascularization, and wavy, oriented tissue. However, ubiquitous adhesions together with impaired function in all cases suggest that small intestinal submucosa grafts in the configuration used are not suitable as full-length intrasynovial grafts in this tendon and animal model.

Animals↗
PubMed2004

The emerging animal health delivery system in the People's Republic of China.

Livestock production in the People's Republic of China has expanded at an unprecedented rate over the last decade and this trend is expected to continue into the foreseeable future. Government and private sector investment supports this growth, and the fact that small farmers are incorporating more animal husbandry into their work is expected to mitigate some of the concerns over recent World Trade Organization accession, particularly in the more precarious grain growing regions. Modernisation and intensification of the livestock industry in the People's Republic of China is subject to significant risks as regards both infectious and production-related diseases and within the framework of food safety and public health challenges. Although historically, the veterinary service system in the People's Republic of China has been successful in the eradication and control of major disease outbreaks, domestic and international market concerns are providing the catalyst for significant reforms in the animal health delivery system in the country. This paper provides an overview of the existing veterinary system in terms of the education and qualifications of veterinary personnel, delivery mechanisms, and future approaches to reforming the system in the context of a dynamic livestock industry in transition.

Animal Husbandry↗
PubMed2003

Factors determining the duration of tracheal intubation in cardiac surgery: a single-centre sequential patient audit.

BACKGROUND AND OBJECTIVE: The study was designed to identify those factors associated with early tracheal extubation following cardiac surgery. Previous studies have tended to concentrate on surgery for coronary artery bypass or on other selected cohorts. METHODS: Sequential cohort analysis of 296 unselected adult cardiac surgery patients was performed over 3 months. RESULTS: In total, 39% of all patients were extubated within 6 h, 89% within 24 h and 95% within 48 h. Delayed extubation (>6 h after surgery) appeared unrelated to age, gender, body mass index, a previous pattern of angina or myocardial infarction, diabetes, preoperative atrial fibrillation, and preoperative cardiovascular assessment, as well as other factors. Delayed tracheal extubation was associated with poor left ventricular, renal and pulmonary function, a high Euroscore, as well as the type, duration and urgency of surgery. Early extubation (<6 h) was not associated with a reduced length of stay in either the intensive care unit or in hospital compared with patients who were extubated between 6 and 24 h. In these groups, it is presumed that organizational and not clinical factors appear to be responsible for a delay in discharge from intensive care. Patients who were extubated after 24 h had a longer duration of hospital stay and a greater incidence of postoperative complications. Postoperative complications were not adversely affected by early tracheal extubation. CONCLUSIONS: In an unselected sequential cohort, both patient- and surgery-specific factors may be influential in determining the duration of postoperative ventilation of the lungs following cardiac surgery. In view of the changing nature of the surgical population, regular re-evaluation is useful in reassessing performance.

Aged↗
PubMed2002

Role of routine intraoperative endoscopy in laparoscopic bariatric surgery.

BACKGROUND: Laparoscopic bariatric surgery is a challenging procedure with a high risk of technical misadventures that may increase postoperative morbidity. Routine intraoperative endoscopy may reduce postoperative morbidity. This article reviews our 6-year experience. METHODS: From April 1995 to September 2001, we performed 825 laparoscopic bariatric procedures: 743 roux gastric bypasses, 55 vertical banded gastroplasties, 18 laparoscopic adjustable gastric bands, and 9 gastric pacemakers. All the patients underwent flexible endoscopy by the primary surgeon at completion of the operation to assess for technical errors. RESULTS: The 34 intraoperative technical errors (4.1%) identified included 29 suture and staple line leaks, 2 bougie perforations, 2 inadvertent stoma closures secondary to the suture line, and 1 mucosal perforation in a gastric pacemaker. All the errors were successfully repaired laparoscopically at the time of the procedure. Three leaks occurred postoperative (0.36%): 1 in the 34 repaired errors (2.9%) and 2 in the remaining 791 patients (0.25%). CONCLUSIONS: Routine intraoperative endoscopy identified 34 correctable technical errors in a series of 825 laparoscopic bariatric procedures. Of these, 33 (97%) were repaired successfully, which reduced postoperative morbidity.

Adolescent↗
PubMed2002

Psychometric validation of an overactive bladder symptom and health-related quality of life questionnaire: the OAB-q.

OBJECTIVE: Overactive bladder (OAB) is characterized by symptoms of urinary frequency and urgency, with and without incontinence, and has been shown to have significant impact on health-related quality of life (HRQL). Currently, no OAB-specific questionnaires exist to evaluate all symptoms of OAB; thus we sought to evaluate the psychometric properties of a newly developed OAB HRQL questionnaire. METHODS: The 33-item, self-administered OAB-q contains a symptom bother and HRQL scale. Both the OAB-q and SF-36 were completed by participants from two sources: (1) a community sample who screened positive for OAB in a random-digit dial telephone survey and participated in a clinical validation study (n = 254); and (2) a clinical study of patients' seeking treatment for OAB symptoms (baseline assessment) (n = 736). Item and exploratory factor analysis were performed to assess the subscale structure of the questionnaire. Psychometric evaluation was conducted to assess reliability and validity. RESULTS: Seventy-four percent of the sample were women with mean age of 58.5. Participants with continent and incontinent symptoms reported significantly greater symptom bother and HRQL impact than normal participants. Significant differences were present among all patient groups in all OAB-q subscales (p < 0.0001) except sleep where the impact of continent and incontinent OAB was similar, but significantly worse than normal participants (p < 0.0001). Internal consistency was high with the subscale Cronbach alpha-values ranging from 0.86 to 0.94. CONCLUSION: The OAB-q is a reliable and valid instrument that discriminates between normal and clinically diagnosed continent and incontinent OAB participants. The OAB-q demonstrates that both continent and incontinent OAB symptoms cause significant symptom bother and have a negative impact on HRQL.

Adaptation, Psychological↗
PubMed2002

Bone marrow derivation of pericryptal myofibroblasts in the mouse and human small intestine and colon.

BACKGROUND AND AIMS: In order to establish whether extraintestinal cells contribute to the turnover and repair of gastrointestinal tissues, we studied the colons and small intestines of female mice that had received a male bone marrow transplant, together with gastrointestinal biopsies from female patients that had developed graft versus host disease after receiving a bone marrow transplant from male donors. METHODS: Using in situ hybridisation to detect Y chromosomes and immunohistochemistry, we demonstrated that cells derived from injected bone marrow frequently engrafted into the intestine and differentiated into pericryptal myofibroblasts. RESULTS: In the human intestine, we confirmed by combining in situ hybridisation with immunostaining for smooth muscle actin that the bone marrow derived cells within the intestine exhibited a myofibroblast phenotype. In female mouse recipients of male bone marrow grafts, we observed colocalisation of Y chromosomes and clusters of newly formed marrow derived myofibroblasts. While few of these were present at seven days after bone marrow transplantation, they were numerous at 14 days, and by six weeks entire columns of pericryptal myofibroblasts could be seen running up the sides of crypts in both the small intestine and colon. These columns appeared to extend into the villi in the small intestine. Within the intestinal lamina propria, these Y chromosome positive cells were negative for the mouse macrophage marker F4/80 antigen and CD34. CONCLUSIONS: Bone marrow derived pericryptal myofibroblasts were present in the mouse intestine following irradiation and bone marrow transplant, and in the intestines of human patients suffering graft versus host disease following a bone marrow transplant. Our data indicate that bone marrow cells contribute to the regeneration of intestinal myofibroblasts and epithelium after damage, and we suggest that this could be exploited therapeutically.

Animals↗
PubMed2001

Elevated plasma surfactant protein-B predicts development of acute respiratory distress syndrome in patients with acute respiratory failure.

Surfactant protein-B is a lung specific protein secreted into the air spaces by pulmonary epithelial type II cells that leaks into the bloodstream in increased amounts in patients with ARDS. To test whether elevated plasma levels of surfactant protein-B would predict the development of ARDS in patients with acute hypoxemic respiratory failure, plasma and lung injury scores were collected at study entry and daily thereafter for 3 d from 54 patients admitted to our intensive care unit. ARDS was defined as a new bilateral infiltrate on chest radiograph and a lung injury score > or = 2.5. Twenty patients developed ARDS, of whom seven died. Although the initial lung injury score was not predictive of ARDS, the initial plasma surfactant protein-B was predictive (area under the curve = 0.77 [0.63 to 0.90], nonparametric receiver-operating characteristic analysis). In this cohort, plasma surfactant protein-B was particularly predictive of ARDS when applied to patients suffering a direct lung insult (area under the curve = 0.87 [0.72 to 1.02]), with a sensitivity of 85% (95% CI: 55 to 98%) and specificity of 78% (40 to 97%) at a cutoff of 4,994 ng/ml.

Acute Disease↗
PubMed2001

Antisense oligonucleotides selected by hybridisation to scanning arrays are effective reagents in vivo.

Transcripts representing mRNAs of three Xenopus cyclins, B1, B4 and B5, were hybridised to arrays of oligonucleotides scanning the first 120 nt of the coding region to assess the ability of the immobilised oligonucleotides to form heteroduplexes with their targets. Oligonucleotides that produced high heteroduplex yield and others that showed little annealing were assayed for their effect on translation of endogenous cyclin mRNAs in Xenopus egg extracts and their ability to promote cleavage of cyclin mRNAs in oocytes by RNase H. Excellent correlation was found between antisense potency and affinity of oligonucleotides for the cyclin transcripts as measured by the array, despite the complexity of the cellular environment.

Animals↗
PubMed2001

Anaphase-promoting complex/cyclosome-dependent proteolysis of human cyclin A starts at the beginning of mitosis and is not subject to the spindle assembly checkpoint.

Cyclin A is a stable protein in S and G2 phases, but is destabilized when cells enter mitosis and is almost completely degraded before the metaphase to anaphase transition. Microinjection of antibodies against subunits of the anaphase-promoting complex/cyclosome (APC/C) or against human Cdc20 (fizzy) arrested cells at metaphase and stabilized both cyclins A and B1. Cyclin A was efficiently polyubiquitylated by Cdc20 or Cdh1-activated APC/C in vitro, but in contrast to cyclin B1, the proteolysis of cyclin A was not delayed by the spindle assembly checkpoint. The degradation of cyclin B1 was accelerated by inhibition of the spindle assembly checkpoint. These data suggest that the APC/C is activated as cells enter mitosis and immediately targets cyclin A for degradation, whereas the spindle assembly checkpoint delays the degradation of cyclin B1 until the metaphase to anaphase transition. The "destruction box" (D-box) of cyclin A is 10-20 residues longer than that of cyclin B. Overexpression of wild-type cyclin A delayed the metaphase to anaphase transition, whereas expression of cyclin A mutants lacking a D-box arrested cells in anaphase.

Amino Acid Sequence↗
PubMed2001

Bone marrow contributes to renal parenchymal turnover and regeneration.

In order to establish whether extra-renal cells contribute to the turnover and repair of renal tissues, this study examined kidneys of female mice that had received a male bone marrow transplant and kidney biopsies from male patients who had received kidney transplants from female donors. By using in situ hybridization to detect Y-chromosomes it could be demonstrated that circulating stem cells frequently engraft into the kidney and differentiate into renal parenchymal cells. In the human renal grafts it was confirmed that some of the recipient-derived cells within the kidney exhibited a tubular epithelial phenotype, by combining in situ hybridization with immunostaining for the epithelial markers CAM 5.2 and the lectin Ulex europaeus. Female mouse recipients of male bone marrow grafts showed co-localization of Y-chromosomes and tubular epithelial markers Ricinus communis and Lens culinaris, and a specific cytochrome P450 enzyme (CYP1A2) indicating an appropriate functional capability of clustered newly formed marrow-derived tubular epithelial cells. Y-chromosome-containing cells were observed within glomeruli, with morphology and location appropriate for podocytes. Within the murine kidney, these Y-chromosome-positive cells were negative for the mouse macrophage marker F4/80 antigen and leukocyte common antigen, but were vimentin-positive. The presence of bone marrow-derived cells was noted in both histologically normal mouse kidneys and in human transplanted kidneys suffering damage from a variety of causes. These data indicate that bone marrow cells contribute to both normal turnover of renal epithelia and regeneration after damage, and it is suggested that this could be exploited therapeutically.

Animals↗
PubMed2001

The use of echocardiographic colour kinetic wall motion to differentiate broad complex tachycardia.

Discrimination between supraventricular tachycardia (SVT) with aberrant conduction from ventricular tachycardia (VT) is vital for the safe and effective management of both conditions. Electrocardiographic algorithms for the differentiation of broad complex tachycardia are complex and difficult to implement in the acute setting, with misdiagnosis occurring in up to 40% of acute presentations. This case study shows the potential for echocardiographic colour kinesis (eck) to support electrocardiographic differentiation. A 74-year old man in sinus rhythm with left bundle branch block (lbbb), a history of myocardial infarction and recurrent sustained VT underwent eck analysis of wall motion propagation during a programmed electrical ventricular stimulation study. Sequential 40 ms time frames of echocardiographic colour coded endocardial wall motion velocity were recorded on video during both induced VT of lbbb configuration and near isochronic atrially paced tachycardia in lbbb. During VT there was initial eck propagation of ventricular septal wall motion from the apex to the atria secondary to electrical depolarisation. During atrially paced tachycardia initial eck motion developed in the interatrial septum and atrial wall followed by propagation in the ventricular endocardial septal wall motion from the atria toward the ventricular apex. This eck technique potentially could be used to support the electrocardiographic diagnosis of a broad complex tachycardia.

Aged↗
PubMed2001

Low contact stress mobile bearing total knee arthroplasty: results at 5 to 13 years.

A total of 139 mobile bearing knee arthroplasties in 104 patients were evaluated at a mean follow-up of 7.8 years (range, 5-13 years). There were 80 cemented knees, 50 uncemented, and 9 hybrid (cemented tibia, uncemented femur). Ten knees were revised. Four knees were revised for aseptic loosening of an uncemented tibial component, and 1 knee was revised for loosening of an uncemented femoral component. One knee was revised for a recurrent dislocating bearing, and 1 knee was revised for instability. No mechanical loosening occurred in the cemented components. Three knee arthroplasties were revised for infection. A total of 66 patients (92 knees) were evaluated clinically and radiographically. Radiographic evaluation showed a 27% incidence of radiolucent lines for the femur and a 31% incidence of radiolucent lines for the tibia. No components were considered radiographically loose. The survivorship of mobile bearing knee arthroplasties was 93% at an average follow-up of 7.8 years. Aseptic loosening was statistically higher in uncemented components (P=.0051).

Aged↗
PubMed2001

The long form of CDK2 arises via alternative splicing and forms an active protein kinase with cyclins A and E.

We have reinvestigated the long form of cyclin-dependent kinase (CDK)2 that is expressed in many rodent cells. We show that the mRNA encoding CDK2L arises by alternative splicing and that the encoded protein can bind to, and be activated by, cyclins A and E. The complex of CDK2L with cyclin A has about half the specific activity of the equivalent CDK2-cyclin A complex. Also, CDK2L--cyclin A is inhibited to the same extent and by the same concentrations of p21(CIP1) as CDK2--cyclin A. The nucleotide sequences of intron V in the human and murine CDK2 genes, where the sequences encoding the 48-residue insert in CDK2L are located, show very high conservation in the position of the alternatively spliced exon and its surroundings. Despite this, we were not able to detect significant expression of CDK2L in human cell lines, although a low level is expressed in COS-1 cells from monkeys.

Alternative Splicing↗