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Biomedical subjects

M Griffin

Publications and source records attributed to M Griffin.

At least 19 recordsLinked to original sources
PubMed2006

Temporal sub units in dendritic trees.

This simulation study examines the possibility that dendritic sub units can be defined according to temporal aspects in the timing of populations of synaptic inputs. A two cell model with passive dendritic trees is used, which is subject to both common and independent synaptic inputs, the presence of common synaptic input results in a tendency for correlated firing in the two cell model. The strength of this correlation is used to measure the efficacy of the common synaptic inputs in modulating the output discharge of each neurone. Our results suggest that a small fraction of the total synaptic input can effectively modulate the timing of output spikes, this phenomenon is not dependent on the physical location of the inputs on the dendritic tree. This phenomenon depends on the presence of temporal correlation between the pre-synaptic spike trains that provide the common input. We propose to refer to these as temporal sub units.

Dendrites↗
PubMed2005

Matrix changes induced by transglutaminase 2 lead to inhibition of angiogenesis and tumor growth.

Administration of active TG2 to two different in vitro angiogenesis assays resulted in the accumulation of a complex extracellular matrix (ECM) leading to the suppression of endothelial tube formation without causing cell death. Matrix accumulation was accompanied by a decreased rate of ECM turnover, with increased resistance to matrix metalloproteinase-1. Intratumor injection of TG2 into mice bearing CT26 colon carcinoma tumors demonstrated a reduction in tumor growth, and in some cases tumor regression. In TG2 knockout mice, tumor progression was increased and survival rate reduced compared to wild-type mice. In wild-type mice, an increased presence of TG2 was detectable in the host tissue around the tumor. Analysis of CT26 tumors injected with TG2 revealed fibrotic-like tissue containing increased collagen, TG2-mediated crosslink and reduced organized vasculature. TG2-mediated modulation of cell behavior via changes in the ECM may provide a new approach to solid tumor therapy.

Animals↗
PubMed2005

Severity of asymptomatic carotid stenosis and risk of ipsilateral hemispheric ischaemic events: results from the ACSRS study.

OBJECTIVES: This study determines the risk of ipsilateral ischaemic neurological events in relation to the degree of asymptomatic carotid stenosis and other risk factors. METHODS: Patients (n=1115) with asymptomatic internal carotid artery (ICA) stenosis greater than 50% in relation to the bulb diameter were followed up for a period of 6-84 (mean 37.1) months. Stenosis was graded using duplex, and clinical and biochemical risk factors were recorded. RESULTS: The relationship between ICA stenosis and event rate is linear when stenosis is expressed by the ECST method, but S-shaped if expressed by the NASCET method. In addition to the ECST grade of stenosis (RR 1.6; 95% CI 1.21-2.15), history of contralateral TIAs (RR 3.0; 95% CI 1.90-4.73) and creatinine in excess of 85 micromol/L (RR 2.1; 95% CI 1.23-3.65) were independent risk predictors. The combination of these three risk factors can identify a high-risk group (7.3% annual event rate and 4.3% annual stroke rate) and a low risk group (2.3% annual event rate and 0.7% annual stroke rate). CONCLUSIONS: Linearity between ECST per cent stenosis and risk makes this method for grading stenosis more amenable to risk prediction without any transformation not only in clinical practice but also when multivariable analysis is to be used. Identification of additional risk factors provides a new approach to risk stratification and should help refine the indications for carotid endarterectomy.

Brain Ischemia↗
PubMed2005

Comparison of DNA extraction from cervical cells collected in PreservCyt solution for the amplification of Chlamydia trachomatis.

OBJECTIVE: The aim of this study was to compare and evaluate three methods of DNA extraction for the amplification of Chlamydia trachomatis in uterine cervical samples collected in PreservCyt solution. ThinPrep is the trade name for the slide preparation. METHODS: Thirty-eight samples collected in LCx buffer medium, which were identified as C. trachomatis infected by ligase chain reaction (LCR), were selected for this study. DNA from the PreservCyt samples was extracted by three methods: (i) QIAamp kit, (ii) boiling in Tris-EDTA buffer with Chelex purification, and (iii) Proteinase K digestion with Chelex purification. Sample DNA was tested for the presence of C. trachomatis by PCR using cryptic plasmid research (CTP) primers and major outer membrane protein research momp gene (MOMP) primers. Real-time (LightCycler) PCR for relative C. trachomatis quantification following DNA extraction was performed using primers (Hsp 60) for the 60 kDa heat-shock protein hsp60 gene. RESULTS: Amplification using CTP primers was the most successful with each of the extraction protocols. Boiling in buffer was the least successful extraction method. QIAamp was the best extraction method, yielding the most positives with both the CTP and MOMP primers. Proteinase K-Chelex extraction gave similar sensitivity to QIAamp extraction with CTP primers but lower for MOMP primers. CONCLUSIONS: The DNA extraction method must be carefully selected to ensure that larger PCR amplicons can be successfully produced by PCR and to ensure high sensitivity of detection of C. trachomatis. In this study it was found that the QIAamp extraction method followed by PCR with the CTP primers was the most successful for amplification of C. trachomatis DNA.

Antigens, Bacterial↗
PubMed2005

Factors associated with mortality in patients with asymptomatic carotid stenosis: results from the ACSRS Study.

AIM: This study determines the factors associated with mortality in patients with asymptomatic carotid stenosis. METHODS: Patients (n=1,101) with asymptomatic internal carotid artery stenosis greater than 50% in relation to the bulb diameter were followed up for a period of 6 to 84 (median 38) months. Stenosis was graded using duplex scanning and expressed as a percentage of the carotid bulb diameter. Clinical and biochemical risk factors were recorded. The end-points were ipsilateral ischemic stroke, cardiovascular death and all cause mortality. RESULTS: In a Cox multivariate analysis 6 factors emerged as independent predictors of risk. Age, male gender, cardiac failure, left ventricular hypertrophy on electrocardiogram (ECG) and myocardial ischemia on ECG were associated with increased risk. Antiplatelet therapy was associated with decreased risk. Based on these risk factors a high-risk group consisting of one third of the population with a 40% cumulative cardiovascular death rate and a 66% all cause death rate at 7 years could be identified. The remaining 2/3 consisted of a low-risk group with a 10% cumulative cardiovascular death rate and a 21% all cause death rate at 7 years (P<0.0001 compared to the high risk group). There was not any significant difference in the cumulative ipsilateral stroke rate, which was 12% in the low and 13% in the high cardiovascular risk group (Log Rank P>0.05). CONCLUSIONS: The methodology and findings from the ACSRS natural history study need to be applied to randomized controlled trials on the value of carotid endarterectomy or stenting in patients with asymptomatic carotid stenosis. They may help refine the indications for intervention in patients with carotid endarterectomy.

Cardiovascular Diseases↗
PubMed2005

Comparison of two intermittent pneumatic compression systems. A hemodynamic study.

AIM: Sequential leg compression has been previously shown to be superior to uniform compression. The aim of our study was to compare the hemodynamic effectiveness of the portable sequential compression device (SCD Express Compression System, Tyco Healthcare Group LP, Mansfield, MA, USA) with a rapid inflation device (VenaFlow, Aircast, Inc, Summit, NJ, USA). The former, by sensing venous refill time, commences compression when the calf veins are refilled. METHODS: The two devices were tested in 12 normal volunteers in the semirecumbent position using duplex ultrasound. Baseline and augmented flow velocity and volume flow were measured at the level of the common femoral vein, above the saphenofemoral junction. Refilling time was determined from velocity recordings of the common femoral vein. Total and peak volume of blood expelled per hour during compression were calculated using flow data and the individual cycling rate. RESULTS: Both devices increased venous flow velocity, up to 3.8 times the baseline (all P<0.001). Refill time of the rapid inflation device was shorter in comparison with the sequential compression device (15+/-2.2 vs 25+/-4 s; P<0.001), suggesting incomplete vein evacuation. The sequential compression device, by augmenting flow throughout a significantly longer compression period per cycle (10.9 s vs 6.3 s), expelled significantly more venous blood (121+/-68 vs 81+/-63 mL; P<0.001). Similarly, the total volume of blood expelled per hour with the sequential compression device was 100% higher than the rapid inflation device (9685+/-5426 vs 4853+/-3658 mL; P<0.001). Although peak velocity enhancement was higher with the rapid inflation device, flow augmentation (a product of average blood flow velocity) was comparable (669+/-367 vs 771+/-574 cm/s; P=0.223) with the sequential compression device, mainly because the rapid inflation device failed to maintain flow enhancement beyond the initial flow surge. CONCLUSIONS: Sequential compression showed hemodynamic superiority compared to a rapid inflation device. This was enhanced further by the sensing of refill time, which resulted in more compression cycles over time. The relative efficacy of the two devices in deep vein thrombosis prevention should be tested in future studies.

Blood Flow Velocity↗
PubMed2004

Tissue transglutaminase in normal and abnormal wound healing: review article.

A complex series of events involving inflammation, cell migration and proliferation, ECM stabilisation and remodelling, neovascularisation and apoptosis are crucial to the tissue response to injury. Wound healing involves the dynamic interactions of multiple cells types with components of the extracellular matrix (ECM) and growth factors. Impaired wound healing as a consequence of aging, injury or disease may lead to serious disabilities and poor quality of life. Abnormal wound healing may also lead to inflammatory and fibrotic conditions (such as renal and pulmonary fibrosis). Therefore identification of the molecular events underlying wound repair is essential to develop new effective treatments in support to patients and the wound care sector. Recent advances in the understating of the physiological functions of tissue transglutaminase a multi functional protein cross-linking enzyme which stabilises tissues have demonstrated that its biological activities interrelate with wound healing phases at multiple levels. This review describes our view of the function of tissue transglutaminase in wound repair under normal and pathological situations and highlights its potential as a strategic therapeutic target in the development of new treatments to improve wound healing and prevent scarring.

Animals↗
PubMed2004

Margin involvement and outcome in oesophageal carcinoma: a 10-year experience in a specialist unit.

AIMS: Positive microscopic margins after major cancer surgery adversely affect prognosis. We questioned whether the benefit of a multimodal approach in oesophageal carcinoma is due to reduced resection margin involvement and whether multimodal therapy alters the disease course when margins are involved. METHODS: Pathology specimens of 212 patients, treated with either multimodal therapy or surgery alone, were re-reviewed to assess margin involvement by tumour. Margin status was compared with recurrence and survival data. RESULTS: Margin involvement was decreased with multimodal therapy (16 of 103 patients) vs surgery (33 of 109 patients), associated with reduced tumour recurrence and a significant survival advantage. However, even with involved margins, multimodal therapy had lower recurrence vs surgery and a small survival benefit. CONCLUSIONS: Multimodal therapy significantly reduces margin involvement. The benefit of multimodal therapy remains highly significant for patients with clear margins. This study confirms for oesophageal carcinoma the value of an aggressive surgical approach in achieving negative resection margins.

Adenocarcinoma↗
PubMed2004

Elevated epsilon-(gamma-glutamyl)lysine in human diabetic nephropathy results from increased expression and cellular release of tissue transglutaminase.

INTRODUCTION: Diabetic nephropathy (DN) is the leading cause of chronic kidney failure, however the mechanisms underlying the characteristic expansion of the extracellular matrix (ECM) in diabetic kidneys remain controversial and unclear. In non-diabetic kidney scarring the protein crosslinking enzyme tissue transglutaminase (tTg) has been implicated in this process by the formation of increased epsilon-(gamma-glutamyl)lysine bonds between ECM components in both experimental and human disease. Studies in db+/db+ diabetic mice and in streptozotocin-treated rats have suggested a similar mechanism, although the relevance of this to human disease has not been addressed. METHODS: We have undertaken a retrospective analysis of renal biopsies from 16 DN patients with type 2 diabetes mellitus using an immunohistochemical and immunofluorescence approach, with tTg and epsilon-(gamma-glutamyl)lysine crosslink quantified by confocal microscopy. RESULTS: Immunofluorescent analysis of human biopsies (confocal microscopy) showed increases in levels of tTg (+1,266%, p < 0.001) and epsilon-(gamma-glutamyl)lysine (+486%, p < 0.001) in kidneys with DN compared to normal. Changes were predominantly in the extracellular periglomerular and peritubular areas. tTg staining correlated with epsilon-(gamma-glutamyl)lysine (r = 0.615, p < 0.01) and renal scarring (Masson's trichrome, r = 0.728, p < 0.001). Significant changes in epsilon-(gamma-glutamyl)lysine were also noted intracellularly in some (< or =5%) tubular epithelial cells. This is consistent with cells undergoing a novel transglutaminase-mediated cell death process in response to Ca2+ influx and subsequent activation of intracellular tTg. CONCLUSION: Changes in tTg and epsilon-(gamma-glutamyl)lysine occur in human DN. Cellular export of tTg may therefore be a factor in the perpetuation of DN by crosslinking and stabilisation of the ECM, while intracellular activation may lead to cell death contributing towards tubular atrophy.

Adolescent↗
PubMed2004

Prevention of venous thrombosis and thrombophlebitis in long-haul flights with pycnogenol.

The aim of this study was to evaluate the occurrence of deep venous thrombosis (DVT) and superficial vein thrombosis (SVT) and its prophylaxis with an oral anti-edema and antithrombotic agent (Pycnogenol, Horphag, Research Management SA, Geneva, Switzerland) in long-haul flights, in subjects at moderate to high-risk of DVT and SVT. The study pre-included 244 pre-selected subjects; 211 were included (33 were excluded for several reasons due to logistic problems) and 198 completed the study; 13 subjects were lost for follow-up at the end of the flight, all for non-medical problems (i.e., for difficult connections). All subjects were scanned within 90 minutes before the flight and within 2 hours after disembarking. Subjects were supplemented with 100 mg Pycnogenol per capsule. Treatment subjects received two capsules between 2 and 3 hours before flights with 250 mL of water; two capsules were taken 6 hours later with 250 mL of water and one capsule the next day. The control group received comparable placebo at the same intervals. The flight duration was on average 8 hours and 15 minutes (SD 55 min) (range, 7.45-12.33). In the control group there were five thrombotic events (one DVT and four superficial thromboses) while only nonthrombotic, localized phlebitis was observed in the Pycnogenol group (5.15% vs. no events; p<0.025). The ITT (intention to treat) analysis detects 13 failures in the control group (eight lost to follow up + five thrombotic events) of 105 subjects (12.4%) vs. five failures (4.7%; all lost, no thrombotic events) in the treatment group (p<0.025). No unwanted effects were observed. In conclusion, this study indicates that Pycnogenol treatment was effective in decreasing the number of thrombotic events (DVT and SVT) in moderate-to-high risk subjects, during long-haul flights.

Aviation↗
PubMed2004

Prevalence and number of Salmonella in irish retail pork sausages.

A national Salmonella control program in the pork industry was enacted in Ireland in August 2002. This study was undertaken as part of a larger project investigating the role of pork as a source of human salmonellosis in Ireland. The objective of this survey was to assess the prevalence of Salmonella in Irish pork sausage at retail level. Samples, comprising branded prepacked sausages and loose sausages from supermarket meat counters and butcher shops, were collected from selected retail sites in four cities from October to December 2001 and from June to August 2002. A three-tube most-probable-number method was used to enumerate Salmonella in a selected number of samples that were positive by enrichment. Salmonella serotypes were detected in 4.4 and 1.7% of samples at each of the respective sampling periods, a level similar to those reported in other U.S. and U.K. studies. Isolates were characterized by serotype, phage type, and antimicrobial susceptibility. Eighteen (70%) were resistant to at least one antimicrobial, and 15 (58%) were resistant to four or more antimicrobials. Most of the isolates exhibited resistance to tetracycline. Five different phage types were detected. DT104 was the predominant phage type among Salmonella Typhimurium isolates. This study revealed that multidrug-resistant salmonellae are present in a proportion of Irish sausages and that further risk analysis work is necessary in order to quantify the risk posed to public health.

Animals↗
PubMed2003

Where exactly is the deep inguinal ring in patients with inguinal hernias?

It is difficult to distinguish direct from indirect inguinal hernias on clinical examination. This study attempted to determine an anatomical basis for this finding. Fifty adult patients with primary inguinal hernias were assessed. The position of the deep inguinal ring (DIR) was estimated from the position of the anterior superior iliac spine (ASIS) and the pubic tubercle (PT) pre-operatively and then the actual distance from these landmarks was measured intra-operatively. The DIR was actually located at a mean of 41% (95% confidence interval (CI) 26-56%) of the way along the inguinal ligament from the PT towards the ASIS (regression slope 1.203; 95% CI 1.141-1.127), compared with the 50% which would be expected from traditional clinical methodology. The DIR was actually found at a mean of 51% (95% CI 33-69%) of the way along a line from the pubic symphysis to the ASIS (regression slope 1.421; 95% CI 1.343-1.499). Pre-operative estimates of the position of the DIR are not accurate measures of its true position in patients with inguinal hernias. Clinical examination of inguinal hernias cannot rely on a constant position of the DIR to determine whether a hernia is direct or indirect.

Adult↗
PubMed2003

Kidney transplantation without calcineurin inhibitors using sirolimus.

INTRODUCTION: With the introduction of new immunosuppressive medicines, it has become possible to determine the extent to which nephrotoxic medicines contribute to CAN. The aim of this study is to compare the safety and efficacy of calcineurin inhibitor (CI) free immunosuppression in a prospective, randomized trial comparing sirolimus-mycophenolate mofetil (MMF)-prednisone to tacrolimus- MMF-prednisone. METHODS: Patients are randomized at the time of transplant to receive either tacrolimus (target level 12 to 15 ng/mL in the first month) or sirolimus (target level 12 to 18 ng/mL in the first month). All patients also receive MMF (750 mg bid) and prednisone tapered to 10 mg/d by 3 months and thymoglobulin induction (1.5 mg/kg/d on days 0, 1, 2, 4 and 6). RESULTS: At this point we have 4-month follow-up in 85 patients. The acute rejection rate is 7.5% (3/40) in the tacrolimus group and 6.7% (3/45) in the sirolimus group. We have discontinued sirolimus in eight patients so far, with wound complications being the most common indication. Renal function appears to be better in the sirolimus group at 1 month after transplantation, but the difference is not statistically significant. CONCLUSIONS: While longer follow-up is needed, these results demonstrate that total avoidance of CI can be achieved with extremely low acute cellular rejection rates using sirolimus-based immunosuppression in combination with thymoglobulin, MMF, and prednisone.

Calcineurin Inhibitors↗
PubMed2003

p16INK4A as a marker for cervical dyskaryosis: CIN and cGIN in cervical biopsies and ThinPrep smears.

AIM: To examine the potential of p16(INK4A) as a biomarker for dysplastic squamous and glandular cells of the cervix in tissue sections and ThinPrep smears. METHODS: Immunocytochemical analysis of p16(INK4A) expression was performed on 22 normal cervical tissue samples, five cervical glandular intraepithelial neoplasia (cGIN), 38 cervical intraepithelial neoplasia 1 (CIN1), 33 CIN2, 46 CIN3, and 10 invasive cancer cases (eight squamous and two adenocarcinomas). All samples were formalin fixed and paraffin wax embedded, and immunohistochemical analysis was carried out using a mouse monoclonal anti-p16(INK4A) antibody after antigen unmasking. The staining intensity was assessed using a 0 to 3 scoring system. In addition, the expression status of p16(INK4A) was examined in 12 normal ThinPrep smears, one smear exhibiting cGIN, and a total of 20 smears exhibiting mild, moderate, and severe dyskaryosis. Human papillomavirus (HPV) detection was carried out using a modified SYBR green assay system. Fluorogenic polymerase chain reaction (PCR) and solution phase PCR were used for specific HPV typing. RESULTS: p16(INK4A) immunoreactivity was absent in all normal cervical tissues examined. Dysplastic squamous and glandular cells were positive for p16(INK4A) expression in all cases included in this study, except for one CIN3 case. p16(INK4A) expression was mainly nuclear in CIN1 cases, and both nuclear and cytoplasmic in CIN2, CIN3, cGIN, and invasive cases. All cases positive for HPV expressed the p16(INK4A) protein, although not all cases found positive for p16(INK4A) were HPV positive. In general, the p16(INK4A) staining intensity was lower in cases negative for HPV or those containing a low risk HPV type. CONCLUSION: This pattern of overexpression demonstrates the potential use of p16(INK4A) as a diagnostic marker for cervical squamous and also glandular neoplastic lesions. In addition, the technique can be used to identify individual dyskaryotic cells in ThinPrep smears. Thus, p16(INK4A) is a useful marker of cervical dyskaryosis.

Biomarkers↗