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Biomedical subjects

D J Scott

Publications and source records attributed to D J Scott.

At least 19 recordsLinked to original sources
PubMed1992

Nitrogenase-catalyzed ethane production and CO-sensitive hydrogen evolution from MoFe proteins having amino acid substitutions in an alpha-subunit FeMo cofactor-binding domain.

Unlike wild type, certain Mo-dependent nitrogenases, which are expressed in non-N2-fixing mutant strains of Azotobacter vinelandii and have single amino acid substitutions within a region of the MoFe protein alpha-subunit proposed to encompass an FeMo cofactor-binding domain, are able to catalyze the reduction of acetylene by both two and four electrons to yield ethylene and ethane, respectively (Scott, D. J., May, H. D., Newton, W. E., Brigle, K. E., and Dean, D. R. (1990) Nature 343, 188-190). Although the V-dependent nitrogenase is also able to catalyze the reduction of acetylene to the same two- and four-electron products (Dilworth, M. J., Eady, R. R., Robson, R. L., and Miller, R. W. (1987) Nature 327, 167-168), we find that ethane formation from acetylene catalyzed by the altered Mo-dependent nitrogenases occurs by a different mechanism, which is distinguished by: (i) an increased sensitivity to CO; (ii) the absence of a lag; and (iii) no temperature dependence of product distribution among ethylene and ethane during acetylene reduction. An altered MoFe protein, which was purified from one such mutant strain having the alpha-subunit glutaminyl 191 residue substituted by lysyl, exhibited both a changed S = 3/2 EPR spectrum and changes in the distribution of electrons to various products when compared to wild type. Also, unlike wild type, this altered MoFe protein catalyzed proton reduction that is inhibited by carbon monoxide (CO). Because proton reduction catalyzed by a nitrogenase that has a FeMo cofactor with citrate rather than homocitrate as its organic constituent (Liang, J., Madden, M., Shah, V. K., and Burris, R. H. (1990) Biochemistry 29, 8577-8581) is also inhibited by CO, the possibility arose that changes in the polypeptide environment of FeMo cofactor might have caused a rearrangement in its molecular structure or composition. However, this possibility was ruled out by biochemical reconstitution studies (using FeMo cofactor isolated from both the wild-type and altered MoFe proteins), which were monitored by EPR spectroscopy and resulting catalytic activity.

Amino Acids↗
PubMed1992

Quality of life following surgery for abdominal aortic aneurysm.

Repair of abdominal aortic aneurysm (AAA) carries a considerable rate of morbidity and mortality, but little information exists on the quality of life following this procedure. During 1988 and 1989, in two hospitals, 211 patients (186 men and 25 women; median age 74 (range 48-87) years) underwent surgery for AAA. There were 77 ruptured aneurysms and 134 electively repaired. Of these, 38 patients died in hospital (27 ruptured, 11 elective); by the time of review a further eight (one ruptured, seven elective) had died from unrelated causes. Of the 165 survivors, 131 (45 ruptured, 86 elective) were reviewed and questioned as to their physical and mental state before and after surgery. Using the Rosser index, a value for quality of life before and after surgery was calculated (1.0, good; 0, dead). The value for the elective group was 0.94 before operation and 0.96 after, but in the ruptured group fell from 0.98 before surgery to 0.87 afterwards. This study shows that patients undergoing elective surgery for repair of AAA retain good quality of life. By contrast, patients surviving emergency surgery following this procedure seem to suffer a deterioration in life quality, which must be endured for the same expected lifetime as that for the elective group. These results support the need for a national AAA ultrasonographic screening programme.

Aged↗
PubMed1992

Pindolol antagonizes the effects on hippocampal rhythmical slow activity of clonidine, baclofen and 8-OH-DPAT, but not chlordiazepoxide and sodium amylobarbitone.

Buspirone, benzodiazepines, barbiturates and ethanol all reliably reduce the frequency of reticular-elicited hippocampal rhythmical slow activity. In the present experiments we tested a number of drugs which are not usually used for treating generalized anxiety disorders but which have been reported to have some anxiolytic properties. Clonidine (0.3 mg/kg, i.p.), baclofen (6 mg/kg, i.p.) and 8-hydroxy-di-n-propylamino tetralin (8-OH-DPAT) (2.5 mg/kg, i.p.) all reduced the frequency of rhythmical slow activity. The effect of all three drugs was reduced by the 5-hydroxytryptamine 1a antagonist pindolol (2 mg/kg, i.p.). Pindolol had no effect on the reduction in rhythmical slow activity produced by sodium amylobarbitone, as has been previously reported for the benzodiazepine chlordiazepoxide. Flumazenil (10 mg/kg, i.p.), a benzodiazepine receptor antagonist, reduced the effects of chlordiazepoxide (5 mg/kg, i.p.), but not buspirone (10 mg/kg, i.p.). A combination of the selective beta 1 adrenergic receptor antagonist metoprolol (20 mg/kg, i.p.) and the beta 2 adrenergic receptor antagonist ICI 118,551 (4 mg/kg, i.p.) did not reduce the effects of either buspirone (10 mg/kg, i.p.) or diazepam (1 mg/kg, i.p.). These data show that there are at least two separate routes through which anxiolytic agents reduce the frequency of hippocampal rhythmical slow activity. Buspirone, clonidine, baclofen and 8-OH-DPAT act via a system dependent on 5-hydroxytryptamine 1a receptor activation. Benzodiazepines act via activation of the benzodiazepine receptor and probably share with barbiturates action at the GABA-benzodiazepine-chloride ionophore complex but do not produce their effects, directly or indirectly, by 5-hydroxytryptamine 1a receptor activation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

The effect of diabetes mellitus on the outcome of angioplasty for lower limb ischaemia.

Angioplasty is an important tool in the armamentarium of the clinician dealing with atherosclerotic disease. Diabetic patients with occlusive disease pose special problems. Four hundred and twenty-five lesions were dilated in 370 patients. No difference in site was found when comparing the diabetic and non-diabetic groups (p less than 0.001), but a significant difference in indication for treatment was observed. Cumulative patency at 5 years for iliac lesions in non-diabetic patients was 61.2% and in diabetic patients was 35.6% (p less than 0.05), for superficial femoral and popliteal artery lesions in non-diabetic patients it was 49.7% and in diabetic patients it was 38.8% (NS). The need for subsequent surgical intervention (p less than 0.01) and risk of death (p less than 0.001) are both significantly greater in the diabetic group. This study shows that angioplasty is a technique that can be used with success in diabetic patients and if the indications for interventions are compared, diabetic patients do not worse.

Angioplasty, Balloon↗
PubMed1992

Quality of life of octogenarians after aneurysm surgery.

Abdominal aneurysm repair in octogenarians is controversial. To justify surgery, survival with a reasonable quality of life is required. Between 1980 and 1988, 34 octogenarians underwent aortic aneurysm surgery (14 elective, 20 emergency). Of the 21 survivors, 20 were interviewed to determine their quality of life. At the time of interview the patients had a median survival of 19 months (range 4-67 months). Twenty age/sex matched normal patients, from the same GP population, were interviewed for comparison. A structured questionnaire was used to assess: physical mobility, activities of daily living, sleep and emotional problems. A symptom survey was also performed. The survival trend of elective patients was similar to that of a demographically similar 'normal' population. The survival trend of emergency patients returned to 'normal' after the first postoperative month. Quality of life of the 20 patients was comparable to the lifestyle enjoyed by normal subjects. Of the 20 patients interviewed, 18 had returned home after surgery. Elective and emergency aortic aneurysm surgery can be performed with reasonable survival and a good quality of life, and therefore cannot be denied to octogenarians on the basis of age alone.

Aged↗
PubMed1992

Vascular surgical training in the UK and Ireland.

Fifty-six vascular surgical trainees and 31 recently appointed consultants with an interest in vascular surgery replied to a postal questionnaire about their training. The majority fulfilled the guidelines recommended by the Vascular Advisory Committee of the Vascular Surgical Society of Great Britain and Ireland, which are--a minimum two years of higher surgical training in units with an interest in vascular surgery and a substantial and comprehensive experience of (operative) vascular surgery. However, the operative experience during training was very variable, ranging between 10 and 574 operations reported by new consultants. Minimum standards of operative experience may need to be defined. The survey also identified that training in carotid endarterectomy is sometimes deficient and noted that as much as one-third of operative experience may be gained 'out of hours' on emergency cases. To obtain this experience trainees have to work very long hours, two-thirds of senior registrars have vascular on call rotas of 1:2 or less. Imminent changes in the structure of higher surgical training and the reduction in hours worked by junior doctors may seriously affect vascular surgical training.

Education, Medical, Graduate↗
PubMed1991

Intra-arterial streptokinase infusion in acute lower limb ischaemia.

Between 1986 and 1988, 38 patients (29 men and nine women), median age 65 years (range 38-85 years), underwent local intra-arterial streptokinase therapy for acute lower limb ischaemia. Three patient groups were identified: 15 with acute on chronic ischaemia (group 1), 12 postangioplasty (group 2) and 11 postfemorodistal bypass (group 3). Distal arteriographic run-off was a significant discriminant between success and failure in group 1 (n = 15, chi 2 = 11.5, P = 0.001) and in the overall group (n = 38, chi 2 = 17.2, P less than 0.001). In group 2, four patients with good run-off had an unsuccessful outcome; this was due in all cases to technical problems (haemorrhage in two and intimal dissection in two). In group 3, two patients with good run-off had unsuccessful streptokinase infusions. In both cases the graft failed in the early postoperative period (less than 30 days). By contrast, the four patients whose grafts occluded after 30 days had successful streptokinase infusions and long-term graft patency was achieved by further surgery and balloon dilatation. In all groups, no patient with a poor run-off had a successful outcome following streptokinase administration. The role of local intra-arterial streptokinase therapy in the critically ischaemic limb remains controversial, but these results suggest that an adequate run-off is an important factor in the selection of patients for treatment.

Acute Disease↗
PubMed1991

Effect of weight on claudication distance.

Conservative measures to improve claudication distance include advice on smoking, exercise, diet and weight reduction. Although the effects of smoking, exercise and diet are established, the effect of weight is less clear. The aim of this study was to investigate the effect of carrying extra weight on the maximum walking distance in stable claudicants. Twenty stable claudicants were exercised on a treadmill (3.5 km/h, 0 degrees slope) carrying 0, 2.5, 5, 7.5 and 10 kg weights in randomized sequence. Maximum claudication distance and ankle: brachial pressure indices were recorded. Patients were categorized into mild or severe claudicants depending on their ability to walk 200 m. A response index (RI) was calculated as the reduction in claudication distance per kilogram load; RI = [CD0-CD10]/10 m/kg, where CD0 and CD10 represent claudication distance with 0 and 10 kg weights, respectively. Claudication distance was significantly reduced in subjects carrying 5 kg or more (P less than 0.01). A linear relationship was demonstrated between the mean claudication distance and the load carried (r = 0.98, P less than 0.01) with a mean response index of 10.2 m/kg. The mean(s.e.m.) RI in mild claudicants (25.9(9.5) m/kg) was greater than the value observed in the severe claudicants (3.3(0.8) m/kg; P less than 0.01, Mann-Whitney U test). This study demonstrates that weight adversely affects claudication distance and suggests that weight reduction may deserve greater emphasis in the management of some patients with intermittent claudication.

Adult↗
PubMed1991

Failure of peripheral arterial balloon angioplasty: does platelet deposition play a role?

The pathophysiological response to peripheral percutaneous transluminal balloon angioplasty in 20 patients was investigated using 111-Indium labelled platelets. Platelet deposition was quantified by measuring the degree of radioactivity uptake at angioplasty and control sites using a computer linked system and expressing the uptake as a ratio of angioplasty/control. Following platelet labelling, scans were performed before angioplasty and at 1, 24 and 48 h after angioplasty. To assess patency of the angioplasty, ankle brachial Doppler pressure indices were performed and supported by repeat angiograms if doubt of patency existed. All patients were followed-up at 1 week, 1 month and 6 months to correlate the degree of early platelet uptake with failure. The mean +/- sem platelet radioactivity ratio at the angioplasty site increased from 1.1 +/- 0.1 prior to the procedure to a peak of 2.1 +/- 0.3 at 1 h (p less than 0.01), 1.6 +/- 0.2 at 24 h (p less than 0.05), and 1.7 +/- 0.3 at 48 h (p less than 0.05). Angioplasties that failed within 6 months tended to have a higher maximum early platelet uptake (3.1 +/- 0.6) compared to successful angioplasties (1.9 +/- 0.3) but the difference was not significant in the numbers studied. This study provides a suitable model to assess the role of platelet accumulation in angioplasty failure and the influence of various antiplatelet regimes.

Adult↗
PubMed1991

Impedance analysis to identify the at risk femorodistal graft.

Computer-assisted impedance analysis is a newly developed technique to identify femoropopliteal and distal vein graft stenoses before failure. Pulsatile flow is measured from the proximal and distal graft by use of an 8Mhz Doppler velocimeter. A pulse volume recorder measures pulsatile pressure within the thigh and calf. Fourier transfer analysis is performed on paired Doppler pulse volume recorder waveforms and an impedance score derived for the thigh and calf, respectively. In a retrospective review of 50 nonreversed femoropopliteal/distal grafts performed for limb salvage, postoperative biplanar intraarterial digital subtraction arteriography was compared with impedance analysis. Arteriography showed graft or runoff stenoses in 22 grafts (at risk) and 28 normal grafts (controls). Impedance scores were significantly higher in the at risk group (0.58 + [0.43 to 0.72]*), when compared with the controls (0.34 + [0.30 to 0.38], p less than 0.001*). A thigh or calf impedance score of greater than 0.45 was able to detect 20 of 22 stenoses, including 6 lesions in grafts with normal resting and postexercise ankle pressures. This score was then applied prospectively and compared with serial biplanar digital subtraction arteriography in a further 56 femoropopliteal/distal bypasses for limb salvage. Thirty-three of 34 lesions were successfully predicted and impedance scores were significantly higher in the at risk limbs (0.56 + [0.44 to 0.68]*) when compared with the controls (0.38 + [0.35 to 0.41], p less than 0.001*). In this series impedance analysis proved more sensitive than resting or stressed ankle pressures and, unlike Duplex scanning, was able to detect runoff as well as graft stenoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Role for the nitrogenase MoFe protein alpha-subunit in FeMo-cofactor binding and catalysis.

Two components constitute Mo-dependent nitrogenase (EC 1.18.6.1)--the Fe protein (a homodimer encoded by nifH) and the MoFe protein (an alpha 2 beta 2 tetramer encoded by nifDK). The MoFe protein provides the substrate-binding site and probably contains six prosthetic groups of two types--four Fe-S centres and two Fe- and Mo-containing cofactors. To determine the distribution and catalytic function of these metalloclusters, we and others are attempting to change the catalytic and spectroscopic features of nitrogenase by substituting specific amino acids targeted as potential metallocluster ligands, particularly those to the FeMo-cofactor, which is responsible for the biologically unique electron paramagnetic resonance signal (S = 3/2) of nitrogenase, and is believed to be the N2-reducing site. Here we describe mutant strains of Azotobacter vinelandii that have single amino-acid substitutions within the MoFe protein alpha-subunit. These substitutions alter both substrate-reduction properties and the unique electron paramagnetic resonance signal, indicating that the FeMo-cofactor is associated with both the alpha-subunit and the substrate-reducing site.

Amino Acid Sequence↗
PubMed1990

Role of duplex scanning in the selection of patients for carotid endarterectomy.

A retrospective review of 63 patients undergoing duplex scanning and angiography for suspected carotid artery disease was performed to evaluate the need for routine angiography before carotid endarterectomy. A consultant surgeon (M.H.) made a simulated management decision on the basis of a clinical summary and a duplex scan report. Twenty-four patients were selected for surgery without angiography; duplex scanning had a sensitivity of 100 per cent and a specificity of 90 per cent in the detection of internal carotid artery stenosis. In two cases duplex scanning misdiagnosed a total occlusion as a critical stenosis. Eighteen patients failed to meet the criteria for surgery and were referred for angiography. Twenty-one patients were selected for conservative treatment on the basis of the duplex scan report. Combining the surgical and conservative groups (45 patients), duplex scanning had a sensitivity of 96 per cent and specificity of 95 per cent for the detection of stenosis greater than 50 per cent. In the identification of a total occlusion, duplex scanning had a poor sensitivity of 50 per cent. These results suggest that routine angiography before carotid endarterectomy is unnecessary in selected patients but that a suspected occlusion should be confirmed by angiography.

Adult↗
PubMed1990

Non-invasive estimation of peripheral resistance using Pulse Generated Runoff before femorodistal bypass.

The measurement of peripheral resistance (PR) is a useful technique for predicting the outcome of femorodistal bypass. In an attempt, noninvasively, to predict PR, Pulse Generated Runoff (PGR) was used to assess 35 consecutive patients undergoing femorodistal non-reversed vein bypass for critical ischaemia. The PGR subscores (anterior tibial, posterior tibial, peroneal, pedal arch status were correlated against the measured PR. Using multiple linear regression three resistance values were derived for runoff at different levels: (1) a single calf vessel (R1); (2) distal popliteal artery (R3); (3) irrespective of the level (R0). There was good agreement between the predicted resistances R0, R1 and R3 and the measured PR. In the single calf vessel group (R1) the limits of agreement (-0.41 to +0.39) and 95 per cent confidence interval (-0.16 to +0.14) with the measured PR were better than in the R0 and R3 groups. These levels of agreement are small enough to replace the measured PR with the predicted PR method. Using the appropriate resistance equation in a further prospective series of 14 cases, there was agreement between the predicted and measured PR (limits of agreement -0.67 to +0.41; 95 per cent confidence interval -0.26 to +0.15). These results confirm the value of PGR in the assessment of critically ischaemic limbs particularly with a single calf vessel. Calf vessel continuity with the pedal arch appears to be a major determinant of PR, particularly in the isolated calf vessel group. A non-invasive resistance value can be derived which will predict the intraoperative peripheral resistance and should help predict subsequent graft outcome.

Aged↗
PubMed1990

The microscopic features of inflammatory abdominal aortic aneurysms: discriminant analysis.

Up to 15% of abdominal aortic aneurysms are designated as inflammatory. They are characterized by marked fibrous thickening of the aneurysmal wall, with the fibrosis extending into the adjacent retroperitoneum. Thirty-five abdominal aortic aneurysms were studied, 15 inflammatory and 20 atherosclerotic. Of the inflammatory group, 10 were symptomatic and five asymptomatic. For each resection specimen, 59 microscopic features (variables) were scored semi-quantitatively. Discriminant function analysis showed that endarteritis obliterans, fibrosis around nerves or ganglia at the outer margin of mural fibrosis, and the thickness of the combined fibrotic media and adventitia gave a satisfactory high discrimination between atherosclerotic and inflammatory aneurysms. When these three variables are used together, a histological diagnosis of inflammatory aneurysm can be made with an expected accuracy in excess of 80%.

Aged↗
PubMed1990

Evidence that conserved residues Cys-62 and Cys-154 within the Azotobacter vinelandii nitrogenase MoFe protein alpha-subunit are essential for nitrogenase activity but conserved residues His-83 and Cys-88 are not.

Metallocluster extrusion requirements, interspecies MoFe-protein primary sequence comparisons and comparison of the primary sequences of the MoFe-protein subunits with each other have been used to assign potential P-cluster (Fe-S cluster) domains within the MoFe protein. In each alpha-beta unit of the MoFe protein, alpha-subunit domains, which include potential Fe-S cluster ligands Cys-62, His-83, Cys-88 and Cys-154, and beta-subunit domains, which include potential Fe-S cluster ligands Cys-70, His-90, Cys-95 and Cys-153, are proposed to comprise nearly equivalent P-cluster environments located adjacent to each other in the native protein. As an approach to test this model and to probe the functional properties of the P clusters, amino acid residue substitutions were placed at the alpha-subunit Cys-62, His-83, Cys-88 and Cys-154 positions by site-directed mutagenesis of the Azotobacter vinelandii nifD gene. The diazotrophic growth rates, MoFe-protein acetylene-reduction activities, and whole-cell S = 3/2 electron paramagnetic resonance spectra of these mutants were examined. Results of these experiments show that MoFe-protein alpha-subunit residues, Cys-62 and Cys-154, are probably essential for MoFe-protein activity but that His-83 and Cys-88 residues are not. These results indicate either that His-83 and Cys-88 do not provide essential P-cluster ligands or that a new cluster-ligand arrangement is formed in their absence.

Amino Acid Sequence↗
PubMed1989

Operative assessment of femorodistal bypass grafts using a new Doppler flowmeter.

Operative measurements using a newly developed Doppler flowmeter were made on 47 in situ femorodistal bypass grafts performed for critical ischaemia. Graft blood flow, peripheral resistance and impedance were measured before and after the injection of 15 mg papaverine down the graft. The proportion of retrograde blood flow at the distal anastomosis was also measured. The success of a graft at 1 month was defined by patency on duplex ultrasound scanning, a rise in the Doppler ankle pressures and an improvement in the clinical state of the limb. By these criteria the 1-month primary success rate was 35 out of 47 (74 per cent). Graft blood flow was of little value in predicting graft outcome but, combined with segmental pressures, accurately located six of eight technical problems which were successfully corrected. After papaverine, the peripheral resistance of all the successful grafts fell below one peripheral resistance unit (PRU). No single measurement was able to completely distinguish between success and failure, although discriminant analysis of all measurements was able to predict success with a sensitivity of 100 per cent and specificity of 97 per cent. A simpler combination of a peripheral resistance after papaverine less than 1 PRU and a retrograde blood flow less than 33 per cent predicted success, with a sensitivity of 97 per cent and specificity 83 per cent. These criteria have been validated on a further 26 grafts, achieving a sensitivity of 88 per cent and a specificity of 75 per cent. Simple operative measurements, using a newly developed Doppler flowmeter, enable the detection of technical problems and the accurate prediction of the early outcome of femorodistal grafting.

Adult↗