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Biomedical subjects

H Drummond

Publications and source records attributed to H Drummond.

12 recordsLinked to original sources

The efficacy of corticosteroid therapy in inflammatory bowel disease: analysis of a 5-year UK inception cohort.

BACKGROUND: Corticosteroids remain the mainstay of first-line therapy in active inflammatory bowel disease. AIMS: To determine the clinical outcome after the first corticosteroid-therapy and to identify factors which predict response/failure. METHODS: 216 (136 ulcerative colitis and 80 Crohn's disease) patients were identified in this 5-year inception cohort. The outcomes of early (30 days) and late (1 year) responses were used. Multivariate analyses were performed to identify factors associated with outcome. RESULTS: 86 (63%) and 60 (75%) ulcerative colitis and Crohn's disease required corticosteroid therapy, respectively. In ulcerative colitis, at 30 days, 69 (51%), 42 (31%) and 25 (18%) patients demonstrated complete response, partial response and no response, respectively. For Crohn's disease, these outcomes were observed in 32 (40%), 28 (35%) and 20 (25%). After 1 year, 75 (55%), 23 (17%) and 29 (21%) patients with ulcerative colitis demonstrated prolonged response, corticosteroid-dependence or required surgery, respectively. For Crohn's disease, these outcomes were observed in 30 (38%), 19 (24%) and 27 (35%) patients. Extensive ulcerative colitis was a predictor of surgery (P = 0.001, OR: 15.2). In Crohn's disease, inflammatory disease behaviour was negatively associated with surgery (P = 0.02, OR: 0.13). CONCLUSION: Although corticosteroids are effective, dependence/resistance remains common. Patients with extensive ulcerative colitis and fistulizing/stricturing Crohn's are most at risk of failing corticosteroid therapy.

Adrenal Cortex Hormones↗

Does extra corticosterone elicit increased begging and submissiveness in subordinate booby (Sula nebouxii) chicks?

We tested whether in two-chick broods of the blue-footed booby (Sula nebouxii) elevated circulating corticosterone in the socially subordinate broodmate facilitates submissive behavior and/or enhances food solicitation. Implanting corticosterone in 17 subordinate chicks (experimental broods) produced changes in the behavior of chicks and parents over the first two days, relative to 17 matched families (control broods) where subordinate chicks were implanted with empty capsules. Experimental broods showed increased activity/wakefulness of the dominant broodmate and, consequently, increased simultaneous activity of both broodmates, but there was scant evidence that subordinates submitted more readily when attacked. Implanted subordinates increased their rate of spontaneous submission over the total observation time, but this increase was mostly explained by the additional time when both broodmates were simultaneously active. There was little sign that extra corticosterone induced more begging, except possibly by eliciting increased activity. Experimental broods increased their rate of feeding, and most if not all of the increase was due to the increased activity and increased feeding rate of dominant broodmates. On the third and fourth days after implantation all effects of implanted corticosterone disappeared, except for the elevated activity and feeding rates of dominant chicks. At the end of four days, subordinates implanted with corticosterone showed no increase in circulating corticosterone and experimental broods showed no gain in mass or body size, relative to controls. Extra corticosterone, above the high level that normally circulates in subordinate chicks, apparently does not enhance submission to aggression or food solicitation, but provokes a cascade of changes in the behavior of broodmates and parents.

Agonistic Behavior↗

DLG5 variants do not influence susceptibility to inflammatory bowel disease in the Scottish population.

INTRODUCTION: Recent data have suggested that specific haplotypic variants of the DLG5 gene on chromosome 10q23 may be associated with susceptibility to inflammatory bowel disease (IBD) in Germany. Haplotype D, notably characterised by the presence of a G-->A substitution at nucleotide 113, was associated with susceptibility to Crohn's disease (CD) whereas an extended haplotype A conferred protection. AIMS: Association of DLG5 haplotypic variants with disease susceptibility, genotype-phenotype relationships, and epistasis with CARD15 was investigated in the Scottish population. PATIENTS AND METHODS: A total of 374 CD, 305 ulcerative colitis (UC), and 294 healthy controls (HC) were studied. Genotyping for the variants rs1248696 (113A, representing haplotype D) and the single nucleotide polymorphism tag rs2289311 (representing haplotype A) were typed using the Taqman system. RESULTS: On analysis of the DLG5 variant 113A, there were no associations with IBD when allelic frequency (11.4% IBD v 13.2% HC; p = 0.30) and carrier frequency (19.2% IBD v 24.6% HC; p = 0.069) were analysed. No associations were observed between 113A variant allelic frequency (p = 0.37), carrier frequency (p = 0.057), and CD. In fact, 113A heterozygosity rates were lower in CD (16%) and IBD (16.9%) than in HC (23%) (p = 0.029 and p = 0.033, respectively). No associations between DLG5 and UC were observed. Haplotype A was not protective and there was no evidence of epistasis between DLG5 and CARD15. CONCLUSIONS: The present data contrast strongly with previous data from Germany. DLG5 113A is not associated with disease susceptibility and haplotype A does not confer resistance. Further work is required to evaluate the significance of DLG5 in other populations from geographically diverse regions.

Adult↗

Thermal benefit of sibling presence in the newborn rabbit.

Newborn rabbits compete vigorously for the mother's milk, and survivors benefit from littermate deaths. Here we report that rabbit pups also may benefit from littermate presence in terms of increased thermal efficiency. Pups nursed normally once a day by their mother but otherwise raised alone had a lower probability of survival, lower body temperature, and lower efficiency of converting milk into body mass than their siblings raised with littermates. The contribution of a more favorable thermal environment to the better growth and survival of group-raised pups was supported by the finding that single pups raised at higher ambient temperatures grew more rapidly than single pups raised at lower temperatures. These effects were most clearly seen across Days 2 to 5, after which time differences between treatment groups were no longer significant. Thus, the results of this study suggest that the benefits as well as costs of having siblings must be weighed against each other when considering the manner in which sibling presence influences individual development and survival.

Animals↗

Epithelial Na+ channels and stomatin are expressed in rat trigeminal mechanosensory neurons.

Caenorhabditis elegans MEC-4 and MEC-10 are subunits of the degenerin/epithelial Na+ channel (DEG/ENaC) ion channel superfamily thought to be associated with MEC-2 (a stomatin-like protein) in a mechanotransducing molecular complex in specialized touch sensory neurons. A key question is whether analogous molecular complexes in higher organisms transduce mechanical signals. To address this question, we selected mechanoreceptors of the rat vibrissal follicle-sinus complex in the mystacial pad and the trigeminal ganglia for an immunocytochemical and molecular biological study. RT-PCR of poly(A+) mRNA of rat trigeminal ganglia indicated that alpha-, beta-, and gamma-ENaC and stomatin mRNA are expressed in rat trigeminal ganglia. Using immunocytochemistry, we found that alpha-, beta-, and gamma-ENaC subunits and stomatin are localized in the perikarya of the trigeminal neurons and in a minor fraction of their termination site in the vibrissal follicle-sinus complex, where longitudinal lanceolate endings are immunopositive. We conclude that alpha-, beta-, and gamma-ENaC subunits as well as the candidate interacting protein stomatin are coexpressed in a mammalian mechanoreceptor, a location consistent with a possible role in mechanotransduction.

Animals↗

The effects of an "El Niño" southern oscillation event on reproduction in male and female blue-footed boobies, Sula nebouxii.

This study attempted to determine endocrine correlates of reproductive success in relation to major deleterious environmental conditions. In 1992, an El Niño southern oscillation event resulted in complete reproductive failure in a colony of blue-footed boobies, Sula nebouxi, on Isla Isabel in the Pacific Ocean off San Blas, Nayarit, Mexico (21.5 degrees N, 105.5 degrees W). In 1993, the El Niño event had waned and reproductive success was high. The mean sea surface temperature in 1992 was 26.69 degrees, the warmest year for 11 years of data (mean, 25.63 degrees ). In 1993, mean sea surface temperature was 25.75 degrees. Plasma levels of testosterone were highest during the egg-laying period in 1993 and declined markedly during incubation. There were no differences between males and females. Comparisons of testosterone levels between 1992 and 1993 (egg-laying time point removed for 1993) showed no significant differences. Thus reproductive failure during an El Niño year was not related to testosterone levels. Baseline plasma levels of corticosterone did not change over the nesting cycle in either sex. There was a trend for plasma levels of corticosterone to be higher in males and females during the earlier stages of breeding in 1992 compared with 1993, and if all levels were combined within years then females showed significantly higher plasma levels of corticosterone in the El Niño year. Plasma levels of corticosterone showed marked increases following capture and handling in both sexes and at every stage of the breeding cycle in each year. There was no variation in the adrenocortical responses to stress with year or stage of nesting in males. However, in females, maximum corticosterone levels were greatest during the parental phase of 1992, the El Niño year, when all nests ultimately failed. Comparisons of the dynamics of corticosterone changes during the capture stress protocol revealed no correlations with body mass in 1992 or 1993. These data suggest that although massive reproductive failure in the El Niño year was not related to testosterone levels, baseline circulating concentrations of corticosterone may have a role in inhibiting onset of breeding. In contrast, after the nesting cycle has been initiated, increased adrenocortical sensitivity to acute stress may be involved in nest abandonment.

Adrenal Cortex↗

Dominance between booby nestlings involves winner and loser effects.

Two-chick broods of the blue-footed booby, Sula nebouxii, ordinarily exhibit stable dominance-subordinance, with the senior (first-hatched) chick habitually aggressive and the junior one habitually submissive (Nelson 1978, The Sulidae: Gannets and Boobies. London: Oxford University Press). But are both the subordinate and the dominant chick affected in their agonistic tendencies by early social experience? To answer this, we permanently paired subordinate and dominant chicks, 2-3 weeks old, with singletons (chicks lacking experience with a nestmate) by cross-fostering. During the first 4 h after pairing, subordinate chicks were seven times less aggressive than singletons and twice as likely to be submissive; dominant chicks were six times as aggressive as singletons. Although most subordinates consistently lost agonistic encounters during the first 10 days after pairing, the proportion of dominants that won decreased progressively until, by day 6, only about half of dominant chicks were winning. Early social experience has a strong but reversable training effect on both subordinates and dominants. Training as a subordinate showed more persistent effects than training as a dominant, possibly in part because our testing situation perpetuated subordinate training and counteracted dominant training. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗

Transfer of a salt-resistant renin allele raises blood pressure in Dahl salt-sensitive rats.

To evaluate the role of the renin gene in the development of hypertension in Dahl salt-sensitive rats (SS/Jr/Hsd), we derived a congenic strain of rats homozygous for the salt-resistant renin allele (S/renrr) and compared them with a control strain homozygous for the salt-sensitive renin allele (S/ren(ss). Mean arterial pressure was significantly higher in 12-week-old S/renrr rats fed a high salt (8.0%) diet for 3 weeks than in S/ren(ss) rats or in SS/Jr/Hsd rats rederived from the foundation colony we used to generate the cogenic strain (195 +/- 3 [n = 49] versus 168 +/- 3 [n = 17] or 161 +/- 3 [n = 16] mm Hg). Mean arterial pressure was also higher in S/renrr rats than in S/ren(ss) rats raised from birth on either a very low salt (0.1%) diet (119 +/- 9 [n = 6] versus 100 +/- 7 [n = 7] mm Hg) or a low salt (0.4%) diet (143 +/- 1 [n = 22] versus 117 +/- 3 [n = 10] mm Hg). Plasma renin activity of S/renrr rats was significantly higher than that of S/ren(ss) rats fed a very low salt diet (5.7 +/- 2.0 versus 1.8 +/- 0.3) ng angiotensin l/mL per hour), a low salt diet (4.4 +/- 1.0 versus 1.1 +/- 0.3), or a high salt diet (1.5 +/- 0.2 versus 0.9 +/- 0.1). Urinary protein excretion was greater in S/renrr rats than in S/ren(ss) rats fed a high salt diet (244.2 +/- 48.5 versus 43.6 +/- 19.5 mg/24 h), and this was associated with significant reductions in renal blood flow (3.3 +/- 0.6 versus 4.6 +/- 0.5 mL/min per gram kidney weight) and glomerular filtration rate (0.49 +/- 0.11 versus 0.82 +/- 0.08 mL/min per gram kidney weight). Captopril (20 mg/kg i.v.) had no effect on blood pressure in S/ren(ss) rats fed a low salt diet, but it lowered blood pressure by 20 mm Hg in S/ren(rr) rats to the same level seen in untreated S/ren(ss) rats. Chronic administration of captopril (5 mg/100 mL drinking water) reduced blood pressure in S/renrr rats fed a high salt diet (170 +/- 5 mm Hg) to the same level seen in untreated S/ren(ss) rats, whereas it had no significant effect on blood pressure in S/ren(ss) rats. These results indicate that transfer of a salt-resistant renin allele to SS/Jr/Hsd rats raises plasma renin activity and augments the severity of hypertension and renal disease.

Alleles↗

Precipitins to dietary proteins in atopic eczema.

Precipitating antibodies to foods have been assayed in three groups of patients with atopy. Forty-five per cent of patients with atopic eczema and IgE-mediated food allergy had precipitins to foods in their serum compared with only 15% of patients with atopic eczema without evidence of food allergy, and 16% of patients with atopic asthma and/or rhinitis. It is likely that this results from increased intestinal permeability in the group with eczema and food allergy.

Adult↗