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Biomedical subjects

R Burnett

Publications and source records attributed to R Burnett.

At least 19 recordsLinked to original sources
PubMed2006

Effects of butyrate precursors on electron relocation when methanogenesis is inhibited in ruminal mixed cultures.

AIMS: Inhibition of ruminal methanogenesis often causes accumulation of H(2), formate and ethanol, which are not energy substrates for ruminants. It was hypothesized that the addition of butyrate precursors would avoid the formation of these products and relocate electrons into butyrate. METHODS AND RESULTS: In four ruminal 24-h incubations, two inhibitors of methanogenesis, each at three different initial concentrations (0, 2 or 4 mmol l(-1) for propynoic acid, and 0, 4 or 8 mmol l(-1) for ethyl 2-butynoate), were combined with two butyrate precursors at two different initial concentrations (0 or 4 mmol l(-1) for crotonic acid or 3-butenoic acid). Ground lucerne hay was the substrate. Propynoic acid at 4 mmol l(-1) decreased CH(4) formation by more than two-thirds. Ethyl 2-butynoate at 8 mmol l(-1) suppressed methanogenesis by more than 90%. Butyrate precursors generally did not decrease the accumulation of H(2) and formate or ethanol production. CONCLUSIONS: Butyrate precursors were ineffective as electron acceptors because they were not completely converted to butyrate and were also metabolized through other pathways. SIGNIFICANCE AND IMPACT OF THE STUDY: Effectiveness of butyrate precursors may be improved by adding them to the fermentation continuously or by enhancing the kinetics of their conversion into butyrate.

Alkynes↗
PubMed2003

Attempts to inhibit ruminal methanogenesis by blocking pyruvate oxidative decarboxylation.

The inhibition of pyruvate oxidative decarboxylation as a means of decreasing ruminal methanogenesis in vitro was studied. In the first experiment, the addition of adenosine and adenine (with and without ribose) to ruminal batch cultures did not decrease methanogenesis. In the second experiment, the addition of oxythiamin decreased methanogenesis by 23%. In the third experiment, three pyruvate derivatives did not inhibit methanogenesis, although hydroxypyruvate improved organic matter fermentation from 57.8% to 64.2%. The additives did not seem to inhibit pyruvate oxidative decarboxylation.

Animals↗
PubMed2002

Effect of murine recombinant IL-2 on the course of lupus-like disease in (NZBxNZW) F1 female mice.

The exacerbation of pre-existing autoimmune diseases is a potential toxic effect of immunoactive drugs. An increase in the incidence of autoimmune thyroiditis has been noted in patients treated with human recombinant interleukin-2 (rIL-2). In contrast, human rIL-2 tends to protect mice from autoimmunity. As the effects of murine rIL-2 on autoimmunity have not been reported in mice, lupus-prone female (NZBxNZW) F1 mice were treated with 20,000 IU murine rIL-2 intraperitoneally, twice weekly for 13 weeks, beginning at 15 weeks of age. No evidence of an exacerbating effect of murine IL-2 on the lupus disease of (NZBxNZW) F1 mice was observed as no change in the following parameters were seen, namely mean survival time, mean body weight, anti-DNA and antinuclear antibody production. These results show that: 1) like human rIL-2, murine rIL-2 does not exacerbate autoimmunity in mice; 2) the biological effects of human as well as murine rIL-2 in mice differ from those seen with human rIL-2 in man. These latter findings suggest that the selection of the relevant animal species for immunotoxicity studies with recombinant cytokines and derivatives may be less straightforward than previously thought.

Animals↗
PubMed2002

Humeral osteonecrosis leading to the early detection of a bronchial carcinoma.

The new Ionising Radiation (Medical Exposure) Regulations 2000 (IR (ME)ER) were implemented in January 2001. These regulations state that "the referrer must record in the patient's notes that a radiograph was taken and what it showed". As a result it is now incumbent upon the orthopaedic surgeon to document formally the findings of all requested radiographs. We present a case in which a left upper bronchial carcinoma was detected initially on a radiograph of the left shoulder. It highlights the importance of careful examination of the entire radiographic image and the documenting of the findings.

Humans↗
PubMed2001

The spatial association between community air pollution and mortality: a new method of analyzing correlated geographic cohort data.

We present a new statistical model for linking spatial variation in ambient air pollution to mortality. The model incorporates risk factors measured at the individual level, such as smoking, and at the spatial level, such as air pollution. We demonstrate that the spatial autocorrelation in community mortality rates, an indication of not fully characterizing potentially confounding risk factors to the air pollution-mortality association, can be accounted for through the inclusion of location in the model assessing the effects of air pollution on mortality. Our methods are illustrated with an analysis of the American Cancer Society cohort to determine whether all cause mortality is associated with concentrations of sulfate particles. The relative risk associated with a 4.2 microg/m(3) interquartile range of sulfate distribution for all causes of death was 1.051 (95% confidence interval 1.036-1.066) based on the Cox proportional hazards survival model, assuming subjects were statistically independent. Inclusion of community-based random effects yielded a relative risk of 1.055 (1.033, 1.077), which represented a doubling in the residual variance compared to that estimated by the Cox model. Residuals from the random-effects model displayed strong evidence of spatial autocorrelation (p = 0.0052). Further inclusion of a location surface reduced the sulfate relative risk and the evidence for autocorrelation as the complexity of the location surface increased, with a range in relative risks of 1.055-1.035. We conclude that these data display both extravariation and spatial autocorrelation, characteristics not captured by the Cox survival model. Failure to account for extravariation and spatial autocorrelation can lead to an understatement of the uncertainty of the air pollution association with mortality.

Adolescent↗
PubMed2000

Oral 9-cis retinoic acid (Alitretinoin) in the treatment of myelodysplastic syndromes: results from a pilot study.

A multicenter phase II study was initiated to investigate the efficacy, toxicity and tolerability of an oral regimen of 9-cis retinoic acid (9CRA) as a differentiation-inducing agent stimulating both retinoic acid receptor (RAR) and retinoic X receptor (RXR). Thirty patients with myelodysplastic syndromes (MDS) were enrolled into the study. The MDS subtypes were distributed as follows: 14 refractory anaemia (RA), four refractory anaemia with ringed sideroblasts (RARS), and 12 refractory anaemia with excess blasts (RAEB). The age ranged from 40 to 81 years (median 70). None of these had previously received treatment for MDS other than supportive therapy. 9CRA (Alitretinoin capsules, kindly provided by Allergan-Ligand Retinoid Therapeutics) was given daily at 60 mg/m2 p.o. for 1 week, followed by an intra-patient escalation to 100 mg/m2 during the second week, up to a maximum of 140 mg/m2. The planned treatment duration was 48 weeks. Twenty-five were available for assessment. One patient (4%) with RA achieved complete hematological remission. Four (16%), two with RA, two with RAEB, had minor responses resulting in decreased transfusion requirements or increased neutrophils. Thus, the overall response rate was 20% in evaluable patients with MDS and 17% in the study group on an intention-to-treat basis. The most frequent side-effects included headache (77%), dry skin (57%), arthralgias (30%), and rash (23%). In conclusion, although modest responses were noted in this study, the treatment tolerability was suboptimal. It is conceivable that a lower dosage schedule may be efficacious and better tolerated so enabling prolonged exposure which may be required to induce a differentiation effect.

Administration, Oral↗
PubMed1999

Fertility and marital rates in first-onset schizophrenia.

BACKGROUND: Many studies have demonstrated that in schizophrenia there are decreased rates of marriage, fertility and marital fertility. However, it is not clear whether this finding occurs as a social consequence of having the illness or is an inherent part of the illness. One would expect it to vary across cultures if it were being mediated by social and cultural factors. METHOD: We investigated this by reviewing the marital and fertility data from a multi-ethnic first-contact group of patients in London with CATEGO broadly defined schizophrenia, and comparing this with similar data from a group of controls who were matched for age, gender and ethnicity. RESULTS: Our sample comprised 38 White British, 38 Caribbean and 24 Asian subjects. The Asian group were significantly older (mean age 38, P < 0.003) and had a greater percentage of females (50%). When compared to controls, the White and Caribbean patients, but not the Asians, had decreased marital and stable relationship rates. There was also decreased fertility and marital fertility as evidenced by number of children among the Whites and Caribbeans, but again significantly not among the Asians. Marital status did not predict fertility rates, particularly among the Caribbeans. Regression analysis demonstrated an effect for age on the number of children but not on marital status. CONCLUSIONS: These findings suggest that marital and reproductive behaviour are reduced in schizophrenia, but this effect may be mediated by social and cultural factors and therefore not apply consistently across ethnicity. Further research is needed to prospectively investigate populations to determine whether impairments of this nature are inherent or consequential to the illness.

Adolescent↗
PubMed1999

The first contact of patients with schizophrenia with psychiatric services: social factors and pathways to care in a multi-ethnic population.

BACKGROUND: African-Caribbean patients have less desirable routes of entry into the psychiatric services than other ethnic groups in Britain but this may not apply to the first contact with services. METHODS: Patients' pathways to care, type of admission or referral and sectioning details were recorded for all first contact patients presenting to south London psychiatric services over a 2-year period. We also conducted a retrospective analysis of data from the Camberwell Register, comparing rates of compulsory admission between 'Whites' and 'African-Caribbeans' for first and readmissions, over a 20-year period. RESULTS: Our first contact sample comprised 38 White, 38 African-Caribbean and 24 Asian patients with CATEGO defined broad schizophrenia. GP referral was found to be the most common mode of contact and there were no significant differences between the ethnic groups with regard to compulsory admission. Similarly, data from the Camberwell Register showed no significant difference in rates of compulsory admission between first admission White and African-Caribbean patients. However, when all readmissions were examined, African-Caribbeans were more likely to be admitted involuntarily. CONCLUSIONS: Our findings suggest that reports of less desirable routes of entry for African-Caribbean patients into the psychiatric service do not apply to their first admission but are likely to develop over time and repeated contact with the services.

Adolescent↗
PubMed1997

Immunohistochemistry for light microscopy in safety evaluation of therapeutic agents: an overview.

The history of immunohistochemistry started in 1941 when Coons identified pneumococci using a direct fluorescent method. Then followed the indirect method, the addition of horseradish peroxidase, the peroxidase anti-peroxidase technique of 1979 and the use of the Avidin and Biotin complex in the early 1980s. This sequence of events can help one appreciate the differences in these various techniques and their increased sophistication and sensitivity. The technique has been applied in the field of safety evaluation of new pharmaceutical products. Examples of current projects are used to illustrate the scope of the application. The use of an antibody to detect proliferating cell nuclear antigen has, in a pilot study with the popliteal lymph node assay, provided a method of differentiating an irritant response to acetone from an immune response to hydrazine. In hydrazine-treated rats the proliferation is mainly in the follicular region whilst it is mainly sinusoidal in animals treated with acetone. In the guinea-pig maximisation test, initial work with dinitrochlorobenzene suggests that detection of Langerhans cells may aid the differentiation of an irritant from an immune response. The preclinical assessment of antibodies intended for therapeutic use in man requires immunohistochemistry to be used to identify any human tissues which show a cross-reactivity. The major problems are not in the test itself but in obtaining suitable material. Identification of hormones is a useful tool for assessing the effects of releasing factors and has proved useful in aiding tumour identification in routine carcinogenicity studies. In a rare case, detection of prolactin in cell deposits in the lungs of a rat confirmed that this was a metastasis from a pituitary carcinoma. The application of immunohistochemical techniques to preclinical assessment of drugs should always be considered. In particular, it is recommended that appropriate samples should be conserved from routine studies in order to permit these techniques to be performed, if considered appropriate in the light of findings during routine histological examination.

Animals↗
PubMed1996

Prediction of radiotherapy response of cervical carcinoma through measurement of proliferation rate.

Estimation of tumour proliferation may allow the design of individualised radiotherapy schedules to optimise response. This prospective study correlates the tumour proliferation rate of cervical carcinoma with response to conventional radiotherapy. The potential tumour cell doubling rate (Tpot) was estimated following flash labelling of the tumours in vivo using the DNA precursor, bromodeoxyuridine (BrdUrd); samples were analysed by flow cytometry. Tumour ploidy, DNA index and mitotic count were also assessed as was histological grade and type. Multiple biopsies from each tumour were obtained from 121 women. The median Tpot was 4.0 days, median S-phase duration 12.8 h and median adjusted labelling index 9.8%. Higher BrdUrd labelling was seen in patients who developed pelvic tumour recurrence following radiotherapy. This was the only biological/histological parameter with univariate and multivariate significance in relation to locoregional recurrence (P = 0.006 and P = 0.034 respectively). This study represents the first assessment of Tpot in relation to long-term response of cervical tumours treated by radiotherapy treatment. The association of high BrdUrd labelling and poor pelvic disease-free survival indicates the need for further research into the potential of radiotherapy schedule alteration to reflect tumour proliferation. The predictive value may be enhanced by combination with other biological parameters.

Aged↗
PubMed1995

DLA-identical bone marrow grafts after low-dose total body irradiation: effects of high-dose corticosteroids and cyclosporine on engraftment.

Previous studies found that marrow allografts from DLA-identical littermates resulted in survival of 60% of recipient dogs after an otherwise lethal dose of 450 cGy of total body irradiation (TBI), either because of successful allografts or autologous recovery after rejection of the allografts. Forty percent of dogs died with marrow aplasia after allograft rejection. The current study asked whether allogeneic engraftment could be enhanced and survival improved by treating allograft recipients with high doses of corticosteroids or with cyclosporine (CSP), administered either before or after transplantation. Five dogs in group 1 received corticosteroids beginning on day -5 and ending on day 32 after transplant. The starting dose was 12.5 mg of prednisone per kilogram orally twice daily. All five dogs rejected their allografts; three died early with marrow aplasia and two showed endogenous marrow recovery. Nine dogs received CSP from day -6 to day -1 before transplantation at a dose of 20 mg/kg/d intravenously administered in divided doses. All nine dogs rejected the marrow allograft; six died with marrow aplasia and three survived with endogenous marrow recovery. Seven dogs received CSP after transplantation at a dose of 30 mg/kg/d orally from day -1 to day 35. All seven had sustained allografts (two mixed chimeras and five complete donor-type chimeras) and became healthy long-term survivors without graft-versus-host disease. These results extend previous observations and confirm that grafts of marrow from DLA-identical littermates improved survival of dogs exposed to low but otherwise lethal doses of TBI. Additional therapy with high-dose corticosteroids administered peritransplantation and posttransplantation or CSP administered before transplantation neither enhanced the rate of allogeneic engraftment nor improved survival; however, CSP administered after transplantation resulted in successful allografts and event-free survival in all cases.

Adrenal Cortex Hormones↗
PubMed1995

The human MLL gene: nucleotide sequence, homology to the Drosophila trx zinc-finger domain, and alternative splicing.

We have previously reported the cloning of several cDNAs corresponding to the MLL gene. The predicted primary amino acid sequence of two of these clones, 14p-18B and 14-7, reveals nearly complete identity with parts of the sequences of HRX, ALL-1, and Htrx-1, including a Zinc-finger region with homology to the Drosophila trithorax gene. However, we found that there is a stretch of 39 amino acids that is absent from 14p-18B when compared to ALL-1 and HRX. Another sequence of three amino acids is present in ALL-1, but is absent from 14p-18B and HRX. Nucleotide sequence examination reveals that these differences arise from alternative splicing, suggesting that MLL, HRX, and ALL-1 each represents a different alternative splicing product from the same gene. At least two cDNA clones, 14-7 and 14p-18C, correspond to incompletely processed transcripts including intron sequences. Northern blots using a subclone of 14p-18B revealed mRNA species of 14-16 kb in size in various human tissues. RNase protection assays show that the splice variant containing exon 8 and lacking a 9-bp extension 3' of exon 12 is predominantly expressed in hematopoietic cell lines.

Alternative Splicing↗
PubMed1995

Depression in male and female patients undergoing cardiac surgery.

The present longitudinal study was designed to determine the prevalence of depression in male and female patients undergoing cardiac surgery, and to examine what factors are associated with depression before and after surgery. One day prior to surgery (T1), and one day prior to discharge from the hospital (T2), 141 patients completed a psychometric test battery including the Center for Epidemiological Studies Depression Scale (CES-D), the State-Trait Anxiety Inventory (STAI), and the Perceived Social Support Scale (PSSS). Data were also collected on 13 physiological measures. Forty-seven per cent of patients were depressed (defined as a score of 16 or above on the CES-D) at T1. Scores on the CES-D significantly increased from T1 (M = 15) to T2 (M = 20), with 61 per cent of patients classified as depressed at T2. Factors associated with depression at T1 were female gender, higher state anxiety, and less social support. Depressed patients at T2 were characterized by higher scores on the STAI at T2 and higher scores on the CES-D at T1. The prevalence of depression in cardiac surgery patients, particularly women, may be underrecognized and warrants increased attention.

Adult↗
PubMed1995

Transcardiac echocardiography during invasive intramedullary procedures.

We performed transoesophageal echocardiography in 111 operations (110 patients) which included medullary reaming for fresh fractures of the femur and tibia, pathological lesions of the femur, and hemiarthroplasty of the hip. Embolic events of varying intensity were seen in 97 procedures and measured pulmonary responses correlated with the severity of embolic phenomena. Twenty-four out of the 25 severe embolic responses occurred while reaming pathological lesions or during cemented hemiarthroplasty of the hip and, overall, pathological lesions produced the most severe responses. Paradoxical embolisation occurred in four patients, all with pathological lesions of the femur (21%); two died. In 12 patients large coagulative masses became trapped in the heart. Extensive pulmonary thromboembolism with reamed bone and immature clot was found at post-mortem in two patients; there was severe systemic embolisation of fat and marrow in one who had a patent foramen ovale and widespread mild systemic fat embolisation in the other without associated foraminal defect. Sequential analysis of blood from the right atrium in five patients showed considerable activation of clotting cascades during reaming.

Aged↗