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Biomedical subjects

N Scott

Publications and source records attributed to N Scott.

At least 55 records · Page 3Linked to original sources

Anxiogenic effects of caffeine in patients with anxiety disorders.

The effects on measures of anxiety from two doses of oral caffeine (250 and 500 mg) and placebo were compared in 12 patients with generalized anxiety disorder (GAD), 12 patients with panic disorder, and 12 normal subjects. Caffeine produced significantly less decrease in electroencephalographic alpha wave activity, greater decrease in N1-P2 auditory evoked potential amplitude, and greater increased in skin conductance level, systolic and diastolic blood pressure, critical fusion flicker frequency, and self-ratings of anxiety and sweating in patients with GAD than in normal patients. Patients with panic disorder showed different reactivity than normal patients did with respect to electroencephalographic alpha waves, N2 latency, N2-P2 auditory evoked potential amplitude, and physical tiredness but were less reactive than patients with GAD on several variables. It is concluded that patients with GAD are abnormally sensitive to caffeine and that the data support the view that panic disorder is a separable disorder from GAD.

Alpha Rhythm↗

Further evidence of increased polymorphonuclear cell activity in patients with Raynaud's phenomenon.

The role of polymorphonuclear cells (PMNs) in the pathophysiology of ischaemic vascular disease has been increasingly recognized in recent years. Activated PMNs may physically obstruct blood flow. Subsequent release of reactive oxygen radicals and lytic enzymes lead to continued damage. Previous studies have shown increased white cell activity in patients with secondary Raynaud's syndrome (RS). However, whether this is related to the underlying condition or to digital vasospasm is not clear. Using a more physiological whole blood PMN aggregation assay, we assessed PMN activity in 38 patients with severe Raynaud's phenomenon (RP) [16 had systemic sclerosis (SSc) and secondary RS; 22 had RP alone and no other features of a connective tissue disease]. Additionally, plasma levels of malondialdehyde (MDA), an indicator of free radical activity, were measured. Results were compared with those obtained from 56 matched volunteers. In order to assess if changes in PMN activity was directly related to digital vasospasm, patients were asked to record the duration and frequency of their Raynaud's attacks during a 2-week period using a pocket sized diary. Correlation between these clinical variables of Raynaud's severity and white cell activity was assessed. Patients with RP, both with and without SSc, showed a significantly greater fall in single PMN count when compared with control subjects [SSc associated RS 48.2 (41.4-56)% versus control, P = 0.04; RP alone 49.3 (46.8-52.1)% versus control, P = 0.01 (Mann-Whitney U-test)].(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Circadian rhythm of white blood cell aggregation and free radical status in healthy volunteers.

Previous studies have demonstrated circadian rhythms in the onset of thrombotic events, which occur most commonly in the morning, and also in the fibrinolytic activity of the blood which has a peak in the evening and a trough in the morning. There has recently been increasing interest in the role of white blood cells (WBCs) and free radicals (FRs) in thrombosis. No one has yet investigated the potential circadian variation of WBC aggregation and FRs in humans. We studied the circadian rhythm of WBC aggregation and FR status in 10 healthy male volunteers. Six blood samples were collected at 4 hourly intervals from 12:00 (mid-day) until 08:00 the following morning. The volunteers carried out normal daily activities until 00:00 at which time they went to bed and they remained in bed until 08:00. The following were measured on each sample: WBC aggregation; thiobarbituric acid reactive substances (TBARs), plasma thiols (PSH), red cell lysate thiols (LSH), glutathione (GSH) and superoxide dismutase (SOD) which are all altered in the presence of FR activity. The following parameters demonstrated significant circadian rhythms, WBC aggregation p less than 0.001, TBARs p less than 0.015, PSH p less than 0.001, LSH p less than 0.002. WBC aggregation was lowest at 09:00 and highest at 00:00-04:00. TBARs and PSH both had a peak at 16:00 and a trough at 04:00. LSH had a peak at 12:00 and a trough at 08:00. As the behaviour of WBCs and FR status influence the flow properties of blood, a circadian rhythm in WBC function and FR status may contribute to the time of onset of thrombotic diseases. Moreover, with many studies being currently undertaken in this area, our work indicates the need to standardize sample times.

Adult↗

Lipid peroxidation and antioxidants in continuous ambulatory dialysis patients.

OBJECTIVE: Oxidative cell damage due to the production of free radical species has been implicated in the pathogenesis of cardiovascular disease for which dialysis patients are at increased risk. Plasma lipid peroxides (malon-dialdehyde), the antioxidants plasma albumin thiol, and red cell superoxide dismutase (SOD) were therefore measured in 18 patients undergoing continuous ambulatory peritoneal dialysis (CAPD), 20 hemodialysis patients, and 30 normal controls. SETTING: Renal dialysis unit. RESULTS: Malondialdehyde (MDA) concentrations were significantly higher in dialysis patients compared to controls (p less than 0.001) and were significantly higher in CAPD patients compared to hemodialysis patients, p less than 0.001 (CAPD, median and range: 11.25 (8.4-15.5) nmol/mL; hemodialysis: 8.75 (7.0-12.6) nmol/mL; controls: 6.65 (5.2-9.6) nmol/mL). Plasma thiol and red cell SOD were significantly lower in dialysis patients compared to controls, but there was no significant difference between CAPD and hemodialysis patients (CAPD thiol: 333.5 (282-480) mumol/L; hemodialysis thiol: 344 (203-468) mumol/L; control thiol: 421.5 (351-504) mumol/L; CAPD SOD: 78.2 (42.4-112.8) u/1/2 mL red cells; hemodialysis SOD: 89.4 (44.6-121.1) u/1/2 mL red cells; control SOD: 96.8 (66.8-153.4) u/1/2 mL red cells). Red cell SOD was significantly negatively correlated with duration of dialysis in CAPD patients (r = -0.683, p less than 0.01). CONCLUSION: In dialysis patients there is indirect evidence for increased free radical activity, which may be further influenced by the mode of dialysis.

Erythrocytes↗

Oxidative effects of laser photocoagulation.

Diabetic proliferative retinopathy is a common and sight-threatening condition. Oxidative stress is an integral and possibly causative part of the pathogenesis. Although laser photocoagulation is usually a beneficial treatment it remains unclear how it works. The possibility that it induces a sudden, temporary increase in free radical activity either by direct thermal damage or by oxygen reperfusion is explored in this clinical study by measuring the oxidative status in the peripheral blood of 13 patients undergoing panretinal photocoagulation. There were significant increases at one hour in malondialdehyde-like material (MDA-LM), 8.1 (6.9-9.6) nmol/mL, to 9.1 (7.6-9.8) nmol/mL, (less than 0.005); plasma thiols (PSH), 423 (352-457) microns/L, to 444 (382-478) microns/L, (p less than 0.005) and red cell reduced glutathione (GSH), 1357 (1295-1655) microns/L, to 1480 (1305-1760) microns/L, (p less than 0.01). Diene conjugates rose over the first hour 0.55 (0.36-0.79) od/mL, to 0.58 (0.34-0.85) od/mL falling to 0.56 (0.36-0.79) od/mL at 2 h but these changes were not significant. At 2 h, MDA-LM 8.4 (6.7-9.6) nmol/mL and PSH 404 (379-462) microns/L had returned to baseline but GSH remained significantly elevated 1500 (1325-1675) microns/L, (p less than 0.005 compared to baseline). This is a new observation and in some circumstances such generation of free radicals could explain the mechanism behind the complications of photocoagulation by direct or indirect damage to vascular endothelium leading to increased vascular permeability manifest as macular oedema or choroidal effusions.

Adult↗

p53 in colorectal cancer: clinicopathological correlation and prognostic significance.

p53 protein was detected by immunohistochemistry in 42% of 52 colorectal adenocarcinomas. Positive tumours were significantly more frequent in the distal colon, and demonstrated a higher rate of cell proliferation. No correlation was found with tumour grade, Dukes' stage, presence of DNA aneuploidy or patient survival. The role of p53 in colorectal carcinogenesis is discussed with particular reference to differences between proximal and distal large bowel cancers.

Colorectal Neoplasms↗

Neuropeptide Y radio-immunoassay: characterization and application.

1. A sensitive and specific neuropeptide Y (NPY) radio-immunoassay has been developed. This radio-immunoassay does not detect the NPY-related peptides pancreatic polypeptide or peptide YY. NPY extracted from rat plasma using sequential C18 sorbent and affinity chromatography co-eluted with synthetic rat NPY when applied to high pressure liquid chromatography. 2. The procedure of stabilization of platelets followed by high speed centrifugation reduced basal values of NPY by 60%, and this may be consistent with removal of platelets that release NPY. Administration of the cholinesterase inhibitor physostigmine (0.3 mg/kg), intravenously, produced a small but significant increase (39%) from basal concentrations of NPY. 3. NPY concentrations in young (2-3-month-old) Sprague-Dawley and Fisher 944 rats were similar; however, NPY concentrations were significantly increased (55%) in 2-year-old Fisher 944 rats. Similar to plasma concentrations of noradrenaline, NPY levels increase with age.

Aging↗

Oxygen free radicals and congestive heart failure.

Plasma lipid peroxides (malondialdehyde) and thiols were measured in 45 patients with congestive heart failure and 45 controls. Malondialdehyde concentrations were significantly higher in the patients with congestive heart failure (median 9.0 nmol/ml interquartile range (IQR) 7.9-10.2) than in the controls (median 7.7 nmol/ml (IQR 6.9-9.2)). Plasma thiols were significantly lower in congestive heart failure (median 420 mumol/l (IQR 379-480)) than in the controls (median 463 mumol/l (IQR 445-525)). There was a significant but weak negative correlation between malondialdehyde and left ventricular ejection fraction (r = -0.35) and a positive correlation between plasma thiols and left ventricular ejection fraction (r = 0.39). This study provides clinical support for experimental data indicating that free radicals may be important in heart failure. It also suggests that the degree of free radical production may be linked to the severity of the disease.

Adult↗

Oxidative damage in chronic heart failure: protection by captopril through free radical scavenging?

The pathogenesis of heart failure is not yet fully understood. In animal models there is some evidence to suggest a role for free radicals (FRs). We have investigated malondialdehyde - LM in plasma of patients with heart failure and found it to be raised when compared to controls. We present data to show that Captopril, a drug with an ACE inhibitory effect is a FR scavenger both in vitro and ex-vivo in patients with heart failure.

Aged↗

Reaction of gallium arsenide with concentrated acids: formation of arsine.

Crystalline particles of gallium arsenide (GaAs) (approximately 2 microns in diameter) react with concentrated hydrochloric acid (HCl) (11.6 to 9 M) to form highly toxic arsine (AsH3) gas. None of the other strong acids that were investigated reacted with gallium arsenide to form AsH3. A spectrophotometric method, based on the reaction of AsH3 with silver diethyldithiocarbamate in a chloroform solution containing morpholine, was used to detect AsH3 gas dissolved in aqueous solutions and to determine the AsH3 gas that was liberated by the reaction of GaAs with HCl. Active sites on the gallium arsenide surface initiate the reaction that forms AsH3 gas. Absorption of oxygen or ions from solution on these active sites inhibits the formation of AsH3.

Arsenic↗

Dissolution of crystalline gallium arsenide in aqueous solutions containing complexing agents.

Crystalline gallium arsenide (GaAs) was found to dissolve in an aqueous solution containing the inorganic anions, chloride, sulfate, bicarbonate, monohydrogen phosphate, and dihydrogen phosphate, and the organic anions, acetate and citrate. The aqueous solution was made up to resemble lung fluid (Gamble solution) and was maintained at a pH of 7.4. The concentrations of arsenic (As) and gallium (Ga) in solution and the As-GA ratio on the surface of the GaAs increased continuously as the time of contact with the aqueous solution increased. X-ray photoelectron spectroscopic studies of the GaAs surface, at various time intervals, showed that As migrated to the surface and was oxidized to a species resembling As2O3 and, finally, was dissolved. The zinc present in the crystalline GaAs also migrated to the surface.

Arsenic↗

Captopril: a free radical scavenger.

The use of captopril in heart failure and hypertension is becoming increasingly accepted. Captopril has a sulphydryl group in its molecular structure. We wondered if this might confer free radical scavenging activity on the drug and have investigated this in an in vitro system. Results show that captopril is a free radical scavenger and we suggest that this action might be relevant in its use in heart failure and other vascular diseases.

Angiotensin-Converting Enzyme Inhibitors↗

Neuropeptide Y and neuropeptide Y18-36. Structural and biological characterization.

Neuropeptide Y (NPY), a 36-residue peptide amide, has been shown by numerous studies to be a potent vasoconstrictor. In order to gain an appreciation of the structural requirements for this action, we have previously synthesized a number of fragments of NPY. It had been shown that sequential deletions from the N-terminus resulted in peptides with decreasing hypertensive activity. In the present study we present data supporting the unexpected finding of two fragments, NPY17-36 and NPT18-36 with substantial hypotensive action in vivo. This action was dose dependent (data not shown) and was also observed to a lesser extent with NPY19-36 but not NPY16-36 or NPY20-36. It was, however, slower in onset and of longer duration than the hypertensive action of NPY. These differing kinetics of action may suggest that NPY and NPY18-36 act through different mechanisms. Structural studies using circular dichroism were performed. While NPY was found to assume an ordered helical structure in both aqueous buffer and trifluoroethanol (TFE), 30% TFE in aqueous buffer was required to induce substantial helicity for NPY18-36. This structural investigation suggests that both NPY and NPY18-36 assume an ordered conformation upon reaching the lipid rich receptor environment.

Animals↗

Morphometric diagnosis of serous effusions: refinement of differences between benign and malignant cases by use of outlying values and larger sample size.

Fifty cytologically malignant, five suspicious, and 27 cytologically benign serous effusions were assessed morphometrically for differences in mean and outlying nuclear and cytoplasmic variables. Significant differences were found between benign and malignant specimens for all nuclear morphometric variables measured, the most significant being largest nuclear area and diameter. No significant differences were found for cytoplasmic size variables. Although measurement of outlying values in serous effusions enhanced the difference between benign and malignant cell populations, it was of insufficient sensitivity or specificity to be of clinical diagnostic use. Increasing the sample size improved test performance but would be tedious to perform manually.

Ascitic Fluid↗