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Biomedical subjects

N H Anderson

Publications and source records attributed to N H Anderson.

At least 55 records · Page 3Linked to original sources

Topical glutamine therapy in experimental inflammatory bowel disease.

This study investigated the effects of glutamine and steroid enemas on disease activity in an animal model of colitis. Colitis was induced in male Wistar rats by intracolonic instillation of 30 mg trinitrobenzenesulphonic acid in 50% ethanol (TNBS/E). Controls were given an isovolumetric bolus of normal saline. After 24 h, animals were randomised to receive enemas (1 mL twice daily) of prednisolone (200 mg/L), or L-glutamine (500 g/L) or the suspending agent (placebo). On day 8, the colon was weighed and the degree of inflammation assessed using a colon macroscopic score (CMS). Thymic weight, splenic weight, percentage gain in body weight (%GBW), food intake, plasma interleukin-6 (IL6) and plasma alpha(2)-macroglobulin (alpha(2)M) were also determined. There was a significant increase in CMS, colon weight, splenic weight, IL6 and alpha(2)M in TNBS/E animals compared to controls (P< 0.01). There was also a significant decrease in %GBW, food intake and thymic weight in TNBS/E animals (P< 0.01). The therapeutic enema of prednisolone reduced colonic inflammation (CMS, colon weight), improved thymic weight, %GBW and food intake, and reduced plasma IL6 concentrations (P< 0.05). In contrast administration of glutamine enemas was associated with an exaggerated acute phase protein (alpha(2)M) response (P< 0.05) and failed to improve the colonic and systemic inflammatory response in this experimental model of colitis.

Journal Article↗

Belief revision in children: serial judgment in social cognition and decision-making domains.

Belief revision in 5- to 9-year-olds was studied with an information integration approach. In the social task, children judged niceness of story children, having heard about their good and bad deeds. In the decision task, of parallel structure, they judged what proportion of a group of turtles' catch of starfish was red or gold. In both tasks, 4-5 samples were presented successively, with children adjusting their judgment after each. All ages took sample composition into account, and judgments could be described by a serial integration model previously supported for adults. Recency effects were found as well and were stronger for younger children and in the social task. Further model analysis showed, however, that much of this recency was short-lived and that a stable opinion, to which early and later informers contributed more evenly, developed underneath. Overall, similar processes may underlie serial belief formation across the age range and across domains.

Attention↗

Colitis and colonic mucosal barrier dysfunction.

Trauma, infection, neoplasia, and inflammation can all disrupt the intact intestinal mucosal barrier to intraluminal bacteria and bacterial antigens. This study investigated the relation between colonic inflammation and colonic mucosal barrier function in three experimental models of colitis. There were significantly increased systemic endotoxin concentrations in rats with acetic acid (7.5 (1.7-119.5) pg/ml), ethanol (13.7 (0-111.2) pg/ml), and hapten induced (14.4 (5-31.1) pg/ml) colitis compared with saline controls (3.3 (0-13.7) pg/ml). Data expressed as median (range). There were significant correlations between the systemic endotoxin concentration and both the severity of colitis and of illness in acetic acid induced colitis. A significant increase in colonic permeability to 14C-polyethylene glycol was shown in rats with acetic acid (3.42 (1.36-5.63)%) and hapten induced colitis (2.86 (1.03-8.10)%) compared with saline controls (1.20 (0.67-1.36)%). Data expressed as median (range) of percentage of the intracolonic bolus excreted in urine. There was a significant positive correlation between the severity of colitis and % colonic permeability to 14C-polyethylene glycol. This and other studies provide evidence that mucosal barrier dysfunction is a feature of colitis irrespective of aetiology or species. Such barrier dysfunction may be responsible for the systemic inflammatory response and complications seen in patients with inflammatory bowel disease.

Acetates↗

Enteral and parenteral anti-endotoxin treatment in experimental colitis.

Systemic endotoxemia has been described in ulcerative colitis and Crohn's disease and shown to correlate positively with disease activity and the extent of intestinal ulceration. This study evaluated the efficacy of antibiotic and anti-endotoxic treatment in reducing systemic endotoxemia in a hapten-induced rat model of colitis. Enteral administration of paromomycin was associated with a significant reduction in systemic endotoxin concentrations (7.4 +/- 1.2 pg/ml) when compared with controls (39.8 +/- 12.6 pg/ml; p = 0.032). Intravenous injection of taurolidine was also found to significantly reduce systemic endotoxemia (3.1 +/- 1.3 pg/ml) in comparison with controls receiving saline injection (17.5 +/- 4.2 pg/ml; p = 0.008). Enteral neomycin, parenteral polymyxin or metronidazole and cefuroxime were ineffective anti-endotoxin treatments in this model. Enteral paromomycin or parenteral tauro-lidine therapy are potential methods of preventing and treating systemic endotoxemia in patients with inflammatory bowel disease.

Animals↗

Colonic bacteria and bacterial translocation in experimental colitis.

The indigenous intestinal flora and an intact mucosa are vital components of body defences against luminal pathogenic bacteria. Disruption of these defences in inflammatory bowel disease may permit bacterial translocation and contribute to disease severity. Support for this hypothesis comes from this study of a hapten-induced rat model of colitis. Induction of colitis was associated with a significantly increased colonic Gram-negative aerobic bacilli count. The results, expressed as log10 [colony-forming units per gram tissue] were: colitic 6.97-8.86 versus control 4.90-6.69 (P < 0.05). Colitis was also associated with a decreased Gram-positive cocci count at 4.00-8.04 versus control 6.45-8.30 (P < 0.05). Bacteria translocated to the mesenteric lymph nodes in five of eight colitic rats (P = 0.01), to the spleen in four (P = 0.04) and to the liver in five (P = 0.01) but to these organs in none of the eight control animals. There was a positive correlation between the severity of colonic inflammation and extent of bacterial translocation in colitic animals (rs = 0.86, P = 0.007).

Animals↗

Adsorbents as antiendotoxin agents in experimental colitis.

The intestinal mucosa protects the body from a large reservoir of intraluminal pathogenic bacteria and endotoxins. This mucosal barrier is disrupted by the inflammation and ulceration of inflammatory bowel disease and may permit the absorption of toxic bacterial products. Systemic endotoxaemia has been demonstrated in ulcerative colitis and Crohn's disease and correlates with the extent and activity of disease. In this study the efficacy of absorbents as antiendotoxin agents in a hapten induced rat model of colitis is investigated. Induction of colitis was associated with systemic endotoxaemia. Enteral administration of terra fullonica and kaolin, but not of charcoal, significantly reduced systemic endotoxaemia (terra fullonica 4.2 (1.40) pg/ml; kaolin 5.29 (1.86) pg/ml; charcoal 32.7 (16.6) pg/ml; water 39.8 (12.6) pg/ml). Data expressed as mean (SE). With increasing severity of colitis, there was a decreasing ability of adsorbent therapy (terra fullonica) to control systemic endotoxaemia. Enteral administration of adsorbents controls gut derived systemic endotoxaemia in experimental colitis in animals and may be a useful antiendotoxin treatment in patients with inflammatory bowel disease.

Adsorption↗

An information integration approach to phenomenal causality.

Phenomenal causality was studied by using Michotte's launch event, in which successive motion of two objects evokes an immediate perception that the first motion causes the second. Information integration theory was used to address the complementary issues of invariant perceptual structure and individual differences in phenomenal causality. Three informational cues were varied conjointly: temporal and spatial contiguity of the two motions, and the ratio of their speeds. The dependent measure was a judgment of degree of causality or naturalness. The results showed that individual differences were related to these instruction conditions; the subjects showed five distinctive response patterns. Two were the modal patterns elicited by the instructions, and the others fell in between. The averaging model gave a good account of the data, with meaningful parameter estimates. Individual differences were localized in cue evaluation, whereas their integration into a unified judgment followed an invariant averaging rule. The results allow some reconciliation between Michotte and his critics.

Causality↗

The enantiomeric resolution of ciprofibrate and related compounds by HPLC using chiral stationary phases.

The attempted chromatographic resolution of the drug ciprofibrate and a range of related compounds, containing the chiral moiety 2,2-dichlorocyclopropylbenzene, using five different chiral stationary phases is described. Aqueous mobile phases were used throughout and the successful separation of nine out of 12 pairs of enantiomers was achieved. Structures remote from the chiral centre were seen to affect chiral recognition.

Cellulose↗

Photostability testing of drug substances and drug products in UK pharmaceutical laboratories.

Results of a survey on photostability testing of drug substances and products by UK pharmaceutical laboratories are presented. The results indicate diverse practices in the form of presentation of the product and particularly in exposure to light (as measured in lx days), although there was more consistency in analytical methods and in the analytical criteria used to classify products as stable or unstable for those laboratories adopting this type of classification. A majority of laboratories use daylight in addition to artificial light sources for tests on drug substances and products. Artificial daylight fluorescent tubes and xenon lamps are the most widely used sources of artificial light and both should provide a reasonable simulation of natural light. All laboratories intend their photostability tests to represent light exposure which exceeds that expected to occur in practice but the tests actually applied vary widely in severity as shown in the wide range in light exposure (8-4500 klx days). Therefore the classification of products as stable or unstable needs to be considered carefully in relation to the severity of the test used. Testing procedures for drug substances are broadly similar to those used for drug products. It is concluded that the variation in testing procedure is the result of differing perceptions regarding product exposure in practical usage and the absence of regulatory guidelines.

Drug Industry↗

Appendiceal goblet cell carcinoids: a clinicopathological and immunohistochemical study.

Goblet cell carcinoids are uncommon but distinctive tumours of the appendix. We have reviewed 11 cases diagnosed within the period 1976-1990. The mean age at presentation was 58 years (range 24-76), with a female:male ratio of 8:3. At presentation, in seven patients tumour was confined to the appendix or mesoappendix (mean age 51) and in four there was extension beyond the appendix (mean age 69). Of the seven patients with localized tumour, six are alive and without clinical disease after a mean follow-up period of 32 months and one died with recurrent tumour after 10 years. Of the four with more extensive disease, two died during follow-up (at 23 months with probable liver metastases and at 16 months with intestinal obstruction) and two are alive, one with disease and one clinically disease-free. Immunohistochemistry showed that all of the tumours stained positively for either neuron-specific enolase, chromogranin A or protein gene product 9.5. No tumour stained with antiserum to substance P and none showed glucagon-like immunoreactivity, but four cases stained positively for pancreatic polypeptide, an unusual feature in midgut carcinoids.

Adult↗

Use of the autopsy in Northern Ireland and its value in perioperative deaths.

A report on the pilot study of the Confidential Enquiry into Perioperative Deaths was published recently in the United Kingdom. The scheme was designed as a specialized form of clinical audit relating to perioperative patient care. Because the report placed little emphasis on autopsy, we have looked at all autopsied perioperative deaths, as defined by the enquiry, over a three-year period (1986-88) in a defined catchment area of Northern Ireland. Class I major discrepancies of diagnosis between clinical and postmortem records were found in 21% of 213 autopsied perioperative deaths. By definition, these represented instances in which an adverse impact on patient survival had resulted from the discrepancy. In an additional 29% of cases, there were Class II major discrepancies, which were discrepancies in the primary diagnosis not relevant to life-saving treatment. In 30% of cases there was a discrepancy in a secondary diagnosis, which might have affected the eventual prognosis, had the patient survived, but which was not related directly to the cause of death; these were termed Class III discrepancies. In 47% of cases, there were Class IV discrepant secondary diagnoses, which were 'incidental' findings and had no bearing on prognosis. To put these findings in context, the autopsy rate in Northern Ireland was 12% in 1987, with a higher rate (23%) in the two main teaching hospitals and a lower rate (8%) in all other hospitals. The rate of coroner's autopsies, 6%, is uniform throughout Northern Ireland. Coroner's autopsies are carried out mostly by the salaried staff of the State Pathologist's department. The observed differences in the rates of hospital autopsies reflect local deficiencies of pathologists in relation to the work load. In a series of consecutive autopsies carried out at one of the main teaching hospitals, the highest autopsy rate (68%) was found for paediatric patients, with rates of 29% for surgical and 23% for medical cases. The proportion of hospital autopsies carried out in perioperative surgical patients was the same as that for medical patients, reflecting the fact that no particular emphasis is placed on use of the autopsy as a form of clinical audit for the perioperative group.

Adolescent↗

Diode array detection of low level co-eluting species in high-performance liquid chromatography.

A simple and sensitive method for detecting low levels (0.5 and 1.0%, w/w) of co-eluting species in HPLC has been developed. This method is based on the subtraction of normalized peak up-slope and down-slope spectra from that of the apex. Visual inspection of the resultant "difference spectra" allows for a qualitative judgement regarding the integrity of the peak under consideration.

Antazoline↗

Value of the necropsy in perioperative deaths.

A series of 213 perioperative deaths was studied out of a total of 1451 consecutive necropsies carried out over three years. Discrepancies between the clinical and the necropsy diagnosis were assessed under four classes of discrepant diagnosis: class I, patient survival affected, treatable; class II, patient survival affected but not treatable; class III, correlated to cause of death but treatable; and class IV, incidental diagnosis which could not have been made before death. Major discrepancies of classes I and II were found in 44 (21%) and 62 (29%) cases, respectively. Minor discrepancies of classes III and IV were found in 63 (30%) and 101 (47%) cases, respectively. No discrepancies were found in 50 (23.5%) cases. These results confirm the continuing value of the necropsy in the assessment of perioperative deaths.

Adolescent↗

Necropsies in clinical audit.

The need for specialised forms of clinical audit was highlighted by the report of the Confidential Enquiry into Perioperative Deaths (CEPOD). Necropsy rates in a Northern Ireland teaching hospital were studied with particular reference to perioperative deaths. To provide an overall context for these observations, the pattern of the necropsy services in Northern Ireland as a whole was also determined. For 600 consecutive deaths in a major teaching hospital, the overall necropsy rate was 180 (30%). In the 74 perioperative deaths in this group (as defined by the CEPOD) the necropsy rate was 26 (35%), compared with 16 out of 72 (22%) for other surgical deaths and 89 out of 386 (23%) for medical cases. More coroners' necropsies were carried out in the perioperative group. These figures are within the range of the CEPOD experience. In 1987, in the whole of Northern Ireland, there were 8859 hospital deaths, 520 (5.9%) hospital necropsies, and 516 (5.8%) coroners' necropsies, giving an overall necropsy rate of 11.7%. Outside the two major Belfast teaching hospitals, however, there were 6799 hospital deaths, 76.6% of all hospital deaths for Northern Ireland. In this group there were 180 (2.6%) hospital necropsies and 383 (5.6%) coroners' cases, the overall necropsy rate being only 8.2%. These wide variations reflect the fact that the number of pathologists in post in the peripheral areas of the province falls substantially short of levels recommended by the Royal College of Pathologists. If clinical audit along CEPOD lines is to be effective nationally, more emphasis should be placed on the value of necropsy and local deficiencies in provision will have to be identified and remedied. It is suggested that this could be achieved by combining audit provisions with budgetary incentives.

Autopsy↗

Thermodynamics of distribution of p-substituted phenols between aqueous solution and organic solvents and phospholipid vesicles.

The distribution of p-substituted phenols between 0.15 M NaCl and a range of organic solvents (including 1-octanol) was examined over a range of temperatures. The thermodynamic parameters of transfer, delta G, delta H, and delta S, were determined and the values examined in the light of Hildebrand and Scott's solubility parameter theory, and the collision complexes between solute and organic solvent. Delta H of transfer was positive for nonpolar solvents and negative for 1-octanol; the transfer processes were entropy and enthalpy dominated, respectively. The distribution of the phenols into phospholipid vesicles was examined below the phase-transition temperature. Although delta G of transfer for vesicle-water systems was similar to that for octanol-water systems, the full thermodynamic analysis indicated that the two systems were dissimilar. The use of vesicle distribution data in structure-activity studies is discussed.

Phenols↗

Bacterial activity associated with the decomposition of woody substrates in a stream sediment.

Ground bark and heartwood from Alnus rubra and Pseudotsuga menziesii were added to a muddy sediment from a small Oregon stream and incubated in situ. Carbon dioxide and methane production rates were increased by all amendments, the biggest increase being shown with A. rubra wood. Except for sediment amended with A. rubra wood, nitrogen fixation rates from all treatments (including the control) were approximately 0.1 nmol/g per h throughout the 6-month study period. Contrary to expectations, neither bark had a noticeable adverse effect on microbial activity, but the A. rubra wood promoted nitrogen fixation. These results help to explain the faster rate of decomposition of A. rubra wood in water compared with that of P. menziesii described in the literature. The uptake kinetics of glucose (V(max)) did not follow the same pattern as gas evolution.

Journal Article↗