Biomedical subjects
Publications and source records attributed to M Ellis.
Invasive fungal infections have emerged as important causes of hospital related morbidity and mortality. They are increasingly seen in patients not previously considered at risk, e.g. patients on an intensive care unit. Candida albicans and Aspergillus spp. are the most common pathogens, posing challenges in epidemiology, control and treatment.
Clinical diagnosis of invasive fungal infections demands a high clinical acumen, but both under- and over-diagnosis are common. Laboratory mycological tests have traditionally been limited by a range of complications. Development of methodologies to detect fungal-specific immunoglobulins, cell wall antigens and nucleic acid have improved dramatically in recent years.
The management of invasive fungal infection utilizes a variable multidisciplinary approach involving antifungals, appropriate surgery and immuno-correction. Conventional amphotericin B has been the mainstay of treatment but newer pathogens and poor outcomes has led to new formulations of this drug as well as to new and novel antifungals.
Crossbred pigs weaned at 17 d of age (n = 1,760; mean initial BW = 5.6 +/- 0.7 kg) were used in two 4-wk trials (four replicates per trial) to evaluate the effects of three pen designs on pig performance. The designs were 1) large group size (100 pigs/pen) with five two-sided feeders in a single, central location in the pen; 2) large group size (100 pigs/pen) with five two-sided feeders in multiple (five) locations in the pen; and 3) small group size (20 pigs/pen) with a single two-sided feeder in a central location in the pen. Each feeder provided two 20.3-cm-wide feeding places on each side. Pigs had free access to feed and water. Feeder-trough space (4 cm/pig) and floor-area allowance (0.17 m2/pig) were the same for all treatments. Pigs in the large-group treatments were lighter (15.6 and 15.6 vs 16.0 kg; P < 0.01) at the end of wk 4 and had lower ADG (358 and 357 vs 373 g; P < 0.01) and ADFI (510 and 521 vs 544 g; P < 0.01) during wk 2 through 4 than pigs in small groups. Gain:feed ratio was similar (P > 0.05) for all treatment groups throughout the study. For large groups, feed disappearance from each of the five feeders was similar (P > 0.05) for both multiple- and single-location treatments. In summary, large group size reduced pig growth performance, but the approach to providing multiple feeding locations that was employed in this experiment did not increase feed intake or growth performance of pigs in the large groups.
The objective of this study was to determine the effects of the Halothane (N) and Rendement Napole (RN) genes on carcass and meat quality characteristics in pigs. Halothane and RN carrier (Nn/RN- rn+) Hampshire boars (n = 4) were mated to dams that were homozygous for the normal allele of both genes (NN/rn+ rn+) to produce progeny of four genotypes: 1, NN/rn+ rn+ (n = 31); 2, Nn/rn+ rn+ (n = 27); 3, NN/RN- rn+) (n = 30); and 4, Nn/RN- rn+ (n = 23). A DNA test was used to determine Halothane genotype, and longissimus glycolytic potential was used to predict the RN genotype. Pigs were reared under standard conditions to approximately 120 kg live weight and slaughtered at a commercial plant, and carcass characteristics and meat quality were evaluated. Halothane carriers (Nn/ _ _), in comparison to Halothane normal (NN/_ _) pigs, had shorter carcasses, lower longissimus ultimate pH, higher Minolta L* and b* values, and greater drip loss. Rendement Napole gene carriers (_ _/RN- rn+) had higher L* and b* values and drip and cooking loss and lower longissimus ultimate pH than homozygous recessive animals (_ _/rn+ rn+). There were Halothane x RN genotype interactions (P < 0.05) for subjective color, firmness, and marbling scores, and for shear force. Animals that were normal for both genes (NN/rn+ rn+) had the highest subjective scores for color (2.60, 1.88, 1.85, and 1.95, SE = 0.181, P < 0.05), firmness (2.53, 2.03, 2.10, and 1.89, SE = 0.182, P < 0 .05), and marbling (2.11, 1.44, 1.53, and 1.55, SE = 0.153, P < 0 .05) for genotypes 1, 2, 3, and 4, respectively, suggesting darker, firmer muscle with a higher level of marbling for this genotype. Shear force was highest for Nn/rn+ rn+ animals (3.83, 4.41, 3.79, and 3.70, respectively, SE = 0.172, P < 0.05). Gilts had less s.c. backfat thickness, greater longissimus muscle area, and lower subjective marbling scores than barrows. There was no effect (P > 0.05) of gender on other meat quality traits. This study illustrates the negative effects of the Halothane and RN genes on fresh pork quality and suggests that in combination the detrimental effects of the two genes are additive for ultimate pH, objective color, and water-holding capacity.
This study was designed to investigate the effects of dietary lysine level on the intramuscular fat content of the longissimus in finishing pigs reared at two environmental temperatures. Seventy-two hybrid gilts were individually penned and given ad libitum access to either a diet formulated to meet their lysine requirement (6.4 g/kg lysine) or a lysine-deficient diet (4.8 g/kg). Pigs were held at one of two environmental temperatures (thermoneutral [18 degrees C] or hot [32 degrees C]). The study was carried out between approximately 90 and 126 kg live weight; pigs in the thermoneutral and hot environments were on test for 5 and 7 wk, respectively. There were no interactions between dietary lysine level and environmental temperature. Dietary lysine content did not influence feed intake or average daily gain; however, pigs on the lysine-deficient diet had a poorer gain:feed ratio than those fed to requirement (P < .01). High environmental temperature decreased feed intake (P < .001) and average daily gain (P < .01) but improved gain:feed ratio (P < .01). Backfat at the 10th rib was increased and loin eye area and estimated percentage lean in the carcass were decreased for pigs on the lysine-deficient diet. The higher environmental temperature resulted in an increase in carcass length but had no effect on other carcass measurements or intramuscular fat. Feeding the lysine-deficient diet resulted in an increase of .55 percentage unit in longissimus intramuscular fat content (P < .01); however, there was no difference in subjective marbling scores between the diets. Warner-Bratzler shear force values were not affected by dietary lysine level or environmental temperature. Results from this study suggest that feeding of lysine-deficient diets at the end of the finishing period can increase intramuscular fat deposition under thermoneutral and hot conditions.
A total of 204 purebred Hampshire pigs were obtained from 23 breeders. These animals were the progeny of 41 sires and 123 dams. A sample of purebred Yorkshire (n = 24) pigs were also used in the study. Animals were classified by glycolytic potential determined on a live-animal longissimus muscle biopsy sample. Hampshire pigs (n = 176) with glycolytic potential greater than 185 micromol/g (x = 238.8 micromol/g; SD = 29.54) were classified as heterozygous or homozygous for the dominant RN- allele (RN-rn+ or RN-RN-, respectively), whereas cohorts (n = 28) with glycolytic potential less than 185 micromol/g (x = 141.3 micromol/g; SD = 24.48) were considered as homozygous normal (rn+rn+). All Yorkshire pigs (n = 24) had a mean glycolytic potential level of 146.1 micromol/g (SD = 20.18) and were considered as homozygous normal (rn+rn+). The Hardy-Weinberg equilibrium yielded frequencies of .630 and .370 for the dominant RN- allele and normal rn+ alleles in the Hampshire population, respectively, and genotypic frequencies of .397 (RN-RN-), .466 (RN-rn+), and .137 (rn+rn+). Hampshires with glycolytic potential > or = 185 micromol/g had significantly lower longissimus muscle ultimate pH, intramuscular fat, subjective marbling scores, and percentage of protein (P < .001) and had greater longissimus muscle percentage of moisture (P < .001), drip loss (P < .01), and cooking loss (P < .001) than rn+rn+ Hampshires and Yorkshires. These data suggest the RN- allele exists at a high frequency within the American Hampshire breed. Higher glycolytic potential levels, which accompany the allele, may cause decreased meat quality.
Crossbred weanling piglets (n = 1,920; mean initial BW, 5.3 +/- .7 kg) were used in two 9-wk trials employing a randomized block design in a 2 x 2 factorial arrangement of treatments to determine effects of group size (20 [Small = S] or 100 [Large = L] pigs/pen) and floor-space allowance (calculated requirement [CR] or calculated requirement less 50% of estimated "free space" [CR-50]) on growth performance. Free space was estimated for each group size. From wk 1 through 4 after weaning, S and L groups at CR were allowed a floor space of .17 m2/pig, and at CR-50, S and L groups were allowed .15 m2/pig and .13 m2/pig, respectively. From wk 5 through 9 after weaning, all CR treatment pigs were provided a floor space of .38 m2/pig, and for the CR-50 treatment, S and L pigs were allowed .32 m2/pig and .28 m2/pig, respectively. Piglets had free access to feed and water. Feeder-trough space per pig was the same for both group sizes. Feed-intake data were collected for only wk 1 through 4. Group size by floor-space allowance interactions (P < .05) were found for gain/feed ratio (G/F) for wk 1 and wk 2 through 4, but not for wk 1 through 4. Piglets in L groups were lighter (P < .001) at the end of wk 1, 4, and 9 by 2, 4, and 5%, respectively, and had lower ADG (6%; P < .001) throughout the trial than S piglets. During wk 1 through 4, feed intake was lower (7%, P < .001) in L piglets than in S piglets, but G/F was similar (P > .05). Piglets in CR groups had greater ADG (5%; P < .01) throughout the trial, with a greater G/F (P < .05) for wk 1 through 4, and were heavier (P < .01) than those in CR-50 groups at the end of wk 4 (3%) and 9 (4%). Pigs in L groups had a greater within-pen coefficient of variation in BW at the end of wk 9 than pigs in S groups. Large groups and reduced floor-space allowance reduced piglet growth performance in the nursery.
Plants, like animals, are obligate aerobes, but due to their inability to move, have evolved adaptation mechanisms that enable them to survive short periods of low oxygen supply, such as those occurring after heavy rain or flooding. Crop plants are often grown on soils subject to waterlogging and many are sensitive to waterlogging of the root zone. The combination of unfavourable weather conditions and suboptimal soil and irrigation techniques can result in severe yield losses. The molecular basis of the adaptation to transient low oxygen conditions has not been completely characterized, but progress has been made towards identifying genes and gene products induced during low oxygen conditions. Promoter elements and transcription factors involved in the regulation of anaerobically induced genes have been characterized. In this paper an account is presented of the molecular strategies that have been used in an attempt to increase flooding tolerance of crop plants.
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The Kaposi's sarcoma-associated human herpesvirus 8 (KSHV/HHV8) encodes a protein similar to cellular cyclins. This cyclin is most closely related to cellular D-type cyclins, but biochemically it behaves atypically in various respects. Complexes formed between the viral cyclin and the cyclin-dependent kinase subunit, cdk6, can phosphorylate a wider range of substrates and are resistant to cdk inhibitory proteins. We show here that the KSHV-cyclin-cdk6 complex phosphorylates p27(Kip) on a C-terminal threonine that is implicated in destabilization of this cdk inhibitor. Expression of the viral cyclin in tissue culture cells overcomes a cell cycle block by p27(Kip). However, full cell-cycle transit of these cells appears to depend on C-terminal phosphorylation of p27(Kip) and seems to involve transactivation of other cellular cyclin-dependent kinases. A p27(Kip)-phosphorylating cdk6 complex exists in cell lines derived from primary effusion lymphoma and in Kaposi's sarcoma, this indicating that virally induced p27(Kip) degradation may occur in KSHV-associated tumours.
BACKGROUND: Falls in elderly people are a common presenting complaint to accident and emergency departments. Current practice commonly focuses on the injury, with little systematic assessment of the underlying cause, functional consequences, and possibilities for future prevention. We undertook a randomised controlled study to assess the benefit of a structured inderdisciplinary assessment of people who have fallen in terms of further falls. METHODS: Eligible patients were aged 65 years and older, lived in the community, and presented to an accident and emergency department with a fall. Patients assigned to the intervention group (n=184) underwent a detailed medical and occupational-therapy assessment with referral to relevant services if indicated; those assigned to the control group (n=213) received usual care only. The analyses were by intention to treat. Follow-up data were collected every 4 months for 1 year. FINDINGS: At 12-month follow-up, 77% of both groups remained in the study. The total reported number of falls during this period was 183 in the intervention group compared with 510 in the control group (p=0.0002). The risk of falling was significantly reduced in the intervention group (odds ratio 0.39 [95% CI 0.23-0.66]) as was the risk of recurrent falls (0.33 [0.16-0.68]). In addition, the odds of admission to hospital were lower in the intervention group (0.61 [0.35-1.05]) whereas the decline in Barthel score with time was greater in the control group (p<0.00001). INTERPRETATION: The study shows that an interdisciplinary approach to this high-risk population can significantly decrease the risk of further falls and limit functional impairment.
BACKGROUND: Mycobacterium tuberculosis of the cervical spine is a rare but dangerous manifestation of extra-pulmonary tuberculosis. The clinical picture ranges from early, nonspecific, insidious symptoms to severe neurological complications and death, attributed to craniocervical junction instability and cervicomedullary compression. The different lines of management include antituberculous medication with traction and external fixation or adjunctive surgery (debridement and stabilization) in patients with severe or persistent neurological complications and/or vertebral instability. METHODS: We describe two patients with advanced craniocervical junction tuberculosis. The early clinical picture was nonspecific in Case 1 and obscured by psychiatric illness in Case 2. The detailed clinical and radiological findings, and the management, will be described. Involvement of the occipital condyles and foramen magnum, which has not been reported previously, will be demonstrated. RESULTS: Both cases underwent transoral biopsy, aspiration, and debridement of retropharyngeal abscess (granuloma). Histological and tissue culture studies proved the abscesses were tuberculous and anti-tuberculous medications were started. Case 1 showed complete resolution of the clinical and radiological findings. Case 2 developed cardiorespiratory arrest while in a halo jacket. He was resuscitated but remained quadriplegic and semiconscious; he developed nosocomial gram negative pneumonia. He was referred back to his local hospital where he died 1 year later. CONCLUSIONS: Tuberculosis is an infrequent but notable cause of cervicomedullary compression. It should be suspected in patients with infective spondylitis who are immunocompromised or reside in an area highly endemic for tuberculosis. Management strategies include antituberculosis medication, transoral biopsy and drainage of the abscess, traction and external fixation, posterior decompression, and internal fixation, according to the clinical and radiological findings.
OBJECTIVE: The aim of this study was the definition of the duplex scan parameters that best select patients for carotid endarterectomy. METHODS: This study was set in a regional vascular unit. Duplex scanning and angiography were performed prospectively on 50 patients who were symptomatic (100 carotid bifurcation) to identify the most accurate and sensitive duplex scan criteria to identify an 80% to 99% stenosis according to the European Carotid Symptomatic Trial. With data from the European Carotid Symptomatic Trial, we estimated the effect of three different approaches used to select patients for carotid endarterectomy. The first approach was the selection of patients for carotid surgery on the basis of duplex scanning alone with the most accurate duplex scan criteria (approach I). The second approach was the selection of patients for carotid surgery on the basis of duplex scanning alone with a 100% sensitive duplex scan criteria (approach II). The third approach was the selection of patients for angiography with duplex scanning (100% sensitive criteria) and then the use of angiography to define which patients should undergo surgery (approach III). RESULTS: All three approaches appeared to have a similar potential in stroke reduction. However, approach I, which minimized the number of patients who underwent surgery (19% less than approach II) or invasive imaging (65% less than approach III), appeared to be the most appropriate. CONCLUSION: These data support the selection of patients for carotid endarterectomy on the basis of duplex scanning alone. The duplex scan criteria should be validated against angiography.
To determine the outcome at 1 year of neonatal encephalopathy (NE) and to estimate the possible contribution of birth asphyxia to childhood disability in a low-income South Asian country, a prospective cohort study was undertaken in the principal maternity hospital of Kathmandu, where over 50% of local women give birth. From a total population cohort of 21609 live births, 131 term infants with NE (after exclusion of cases associated with neonatal sepsis, congenital malformations, or primary hypoglycaemia) and 208 term control infants were recruited. Of these, 102 (78%) infants with NE and 106 (51%) control infants were followed-up to 1 year of age. Outcome measures were death or neurodevelopmental impairment, graded as major, minor or none. Of the 131 term infants with NE, 83 were graded with moderate or severe NE according to conventional definition. By 1 year of age, 45 (44%) of the infants with NE had died, 18 (18%) had severe impairments, and two (2%) had minor impairments; four (4%) of the control subjects had died and two (2%) had minor impairments. Most deaths in subjects with NE occurred in the early neonatal period; NE carried no excess risk of death beyond the neonatal period. Of the 18 children with major impairment, 14 (78%) had spastic tetraplegic cerebral palsy and eight (44%) had multiple impairments. Compared with the control group the relative risk of death by 1 year was 5 (95% CI 1.4 to 15) for mild NE, 8 (95% CI 3 to 23) for moderate, and 26 (95% CI 10 to 67) for severe. Twenty-seven of 38 (71%) infants with moderate NE either died or survived with major impairment. An upper estimate for the prevalence of major neuroimpairment at 1 year attributable to birth asphyxia is 1 per 1000 live births in this population.
There has been growing consensus that children with conduct disorder (CD) constitute a very heterogeneous group containing children who vary substantially on the development, course, and causes of the disorder. While many have recognized the importance of this heterogeneity for developing better causal theories and for developing more effective treatments, there has been little consensus as to the best way to subtype children with CD. In this paper, we review a number of approaches to subtyping, each with some evidence for its validity for certain purposes. We focus on two recent approaches that have great potential for integrating past subtyping approaches and for advancing causal theory. The first approach is the division of children with CD into those with a childhood onset to their severe antisocial behavior and those with an adolescent onset to their behavior. The second approach is to designate children within the childhood-onset group who show callous and unemotional traits, which is analogous to adult conceptualizations of psychopathy. Both approaches help designate children who many show different causal processes underlying their severe aggressive and antisocial behavior, and who may warrant different approaches to treatment.