Biomedical subjects
Publications and source records attributed to J S Mann.
OBJECTIVE: To determine whether CD-ROMs are as fast as everyone thinks they are. METHODS: A grand contest between 2 textbooks and their electronic versions, held with the help of 10 victims. RESULTS AND INTERPRETATION: We can't be expected to tell you that now. You'll have to read the paper.
The purpose of this study was to demonstrate a technique, in a pilot study, for measuring abnormal capillary permeability in synovial tissue of rabbit arthritic knees using dynamic MRI with a gadolinium-based blood pool agent. Arthritis, simulating rheumatoid arthritis, was induced in knees of 8 rabbits by intra-articular injection of carrageenan (n = 4) or ovalbumin (n = 4). Sequential fat presaturated T1-weighted Spoiled Grass images were obtained before and up to 30 min after intravenous administration of albumin-(Gd-DTPA)30. Estimates of synovial tissue plasma-volume (PV), fractional-leak-rate (FLR), and permeability-surface-area-product (PS) were computed. Histologic correlation was obtained in the corresponding regions. Dynamic MRI showed extravasation of albumin-(Gd-DTPA)30 into hypertrophic synovium in six of the eight arthritic knees. Histologic examination of these six knees showed markedly inflamed synovium. The two knees that did not show abnormal vascular permeability contained non-hypertrophic synovium. None of the rabbits showed abnormal permeability in muscle. MRI derived microvascular characteristics (PV, FLR and PS) correlated positively (r2 = 0.51, 0.97 and 0.86) with the histology. Factors involving the structural and functional microvascular characteristics of synovial tissue can be estimated non-invasively using albumin-(Gd-DTPA)30. This technique may be useful for monitoring disease progression and treatment response in rheumatoid arthritis.
1. As part of a programme investigating the causation of pecking damage in fowls, this experiment tested a proposal that birds may receive more feather pecks when their plumage colour contrasts with floor litter colour, because litter particles on plumage (as a consequence of dustbathing) may then have greater stimulus value. 2. Groups consisting of 7 light- and 7 dark-coloured bantams were reared from 1 to 11 weeks of age in pens with either wood shavings (light coloured, n=6) or peat (dark coloured, n=6) floor litter. 3. Feather loss from pecking commenced in the 3rd week of life and increased thereafter, but observed pecking damage scores were not consistent with the hypothesis being tested. 4. Despite many more pecks at birds being seen (over 10 weeks) in the wood shavings groups' (661 at particles on plumage, 1795 not at particles) than in peat groups (205, 787), there was no effect of litter substrate on pecking damage. The only evidence supporting the proposal was the finding that, in groups on wood shavings, significantly more pecks at particles on plumage were directed from light coloured birds towards dark ones, than from light to light, dark to light, or dark to dark. 5. Feather eating was confirmed from the presence of feather material in 2% to 15% of faecal droppings collected from each group at 11 weeks, but these proportions were not correlated with pecking damage scores. 6. The results imply that only some feather pecks/pulls were damaging and only some eaten feathers were pulled from other birds.
1. This paper reports 4 experiments with groups of 10 to 20 growing bantams in multi-unit brooders, which investigated effects of certain environmental and dietary factors on development of feather pecking damage to 6 weeks of age. Damage was assessed according to a subjective scoring system. 2. A test of food form (pellets, mash, mash diluted with 100 g/kg powdered cellulose) confirmed that pecking damage tends to be greater with pellets than with mash but there was no significant difference between the low damage scores associated with undiluted and diluted mash treatments. 3. A test of group size (10, 20 birds) and stocking density (744, 372, 186 cm2/bird) showed that variation in pecking damage was associated with group size x density interactions. 4. A test of dietary supplementation with L-tryptophan (0, 10, 20 g/kg) showed suppression of pecking damage with the higher (20 g/kg) dose, compared with the control (0 g/kg) treatment. 5. A test of dietary protein source (plant, mainly animal, mainly semipurified) showed no difference in pecking damage scores between treatments.
The idiopathic inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), are chronic, frequently disabling diseases of the intestines. Segregation analyses, twin concordance, and ethnic differences in familial risks have established that CD and UC are complex, non-Mendelian, related genetic disorders. We performed a genome-wide screen using 377 autosomal markers, on 297 CD, UC, or mixed relative pairs from 174 families, 37% Ashkenazim. We observed evidence for linkage at 3q for all families (multipoint logarithm of the odds score (MLod) = 2.29, P = 5.7 x 10(-4)), with greatest significance for non-Ashkenazim Caucasians (MLod = 3.39, P = 3.92 x 10(-5)), and at chromosome 1p (MLod = 2.65, P = 2.4 x 10(-4)) for all families. In a limited subset of mixed families (containing one member with CD and another with UC), evidence for linkage was observed on chromosome 4q (MLod = 2.76, P = 1.9 x 10(-4)), especially among Ashkenazim. There was confirmatory evidence for a CD locus, overlapping IBD1, in the pericentromeric region of chromosome 16 (MLod = 1.69, P = 2.6 x 10(-3)), particularly among Ashkenazim (MLod = 1.51, P = 7.8 x 10(-3)); however, positive MLod scores were observed over a very broad region of chromosome 16. Furthermore, evidence for epistasis between IBD1 and chromosome 1p was observed. Thirteen additional loci demonstrated nominal (MLod > 1.0, P < 0.016) evidence for linkage. This screen provides strong evidence that there are several major susceptibility loci contributing to the genetic risk for CD and UC.
A rapid and automated method for two-dimensional spatial depiction (mapping) of quantitative physiological tissue characteristics derived from contrast enhanced MR imaging was developed and tested in disease models of cancer, inflammation, and myocardial reperfusion injury. Specifically, an established two-compartment kinetic model of unidirectional mass transport was implemented on a pixel-by-pixel basis to generate maps of tissue permeability surface area product (PS) and fractional blood volume (BV) based on dynamic MRI intensity data after administration of albumin-(Gd-DTPA)30, a prototype macromolecular contrast medium (MMCM) designed for blood pool enhancement. Maps of PS and BV in disease models of adenocarcinoma, intramuscular abscess inflammation, and myocardial reperfusion injury clearly depicted zones of increased permeability (up to approximately 500 microl/cc/h--compared to <25 microl/cc/h in normal tissues). As revealed on PS maps, the rank ordering of studied permeability abnormalities was reperfusion injury > inflammation > tumors. A rapid, automated mapping technique derived from dynamic contrast-enhanced MRI data can be used to facilitate the identification and characterization of pathophysiologic abnormalities, specifically relative increases in blood volume and/or microvascular permeability.
Growing parent stock (breeders) of meat-type chickens (broilers), subjected routinely to chronic food restriction, show increased pacing before a single daily meal and increased drinking and pecking at non-food objects (oral stereotypies) afterwards. Expression of these activities is correlated positively with the level of restriction imposed, and is thought to be controlled mainly by central dopaminergic mechanisms. There is published evidence that glucocorticoids can amplify dopamine mediated behaviours, and this paper describes four experiments examining the relationship between corticosterone and behaviour in individually caged broiler breeders. In Experiment 1 (with 3 levels of food restriction), plasma corticosterone concentration was correlated positively with the level of restriction imposed when blood samples were taken in the morning, but not when they were taken in the afternoon. This may be because corticosterone level declines from morning to afternoon with mild but not severe restriction. In Experiment 2 (severe restriction only), plasma corticosterone level did not change significantly with time of day, and mean values of individual birds were not correlated with their observed times spent in oral stereotypies. In Experiment 3 (severe restriction), object pecking increased in a dose-related way after systemic injection of 1-4 mg/kg corticosterone (significant) and 7.5-30 IU/kg ACTH (not significant), and 10-40 mg/kg metyrapone (corticosterone synthesis inhibitor) had no effect. In Experiment 4 (severe restriction), 180 mg/day metyrapone administered in food for 5 days reduced the plasma corticosterone response to injection of 15 IU/kg ACTH on the fourth day, but otherwise had no effect. Significant increases in drinker directed activity after injection of ACTH on the fourth day and 4 mg/kg corticosterone on the fifth day coincided with greatly elevated plasma levels of corticosterone. It is concluded that the oral stereotypies of restricted-fed broiler breeders do respond to induced increases in plasma corticosterone concentration that are supra-physiological, but there may be only a weak association between behaviour and corticosterone within the physiological range.
1. Behavioural development in groups of 8 pullets kept in pens with litter floors, and fed on either mash or pellets, was studied from 0 to 10 weeks in a White Leghorn x broiler (F2) hybrid line (experiment 1) and from 0 to 24 weeks in Hisex, White Leghorn and Brown Leghorn strains (experiment 2). The aim was to identify precursors of feather pecking and cannibalism. 2. Rates of body weight gain were consistently greater with pellets than with mash in both experiments. In experiment 2, the onset of lay was at 17 weeks of age in Hisex, 21 weeks in White Leghorns and 23 weeks in Brown Leghorns. 3. Persistent feather pecking, which was not seen in experiment 1, developed in 2 of 12 groups (one Hisex and one White Leghorn, both fed on pellets) in experiment 2, and was studied in detail at 23 and 24 weeks. The more damaging pecking in the Hisex group was followed by cannibalism in the same group. 4. Based on the (often inconsistent) effects of genetic strain, age and food form on behaviour that were observed, a working hypothesis was constructed to account for the aetiology of feather pecking and cannibalism in situations where there is floor litter. 5. An age-related decline in one or more foraging activities may coincide with increases in preening and non-damaging pecking at other birds. Consumption of litter particles and moulted feathers may be reinforcing. Dustbathing may enhance the stimulus value of litter particles when they are contrasted against background plumage colour. This may direct pecking towards the backs of birds, where feathers as well as litter particles may be removed and eaten. Regular pecking and feather removal may lead eventually, after the onset of lay, to vent pecking and cannibalism. This sequence of events may be more likely in groups where activity levels are high.
A quick and automated method for quantitative spatial mapping of tissue characteristics derived from contrast enhanced MR imaging by a macromolecular contrast medium (MMCM) was used in normal rats. Specifically, an established two compartment unidirectional flow kinetic model was automatically implemented on a pixel by pixel basis to calculate permeability surface area product (PS) and tissue fractional blood volume (BV) from MRI dynamic intensity data. The utility of PS and BV maps were evaluated in the normal rat abdomen where a range of fractional BV was found: from 100% in the vena cava to 1% in skeletal muscles, with intermediate values for liver and kidney. Tissue permeability depicted on the PS maps was generally low for normal tissues.
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PURPOSE: To determine the relationship between capillary density, a recognized surrogate of tumor angiogenesis, and magnetic resonance (MR) imaging-derived estimates of plasma volume (PV) and microvascular permeability in two mammary carcinoma models. MATERIALS AND METHODS: Dynamic spin-echo imaging was performed by using albumin-(gadolinium-diethylenetriaminepentaacetic acid)34, a prototype blood-pool contrast medium, in 14 rats with a subcutaneously implanted slow- or fast-growing subtype of R3230 mammary carcinoma. Data were fitted to an established two-compartment kinetic model to estimate PV and permeability. RESULTS: MR imaging-derived tumor PVs and permeabilities increased exponentially with increasing capillary density. MR imaging-derived microvascular characteristics correlated strongly with histologic capillary density, with an r2 of .85. CONCLUSION: Contrast medium-enhanced MR imaging may prove useful in estimating angiogenic activity in carcinomas. MR imaging may be superior to histologic assay because it is noninvasive, can be used to "sample" the entire tumor, and reflects both anatomic and physiologic characteristics.
An ultra-short TI inversion recovery echo-planar imaging (ULSTIR-EPI) sequence was designed to reduce the influence of water exchange on fractional tissue blood volume (BV) estimation by measurement of T1-changes induced by a gadolinium-based macromolecular contrast medium (MMCM). Fractional liver BV in rats, estimated by ULSTIR-EPI was compared for accuracy to a fast T1-weighted three-dimensional gradient-echo (3D-SPGR, 3D-spoiled gradient recalled acquisition in a steady state) sequence using an in vitro inductively coupled plasma atomic emission spectroscopy (ICP-AES) assay for BV as a standard. Liver images for fractional BV estimation were acquired in eight rats using both ULSTIR-EPI and 3D-SPGR before and after (within 3 to 12 min) intravenous bolus administration of albumin-Gd-DTPA30 (0.05 mmol Gd/kg). Whereas both MR techniques may be useful for fractional tissue BV estimation, ULSTIR-EPI offers certain advantages including greater accuracy, direct T1 maps, and minimization of transendothelial proton exchange effects. 3D-SPGR imaging offers better spatial resolution, current availability on standard clinical MR systems, and acceptable accuracy.
RATIONALE AND OBJECTIVES: We compared the peritumoral vascular definition in rats using either a paramagnetic extracellular or a macromolecular contrast medium in combination with high-resolution magnetic resonance (MR) imaging. METHODS: High-resolution, three-dimensional spoiled gradient-refocused acquisition in a steady state (SPGR) images were acquired from tumor-bearing Fischer-344 rats before, immediately after, and again 40 min after administration of gadopentetate dimeglumine (0.1 mmol Gd/kg; n = 10) and albumin-(Gd-DTPA)30 (0.05 mmol Gd/kg; n = 5). Small peritumoral vessels were analyzed semiquantitatively on maximum intensity projection angiograms using a 4-point scoring system; quantitative analyses included signal-to-background ratios (SBRs) and signal-to-noise ratios. RESULTS: Gadopentetate dimeglumine caused a transient and low-scoring (0.2 +/- 0.1, SBR = 1.9 +/- 0.2) vessel definition but strong rim enhancement (score = 1.4 +/- 0.2). Albumin-(Gd-DTPA)30 produced persistent, high-quality angiograms (score = 2.6 +/- 0.2, SBR = 7.4 +/- 0.2) but minimal rim enhancement (score = 0.3 +/- 0.2). CONCLUSION: Albumin-(Gd-DTPA)30 combined with high-resolution MR imaging produces time-persistent, detailed angiographic definition of peritumoral vessels. Vascular maps obtained with gadopentetate dimeglumine enhancement are not time persistent or of equal quality.
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