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Biomedical subjects

D Sumner

Publications and source records attributed to D Sumner.

At least 19 recordsLinked to original sources

Transendothelial permeability of chlorpyrifos in RBE4 monolayers is modulated by astrocyte-conditioned medium.

The immortalized rat brain endothelium 4 (RBE4) cell line preserves many features of the in vivo brain endothelium. It has been used as an in vitro model of the blood-brain barrier (BBB). Astrocyte-endothelial cell interactions are crucial for maintenance of BBB characteristics. The present study investigated morphological and permeability properties of the RBE4 cell line. Immunohistochemical studies showed positive staining in RBE4 cells for E-cadherin, a Ca(2+)-dependent cell-cell adhesion molecule. Western blot immunoassay showed that RBE4 cells consistently express E-cadherin and that its expression significantly increased (P<0.001) in the presence of astrocyte-conditioned medium (ACM). The transendothelial permeability of chlorpyrifos, an organophosphorus insecticide, was significantly decreased (P<0.001) when the RBE4 cells were grown in ACM compared with control medium. Additional studies were carried out to determine whether chlorpyrifos is a substrate for the multidrug resistance protein, P-glycoprotein (P-gp). No significant change in chlorpyrifos transendothelial permeability was noted in the presence of verapamil, a P-gp blocker. Thus, in this system, chlorpyrifos is not a substrate for P-gp. This work demonstrates that with additional refinements the RBE4 monolayers might serve as a useful in vitro model for the study of BBB permeability and modulation by astrocyte-derived soluble factors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Consultative exercise on dose assessments.

A summary is given of a meeting held at Sussex University, UK, in October 2000, which allowed the exchange of ideas on methods of assessment of dose to the public arising from potential authorised radioactive discharges from nuclear sites in the UK. Representatives of groups with an interest in dose assessments were invited, and hence the meeting was called the Consultative Exercise on Dose Assessments (CEDA). Although initiated and funded by the Food Standards Agency, its organisation, and the writing of the report, were overseen by an independent Chairman and Steering Group. The report contains recommendations for improvement in co-ordination between different agencies involved in assessments, on method development and on the presentation of data on assessments. These have been prepared by the Steering Group, and will be taken forward by the Food Standards Agency and other agencies in the UK. The recommendations are included in this memorandum.

Environmental Exposure↗

In defence of collective dose.

Recent proposals for a new scheme of radiation protection leave little room for collective dose estimations. This article discusses the history and present use of collective doses for occupational, ALARA, EIS and other purposes with reference to practical industry papers and government reports. The linear no-threshold (LNT) hypothesis suggests that collective doses which consist of very small doses added together should be used. Moral and ethical questions are discussed, particularly the emphasis on individual doses to the exclusion of societal risks, uncertainty over effects into the distant future and hesitation over calculating collective detriments. It is concluded that for moral, practical and legal reasons, collective dose is a valid parameter which should continue to be used.

Humans↗

Pediatric pesticide poisoning in the Carolinas: an evaluation of the trends and proposal to reduce the incidence.

Studies from North and South Carolina on hospitalizations following pesticide exposure have shown that about 30% involve children. During 1990-1993, 29% of North Carolinians hospitalized for pesticide poisoning were children. Between 1971 and 1996, 28% to 37% of the patients hospitalized following pesticide exposure in South Carolina were children. Data from a South Carolina study, from the Association of American Poison Control Centers and the Vital Statistics of the US, suggest that pesticide poisonings in children are part of the overall problem of children being poisoned by household chemicals. Most poisonings occur in toddlers about 1-y-of-age. Pesticide-related fatalities in children have steadily decreased for the last 20-y while poisonings from other household chemicals have not decreased dramatically. The data suggest that increased public awareness of the risks of household chemicals could decrease that poisoning incidence.

Child, Preschool↗

Comparative clinical pharmacokinetics of single doses of sumatriptan following subcutaneous, oral, rectal and intranasal administration.

Sumatriptan, a 5-HT1 receptor agonist active for the acute treatment of migraine, is currently available as subcutaneous injection and oral tablets. Rectal or intranasal formulations may offer advantages over those marketed. This study compared the pharmacokinetics of sumatriptan via all four routes. Usual absorption parameters were described and the rate of absorption was assessed using deconvolution technics. There were no statistical differences between the non-parenteral routes for tmax or Cmax/AUCinfinity. However, Cmax and AUCtmax were statistically greater with the suppository than with the tablet, but there was no difference between intranasal and oral routes. The highest rate of absorption occurred earlier with the intranasal than with the oral route. Relative to the subcutaneous route, the bioavailability for the suppository was greater than for intranasal spray and oral tablet. The amount of sumatriptan excreted in the urine unchanged was similar for all routes. Sumatriptan in this study was well tolerated.

Administration, Intranasal↗

Screening of pregnant women for evidence of current hepatitis B infection: selective or universal?

This paper reports the findings of a retrospective survey which assessed the accuracy of the selective screening programme for hepatitis B infection. The survey was undertaken in the antenatal clinics of West Lambeth Health Authority during 1988 and 1990. Forty per cent of hepatitis B positive patients were not screened, which highlights the problems associated with selective screening programmes. The implications for obstetricians and midwives are discussed, and recommendations are made.

Ethnicity↗

Patient acceptability of laser and cold coagulation therapy for pre-malignant disease of the uterine cervix.

OBJECTIVE: To determine patient acceptability of cold coagulation and laser treatment for cervical intraepithelial neoplasia (CIN). DESIGN: A prospective study with alternate allocation. SETTING: Teaching hospital in London. SUBJECTS: 155 women requiring treatment for CIN. MAIN OUTCOME MEASURES: Time taken to complete the treatment; visual analogue scores for pain experienced, anxiety felt and acceptability of the procedure; post treatment bleeding and discharge, and follow-up smear. RESULTS: Cold coagulation treatment was found to be quicker and less painful than laser treatment, there were no other significant differences between the two methods of treatment. CONCLUSION: Cold coagulation is a more acceptable form of treatment for CIN than laser.

Adult↗

Impaired pressor reactivity in cirrhosis: evidence for a peripheral vascular defect.

The blood pressure responses to intravenous infusions of norepinephrine and angiotensin II, sympathetic and nonsympathetic vasoconstricting agents, respectively, were measured in 20 patients with cirrhosis (10 Child-Pugh grade A and 10 Child-Pugh grades B or C) and in 20 healthy subjects. The log PD20 (dose of agonist required to raise blood pressure by 20 mm Hg) for norepinephrine was 4.78 +/- 0.36 (mean +/- S.D.) in patients with severe cirrhosis and 4.36 +/- 0.37 in controls, p less than 0.01. Log PD20 for angiotensin II was 3.16 +/- 1.06 in patients with severe cirrhosis and 1.97 +/- 0.74 in controls, p less than 0.01. Cardiovascular responses to selective sympathetic agonists were measured in 10 other cirrhotic patients (all Child-Pugh grades B or C) and in 10 healthy controls. Log PD20s for phenylephrine, an alpha-1 adrenoceptor agonist, and for alphamethylnorepinephrine; an alpha-2 adrenoceptor agonist, were increased in cirrhosis (phenylephrine = 5.35 +/- 0.49 vs. 4.95 +/- 0.35, p less than 0.05; alphamethylnorepinephrine = 4.05 +/- 0.26 vs. 3.44 +/- 0.55, p less than 0.001). In contrast, log CD20 (dose of agonist required to raise the heart rate by 20 beats/min) for isoproterenol, a beta-adrenoceptor agonist, was similar in cirrhotic patients and controls (2.81 +/- 0.38 vs. 2.94 +/- 0.45, p = 0.49). These studies demonstrate that pressor reactivity to both sympathetic and nonsympathetic agonists is impaired in severe cirrhosis, that the impaired sympathetic responses are not caused by generalized sympathetic desensitization and that the site common to the four agonists with impaired responses is the peripheral vascular smooth muscle.

Adult↗

Absorption of irrigating fluid during laser photocoagulation of the endometrium in the treatment of menorrhagia.

Twelve women undergoing laser ablation of the uterus for menorrhagia were studied by haemodynamic, biochemical and haematological indices including radioisotope dilution studies of plasma volume to assess the degree of fluid absorption into the circulation during laser surgery. There was a significant rise in central venous pressure and serum chloride and a significant decrease in plasma protein, albumin and haematocrit. Absorption of the irrigating fluid used was demonstrated and in one woman whose case history is illustrated this was excessive.

Absorption↗

Prospective survey of use of therapeutic drugs, alcohol, and cigarettes during pregnancy.

Use of drugs during pregnancy was recorded prospectively in 2765 women attending the antenatal clinics of a general hospital from October 1982 to March 1984. Of these women, 2588 (93.6%) avoided exposure to drugs during the first trimester, 1802 (65.2%) took no drugs at any stage, 963 (34.8%) took a total of 154 different drugs from 35 groups of drugs, and 243 (8.8%) took a self administered drug. The most commonly used drugs were non-narcotic analgesics, usually self administered, and antibacterials. The last survey of use of drugs in pregnancy in the United Kingdom 20 years ago showed fewer women avoiding drugs throughout pregnancy (195 of 911 (21.4%), p less than 0.001) and in taking a self administered drug (586 (64.4%), p less than 0.001) than at present. Most women nowadays abstain totally from alcohol (1786 (64.6%) v 109 (12.0%) previously, p less than 0.001), but while more women are non-smokers compared with previously (1811 (65.5%) v 392 (43%), p less than 0.001) the trend has been far less dramatic than that for use of alcohol.

Alcohol Drinking↗

Ipsilateral blepharospasm and contralateral hemidystonia and parkinsonism in a patient with a unilateral rostral brainstem-thalamic lesion: structural and functional abnormalities studied with CT, MRI, and PET scanning.

A patient developed progressive right hemidystonia in childhood. Subsequently, left-sided blepharospasm, slurred and stuttering speech, and right-sided rigidity and bradykinesia, responsive to dopamine agonists, appeared. Investigation with computed tomography and magnetic resonance imaging (MRI) at age 43 years revealed a left-sided calcified rostral brainstem-thalamic lesion of uncertain aetiology. Although no structural lesion was seen in the striatal regions, L-[18F]-fluorodopa uptake was severely diminished in the left striatum but normal on the right. Dopamine receptor binding identified by [11C]-methylspiperone was in the normal range on both sides.

Adult↗

An improved approach for the determination of plasma [3H]noradrenaline kinetics using high-performance liquid chromatography.

An improved approach for the determination of plasma [3H]noradrenaline ([3H]NA) kinetics in man is described, incorporating the extraction of plasma [3H]catechols on alumina and separation of [3H]NA from [3H]dihydroxymetabolites by high-performance liquid chromatography (HPLC). After a 30 min intravenous infusion, [3H]NA accounted for 57.2 +/- 13.2% of the radioactivity recovered by the procedure, while the dihydroxy-metabolites 3,4-[3H]dihydroxyphenylethylene. glycol ([3H]DHPG) and 3,4-[3H]dihydroxymandelic acid ([3H]DOMA) accounted for 32.3 +/- 11.5% and 4.9 +/- 6.0% respectively. After 90 min of constant infusion the proportion due to [3H]NA fell to 44.4 +/- 10.4%, while that due to [3H]DHPG rose to 45.9 +/- 9.5% because of an increase in the amount of [3H]DHPG at the later time. Plasma [3H]NA radioactivity rose rapidly during the constant infusion and usually reached a plateau by 30 min. However, in individual subjects large variations in plasma [3H]NA radioactivity occurred during the course of the infusion, implying rapid and variable changes in plasma [3H]NA clearance. The inclusion of a step to separate [3H]NA from [3H]dihydroxymetabolites is necessary if the aim is to determine plasma [3H]NA kinetics, as a large proportion of the radioactivity recovered from plasma on alumina is due to the presence of these metabolites.

Adult↗