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Biomedical subjects

D J Scott

Publications and source records attributed to D J Scott.

At least 37 records · Page 2Linked to original sources

Role of the neutrophil in the development of systemic inflammatory response syndrome and sepsis following abdominal aortic surgery.

INTRODUCTION: There is evidence to suggest that the polymorphonuclear neutrophil (PMN) plays a critical early step in the development of the ischaemia-reperfusion syndrome, the systemic inflammatory response syndrome (SIRS) and sepsis. The PMN receptor CD16 plays an important role in phagocytosis, cell-mediated cytotoxicity and the release of free radicals and proteolytic enzymes. The aim of this study was to determine whether there is any relationship between PMN CD16 expression, phagocytosis and the development of sepsis. METHODS: Fifty patients who underwent elective infrarenal abdominal aortic aneurysm repair were studied. Venous blood was taken before operation, throughout surgery and for 7 days after operation. CD16 expression was measured, unstimulated and following further stimulation, by means of flow cytometry. Phagocytosis was determined using flow cytometry. RESULTS: Some 36 patients had an uncomplicated recovery; 14 developed SIRS or sepsis. There was no difference between the two groups with respect to nutritional, co-morbid or technical factors. In the group that developed septic complications after operation, the level of PMN CD16 expression was significantly higher before surgery (mean channel fluorescence (MCF) 30.2 versus 10.4; P < 0.05, Mann-Whitney U test) and throughout the postoperative period. Surgery produced no change in CD16 expression. After operation, stimulation of PMNs in the septic group resulted in a fall in CD16 expression (40.8 versus 20.4 MCF; P < 0.05, Mann-Whitney U test); surgery produced no change in the level of expression in the uncomplicated group. CONCLUSION: This study provides evidence of phenotypic and functional differences in neutrophil behaviour in patients who develop sepsis following aneurysm surgery.

Aged↗

Dual phase helical CT versus portal venous phase CT for the detection of colorectal liver metastases: correlation with intra-operative sonography, surgical and pathological findings.

AIM: To assess whether dual phase helical computed tomography (DPCT) of the liver improves the detection of colorectal liver metastases compared with portal venous phase (PVP) imaging alone. MATERIALS AND METHODS: DPCT was performed in 33 consecutive patients before laparotomy for resection of colorectal liver metastases. CT comprised 8-mm slice collimation with a pitch of 1 to 1.25; imaging was commenced 20-25 and 65-70 s after the start of injection of 150 ml of contrast medium at 5 ml/s to coincide with hepatic arterial phase (HAP) and PVP contrast enhancement, respectively. Four blinded observers independently reviewed the HAP, PVP and DPCT images recording the site and size of all lesions. Alternative-free response receiver operating characteristic (AFROC) methodology was used to analyse the results, which were correlated with surgery, intra-operative ultrasound and histology. RESULTS: The mean observer sensitivities for malignant lesion detection were 75.3% for DPCT, 69.7% for PVP imaging and 66.7% for HAP imaging alone. There was a statistically significant improvement in malignant lesion detection using DPCT when compared with PVP imaging alone (P < 0.05). The mean areas under the AFROC curves were 0.84 for DPCT and 0.82 for PVP (P < 0.03) imaging alone. CONCLUSION: The detection of colorectal liver metastases was marginally better with DPCT than with PVP imaging alone, but the discovery of additional lesions did not affect the management of any of the patients in this study.

Aged↗

Do patients with critical limb ischaemia undergo multiple amputations after infrainguinal bypass surgery?

BACKGROUND: it has been suggested that an aggressive policy of bypass for limb salvage in critical ischaemia may result in patients subsequently undergoing multiple amputations. The aim of this study was to test this suggestion in the context of a dedicated Vascular Surgical Unit in a U.K. teaching hospital. METHODS: three hundred and sixty-eight patients undergoing lower limb bypass operations for critical limb ischaemia between April 1991 and March 1999 were studied retrospectively. Their median age was 69 years (IQR 64--75) and 243 (66%) were men. RESULTS: seventy-five operations were followed by one or more amputation (20%). Only 2% were multiple amputations. Age and sex had no effect on amputation rates, but emergency bypass operations led to a higher rate of amputation in those with critical limb ischaemia. CONCLUSION: patients with critical limb ischaemia who undergo lower limb bypass surgery rarely have subsequent multiple amputation.

Aged↗

Long saphenous vein stripping and quality of life--a randomised trial.

OBJECTIVES: To assess the quality of life of patients undergoing sapheno-femoral junction (SFJ) ligation and long saphenous vein stripping (LSV), using two different techniques. DESIGN: Prospective, randomised trial. MATERIALS AND METHODS: Eighty patients were recruited and randomised to either Perforate Invagination (PIN) stripping (43) or Conventional stripping (37). Patients completed the Short Form 36 (SF-36) and EuroQol (EQ) questionnaires preoperatively, and postoperatively at 6 weeks and 6 months. RESULTS: Bodily pain, role function and physical summary were significantly improved at 6 months in the PIN stripping group. In the Conventional group, bodily pain and physical function were similarly improved, but not role function. EQ global quality of life was significantly and progressively improved at 6 weeks and 6 months in the PIN group (global score p<0.003; self-rated score p <0.001). In the Conventional group there was no overall improvement in global score or self-rated health. CONCLUSIONS: Primary varicose vein surgery is associated with significant and progressive improvements in quality of life scores. Whilst overall quality of health does improve in the Conventional group, this appears to be to a lesser extent than in the PIN group.

Adult↗

The use of impedance index in the surveillance of PTFE femorodistal grafts.

BACKGROUND: Impedance is the equivalent in pulsatile flow of resistance in steady flow. The impedance index has been used successfully in the surveillance of vein grafts, but its use has not been reported in the context of PTFE femorodistal grafts. METHODS: Twenty-eight patients (median age 68 years (IQR 59-73 years) and 20 men) undergoing 28 PTFE femorodistal grafts with a vein cuff were evaluated prospectively comparing the impedance index with standard duplex graft surveillance. All grafts were performed for critical ischaemia. At risk grafts were identified and treated appropriately after angiography. RESULTS: The primary patencies at 1 and 2 years were 82% and 50% respectively. Duplex identified 11 at risk grafts of which 9 had an identifiable correctable lesion. Impedance analysis overpredicted at risk status when compared with duplex in the immediate postoperative phase and was unsuccessful in detecting inflow disease or low flow relating to cardiac failure. Using a threshold index of 0.5, impedance analysis has a sensitivity of 87%, specificity of 88%, with positive and negative predictive values of 76% and 94% respectively. CONCLUSIONS: Impedance index is a non-invasive method of graft surveillance which is applicable to PTFE femorodistal bypasses and may be a useful alternative to duplex although formal validation studies will be required.

Aged↗

A new device for the measurement of disease severity in patients with intermittent claudication.

OBJECTIVES: To assess a new method of determining functional impairment in patients with intermittent claudication, the Double Physiological Walking Test (DPWT) using the PADHOC (Peripheral Arterial Disease Holter Control) device, against a standard treadmill test. DESIGN: Patients with intermittent claudication presenting to the department were considered for both the DPWT and a standard treadmill test. METHODS: initial claudicating distance, maximal walking distance and speed of walking were determined for both parts of the DPWT. Initial claudicating distance and maximal walking distance were determined from the treadmill test. Comparisons were made between the treadmill test and the DPWT. RESULTS: The treadmill test was unable to be performed in 22% of patients due to defined contraindications. There were strong correlations in both walking distances and disease severity when comparing the DPWT and the treadmill test. Patients in whom the treadmill test was contraindicated had significantly shorter walking distances on the DPWT than those who were able to complete a treadmill walking test. CONCLUSIONS: The DPWT correlates strongly with walking distances obtained from a standard treadmill test. However, the PADHOC can be used in a number of differing locations and settings as well as in patients in whom a treadmill test is contraindicated. It therefore has a role to play in the initial assessment of patients presenting with intermittent claudication.

Aged↗

Lack of inducible nitric oxide synthase promotes intestinal tumorigenesis in the Apc(Min/+) mouse.

BACKGROUND & AIMS: The role of the inducible isoform of nitric oxide synthase (Nos2 or iNOS) in intestinal tumorigenesis is unclear. Conflicting data also exist regarding the ability of Nos2 to modulate expression and/or activity of cyclooxygenase 2 (Cox-2), which promotes intestinal tumorigenesis. Therefore, we determined the effect of a null Nos2 genotype on intestinal tumorigenesis and Cox-2 expression/activity in the Apc(Min/+) mouse model of familial adenomatous polyposis. METHODS: Apc(Min/+)Nos2(-/-) mice were generated by successive crosses between C57BL/6-Apc(Min/+) and C57BL/6-Nos2(tm1Lau) mice. Adenoma characteristics of age-matched Apc(Min/+)Nos2(+/+) and Apc(Min/+)Nos2(-/-) mice were compared. The level and cellular localization of Nos2 messenger RNA (mRNA) expression in Apc(Min/+)Nos2(+/+) mouse intestine was determined. Cox-2 expression and activity were measured in both intestinal tissue and bone marrow-derived macrophages in vitro. RESULTS: Apc(Min/+)Nos2(-/-) mice developed significantly more intestinal adenomas than Apc(Min/+)Nos2(+/+) littermates. Epithelial cell Nos2 mRNA expression was decreased in adenomas compared with histologically normal Apc(Min/+)Nos2(+/+) intestine. There was no significant difference in Cox-2 expression or activity in either intestine or bone marrow-derived macrophages from Apc(Min/+)Nos2(+/+) and Apc(Min/+)Nos2(-/-) animals. CONCLUSIONS: Nos2 plays an antineoplastic role in the Apc(Min/+) mouse model of familial adenomatous polyposis. Nos2 does not modulate Cox-2 expression or activity in the Apc(Min/+) mouse.

Adenomatous Polyposis Coli Protein↗

Endovascular repair of an inflammatory abdominal aortic aneurysm complicated by aortoduodenal fistulation with an unusual presentation.

Aortoenteric fistulation (AEF) is a well-documented late complication of open abdominal aortic aneurysm (AAA) repair, occurring in between 0.4% and 4% of cases. In the absence of an anastomosis, AEF is likely to be rare after endovascular aneurysm repair (EVAR) and has only recently been described in the literature as a result of mechanical stent failure or migration. We present the case of a 61-year-old man who underwent EVAR for an AAA with a "nonspecific" periaortic inflammatory mass. Six months postoperatively, an AEF developed, presenting with metastatic sepsis followed by septic infective thromboembolization to his right leg, and amputation was necessary. His stent was well positioned and mechanically intact. We emphasize the need for vigilance about the risk of AEF when adopting an endovascular approach to repair the AAA with a nonspecific periaortic inflammatory mass and highlight the need for awareness about the unusual septic manifestations of AEF.

Aortic Aneurysm, Abdominal↗

Laparoscopic marsupialization and hemisplenectomy for splenic cysts.

BACKGROUND: Splenic cysts are a rare clinical entity in the United States, and historically, management has consisted of either partial or total splenectomy via an open approach. Laparoscopic treatment of splenic cysts with preservation of splenic parenchyma offers several advantages. Compared with the open approach, a laparoscopic approach may result in less postoperative pain and a more rapid return to full activity. Compared with total splenectomy, splenic preservation eliminates the risk of overwhelming postsplenectomy infection. PATIENTS AND METHODS: We present two patients with splenic cysts. One patient was treated with laparoscopic marsupialization of the cyst and the other with laparoscopic hemisplenectomy. RESULTS: Both patients are without further symptoms at 26 and 5 months' follow-up, respectively. CONCLUSIONS: Laparoscopic marsupialization and hemisplenectomy are appropriate treatment options for patients with splenic cysts.

Adult↗

The use of a standard proforma in breast cancer reporting.

AIM: To determine whether the introduction of a standard reporting proforma has led to an improvement in the completeness of histopathology reports for breast cancer excision specimens. METHODS: A standard reporting proforma was designed using the Royal College of Pathologists' minimum dataset for breast cancer histopathology reports and the national histopathology reporting form of the National Health Service (NHS) breast screening programme. This was introduced into our department in June 1999, with reports generated from the proforma replacing the standard text reports. The pathological information contained in 50 text reports issued before the introduction of the proforma and 50 reports generated using the proforma was compared with the minimum dataset and NHS breast screening programme guidelines. RESULTS: A general improvement in documentation of individual pathological features was noted after introduction of the proforma. This was most significant in relation to documentation of features, such as microcalcification and ductal carcinoma in situ. In addition, important features such as tumour grade, tumour size, and hormone receptor status were documented more frequently in the proforma group. There was an overall increase in the number of reports regarded as complete after introduction of the proforma. CONCLUSIONS: The introduction of a standard proforma led to a significant improvement in the completeness of breast cancer histopathology reports in this centre, but continued vigilance is needed to ensure that standards continue to improve.

Breast Neoplasms↗

Laparoscopic Roux-en-Y gastric bypass using the porcine model.

BACKGROUND: The laparoscopic Roux-en-Y gastric bypass (LRYGBP) may be performed using a variety of methods. The purpose of this study was to learn how to perform the Roux-en-Y gastric bypass operation laparoscopically, using a porcine model. MATERIALS AND METHODS: 11 domestic pigs (mean weight 47 kg) underwent LRYGBP. In 8 animals, a completely laparoscopic approach was attempted, while in 3 animals a hand-assist device was used. Techniques for anvil placement, pouch calibration, and limb-length measurement were evaluated. Animals were sacrificed at the end of the procedure, and operative results were recorded. RESULTS: The hand-assist device restored tactile feedback but obscured visualization. The gastrojejunostomy leak rate was 64%, and the jejunojejunostomy leak rate was 73%. Anvil placement using transgastric and transoral methods was feasible. Calibrating the pouch with a Baker's tube was more accurate than using anatomical landmarks. Measuring limb-lengths using Babcock clamps was reliable with practice. CONCLUSION: The frailty of the porcine small intestine may limit one's ability to achieve intact anastomoses. Despite the anatomic limitations, the porcine model was well-suited for skill development and evaluation of techniques for performing the LRYGBP operation.

Anastomosis, Roux-en-Y↗

Use of insulin pumps in pregnancies complicated by type 2 diabetes and gestational diabetes in a multiethnic community.

OBJECTIVE: To describe the use of insulin pump therapy in women with gestational diabetes mellitus (GDM) or type 2 diabetes in pregnancy and persistent hyperglycemia despite multiple injections of subcutaneous insulin. RESEARCH DESIGN AND METHODS: As part of a service audit, deliveries to women with diabetes at a single South Auckland hospital were reviewed from 1991 through 1994. Glycemic control was estimated by the mean of self-recorded and laboratory postprandial glucose concentrations. In a nested case-control study, pregnancies complicated by GDM/type 2 diabetes with use of an insulin pump were compared with those without insulin pump therapy and peak insulin requirements of 100-199 units/ day, matched for ethnicity and type of diabetes. RESULTS: A total of 30 of 251 Polynesian, European, and South Asian women with singleton pregnancies complicated by insulin-requiring GDM/type 2 diabetes used an insulin pump. An additional two women with high insulin requirements discontinued pump therapy. None of the women with GDM/type 2 diabetes experienced severe hypoglycemia, whereas 79% of the women had improved glycemic control within 1-4 weeks. Mothers using a pump had greater insulin requirements (median maximum 246 vs. 130 units per day) and greater weight gain (10.6 vs. 5.0 kg). Their babies were more likely to be admitted to the Special Care Baby Unit but were neither significantly heavier nor experienced greater hypoglycemia than control subjects. CONCLUSIONS: Insulin pump therapy seems to be safe and effective for maintaining glycemic control in pregnancies complicated by GDM/type 2 diabetes and requiring large doses of insulin.

Adult↗

The impact of intense laparoscopic skills training on the operative performance of urology residents.

PURPOSE: As laparoscopy has become more commonplace in urology, increased emphasis has been placed on laparoscopic education. We assessed the impact of laparoscopic skills training on the operative performance of urological surgeons inexperienced with laparoscopy. MATERIALS AND METHODS: Urology residents were prospectively randomized to undergo laparoscopic skills training (6) or no training (6). Baseline assessment of operative performance (scale 0 to 35) during porcine laparoscopic nephrectomy was completed by all subjects. Cumulative time to complete laparoscopic tasks using an inanimate trainer was also recorded. The skills training group then practiced inanimate trainer tasks for 30 minutes daily for 10 days. The 2 groups then repeated the timed inanimate trainer tasks and underwent repeat assessment of the ability to perform porcine laparoscopic nephrectomy. RESULTS: At baseline no statistical difference was noted in laparoscopic experience, inanimate trainer time or overall operative assessment in the 2 groups. In the skills training group mean cumulative time to complete inanimate trainer tasks decreased from 341 to 176 seconds (p = 0.003), while in the control group it decreased from 365 to 301 (p = 0.15). Operative assessment improved from initial to repeat porcine laparoscopic nephrectomy regardless of the trained versus control randomization grouping (22.0 to 27.8, p = 0.0008 and 20.8 to 26.5, p = 0.00007, respectively). CONCLUSIONS: In vivo experience enables urological surgeons inexperienced with laparoscopy to improve significantly in all aspects of complex laparoscopic procedures. In this pilot study the magnitude of improvement was independent of additional training in laparoscopic skills. Educational curriculum should include in vivo practice in addition to skills training.

Animals↗

Simplifying the internal iliac artery aneurysm.

Isolated aneurysms of the internal iliac (hypogastric) artery are a rare variant of aorto-iliac aneurysm disease, with an incidence at around 0.04% of all aorto-iliac aneurysms. Because of their location deep within the pelvis, they may present late and are often large. The incidence of rupture is high and may be up to 38% at initial presentation; furthermore, this has been reported to carry a 58% mortality rate. As such the early and aggressive management of isolated internal iliac artery aneurysms (IIAAs) is mandatory to avoid the high morbidity and mortality associated with rupture. This article includes a literature review regarding IIAAs and outlines the current surgical and endovascular management options for this most rare and technically challenging of aneurysms.

Aged↗

Metastasis-associated protein Mts1 (S100A4) inhibits CK2-mediated phosphorylation and self-assembly of the heavy chain of nonmuscle myosin.

A role for EF-hand calcium-binding protein Mts1 (S100A4) in the phosphorylation and the assembly of myosin filaments was studied. The nonmuscle myosin molecules form bipolar filaments, which interact with actin filaments to produce a contractile force. Phosphorylation of the myosin plays a regulatory role in the myosin assembly. In the presence of calcium, Mts1 binds at the C-terminal end of the myosin heavy chain close to the site of phosphorylation by protein kinase CK2 (Ser1944). In the present study, we have shown that interaction of Mts1 with the human platelet myosin or C-terminal fragment of the myosin heavy chain inhibits phosphorylation of the myosin heavy chain by protein kinase CK2 in vitro. Mts1 might also bind directly the beta subunit of protein kinase CK2, thereby modifying the enzyme activity. Our results indicate that myosin oligomers were disassembled in the presence of Mts1. The short C-terminal fragment of the myosin heavy chain was totally soluble in the presence of an equimolar amount of Mts1 at low ionic conditions (50 mM NaCl). Depolymerization was found to be calcium-dependent and could be blocked by EGTA. Our data suggest that Mts1 can increase myosin solubility and therefore suppress its assembly.

Blood Platelets↗

Interaction of sigma factor sigmaN with Escherichia coli RNA polymerase core enzyme.

The equilibrium binding and kinetics of assembly of the DNA-dependent RNA polymerase (RNAP) sigma(N)-holoenzyme has been investigated using biosynthetically labelled 7-azatryptophyl- (7AW)sigma(N). The spectroscopic properties of such 7AW proteins allows their absorbance and fluorescence to be monitored selectively, even in the presence of high concentrations of other tryptophan-containing proteins. The 7AWsigma(N) retained its biological activity in stimulating transcription from sigma(N)-specific promoters, and in in vitro gel electrophoresis assays of binding to core RNAP from Escherichia coli. Furthermore, five Trp-->Ala single mutants of sigma(N) were shown to support growth under conditions of nitrogen limitation, and showed comparable efficiency in activating the sigma(N)-dependent nifH promoter in vivo, indicating that none of the tryptophan residues were essential for activity. The equilibrium binding of 7AWsigma(N) to core RNAP was examined by analytical ultracentrifugation. In sedimentation equilibrium experiments, absorbance data at 315 nm (which reports selectively on the distribution of free and bound 7AWsigma(N)) established that a 1:1 complex was formed, with a dissociation constant lower than 2 microM. The kinetics of the interaction between 7AWsigma(N) and core RNAP was investigated using stopped-flow spectrofluorimetry. A biphasic decrease in fluorescence intensity was observed when samples were excited at 280 nm, whereas only the slower of the two phases was observed at 315 nm. The kinetic data were analysed in terms of a mechanism in which a fast bimolecular association of sigma(N) with core RNAP is followed by a relatively slow isomerization step. The consequences of these findings on the competition between sigma(N) and the major sigma factor, sigma(70), in Escherichia coli are discussed.

DNA-Directed RNA Polymerases↗

Interaction of sigma 70 with Escherichia coli RNA polymerase core enzyme studied by surface plasmon resonance.

The interaction between the core form of bacterial RNA polymerases and sigma factors is essential for specific promoter recognition, and for coordinating the expression of different sets of genes in response to varying cellular needs. The interaction between Escherichia coli core RNA polymerase and sigma 70 has been investigated by surface plasmon resonance. The His-tagged form of sigma 70 factor was immobilised on a Ni2+-NTA chip for monitoring its interaction with core polymerase. The binding constant for the interaction was found to be 1.9x10(-7) M, and the dissociation rate constant for release of sigma from core, in the absence of DNA or transcription, was 4x10(-3) s(-1), corresponding to a half-life of about 200 s.

Bacterial Proteins↗