Biomedical subjects

J E Brown

Publications and source records attributed to J E Brown.

At least 37 records · Page 2Linked to original sources

PubMed2002

Radioactive contamination in the marine environment adjacent to the outfall of the radioactive waste treatment plant at ATOMFLOT, northern Russia.

RTP "ATOMFLOT" is a civilian nuclear icebreaker base located on the Kola Bay of northwest Russia. The objectives of this study were to determine the distributions of man-made radionuclides in the marine environment adjacent to the base, to explain the form of the distributions in sediments and to derive information concerning the fate of radionuclides discharged from ATOMFLOT. Mean activity concentrations (d.w.) for surface sediment, of 63 Bq kg(-1 137Cs, 5.8 Bq kg(-1) 90Sr and 0.45 Bq kg(-1 239,240)Pu were measured. Filtered seawater activity levels were in the range of 3--6.9 Bq m(-3) 137Cs, 2.0-11.2 Bq m(-3) 90Sr, and 16-40 m Bq m(-3), 239,240Pu. Short-lived radionuclides were present at sediment depths in excess of 10cm indicating a high degree of sediment mixing. Correlations of radionuclide activity concentrations with grain-size appear to be absent; instead, the presence of relatively contaminated sediment appears to be related to the existence of radioactive particles.

Environmental Monitoring↗

PubMed2002

Analysis of the morbidity of submerged deciduous molars: the use of imaging techniques.

A case is presented of a 13-year-old patient who had a class I occlusion on a class I skeletal base but with a retained and submerged deciduous molar causing impaction of the second premolar. Diagnostic imaging illustrates the potential challenges of the removal of the retained deciduous molar. Magnetic resonance imaging used to identify the path of the inferior alveolar neurovascular bundle clearly delineates its intimate association with the impacted teeth and underscores the risk of trauma during extraction. This is discussed with regard to other cases of submerged molars, and a strategy is outlined.

Adolescent↗

PubMed2001

Recall of diet during a past pregnancy.

The authors conducted a study of women's ability to recall diet during a past pregnancy. For a prospective study, women completed self-administered food frequency questionnaires (FFQs) before and during pregnancy (1989-1992). These women, mostly White and well-educated, were contacted 3-7 years later (1996-1997) for a retrospective dietary assessment performed by either telephone interview (n = 154) or self-administered FFQ (n = 115). Energy-adjusted Pearson correlations ranged from 0.10 to 0.49 for the telephone interview group and from 0.02 to 0.67 for the self-administered questionnaire group. When participants' intakes were ranked, quintile agreement (within one quintile) between original diet and recalled diet ranged from 60% to 69% in the telephone interview group and from 69% to 79% in the self-administered questionnaire group. Correlations and percentages of agreement were higher among women who used the same questionnaire for both dietary assessments than among those who used different questionnaires. These results suggest that diet during pregnancy is recalled with similar accuracy as or perhaps slightly lower accuracy than adult diet generally. This may reflect, in part, the influence of current (nonpregnancy) diet on recall of past (pregnancy) diet. While the results of this study may not be generalizable to those obtained from other populations, to the authors' knowledge it is the first study of recall of diet during pregnancy.

Adult↗

PubMed2001

Increased circulating monocyte activation in patients with unstable coronary syndromes.

OBJECTIVES: The primary objective of this research was to assess the activation level of circulating monocytes in patients with unstable angina. BACKGROUND: Markers of systemic inflammatory responses are increased in patients with unstable coronary syndromes, but the activation state and invasive capacity of circulating monocytes have not been directly assessed. METHODS: Peripheral blood mononuclear cell (MC) activation in blood samples isolated from patients with stable and unstable coronary artery disease was measured in two studies. In study 1, a modified Boyden chamber assay was used to assess spontaneous cellular migration rates. In study 2, optical analysis of MC membrane fluidity was correlated with soluble CD14 (sCD14), a cellular activation marker. RESULTS: Increased rates of spontaneous monocyte migration (p < 0.01) were detected in patients with unstable angina (UA) (Canadian Cardiovascular Society [CCS] angina class IV) on comparison to patients with acute myocardial infarction (MI), stable angina (CCS angina classes I to III) or normal donors. No significant increase in lymphocyte migration was detected in any patient category. Baseline MC membrane fluidity measurements and sCD14 levels in patients with CCS class IV angina were significantly increased on comparison with MCs from normal volunteers (p < 0.001). A concomitant reduction in the MC response to activation was detected (p < 0.05). CONCLUSIONS: Using two complementary assays, activated monocytes with increased invasive capacity were detected in the circulation of patients with unstable angina. This is the first demonstration of increased monocyte invasive potential in unstable patients, raising the issue that systemic inflammation may both reflect and potentially drive plaque instability.

Analysis of Variance↗

PubMed2001

A novel strategy for NQO1 (NAD(P)H:quinone oxidoreductase, EC 1.6.99.2) mediated therapy of bladder cancer based on the pharmacological properties of EO9.

The indolequinone EO9 demonstrated good preclinical activity but failed to show clinical efficacy against a range of tumours following intravenous drug administration. A significant factor in EO9's failure in the clinic has been attributed to its rapid pharmacokinetic elimination resulting in poor drug delivery to tumours. Intravesical administration of EO9 would circumvent the problem of drug delivery to tumours and the principal objective of this study is to determine whether or not bladder tumours have elevated levels of the enzyme NQO1 (NAD(P)H:quinone oxidoreductase) which plays a key role in activating EO9 under aerobic conditions. Elevated NQO1 levels in human bladder tumour tissue exist in a subset of patients as measured by both immunohistochemical and enzymatic assays. In a panel of human tumour cell lines, EO9 is selectively toxic towards NQO1 rich cell lines under aerobic conditions and potency can be enhanced by reducing extracellular pH. These studies suggest that a subset of bladder cancer patients exist whose tumours possess the appropriate biochemical machinery required to activate EO9. Administration of EO9 in an acidic vehicle could be employed to reduce possible systemic toxicity as any drug absorbed into the blood stream would become relatively inactive due to an increase in pH.

Antineoplastic Agents↗

PubMed2001

Synthesis and evaluation of cryptolepine analogues for their potential as new antimalarial agents.

The indoloquinoline alkaloid cryptolepine 1 has potent in vitro antiplasmodial activity, but it is also a DNA intercalator with cytotoxic properties. We have shown that the antiplasmodial mechanism of 1 is likely to be due, at least in part, to a chloroquine-like action that does not depend on intercalation into DNA. A number of substituted analogues of 1 have been prepared that have potent activities against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum and also have in common with chloroquine the inhibition of beta-hematin formation in a cell-free system. Several compounds also displayed activity against Plasmodium berghei in mice, the most potent being 2,7-dibromocryptolepine 8, which suppressed parasitemia by 89% as compared to untreated infected controls at a dose of 12.5 mg kg(-1) day(-1) ip. No correlation was observed between in vitro cytotoxicity and the effect of compounds on the melting point of DNA (DeltaT(m) value) or toxicity in the mouse-malaria model.

Alkaloids↗

PubMed2001

Maternal waist-to-hip ratio does not predict child gender.

It has been suggested that a high pre-conceptual waist-to-hip ratio (WHR) is a good predictor of male offspring and, thus, in cultures that value male children, an androgenous body shape may be judged as most attractive. The predictive value of WHRs is based on studies measuring women who already have children and correlating their WHRs with the proportion of existing male offspring. However, carrying a male child may alter WHRs in a different way to carrying a female child, and a high WHR may be an effect rather than a cause of male offspring. In order to test the predictive power of a pre-conceptual WHR and offspring gender, we took WHR measures from 458 women who intended to become pregnant and then correlated this with the genders of their subsequent children. We found no significant correlation. It is therefore not clear why a high WHR is preferred in some cultures. We suggest that differences in attractiveness preferences between different ethic groups are actually based on weight scaled for height (the body mass index or BMI) rather than the WHR since although there will be a preferred optimal BMI for each ethnic group, which will balance environmental and health factors, this optimal BMI may differ between groups and environments.

Body Constitution↗

PubMed2001

Pregnancy-related changes in body fat.

OBJECTIVE: To determine patterns of subcutaneous body fat change from preconception through 6 weeks postpartum, and factors that modify them. STUDY DESIGN: A prospective study of 557 healthy women enrolled prior to pregnancy. MAIN OUTCOME MEASURE: Body weight and skinfold thickness at the thigh, triceps, and subscapula, preconception, in each trimester, and 6 weeks postpartum, along with other variables. RESULTS: Subcutaneous body fat stores remained stable (P>0.13) during the first 6 weeks after conception, and increased from 6 to 35 weeks by 1.5 mm at the triceps, 4.2 mm at the subscapular, and 7.3 mm (P<0.01) at the thigh areas. Body fat changes correlated poorly with weight changes, reflecting differences in the time course for the changes. They differed by preconceptional body mass index (BMI), parity, and infant gender (P<0.05). Women with the highest BMIs tended to gain less subcutaneous fat early, primiparous women gained more at thigh (P=0.01) and subscapular (P=0.027), and women carrying males had higher gains at the thigh (P=0.032) and subscapular sites (P=0.058) than other women. Breastfeeding status did not affect postpartum body fat changes, but women who breastfed exclusively had significantly lower skinfold thicknesses than non-exclusive breastfeeders from preconception through 6 weeks postpartum (P=0.041). CONCLUSION: Subcutaneous body fat is stored and utilized at different sites at specific times during and after pregnancy. The pattern and amount of change varies depending on characteristics of women and their pregnancies.

Adipose Tissue↗

PubMed2001

Short-term dosing of alpha-hydroxytamoxifen results in DNA damage but does not lead to liver tumours in female Wistar/Han rats.

It is now generally accepted that activation of tamoxifen occurs as a result of metabolism to alpha-hydroxytamoxifen. In this study, alpha-hydroxytamoxifen was given to female Wistar/Han rats (0.103 or 0.0103 mmol/kg, intraperitoneally, daily for 5 days). This resulted in liver DNA damage, determined by (32)P-post-labelling, of 3333 +/- 795 or 343 +/- 68 adducts/10(8) nucleotides, respectively (mean +/- SD, n = 4). Following HPLC separation, the retention times of the major alpha-hydroxytamoxifen DNA adducts were similar to those seen following the administration of tamoxifen. However, after rats were treated with alpha-hydroxytamoxifen (0.103 mmol/kg) for 5 days and the animals kept for up to 13 months, no liver tumours developed (0/7 rats), even with phenobarbital promotion (0/5 rats). GST-P foci were detected in the liver, but only after 13 months was their number or area significantly increased over the corresponding controls. When alpha-hydroxytamoxifen was given to female lambda/lacI transgenic rats (0.103 mmol/kg orally for 10 days) and the animals killed 46 days later, there was an approximate 1.8-fold increase in mutation frequency but no significant increase in G:C to T:A transversions as described after tamoxifen treatment. It is concluded that DNA damage alone, resulting from the short-term administration of alpha-hydroxytamoxifen, is not sufficient to initiate liver tumours even with phenobarbital promotion. As with tamoxifen, long-term exposure may be required to allow promotion and progression of transformed cells.

Animals↗

PubMed2001

The associations of maternal caffeine consumption and nausea with spontaneous abortion.

To examine whether maternal caffeine consumption is associated with the risk of spontaneous abortion, we analyzed data from a population-based prospective study. The study population comprised 575 women delivering singleton livebirths and 75 women who had spontaneous abortions. The subjects were predominantly white, middle-class women enrolled before pregnancy. Study participants were traced to delivery of a liveborn, singleton infant or a spontaneous abortion. Of the 71 women who did not experience nausea, 29.6% had a spontaneous abortion, compared with 7.2% of 514 women who did experience nausea. Maternal caffeine consumption before pregnancy, or in women without nausea, did not increase the risk of spontaneous abortion, whereas maternal caffeine consumption during the first trimester after nausea started might increase risk of spontaneous abortion (risk ratio = 5.4, 95% confidence interval = 2.0-14.6 for caffeine consumption > or = 300 mg per day compared with < 20 mg per day). These results suggest that maternal caffeine consumption during pregnancy may influence fetal viability in women with nausea.

Abortion, Spontaneous↗

PubMed2001

Varieties of male circumcision: a study from Kenya.

BACKGROUND: Because male circumcision has been linked to a lower risk of HIV infection, it is advocated tentatively as a possible preventive intervention. Most studies, however, have relied on men's self-reports of their circumcision status. GOAL: To document varied techniques of male circumcision in one area of Kenya and the visible results. STUDY DESIGN: Researchers interviewed men who had performed or undergone various forms of circumcision. They also did genital observations on a subsample of respondents. RESULTS: All the men reported undergoing circumcision during adolescence, and most were able to tell which technique was used. According to the circumcisers, in type A, approximately 4 cm of the prepuce is removed; in type B, 1 to 2 cm of the prepuce and some of its inner surface are removed. Types A and B result in the same genital appearance. In type C, 1 to 2 cm of the prepuce and some of the inner surface are removed. The remaining prepuce is slit and suspended below the penile shaft. CONCLUSIONS: Asking a man "Are you circumcised?" is not sufficient. Classifying his circumcision status requires both a genital examination and an understanding of the precise local surgical techniques used. Even in a small geographic area, considerable variety may exist in the techniques of cutting, removing, altering, or leaving different portions of the foreskin. Each variation may affect the transmission of HIV and other infections.

Adolescent↗

PubMed2001

Advances in dental imaging.

The number of dental radiographs taken in the UK has steadily increased over the past 20 years--recently estimating around 18 million taken in the general dental services alone, and dental radiographs now account for nearly 25% of all medical radiographic exposures. Radiographs remain our most useful diagnostic aid. Their strength is in demonstrating hard tissue pathology, which makes radiographs particularly effective in the maxillofacial region. Although well accepted in this capacity, there remain a number of limitations and drawbacks to conventional radiographs which recent developments have begun to overcome. There have been improvements in the scope and capabilities of dental imaging equipment. There has also been a continuing effort to reduce radiation-induced harm by limiting our exposure to it. This has been possible both through the introduction of new methods and protocols for reducing individual radiation exposures and by the creation of guidelines for selecting radiographs more effectively and thereby reducing the total number of radiographs taken.

Humans↗

PubMed2001

Massive congenital coronary arteriovenous malformation presenting with exertional dyspnea and desaturation in an adult: a case report and review of the literature.

A coronary arteriovenous fistula is a congenital or acquired coronary artery anomaly in which blood is shunted into a cardiac chamber, great vessel or other structure, superceding the myocardial capillary network. The clinical presentation may be heralded by the development of dyspnea, congestive heart failure, angina, endocarditis, dysrhythmias or myocardial infarction. The authors describe a left to right coronary artery to coronary sinus shunt that produced an elevation in right atrial pressure during exercise and thereby opened a patent foramen ovale and manifested as exercise-induced desaturation. Although noninvasive imaging may facilitate the diagnosis and identification of the origin and insertion of coronary arteriovenous fistulae, cardiac catheterization is necessary for the precise delineation of coronary anatomy, and to show the presence of concomitant atherosclerosis and structural anomalies. Possible therapeutic options in the management of coronary arteriovenous malformations include transcatheter embolization, surgical correction or expectant management.

Aged↗

PubMed2000

Reduced vas deferens contraction and male infertility in mice lacking P2X1 receptors.

P2X1 receptors for ATP are ligand-gated cation channels, present on many excitable cells including vas deferens smooth muscle cells. A substantial component of the contractile response of the vas deferens to sympathetic nerve stimulation, which propels sperm into the ejaculate, is mediated through P2X receptors. Here we show that male fertility is reduced by approximately 90% in mice with a targeted deletion of the P2X1 receptor gene. Male mice copulate normally--reduced fertility results from a reduction of sperm in the ejaculate and not from sperm dysfunction. Female mice and heterozygote mice are unaffected. In P2X1-receptor-deficient mice, contraction of the vas deferens to sympathetic nerve stimulation is reduced by up to 60% and responses to P2X receptor agonists are abolished. These results show that P2X1 receptors are essential for normal male reproductive function and suggest that the development of selective P2X1 receptor antagonists may provide an effective non-hormonal male contraceptive pill. Also, agents that potentiate the actions of ATP at P2X1 receptors may be useful in the treatment of male infertility.

Animals↗

PubMed2000

Disruption of the talin gene arrests mouse development at the gastrulation stage.

Studies on cultured cells show that the cytoskeletal protein talin plays a key role in cell spreading and the assembly of cell-extracellular matrix junctions. To examine the role of talin in vivo, we have generated mice with a targeted disruption of the talin gene. Heterozygotes are normal, but no surviving homozygous mutant animals were obtained, proving that talin is required for embryogenesis. Mutant embryos develop normally to the blastocyst stage and implant, but there is a gross disorganization of the embryos at gastrulation (6.5-7.5 days post coitum), and they die around 8.5-9.5 days post coitum. The embryonic ectoderm is reduced in size, with fewer cells, and is incompletely organised compared with wild-type embryos. The mutant embryos show disorganised extraembryonic tissues, and the ectoplacental and excocoelomic cavities are not formed. This seems to be because embryonic mesoderm accumulates as a mass on the posterior side of the embryos and fails to migrate to extraembryonic regions, although mesodermal cells are evident in the embryo proper. Spreading of trophoblast cells derived from cultured mutant blastocysts on fibronectin and laminin is also considerably reduced. Therefore, the fundamental deficit in these embryos seems to be a failure of cell migration at gastrulation.

Animals↗

PubMed2000

Linoleic acid metabolism in the spontaneously diabetic rat: delta6-desaturase activity vs. product/precursor ratios.

The activity of delta6-desaturase of linoleic acid, a rate-limiting step in the formation of arachidonic acid, is decreased in animal models of severe, uncontrolled diabetes. The aim of the study was to measure the activity of liver microsomal delta6-desaturase of spontaneously diabetic BioBreeding/Edinburgh rats receiving subcutaneous insulin daily and of genetically related nondiabetic animals. The activity of delta6-desaturase was then compared with indices of activity (plasma lipid fatty acid product/precursor ratios) frequently used in human studies. Diabetic rats treated with insulin had 75 +/- 8% of the activity of microsomal delta6-desaturase of nondiabetic controls (P < 0.05). Insulin withdrawal tended to reduce the activity further (61% of control), although the activity did not differ from insulin-treated diabetic rats. The ratio of plasma phospholipid or cholesteryl ester gamma-linolenic over linoleic acid was not decreased in insulin-treated diabetic rats. By contrast, the ratio of gamma-linolenic over linoleic acid of microsomes was almost three-fold higher in insulin-treated diabetic rats (P < 0.05). The gamma-linolenic over linoleic acid ratio as an index of activity gave inconsistent results in insulin-deprived rats. The ratio of gamma-linolenic over linoleic acid of cholesteryl esters did not differ between control and diabetic rats, nor did it correlate with microsomal delta6-desaturase activity. Furthermore, the index of delta6-desaturase activity, derived from the fatty acid composition of microsomal phospholipids, did not correlate with microsomal delta6-desaturase activity. Diabetes, even when controlled by regular insulin injections, reduces the metabolism of linoleic acid, but the effect is less than previously published. The fatty acid compositions of plasma and liver microsomal lipids are not reliable indices of delta6-desaturase activity in diabetes.

Animals↗

PubMed2000

Nutrition and multifetal pregnancy.

Largely because of assisted reproduction, the rate of multifetal pregnancy is rising rapidly in the United States. Accordingly, dietitians are increasingly being called upon to provide nutrition services for these high-risk pregnancies. This article gives an overview of the incidence of and risks associated with multifetal pregnancy and reviews studies that contribute to our knowledge of nutrition and multifetal pregnancy. Practice guidelines for promoting healthy outcomes based on the best available scientific data are suggested. Guidelines for weight gain for twin and triplet pregnancy, dietary intake, and supplement use are included. Suggested practice guidelines for multifetal pregnancy include a positive rate of weight gain early in pregnancy, the use of prepregnancy weight status to determine total weight gain goals in twin pregnancy, a 50-lb weight gain goal for triplet pregnancy, and higher minimal number of servings of foods from several of the Food Guide Pyramid groups. The need for additional information on the effects of nutritional status on the course and outcome of multifetal pregnancy is critical. Preliminary evidence of the benefits of nutrition services suggests that both the incorporation of dietetics services into care programs and additional research on nutrition and multifetal gestation are warranted.

Diet↗

PubMed2000

Patterns over time in quality of life, coping and psychological adjustment in late stage melanoma patients: an application of multilevel models.

BACKGROUND: Quality of life (QOL) assessment is an important component within cancer research. There is often variability in QOL scores both between patients and across time. Understanding this variability in terms of personal characteristics and psychosocial factors would be useful but is often obstructed by the types of analyses that are applied to longitudinal data sets. Improved understanding can be gained with the application of multi-level or hierarchical models that allow for greater flexibility for modelling individual patterns of change over time. METHODS AND PATIENTS: Questionnaires were sent to a cohort of stage IV melanoma patients seen at the Sydney Melanoma Unit between 1991 and 1996, approximately every 3 months for up to 2 years. The data reported here are from a sub-sample of 44 patients who each completed between 3 and 8 questionnaires. Three aspects of QOL were measured (effort to cope, mood and physical well-being), each with a single LASA line. Multilevel techniques were used to model the patterns of QOL over time. Covariates were added to explain variation between patients in their average QOL and change in QOL over time. RESULTS: The scores of each of the three QOL measures showed marked fluctuations over time. However, there was little systematic change during the study in either effort to cope (p = 0.32) or mood (p = 0.06). In contrast, the physical well-being scores of some patients improved while others deteriorated (p < 0.001). On average, physical well-being deteriorated (p < 0.001). Variability between patients accounted for 60% (effort to cope), 45% (mood) and 44% (physical well-being) of the total variance of each scale. A range of psycho-social factors including active and avoidant coping styles and psychological adjustment accounted for significant amounts of the variability between patients in each QOL measure. CONCLUSION: Individual coping and psychological adjustment are related to individual changes in QOL and to differences among patients' QOL. The study illustrates the use of multi-level techniques to further our understanding of differences between patients in their QOL and how it changes over time.

Adaptation, Psychological↗