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Biomedical subjects

A Bristow

Publications and source records attributed to A Bristow.

At least 19 recordsLinked to original sources
PubMed2004

Somatropin and its variants: structural characterization and methods of analysis.

Human Growth hormone (hGH, somatotrophin) is a 22 kDa, 191 amino-acid single chain protein produced by somatroph cells of the anterior pituitary gland. It is the major physiological regulator of growth, and deficiencies in growth hormone levels have long been recognized as the underlying cause of growth disorders (dwarfism). The ability of exogenous hGH to restore normal rates of growth in both human and animal models of growth retardation has long been recognized and the use of hGH in therapy goes back several decades. Initial preparations were prepared by extraction and purification from cadaveric pituitary tissue, and since 1984, hGH has been prepared by recombinant Deoxyribosenucleic acid (rDNA) technology. As is usually the case with "biologicals", characterization of the drug substance depended on a combination of physico-chemical and biological methods, and the hGH molecule became well characterized fairly early in its life as a drug. Indeed, by 1980 the major degradation forms and structural variants of the hGH molecule had been described and reviewed. Little satisfactory progress had been made in refining biological assays for hGH, and, although in vitro assays were described, potency-defining assays remained dependant on the whole body growth response in rats, and were both invasive and imprecise. In the early 1990's a series of collaborative studies on analysis of recombinant hGH (somatropin) established that available bioassays were much less selective that physico-chemical methods in detecting and quantifying structural degradation, and 1994 saw an international consensus to replace the bioassays with physico-chemical analytical methods for the routine batch release of somatropin. During the last decade in most markets somatropin has, unusually for a protein, been subject to batch release and control dependent entirely on physico-chemical analysis, without the routine use of any form of bioassay. During that time there has been a continuous development and refinement of methods, and the identification of a range of structural variants and degradation products of the molecule. The present review sets out to summarise the current knowledge on physico-chemical analytical methods for somatropin, and the structural variants that have been identified and characterized. A survey of available biological analytical methods is beyond the scope of this review, as is consideration of the earlier pituitary preparations and the recombinant 192 amino-acid methionyl form of the molecule (somatrem), although it is likely that many of the methods and variants described would be equally applicable to somatrem.

Chromatography, High Pressure Liquid↗
PubMed2001

Central injection of interleukin-13 potentiates LPS-induced sickness behavior in rats.

Systemic administration of the bacterial endotoxin lipopolysaccharide (LPS) has profound depressive effects on behavior that are mediated by the inducible expression of proinflammatory cytokines such as interleukin-1 (IL-1), IL-6 and tumor necrosis factor-alpha (TNF-alpha) in the brain. To assess the regulatory effects of the anti-inflammatory cytokine IL-13 on LPS-induced sickness behavior, rats injected i.p. with LPS were administered rat recombinant IL-13 i.c.v. IL-13 (300 ng) potentiated the behavioral effects of LPS (125 microg/kg) when both molecules were co-injected. Administration of IL-13 (300 ng) 12 h prior to LPS (150 microg/kg) did not block the depressing effects of LPS on social exploration. These results indicate that IL-13 acts as a proinflammatory cytokine in the brain.

Animals↗
PubMed2001

Multicenter collaborative study to calibrate salmon calcitonin by bioassay and high-performance liquid chromatography: establishment of the third international standard.

Salmon calcitonin (sCT) is widely used therapeutically in the treatment of patients with postmenopausal osteoporosis, Paget's disease, and some forms of hypercalcemia. Preparations of synthetic calcitonin peptides of high purity and reproducibility are now routinely produced and physicochemical methods, particularly reverse-phase high-performance liquid chromatography (RP-HPLC), are replacing the in vivo biological assay for monitoring and calibration. Although the bioassay is no longer required for routine batch control in Europe, calcitonin bioassays are still required in some countries and in the development of new products. Stocks of the Second International Standard (IS) for salmon calcitonin are now depleted and, to replace it with a new calibrant, an international collaborative study was organized in which the aims were to: determine the activity of the candidate sCT by in vivo bioassay in terms of the second IS; assess the stability of the preparation after accelerated thermal degradation; estimate the purity of the ampouled candidate preparation; and determine the sCT content in gravimetric units by HPLC. The HPLC data in terms of ampoule content were in good agreement giving an estimate of 23.1 (coefficient of variation [CV] 3.8%) microg per ampoule. The HPLC chromatograms revealed a small, but detectable, degree of heterogeneity, which possibly occurred during the formulating or ampouling procedures, resulting in a reduction in monocomponent content (purity) from 96% to 92%. The biological activity of the ampoule contents in international units (IU) was calculated from the mass value and the internationally agreed-upon figure of 6000 IU/per mg for the specific activity of salmon calcitonin. This gave a value of 138 IU per ampoule, which was in good agreement with the biological assay estimate (140 IU per ampoule). The preparation of sCT was subsequently adopted as the Third International Standard by the World Health Organization with an assigned content of 138 IU per ampoule.

Animals↗
PubMed2000

Production of interleukin-1 receptor antagonist isoforms by microglia in mixed rat glial cells stimulated by lipopolysaccharide.

Although the natural interleukin-1 receptor antagonist (IL-1Ra) has been shown to be produced by microglial cells in response to immune stimuli, nothing was known about the ability of these cells in primary culture to produce the different isoforms of IL-1Ra. Using RT-PCR, we first confirmed that mixed glial cell cultures from newborn rats respond to the cytokine inducer, lipopolysaccharide, by synthesizing IL-1Ra mRNA. Using double immunostaining, we showed that IL-1Ra was detected in microglia but not in astrocytes. Using Western blotting, we finally demonstrated that the IL-1Ra1 isoform was secreted in the supernatant of mixed glial cell cultures, and its production increased in response to lipopolysaccharide. The three different IL-1Ra isoforms were constitutively expressed in cell lysates and their levels increased after lipopolysaccharide treatment, except for IL-1Ra3. These results point to the ability of microglial cells in primary culture to produce the different isoforms of IL-1Ra.

Animals↗
PubMed1999

Central injection of IL-10 antagonizes the behavioural effects of lipopolysaccharide in rats.

Peripheral (i.p.) and central (i.c.v.) injections of lipopolysaccharide (LPS) have been shown to induce brain expression of proinflammatory cytokines and to depress social behaviour in rats, increase duration of immobility and induce body weight loss. To determine if the anti-inflammatory cytokine, interleukin-10 (IL-10) is able to modulate these effects, recombinant rat IL-10 was injected in the lateral ventricle of the brain (30, 100, 300 ng/rat) prior to i.p. or i.c.v. injection of LPS (250 micrograms/kg or 60 ng/rat, respectively). Social exploration was depressed for 6 h after i.p. LPS injection. This effect was attenuated by IL-10 (30 and 100 ng) 2 h after injection, whereas the highest dose of IL-10 blocked the depression of social interaction for 6 h after LPS injection. IL-10 produced the same effects on the increase of immobility although the results did not reach significance. Social exploration was depressed 3 h after i.c.v. LPS injection, and this was accompanied by increased immobility. These effects were totally blocked by i.c.v. IL-10 (300 ng/rat). Rats lost body weight after i.c.v. LPS, and this effect was attenuated by i.c.v. IL-10. These results indicate that IL-10 is able to modulate the production and/or action of central proinflammatory cytokines.

Animals↗
PubMed1998

Biological activity and brain actions of recombinant rat interleukin-1alpha and interleukin-1beta.

IL-1alpha and IL-1beta have potent effects on the central nervous system resulting in fever, activation of the hypothalamic-pituitary-adrenal axis and behavioural depression. These effects have mainly been studied in rats, using recombinant human and mouse IL-1. Because IL-1alpha and IL-1beta show some species specificity in the potency of their biological activities, the objective of the present work was to directly compare the effects of recombinant rat IL-1alpha and IL-1beta in the rat system as a first step to dissect out the mechanisms that are involved in these effects. In vitro, recombinant rat IL-1alpha and IL-1beta bound with the same affinity as human IL-1 to the rat insulinoma Rin m5F cell line that mainly expresses type I IL-1 receptors. This binding activated IL-1 receptors, as shown by induction of the synthesis of TNF-alpha mRNA. In vivo, recombinant rat IL-1alpha and IL-1beta enhanced body temperature, increased plasma levels of corticosterone and ACTH, and depressed social behaviour. All these effects were obtained at doses 100-1,000 fold lower when IL-1 was injected centrally than when it was administered peripherally, indicating that they are centrally mediated. The relative potencies of recombinant rat IL-1alpha and IL-1beta were not the same depending on the endpoint and the route of injection, indicating that different mechanisms are likely to be involved in the various effects of IL-1 on the brain.

Animals↗
PubMed1997

The use of nutritional supplements by 4-12 year olds in England and Scotland.

OBJECTIVE: To determine the levels of and factors associated with the use of nutritional supplements by children participating in the National Study of Health and Growth (NSHG). DESIGN: Cross-sectional study. SETTING: Fifty-six study areas in England and Scotland. SUBJECTS: Fifteen thousand, two hundred and seventy five children aged between 4 and 12 y. INTERVENTIONS: Parental completion of a self-administered questionnaire on the child's health, social background and supplement use. Height, weight and skinfold measurements. RESULTS: An 88% response rate to the supplement question, 15.9% of responders reported using a supplement. Multivitamins were the most commonly consumed supplement (84%) with 52% taking a supplement daily. Younger children, those whose mothers reached further education, whose fathers were in non-manual occupations or who lived in the Midlands or South were significantly more likely to use a supplement, as were children from smaller families or whose parents were non-smokers. There was no significant association between supplement use and sex, height, birthweight, length of gestation, father's education, number of parents in the home or vegetarianism. Significant differences were found in the use of supplements between the ethnic origin groups. Children of Afro-Caribbean, Asian or other origin were more likely to take a supplement compared to white English and Scottish groups. There were differences in the type of supplements used with Afro-Caribbean and other origin children using more cod liver oil. CONCLUSION: We support the findings of other studies which show that children with the least need for supplements as defined by socio-economic variables are more likely to receive them and suggest that cultural background is also an important factor in influencing supplement use. SPONSORSHIP: This study was supported by grants from the Department of Health in England and the Scottish Home and Health Department.

Africa↗
PubMed1997

Can dietary interventions change diet and cardiovascular risk factors? A meta-analysis of randomized controlled trials.

OBJECTIVES: This study evaluated the effectiveness of dietary advice in primary prevention of chronic disease. METHODS: A meta-analysis was conducted of 17 randomized controlled trials of dietary behavior interventions of at least 3 months' duration. Results were analyzed as changes in reported dietary fat intakes and biomedical measures (serum cholesterol, urinary sodium, systolic and diastolic blood pressure) in the intervention group minus changes in the control group at 3 to 6 months and 9 to 18 months of follow-up. RESULTS: After 3 to 6 months, mean net changes in each of the five outcomes favored intervention. For dietary fat as a percentage of food energy, the change was -2.5% (95% confidence interval [CI] = -3.9%, -1.1%). Mean net changes over 9 to 18 months were as follows: serum cholesterol, -0.22 (95% CI = -0.39, -0.05) mmol/L; urinary sodium, -45.0 (95% CI = -57.1, -32.8) mmol/24 hours; systolic blood pressure, -1.9 (95% CI = -3.0, 0.8) mm Hg; and diastolic blood pressure, -1.2 (95% CI = -2.6, 0.2) mm Hg. CONCLUSIONS: Individual dietary interventions in primary prevention can achieve modest improvements in diet and cardiovascular disease risk status that are maintained for 9 to 18 months.

Cardiovascular Diseases↗
PubMed1993

Anaesthesia for procedures on the larynx and pharynx. The use of the Bullard laryngoscope in conjunction with high frequency jet ventilation.

Twenty patients undergoing elective procedures on the larynx and pharynx were anaesthetised using a propofol infusion and a bolus of vecuronium. High frequency jet ventilation was employed via a 7 French gauge catheter, with a second catheter being used to measure expired carbon dioxide levels. The Bullard laryngoscope was compared with the Macintosh instrument both for visualising the larynx and subsequently inserting a catheter. One catheter was left in place until the patient was fully awake, and in one case this enabled gas exchange to be maintained in the presence of laryngospasm. Using the Bullard laryngoscope, intubation was possible in all 20 patients, in a mean time of 22 (6.8) s. Using the Macintosh laryngoscope only 16 patients could be intubated and this took significantly longer at 34 (18.3) s (p < 0.05). The Bullard laryngoscope and high frequency jet ventilation offer a reliable method of intubating and anaesthetising patients with upper airways pathology and further benefits may accrue in the recovery period.

Adolescent↗
PubMed1992

New methods of dealing with the complications of panendoscopy.

A 70-year-old man with chronic obstructive airways disease was scheduled to undergo panendoscopy following a course of radiotherapy for carcinoma of the larynx. He was anaesthetized using a propofol infusion and high frequency jet ventilation (HFJV). The jet ventilation catheter was left in situ at the end of the procedure. This enabled oxygenation to be maintained in the presence of post-operative laryngospasm by re-attaching the jet ventilator. Subsequently he developed respiratory failure, and a Bullard laryngoscope was used to visualize the vocal folds despite oedema of the tumour which made direct laryngoscopy impossible. A catheter was passed through the biopsy channel of the Bullard, enabling HFJV to be commenced. A conventional endotracheal tube was then railroaded over the catheter to facilitate conventional ventilation.

Aged↗
PubMed1991

Interhospital transfer of a patient undergoing extracorporeal carbon dioxide removal.

Extracorporeal circulation techniques are being used increasingly in patients with acute cardiac or pulmonary failure. Some of these patients may subsequently require transportation, which has limited the use of these techniques in hospitals without on site transplantation facilities. We report a case of adult respiratory distress syndrome that demonstrates a solution to this problem.

Adolescent↗
PubMed1991

A new portable oxygen system using liquid oxygen.

Liquid oxygen provides both practical and financial advantages in comparison with compressed oxygen when transferring patients within and between hospitals. We describe a portable liquid oxygen system and evaluate its uses and shortcomings in this area.

Ambulatory Care↗
PubMed1991

A survey of secondary transfers of head injured patients in the south of England.

A survey by questionnaire was carried out to look into the provision of facilities for the secondary transfer of head injured patients, as well as difficulties encountered. An 84.6% response rate was achieved from 110 hospitals in six regions in the south of England. The results showed that 21% of hospitals had been unable to make a transfer in the previous year, and delays were commonly experienced by 23.7% of hospitals. The nursing attendance during transfer was satisfactory, but the quality of medical escort was poor, and the standard of monitoring equipment available was unacceptable. Methods of improving the situation include implementation of the recommendations of the Royal College of Surgeons, as well as the Association of Anaesthetists' recommendations for standards of monitoring and provision of intensive care.

Craniocerebral Trauma↗
PubMed1991

International repatriation following overseas disasters.

The repatriation of 33 hospitalized patients to the United Kingdom following the Joigny coach accident in 1990 is described. The repatriation was undertaken by medical staff from St Bartholomew's Hospital Careflight project and EuropAssistance using a chartered McDonnell Douglas 83 aircraft. All patients were repatriated without mishap, but a number of difficulties were encountered. It is recommended that agreement is reached in advance as to the organization that should handle overseas disasters involving British citizens. The organization should have expertise in repatriation as well as close ties with the NHS. A protocol should be designed and adhered to. The initial response should involve despatching a team to the disaster country and provision of a control centre in the U.K. Special arrangements need to be made for staff and equipment. Liason with the airlines and ambulance services is essential.

Accidents, Traffic↗