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Biomedical subjects

N A Scott

Publications and source records attributed to N A Scott.

At least 91 records · Page 5Linked to original sources
PubMed1993

Circadian variation of tissue plasminogen activator and its inhibitor, von Willebrand factor antigen, and prostacyclin stimulating factor in men with ischaemic heart disease.

OBJECTIVES: To determine whether plasma concentrations of tissue plasminogen activator antigen, von Willebrand factor antigen, and prostacyclin stimulating factor and plasminogen activator inhibitor activity show circadian variation in men with ischaemic heart disease. DESIGN: Blood samples were obtained every four hours for 24 hours from 10 men with ischaemic heart disease. The men were ambulant from 08:10 until 00:00 when they went to bed and they remained in bed until 08:00 the following morning. PATIENTS: Ten men with positive diagnostic exercise tolerance tests with no significant past history, who were not regularly taking any medical treatment except for glyceryl trinitrate. RESULTS: There was significant circadian variation in plasminogen activator inhibitor activity (p = 0.001) (peak value 04:00 and trough value 20:00), but not in plasma concentrations of tissue plasminogen activator antigen, von Willebrand factor, or prostacyclin stimulating factor. CONCLUSION: Men with ischaemic heart disease showed a significant circadian variation in fibrinolysis. The combination of peak values of plasminogen activator inhibitor activity and failure of plasma concentrations of tissue plasminogen activator antigen to increase in the early morning must predispose to thrombosis at this time. The circadian variation in fibrinolysis may contribute to the increased incidence of myocardial infarction in the morning.

Aged↗
PubMed1993

Age, sex, cigarette smoking and indices of free radical activity in healthy humans.

OBJECTIVES: To determine the effect of age, sex and smoking on free radical (FR) indices. There is currently considerable research interest into the role of FRs in the pathogenesis of many diseases and it is therefore important to identify factors in healthy subjects which influence the markers used to assess FR activity. METHODS: Blood samples were obtained from 123 healthy subjects whose age, sex and smoking habits were recorded. The following were measured on each sample: malondialdehyde (MDA) which is a product of FR mediated lipid peroxidation and the FR scavengers plasma thiols (PSH), red cell glutathione (GSH) and superoxide dismutase (SOD). RESULTS: Malondialdehyde levels were significantly increased in cigarette smokers (p < 0.02) but no significant age related increase in MDA was detected for the group as a whole. However, female smokers had the highest rate of MDA increase with age followed by male smokers and female non-smokers. MDA levels of male non-smokers were unaffected by age. A significant negative correlation was detected between PSH and age (p < 0.001). GSH was significantly higher in females (p < 0.05) and the red cell content of GSH and SOD were significantly inversely related (p < 0.01). CONCLUSION: This study of normal subjects describes an age related increase in malondialdehyde levels, the rate of which is influenced by sex and smoking status. In humans, plasma thiol levels decrease with increasing age, females have higher red cell glutathione and there is a significant inverse relationship between red blood cell superoxide dismutase and glutathione levels. Furthermore, cigarette smoking increases plasma malondialdehyde levels. With the considerable current interest in free radicals, it is important to identify factors which influence the indices used to assess free radical activity in disease states.

Adolescent↗
PubMed1992

Structural requirements for neuropeptide Y18-36-evoked hypotension: a systematic study.

It has been shown that NPY and select C-terminal fragments of NPY that evoke a hypotensive response upon intraarterial administration in the rat also cause mast cell degranulation and histamine release in vitro. Additionally, elevation of plasma histamine levels has been observed concomitant with the hypotensive effect of NPY and various C-terminal fragments. In order to investigate whether the hypotensive response to NPY18-36 is correlated to this observed elevation of histamine in vivo, we sought to characterize the structural requirements for each activity. We conducted a systematic replacement of each amino acid in NPY18-36 by its D-isomer. Additionally, various modifications were made to the N- or C-terminii of NPY18-36. The following rank order of potency was obtained for the hypotensive action of these analogues of NPY18-36 relative to NPY18-36. Only one analogue ([D-Tyr21]NPY18-36) exhibited significantly enhanced potency. Eleven analogues of NPY18-36, ([D-Thr32]-, [D-Arg35]-, [D-Ile31]-, [D-Leu30]-, [D-Tyr27]-, [D-Ser22]-, [D-Tyr36]-, [D-Gln34]-, [D-Asn29]-, [D-Ala23]-, and [D-Arg33]NPY18-36) were equipotent with NPY18-36. Four analogues ([D-His26]-, [D-Ile28]-, and [D-Ala18]NPY18-36 and -NPY18-27) had reduced potency (10-80%) while eight analogues ([D-Arg19]-, [D-Tyr20], [D-Leu24]-, [D-Arg25]-, [Ac-Ala18]-, [Me-Ala18]-, [desamino-Ala18]NPY18-36 and NPY18-36 free acid) failed to produce a significant hypotensive response (less than 10%) at the doses tested. The sensitivity of NPY18-36 to chiral inversion of single residues or other modifications at the N-terminus suggested the presence of a conformationally well defined N-terminal pharmacophore. Additionally, five NPY18-36 analogues were tested for elevation of plasma histamine levels. The rank order of potency ([D-Thr32]NPY18-36 = [D-Tyr21]NPY18-36 much greater than NPY18-36 greater than [D-Ala18]NPY18-36 greater than [Ac-Ala18]NPY18-36) was correlated with each analogue's potency at evoking a hypotensive response. In contrast, NPY1-36 failed to evoke an elevation in plasma histamine levels despite its hypotensive effects. Hence, we conclude that the magnitude of the hypotensive response evoked by an NPY18-36 analogue is primarily a function of its ability to elevate plasma histamine levels. However, the mechanism underlying NPY1-36-evoked hypotension appears to be different.

Animals↗
PubMed1992

Anovaginal and rectovaginal fistula in patients with Crohn's disease.

Between 1971 and 1991, details of 67 women with perianal Crohn's disease were recorded prospectively using the Cardiff classification. Two groups were identified according to the presence (n = 29) or absence (n = 38) of anorectal Crohn's fistula involving the vagina. Patients in both groups were of a similar age and had had Crohn's disease for a similar period before diagnosis of perianal involvement. The incidence of associated perianal lesions, superficial ulcers, cavitating ulcers, other fistulas and strictures was not significantly different between the two groups. A greater proportion of patients with anorectal-vaginal fistulation (n = 15) had distal intestinal Crohn's disease (rectal or contiguous colorectal) compared with women with no vaginal fistulation (n = 14). A range of therapies was used to manage women with perianal Crohn's disease, from local surgery to a defunctioning stoma and/or proctectomy. Only 13 of 38 women with perianal Crohn's disease but no vaginal fistula required a defunctioning stoma or proctectomy, whereas 18 of 29 with anorectal-vaginal fistulation underwent these procedures (P < 0.05). A vaginal fistula has a considerable adverse effect on the outcome of perianal Crohn's disease.

Adult↗
PubMed1992

Relationship between the extent of coronary artery disease and indicators of free radical activity.

Clinical studies have demonstrated that patients with coronary artery disease (CAD) have markers suggestive of increased free radical (FR) activity when compared with normal subjects; however, the relationship between the extent of CAD and level of FR markers is not known. The following indices of FR activity, plasma malondialdehyde (MDA), plasma thiols (PSH), red blood cell (RBC) glutathione (GSH), and RBC superoxide dismutase (SOD) were measured in 58 patients admitted for coronary angiography and in 50 matched controls. Regression analysis demonstrated no significant correlation between MDA, PSH, GSH, or SOD, and the angiographic grade which indicated the severity of the CAD. Patients with angiographically proven CAD (median 7.9 nmol/ml IQR 6.9-9.2) and patients with a history suggestive of angina pectoris but normal coronary angiograms (median 8.4 nmol/ml IQR 7.4-9.9) had significantly raised MDA levels compared with the controls (median 6.85 nmol/ml IQR 6.1-7.4), p less than 0.001 and p less than 0.005, respectively. The patients with angiographically proven CAD had significantly lower GSH levels (median 1461 microM IQR 1348-1709, p less than 0.002) compared with the controls (median 1754 microM IQR 1492-1930). Significantly raised SOD levels also were detected in patients with angiographically proven CAD (median 121.8 U/ml RBC, IQR 113.8-143.9) and in patients with a history of suggestive of angina pectoris but normal coronary angiograms (median 146 U/ml RBC, IQR 96.8-156.7) when compared with controls (median 96.3 U/ml RBC, IQR 82.4-115.6), p less than 0.001 and p less than 0.02, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Effects of gliclazide on platelet reactivity and free radicals in type II diabetic patients: clinical assessment.

In vitro studies have demonstrated that gliclazide has free radical scavenging and antiplatelet activities. To assess this clinically, we studied gliclazide in a blinded, randomized, glibenclamide-controlled trial in 30 type II diabetic patients with retinopathy. All patients had been taking glibenclamide for more than 12 months before being randomized to receive either an equipotent dose of gliclazide or to continue on glibenclamide. Diabetic control was not modified. The patients were well matched at randomization (mean age, 58 years; duration of diabetes, 8 years; 20 males; mean hemoglobin A1 [HbA1], 8.6%) and their degree of diabetic control was not altered during the trial. Free radical activity was assessed as oxidative status by plasma thiols (PSH), lipid peroxides (MDA-LM), and red blood cell superoxide dismutase activity (SOD). Platelet aggregation in whole blood to collagen (Plt-ag) was used as the measure of platelet reactivity. There were no differences between these measurements at baseline. At 3 months, the oxidative status and platelet aggregation in the gliclazide group had improved significantly compared with baseline and had also showed significant differences in all parameters when compared with the glibenclamide group. Therefore, comparing gliclazide with glibenclamide-treated patients at 3 months, we found: PSH, 458 +/- 38 versus 414 +/- 34 mumol/L, P less than .004; MDA-LM, 7.0 +/- 0.6 versus 8.3 +/- 0.8 mumol/L, P less than .0002; SOD, 152 +/- 36 versus 123 +/- 15 micrograms/mL, P less than .016; Plt-ag, 50.8 +/- 24 versus 72.3% +/- 15%, P less than .006. These changes were maintained at 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Alterations of phasic coronary artery flow velocity in humans during percutaneous coronary angioplasty.

BACKGROUND AND OBJECTIVES: Studies using Doppler catheters to assess blood flow velocity and vasodilator reserve in proximal coronary arteries have failed to demonstrate significant improvement immediately after coronary angioplasty. Measurement of blood flow velocity, flow reserve and phasic diastolic/systolic velocity ratio performed distal to a coronary stenosis may provide important information concerning the physiologic significance of coronary artery stenosis. This study was designed to measure these blood flow velocity variables both proximal and distal to a significant coronary artery stenosis in patients undergoing coronary angioplasty. METHODS: A low profile (0.018-in.) (0.046-cm) Doppler angioplasty guide wire capable of providing spectral flow velocity data was used to measure blood flow velocity, flow reserve and diastolic/systolic velocity ratio both proximal and distal to left anterior descending or left circumflex coronary artery stenosis. These measurements were made in 38 patients undergoing coronary angioplasty and in 12 patients without significant coronary artery disease. RESULTS: Significant improvement in mean time average peak velocity was noted in distal coronary arteries after angioplasty (before 19 +/- 12 cm/s; after 35 +/- 16 cm/s; p less than 0.01). Increases in proximal average peak velocity after angioplasty were less remarkable (before 34 +/- 18 cm/s; after 41 +/- 14 cm/s; p = 0.04). Mean flow reserve remained unchanged after angioplasty both proximal (1.5 +/- 0.5 vs. 1.6 +/- 1; p greater than 0.10) and distal (1.6 +/- 1 vs. 1.5 +/- 0.8; p greater than 0.10) to a coronary stenosis. Before angioplasty, mean diastolic/systolic velocity ratio measured distal to a significant stenosis was decreased compared with that in normal vessels (1.3 +/- 0.5 vs. 1.8 +/- 0.5; p less than 0.01). After angioplasty, distal abnormal phasic velocity patterns generally returned to normal, with a significant increase in mean diastolic/systolic velocity ratio (1.3 +/- 0.5 vs. 1.9 +/- 0.6; p less than 0.01). Phasic velocity patterns and mean diastolic/systolic velocity ratio measured proximal to a coronary stenosis were not statistically different from values in normal vessels (1.8 +/- 0.8 vs. 1.8 +/- 0.5; p greater than 0.10) and did not change significantly after angioplasty (1.8 +/- 0.8 vs. 2.13 +/- 0.9; p greater than 0.10). CONCLUSIONS: Flow velocity measurements may be performed distal to a coronary stenosis with the Doppler guide wire. Phasic velocity measurements made proximal to a coronary stenosis differed from those in the distal coronary artery. Both proximal and distal flow reserve measurements made immediately after angioplasty were of limited utility. Changes in distal flow velocity patterns and diastolic/systolic velocity ratio appeared to be more relevant than the hyperemic response in assessing the immediate physiologic outcome of coronary angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1992

Circadian variation of white blood cell aggregation and free radical indices in men with ischaemic heart disease.

The fibrinolytic activity of blood has a circadian variation with increased thrombotic tendency in the morning. This may be a contributory factor to the circadian variation in the time of onset of thrombotic events. However, there has recently been increasing interest to the role of the white blood cells (WBC) and free radicals (FRs) in thrombosis. We have previously reported a circadian variation in WBC aggregation and FR status in normal volunteers. No one has yet studied possible circadian variations in these parameters in patients with stable ischaemic heart disease (IHD). Ten men with stable IHD had blood samples collected at four-hourly intervals from midday until midday the following day. The patients were ambulant until midnight at which time they went to bed and remained in bed until 0800 h. The following were measured on each sample: WBC aggregation, malondialdehyde (MDA) which is a product of lipid peroxidation by FRs; the FR scavengers, plasma thiol (PSH), red cell glutathione (GSH) and superoxide dismutase (SOD) which are all altered in the presence of increased FR activity. WBC aggregation and PSH had significant circadian variations, P < 0.015 and P < 0.001 respectively. The WBC aggregation peak was at 1200 h and trough at 1600 h, the PSH peak was at midnight and the trough at 0400 h. WBC behaviour and FR status influence the flow properties of blood. The largest rise in WBC aggregation occurred from 0800 h to 1200 h; such an increase in aggregation could predispose to microcirculatory occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Intestinal failure--the clinical problem.

Intestinal failure can be the end result of a wide variety of disease processes that impair the ability of the gut to adequately digest and absorb food. Patients with established intestinal failure may require parenteral nutrition support and/or abdominal surgery to reverse the disease process involved. Selected patients with irreversible intestinal failure can be managed in experienced units by home parenteral nutrition.

Chronic Disease↗
PubMed1991

Gliclazide: a general free radical scavenger.

Free radical mechanisms have been implicated in diabetic microangiopathy. Agents that scavenge free radicals may be beneficial. We assessed the scavenging ability of two sulphonylureas, gliclazide and glibenclamide, in vitro. The assay which employs o-dianisidine sensitised by riboflavin can be used to distinguish between superoxide scavengers and general scavengers. The former species lead to an augmentation while the latter has an inhibitory effect. The drugs were added in final concentrations of 0.5, 1.0, 2.5 and 5.0 micrograms/ml. The percentage inhibition (mean +/- S.D.) for each concentration of gliclazide respectively was 11.0 +/- 2.5%, 20.8 +/- 2.9%, 31.4 +/- 2.2% and 47.2 +/- 0.8%. Glibenclamide had no scavenging effects. The results demonstrate that gliclazide is a powerful general free radical scavenger in vitro. We postulate that this scavenging quality of gliclazide may be important in diabetes.

Dianisidine↗
PubMed1991

Spectrum of intestinal failure in a specialised unit.

300 consecutive admissions over 7 years to a purpose-built intestinal failure unit are reviewed. The commonest underlying condition was Crohn's disease (42%), and the commonest complication precipitating admission was intestinal fistula (42%). Total parenteral nutrition was used in 85% and surgery in 50%. A multidisciplinary approach to management gave a high success rate--90% of patients were discharged from hospital, although nearly 25% needed home parental nutrition. These results suggest that chronic intestinal failure should be managed in specialised units in the same manner as other types of organ failure.

Adolescent↗
PubMed1991

Probucol, a superoxide free radical scavenger in vitro.

Free radical (FR) mediated oxidation of low density lipoproteins (LDL) has been implicated in atherogenesis. Probucol is a lipid lowering agent with antioxidant properties which may protect the LDL from FR mediated damage. The specific mechanism by which probucol acts as an antioxidant has not previously been reported. We therefore studied the FR scavenging properties of probucol in vitro and results show that this drug is a powerful superoxide scavenger. This property may be relevant in its use as a lipid lowering drug in the retardation of the atherosclerotic process.

Antioxidants↗
PubMed1991

Lipid infusion increases oxygen consumption similarly in septic and nonseptic patients.

This investigation compared the metabolic effects of lipid infusion in five septic and five nonseptic patients. Oxygen consumption was determined by indirect calorimetry over 1 h of rest and during 2 h when Intralipid (20%) was infused [166 mL/h; 23 kJ/min (5.5 kcal/min)]. Septic patients had a resting metabolic rate 17% higher than that of their nonseptic control subjects and a significant (P less than 0.05) rise (13%) in oxygen uptake was measured in both groups of subjects during the 2-h infusion of lipid. Preinfusion respiratory quotient (RQ) was 7% higher in the septic patients (P less than 0.05), and during the infusion period RQ decreased similarly (approximately 6%; P less than 0.05) in both groups. Plasma catecholamines were elevated in the septic patients preinfusion and the concentrations remained unaltered during the infusion. Norepinephrine rose significantly in the nonseptic group with the lipid infusion. The results show that sepsis has little or no influence on the characteristic rise in metabolic rate that occurs with intravenous lipid.

Adult↗
PubMed1991

The relationship of oxidative stress to thrombotic tendency in type 1 diabetic patients with retinopathy.

Increased free radical activity may contribute to thrombosis via effects on platelet aggregation and the prostanoid balance. To investigate this further we studied 15 Type 1 diabetic patients with retinopathy, matched with uncomplicated Type 1 patients for age, duration of diabetes and HbA1, together with matched healthy non-diabetic control subjects. The oxidative effects of free radicals as total diene conjugates and lipid peroxides were measured, together with redox status extracellularly as plasma albumin-thiols and intracellularly as erythrocyte superoxide dismutase activity. Platelet count, aggregation of platelets in whole blood to collagen, thromboxane B2, and prostacyclin stimulating factor (PGI2SF) were also assessed. Free radicals measured as lipid peroxides were significantly higher (9.6 (8.1-11.6) mumol l-1 (median and interquartile range) in diabetic patients with retinopathy than in control subjects (8.1 (7.4-9.2) mumol l-1; p less than 0.05). There were also significant reductions in redox status both extracellularly as plasma albumin thiols (408 (383-473) vs 490 (456-517) mumol l-1, p less than 0.001) and intracellularly as erythrocyte superoxide dismutase activity (34 (27-41) vs 44 (36-51) g l-1, p less than 0.05) between patients with retinopathy and control subjects. Platelet counts were increased in diabetic patients with retinopathy (p less than 0.05), as was collagen-induced platelet aggregation (p less than 0.01). Prostacyclin stimulating factor was reduced in patients with retinopathy (p less than 0.05) and correlated within the plasma with lipid peroxides (r = -0.53, p less than 0.04) and albumin thiols (r = 0.64, p less than 0.01). The results suggest that diabetic patients, particularly with retinopathy, are under oxidative stress and have an increased thrombotic tendency with increased platelet reactivity and a reduction in prostacyclin stimulating factor.

Adult↗
PubMed1991

Sequence characteristics of a gene in equine herpesvirus 1 homologous to glycoprotein H of herpes simplex virus.

A gene in equine herpesvirus 1 (EHV-1, equine abortion virus) homologous to the glycoprotein H gene of herpes simplex virus (HSV) was identified and characterised by its nucleotide and derived amino acid sequence. The EHV-1 gH gene is located at 0.47-0.49 map units and contains an open reading frame capable of specifying a polypeptide of 848 amino acids, including N- and C-terminal hydrophobic domains consistent with signal and membrane anchor regions respectively, and 11 potential sites for N-glycosylation. Alignment of the amino acid sequence with those published for HSV gH, varicella zoster virus gpIII, Epstein Barr virus gp85 and human cytomegalovirus p86 shows similarity of the EHV gene with the 2 other alpha-herpesviruses over most of the polypeptide, but only the C-terminal half could be aligned for all 5 viruses. The identical positioning of 6 cysteine residues and a number of highly conserved amino acid motifs supports a common evolutionary origin of this gene and is consistent with its role as an essential glycoprotein of the herpesvirus family. An origin of replication is predicted to occur at approximately 300 nucleotides downstream of the EHV-1 gH coding region, on the basis of similarity to other herpesvirus origins.

Amino Acid Sequence↗
PubMed1990

Ileal pouch-anal anastomosis. Reoperation for pouch-related complications.

The aim was to assess the value of reoperative surgery for pouch-related complications after ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis and familial adenomatous polyposis. Between January 1981 and August 1989, 114 of 982 IPAA patients (12%) seen at the Mayo Clinic had complications directly related to IPAA that required reoperation. Among the 114 patients, the complications prevented initial ileostomy closure in 33 patients (25%), occurred after ileostomy closure in 68 patients (60%), and delayed ileostomy closure in the remaining patients. The salvage procedures performed included anal dilatation under anesthesia for anastomotic strictures, placement of setons and/or fistulotomy for perianal fistulae, unroofing of anastomotic sinuses, simple drainage and antibiotics for perianal abscesses, abdominal exploration with drainage of intra-abdominal abscesses with or without establishment of ileostomy, and complete or partial reconstruction of the reservoir for patients with inadequate emptying. None of the reoperated patients died. Reoperation led to restoration of pouch function in two thirds of patients and, of these, 70% had an excellent clinical outcome. However approximately 20% of the 114 pouches required excision. Excision was common, especially among patients who had pelvic sepsis. Salvage procedures for pouch-specific complications can be done safely and will restore pouch function in two thirds of patients. Complications after reoperation, however, may ultimately lead to loss of the reservoir in one in five patients.

Adenomatous Polyposis Coli↗