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Biomedical subjects

A Robson

Publications and source records attributed to A Robson.

At least 19 recordsLinked to original sources

Effects of diet and sexual maturation on low-density lipoprotein cholesterol during puberty: the Dietary Intervention Study in Children (DISC).

BACKGROUND: The Dietary Intervention Study in Children (DISC) is a multicenter, randomized, controlled clinical trial designed to examine the efficacy and safety of a dietary intervention to reduce serum LDL cholesterol (LDL-C) in children with elevated LDL-C. METHODS AND RESULTS: The effects of dietary intake of fat and cholesterol and of sexual maturation and body mass index (BMI) on LDL-C were examined in a 3-year longitudinal study of 663 boys and girls (age 8 to 10 years at baseline) with elevated LDL-C levels. Multiple linear regression was used to predict LDL-C at 3 years. For boys, LDL-C decreased by 0.018 mmol/L for each 10 mg/4.2 MJ decrease in dietary cholesterol (P<.05). For girls, no single nutrient was significant in the model, but a treatment group effect was evident (P<.05). In both sexes, BMI at 3 years and LDL-C at baseline were significant and positive predictors of LDL-C levels. In boys, the average LDL-C level was 0.603 mmol/L lower at Tanner stage 4+ than at Tanner stage 1 (P<.01). In girls, the average LDL-C level was 0.274 mmol/L lower at Tanner stage 4+ than at Tanner stage 1 (P<.05). CONCLUSIONS: In pubertal children, sexual maturation, BMI, dietary intervention (in girls), and dietary cholesterol (in boys) were significant in determining LDL-C. Sexual maturation was the factor associated with the greatest difference in LDL-C. Clinicians screening for dyslipidemia or following dyslipidemic children should be aware of the powerful effects of pubertal change on measurements of lipoproteins.

Body Mass Index

Proliferative myositis: an unusual cause of multiple subcutaneous nodules.

Proliferative myositis is a rare inflammatory condition which clinically has an apparently aggressive growth pattern reminiscent of a sarcoma. Histopathological features are characteristic but not widely recognized, so misdiagnosis may occur. We describe a patient presenting to the Dermatology Department and review the literature and current diagnostic techniques.

Adult

Evaluation of the flow cytometric crossmatch. Preliminary results of a multicenter study.

The flow cytometric crossmatch is a technique that is increasingly being used by clinical transplant laboratories. In this multicenter study by the British Society for Histocompatibility and Immunogenetics Flow Cytometry Group, a series of crossmatches were carried out to determine whether different centers obtained same results when performing the same crossmatch. There was greater than 80% agreement among participating laboratories on the results of 35/54 tests. There was no clear agreement in the remaining 20 cases. Quantitative analysis, estimating the number of cell-bound fluorescein molecules, demonstrated that differences in the criteria used by each center to define a positive crossmatch were responsible for some discordant results. When applied, definition of positivity based on the molecules of fluorescein increased concordance from 57.5% to 81.4%.l. These results suggest that a criterion for the interpretation of results based on quantitative analysis of bound antibody may be more reliable than methods in current routine use.

Flow Cytometry

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Dentists

T and B cell crossmatching using three-colour flow cytometry.

We have developed a highly sensitive method for the simultaneous crossmatching of T and B cells using three-colour flow cytometry. This method identifies T and B cell populations in a lymphocyte sample and analyses each for the presence of bound patient IgG alloantibodies. A fluorescein isothiocyanate conjugated rabbit anti-human IgG antibody was used to detect bound IgG following incubation of donor lymphocytes with patient serum. R-phycoerythrin conjugated anti-human CD19, and Quantum Red conjugated anti-human CD3 monoclonal antibodies were used to detect T and B cell populations, respectively. A comparison of results between conventional and three-colour flow cytometry crossmatches showed that there was no difference in detection of bound IgG between the two methods for ten test sera, doubling dilutions of a positive control serum and 72 donor-recipient pairs. Three-colour flow cytometry has proved particularly helpful in determining whether an antibody is directed against donor T and/or B cells and was shown to be more sensitive than complement-dependent cytotoxicity assay in eight out of 72 crossmatches.

B-Lymphocytes

Do parents and professionals agree on the developmental status of high-risk infants?

OBJECTIVES: To examine the degree of agreement between parental reporting of the development of high-risk infants and professional assessment by a multidisciplinary team. METHODS: The developmental status of 196 infants discharged from neonatal intensive care units (NICUs) was assessed by their parents using the Infant Monitoring Questionnaire (IMQ) at 4, 8, or 12 months' corrected age. On the same day, a clinical assessment was done by a multidisciplinary team consisting of a developmental pediatrician, physical therapist, and psychologist. The kappa statistic was used to measure agreement between the assessments. Logistic regression was used to investigate factors that might influence agreement. RESULTS: Both the IMQ and the multidisciplinary team classified infants as developing normally ("normal"), being at risk for abnormal development ("suspect"), or developing abnormally ("abnormal"). Although the same proportion of children fell into the three categories by both assessments, parents and the multidisciplinary team showed poor agreement with respect to the classification of individual infants (kappa = 0.276). No infant or family characteristic was found to have an influence on agreement. CONCLUSIONS: For a group of high-risk infants discharged from NICUs, the agreement between parental assessment of developmental status using the IMQ and the professional assessment by a multidisciplinary team is poor in the first year of life. We do not recommend the use of this questionnaire as a substitute for clinical assessment of biologically at-risk infants discharged from NICUs. However, it may be useful for those groups of infants for whom no other information is available or as an adjunct to clinical assessment when infants are not behaving typically because of an unfamiliar setting or concurrent illness.

Adult

The association between a positive T and B cell flow cytometry crossmatch and renal transplant failure.

Between January 1989 and June 1991 329 consecutive cadaveric renal transplants were carried out at this centre and, of those, 36 (10.9%) have failed. In order to assess whether the use of flow cytometry crossmatching (FCXM) would have predicted these failures, we carried out a retrospective T and B cell FCXM study comparing the failure group with a control group of 30 recipients carefully selected from patients transplanted during the same period. The number of first and second transplants in the control and failure groups was 25,5 and 23,8 respectively with six of the controls and three of the failures having panel reactive lymphocytotoxic antibodies > 50%. Stored donor material was available for 31 of the 36 failures. Two colour FCXM was performed using R-phycoerythrin-conjugated antihuman CD3 and antihuman CD19 to identify T and B cells respectively. For each recipient, three pretransplant and one post-transplant sera were tested against lymphocytes from the recipient's kidney donor. A fluorescein isothiocyanate conjugated F(ab')2 rabbit antihuman IgG was used to detect recipient IgG alloantibodies bound to donor T and/or B cells. There were no T or B cell FCXM positive (+) results in the control group whereas 11 of the 31 (35%) failures overall and nine of the 23 (39%) who failed within three months were T and B cell FCXM+ pretransplant (p = 0.0002). Seven of the nine FCXM+ results in the early failure group were with historic sera and two with historic and current sera.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes

An in vivo preparation for measurement of plasma protein and lysozyme output in the ferret tracheal lumen.

An in-vivo ferret tracheal preparation has been developed to study the appearance in the liquid-filled trachea of fluorescein-labelled plasma proteins (FLP) and of lysozyme from submucosal gland serous cells. In order to investigate the influence of nervous activity on the appearance of FLP and lysozyme in the tracheal lumen, the effects of intraluminal bradykinin (an inflammatory mediator and sensory nerve stimulant), intraluminal capsaicin (a stimulant of C-fibres) and electrical stimulation of the cut peripheral end of the right cervical vagus nerve have been measured. Vagal stimulation (10 V, 10 Hz, 1 ms, 90-120 s) increased the secretory rate of lysozyme. It had no effect on FLP rate of output. Intraluminal bradykinin (100 microM) produced a small but significant increase in FLP output but had no effect on lysozyme secretion. Intraluminal capsaicin (33 microM) had no effect on FLP output and had variable effects on lysozyme output. Tracheal pressure was increased by vagal stimulation but was unaffected by bradykinin and capsaicin. Thus, bradykinin increases plasma protein output, probably by an action on the epithelium, whilst vagal stimulation and capsaicin stimulate submucosal glands. This method could be used to determine the factors which alter the rate of movement of plasma proteins into the airway lumen and the secretion of submucosal glands in vivo.

Animals

Orthotopic liver transplantation for hepatic GVHD following allogeneic BMT for chronic myeloid leukaemia.

A 21-year-old man who had an HLA-identical sibling donor BMT for chronic myeloid leukaemia developed grade IV acute GVHD of the liver that was unresponsive to corticosteroids and anti-IL2 receptor monoclonal antibody. He was treated with an orthotopic liver transplant and is currently well 6 months later with normal liver function and no evidence of GVHD in the transplanted liver.

Adult

Ambulatory and laboratory blood pressure in individuals with negative and positive family history of hypertension.

Undertook 24-hr ambulatory blood pressure (BP) monitoring in men and women with and without family history of essential hypertension. Cardiovascular functions were also recorded in the laboratory during mental arithmetic, image star tracing, isometric exercise, and the cold pressor test. Ambulatory daytime, but not nighttime, systolic and diastolic BP as well as heart rate (HR) level and variability was higher in those with than without family history. During sleep, HR level and variability were higher among those with family history; at rest in the laboratory, however, all cardiovascular functions were similar in both groups. The strongest laboratory-based predictor of daytime BP was stress-induced BP levels. BP reactivity also significantly predicted daytime BP but with less accuracy. The best predictor of BP and HR at sleep was resting cardiovascular functions. Thus, ambulatory BP recordings add information to resting and stress-induced levels in identifying cardiovascular risk reactions.

Adult

Analysis of gene-dosage effects on the expression of CD18 by trisomy 21 lymphoblastoid cell-lines using a statistical model to fit flow cytometry profiles.

It is not clear whether Down syndrome, the phenotypic expression of constitutional trisomy for chromosome 21 (T21), is the result of generalised disruption of homeostasis resulting from genetic imbalance, or the over-expression of specific genes on chromosome 21. In order to understand the effect of gene dosage more clearly, we have analysed the predicted and actual levels of expression of the leucocyte integrin beta subunit CD 18 on the surface of T21 leucocytes. Previous studies showed that CD18 expression by T21 lymphoid cell lines (LCL) is greater than on normal LCL. We have now developed a computer model that compares the observed and predicted CD18 flow cytometric profiles for trisomy 21 LCL. Three parameters (alpha, beta and gamma) have been defined that measure different aspects of gene dosage. Using the computer model to calculate these parameters, we have carried out a series of paired comparisons between normal and T21 LCL. The results show that, in some T21 LCL, increased CD18 expression is proportional to the existing gene dosage, in another set the effect is additive, whereas in others there is a combination of proportional and additive effects. The results suggest that gene regulation can exert pleiotropic effects on gene-dosage, and is consistent with a model in which gene dosage itself is the cause of disrupted homeostasis.

CD18 Antigens

Continuing tooth eruption and alveolar crest height in an eighteenth-century population from Spitalfields, east London.

Earlier studies on dried skulls have shown that continuing eruption occurs throughout life to an extent which appears to compensate for occlusal attrition. Some investigators have interpreted the increasing distance between the tooth cervical margin and the alveolar crest as an indication of horizontal bone loss due to chronic inflammatory periodontal disease. In order to determine whether continuing eruption occurs in the absence of attrition, measurements were made on the jaws of an eighteenth-century population whose tooth wear had been minimal. Horizontal bone loss at the alveolar margin was minimal or absent. Continuing eruption had occurred, indicating that facial height probably increased throughout the life time of the individuals.

Adolescent

Effect of formoterol, a long-lasting beta 2-adrenoceptor agonist, against methacholine-induced bronchoconstriction.

1. The effects of a new long-acting inhaled beta 2-adrenoceptor agonist aerosol formoterol (12 micrograms), on FEV1, and on methacholine-induced bronchoconstriction, were compared with those of terbutaline (250 micrograms) and placebo in 12 midly asthmatic subjects. 2. PC20, the concentration of methacholine needed to cause a 20% fall in baseline FEV1, was determined 2 and 5 h after formoterol, terbutaline and placebo on separate days. Baseline PC20 was determined on a different day. 3. Compared with terbutaline and placebo, formoterol hastened recovery from methacholine-induced bronchoconstriction, and significantly increased mean PC20 (by 2.2- and 2.9-fold at 2 and 5 h respectively). 4. Thus, formoterol has a protective effect against methacholine-induced bronchoconstriction which lasts for at least 5 h.

Adrenergic beta-Agonists

Pharmacological properties of FPL 63547, a novel inhibitor of angiotensin-converting enzyme.

1. FPL 63547, in its active diacid form, was a potent inhibitor of rabbit lung angiotension converting enzyme (ACE) in vitro (IC50 0.51 nM). 2. In conscious normotensive dogs, FPL 63547 (10-300 micrograms kg-1 i.v.) produced prolonged, dose-related inhibition of plasma ACE activity and angiotensin I pressor responses, without affecting basal blood pressure, heart rate or pressor responses to angiotensin II. 3. In anaesthetized dogs, FPL 63547 diacid (3-300 micrograms kg-1 i.v. cumulatively) produced dose-related increases in cardiac output accompanied by falls in total peripheral resistance indicative of vasodilatation. Mild stimulation of cardiac rate and contractility was also observed. Enalapril diacid had a similar profile. 4. FPL 63547 was a highly effective antihypertensive agent after oral administration to spontaneously hypertensive rats (SHR) pretreated with a diuretic. It lowered systolic blood pressure (SBP) on acute administration over the range 3 X 10(-7)-10(-5) mol kg-1 p.o. (congruent to 0.13-4.5 mg kg-1 p.o.). FPL 63547 was more potent than other ACE inhibitors tested, threshold active doses for lisinopril, enalapril and captopril being 10(-6), 10(-6) and 3 X 10(-5) mol kg-1 p.o., respectively. The antihypertensive effects of FPL 63547, unlike those of enalapril and captopril, were of long duration. 5. The antihypertensive efficacy of FPL 63547 was also observed following chronic oral administration. A dose of 0.5 mg kg-1 day-1 once daily for 23 days produced a sustained reduction of SBP. By the end of the treatment period, SBP was significantly lowered both pre- and post-dose, i.e. effective 24 h control had been achieved. 6. The profile of FPL 63547 is consistent with it being a potent, selective and long-acting ACE inhibitor. As an antihypertensive agent in SHR it compared favourably with other members of this class with respect to potency and duration of action.

Angiotensin I

The cardiovascular effects of nebulized adenosine in man.

We have studied the cardiovascular effects of inhaled adenosine in healthy subjects. Adenosine at a concentration of 5 mg.ml-1 is absorbed and produces an increase in heart rate of 6-7 beats per min, blood pressure and skin temperature being unaltered. The rise in heart rate is less than that seen with an infusion of a comparable dose and is unlikely to be adequate for therapeutic termination of supraventricular tachycardia. Higher doses are limited by the poor solubility of adenosine. Inhalation as a method of delivering adenosine has possibilities as an alternative route of administration, but some practical problems remain to be overcome.

Adenosine

The spasmogenic action of oxytocin in the rat uterus--comparison with other agonists.

A low concentration (0.2 nM) of oxytocin induced phasic tension development in the isolated uterus of the day-22 pregnant rat. Tonic spasm was also induced by higher concentrations of oxytocin (2 and 20 nM). Spasmogenic responses to bradykinin and potassium chloride (KCl) also contained phasic and tonic components while acetylcholine induced tonic spasm only. The phasic component of the responses to oxytocin and to bradykinin and both components of the response to KCl were inhibited by (+)-cis diltiazem (0.1 and 1 microM). The tonic component of the responses to oxytocin and to bradykinin and the responses to acetylcholine were only reduced by (+)-cis diltiazem at concentrations greater than 10 microM. (-)-cis Diltiazem was less potent than (+)-cis diltiazem as an inhibitor of calcium (Ca2+)-induced spasm in a depolarizing medium and of the phasic spasms induced by oxytocin. The two isomers were of similar potency as inhibitors of oxytocin-induced tonic spasm. Spasmogenic responses to oxytocin, bradykinin, acetylcholine and KCl were decreased when uteri were bathed in media which were Ca2+-free or of low Na+ content. However, there was no correlation between the rank order of sensitivity of the four spasmogens to the changed media and to their inhibition by (+)-cis diltiazem. Oxytocin (0.2 nM) increased the frequency, duration and amplitude of spike activity, measured by extracellular electrical recording, in parallel with enhancement of phasic tension development. With higher concentrations of oxytocin (2 and 20 nM) spike firing was initially continuous but often subsequently ceased despite the associated tonic contracture. After incubation in (+)-cis diltiazem (10 microM), oxytocin (0.2, 2 and 20 nM) produced graded tonic spasm without spike activity. Oxytocin (0.2 nM) produced a small increase in 45Ca2+ influx into myometrium as assessed by the 'lanthanum method'. Higher concentrations of oxytocin (2 and 20 nM) did not increase 45Ca2+ influx. It is concluded that the phasic component of the response of the uterus to oxytocin and bradykinin is associated with Ca2+ influx via voltage-dependent Ca2+ channels. The tonic component is due to another mechanism(s) which does not appear to involve Ca2+ influx. All of the spasmogenic response to KCl can be explained by Ca2+ influx through voltage-dependent Ca2+ channels. These channels do not appear to be involved in the spasmogenic response to acetylcholine.

Acetylcholine

The radiological impact of electricity generation by U.K. coal and nuclear systems.

Radiological impact is discussed for U.K. coal and nuclear power cycles under normal operation. The type having the greater impact depends on the radiological basis of the comparison, the particular nuclear reactor system considered and whether or not the whole fuel cycle, especially irradiated nuclear fule reprocessing , is included in the analysis. More importantly, the various impacts are shown to be generally acceptable in an absolute sense i.e. exposures are less than and usually low in comparison with radiological safety guidelines and everyday natural radiation exposures.

Coal