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Biomedical subjects

A Barnett

Publications and source records attributed to A Barnett.

At least 37 records · Page 2Linked to original sources
PubMed2000

Comprehensive analysis of uterine artery flow velocity waveforms for the prediction of pre-eclampsia.

OBJECTIVES: To evaluate the performance of velocimetric indices of uterine artery flow velocity waveforms (FVW's) at 20 weeks' gestation, alone or in combination with qualitative analysis, and establish the optimal screening method for the prediction of pre-eclampsia. METHODS: A total of 614 primiparous women had color flow/pulsed Doppler (CFPD) imaging of both uterine arteries at 20 weeks gestation. Receiver operator characteristic (ROC) curves were created for the systolic/end-diastolic (A/B) ratio, resistance index (RI) and systolic/early diastolic (A/C) ratio for placental and non-placental uterine arteries, individually or in combination with the presence of unilateral or bilateral notches. Based on data from ROC curves, the sensitivity of each method was compared with the false-positive rate set at 17 and 11%. RESULTS: The highest sensitivity (88%) and specificity of (83%) was obtained using bilateral notches/mean RI > or = 0.55 (50th centile) and unilateral notches/mean RI > or = 0.65 (80th centile). When the false-positive rate was set at 17%, the inclusion of bilateral notches significantly improved the sensitivity of RI (P < 0.001), placental RI (P < 0.01), placental A/C ratio (P < 0.05), mean A/C ratio (P < 0.01) and mean A/B ratio (P < 0.05). Bilateral notches/mean RI or A/B cut-offs were also superior to the persistence of a notch in either artery combined with RI (P < 0.01) or A/B ratio (P < 0.05). When the false-positive rate was set at 11%, the inclusion of bilateral notches did not improve the sensitivity of the A/C (P = 1.00) or A/B ratio (P > 0.10). Placental velocimetric indices performed better than mean indices but the differences in sensitivity at the set false-positive rates were not statistically significant. CONCLUSION: At 20 weeks' gestation, bilateral notches with mean RI cut-offs is the best screening method if further screening later in pregnancy is proposed. The A/C ratio is complementary to bilateral notches when the false-positive rate is set at 17% and an effective quantitative substitute when the false-positive rate is set at 11%.

Adult↗
PubMed2000

Preclinical pharmacology of desloratadine, a selective and nonsedating histamine H1 receptor antagonist. 1st communication: receptor selectivity, antihistaminic activity, and antiallergenic effects.

Desloratadine (descarboethoxyloratadine, CAS 100643-71-8) is an active metabolite of loratadine (CAS 79794-75-5) that exhibits qualitatively similar pharmacodynamic activity with a relative oral potency in animals 2.5-4 times greater than loratadine. Its antihistaminic effect lasts 24 h. Desloratadine was shown to be a selective H1 antagonist with more potent antihistaminic activity in vitro than either loratadine or terfenadine (CAS 50679-08-8), as indicated by its displacement of 3H-mepyramine from H1 receptors in rat brain, guinea pig brain, and guinea pig lung, and by its antagonism of histamine-induced contractions of guinea pig ileum. Antihistaminic activity and anitallergic effects also were observed in vivo. After oral administration, desloratadine was 2.5 to 4 times more potent than loratadine in protecting against histamine-induced lethality in the guinea pig and paw edema in the mouse; after topical administration, it was almost 10 times more potent in antagonizing histamine-induced increases in nasal microvascular permeability in the guinea pig. Histamine-induced changes in pulmonary resistance and compliance were also prevented by oral administration of desloratadine and loratadine in the monkey. An oral antiallergic effect was demonstrated by important reductions of acute bronchospasm in the allergic monkey and potent inhibition of allergic cough in the guinea pig. These preclinical studies provide evidence that desloratadine is an antihistaminic agent with a greater potency than loratadine and, together with results from numerous published studies, suggest an antiallergic effect of desloratadine.

Animals↗
PubMed2000

Preclinical pharmacology of desloratadine, a selective and nonsedating histamine H1 receptor antagonist. 2nd communication: lack of central nervous system and cardiovascular effects.

Desloratadine (descarboethoxyloratadine, CAS 100643-71-8) is a selective histamine H1 antagonist that exhibits qualitatively similar pharmacodynamic activity to its parent, loratadine (CAS 79794-75-5), but is 2.5-4 times more potent orally. In studies of central nervous system (CNS) effects that might lead to sedation, desloratadine had no behavioral, neurological or autonomic effects in the conscious mouse and rat. At large multiples of the antihistaminic dose in the mouse, it did not inhibit convulsions caused by electroconvulsive shock and inhibited acetic acid-induced writhing only at a dose approximately 1,000 times the antihistaminic dose in the mouse. Desloratadine had no effects on blood pressure, heart rate or electrocardiographic parameters in the rat or guinea pig or on electrocardiographic parameters in the monkey. Notably, there was no effect on the corrected Q-wave to T-wave (QTc) interval. Desloratadine did not inhibit IKr channel human ether-a-go-go-related gene (HERG)-induced current in a study in which HERG was expressed in Xenopus oocytes. In the rat, desloratadine did not cause effects in urine volume, electrolytes or creatinine, or inhibit gastric emptying or intestinal transit, or cause any harmful effects on gastric mucosa. The results of these preclinical studies provide evidence that desloratadine is a safe antihistamine without CNS or cardiovascular effects.

Animals↗
PubMed2000

The thiazolidinediones: a new class of antidiabetic agents.

Insulin resistance is a fundamental feature of type 2 diabetes and is strongly associated with metabolic disorders which predict increased cardiovascular risk, including hypertension and dyslipidaemia. A new class of insulin-sensitizing agents, the thiazolidinediones, reduce insulin resistance and improve glycaemia both as monotherapy and in combination with sulphonylureas or metformin.

Blood Glucose↗
PubMed2000

The costs of cancer to a major employer in the United States: a case-control analysis.

BACKGROUND: Detailed data will be increasingly important in determining the cost of cancer care in the managed care setting. OBJECTIVES: To estimate the full cost of cancer to a major employer in the United States and to determine the nature of the expenditures. STUDY DESIGN: Analysis of medical, pharmaceutical, and disability claims data from 1995 to 1997 for a major employer with more than 100,000 employees. METHODS: The cost of cancer is determined on a per-patient and per-employee basis. Based on a case-control method, cancer patients are matched to individuals with no record of cancer diagnosis or treatment. The incremental cost per employee and the percentage of total healthcare expenditures for cancer are quantified. RESULTS: Approximately $224 per active employee, or 6.5% of the corporation's total healthcare costs, was spent on incremental care for cancer patients in 1997. Medical conditions not directly related to cancer account for approximately half the total excess expenditures for patients with cancer. On average, annual healthcare and disability costs for persons with cancer were approximately 5 times higher than for their counterparts without cancer. CONCLUSIONS: The costs of cancer care are a substantial proportion of healthcare costs for employers. When the full cost of cancer is included in a cost-benefit analysis, expenditures for programs to reduce the risk of cancer in the working population may be justified. Expenditures to reduce the incidence and severity of conditions indirectly associated with cancer may also reduce overall employer healthcare expenses.

Case-Control Studies↗
PubMed1999

Estimating the prevalence of malformation of the heart in the first year of life using capture-recapture methods.

The authors estimated the prevalence of heart malformation during the first year of life, using five data sets with varying degrees of completeness from two English regional health authorities. These areas covered a total population of 6,872,000. Analysis was carried out using capture-recapture methods, including log-linear modeling, on data collected between June 1993 and August 1994. A large number of cases in the community were unrecorded by any of the current sources of information. In South East Thames, where an antenatal training screening program for detecting heart malformations had been implemented in the late 1980s, the estimated prevalence rate varied from 5.5 per 1,000 births (95% confidence interval (CI): 3.5, 10.8) to 9.0 per 1,000 births (95% CI: 6.4, 14.2), depending on the assumptions in the model and the number of sources used in the analysis. In the Wessex region, which did not have a formal training program, prevalence was lower and varied little, from 4.3 per 1,000 (95% CI: 3.4, 6.0) to 5.1 per 1,000 (95% CI: 4.0, 7.2), according to assumptions. These two estimates were reasonable rates in comparison with reports in the literature. This analysis was helpful in demonstrating that the training program designed to identify severe heart malformations during the antenatal period in one of these regions had no lasting impact on prevalence.

England↗
PubMed1999

MR image segmentation and tissue metabolite contrast in 1H spectroscopic imaging of normal and aging brain.

The impact of image segmentation on 0.84-ml nominal voxel volume proton spectroscopic imaging in normal brain and in age-related cortical atrophy was investigated. Segmentation improved the gray matter-white matter (GM-WM) contrast for N-acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr in normal brain, and for NAA/Cho and NAA/Cr in atrophic brain. NAA(GM/WM) (approximately 0.7), Cho(GM/WM) (approximately 0.8), and Cr(GM/WM) (approximately 1.3) in normal brain obtained with segmentation agreed with values obtained with quantitative magnetic resonance spectroscopy. Age-related cortical atrophy led to decreased cortical GM NAA/Cho and NAA/Cr; no changes were evident in WM or in NAA(GM/WM), Cho(GM/WM), or Cr(GM/WM). GM/WM metabolite analysis may be of limited use in conditions in which parallel metabolite changes occur in WM and GM.

Adult↗
PubMed1999

Second-trimester maternal serum inhibin A concentration as an early marker for preeclampsia.

OBJECTIVE: Maternal serum inhibin A concentration is elevated in established preeclampsia. The aim of this study was to investigate whether this relationship antedates the appearance of the classic signs of preeclampsia. STUDY DESIGN: A retrospective analysis was performed on trisomy 21 screening data from 685 women at between 15 and 19 weeks' gestation. The main outcome measures were preeclampsia and small for gestational age (<5th percentile) infants. RESULTS: Preeclampsia developed in 35 women (5.5%). Women with inhibin A concentration >2.0 multiples of the median were significantly more likely to acquire preeclampsia (P <.00001) and to be delivered of a small for gestational age infant (<5th percentile, P <.00001) than were women with inhibin A concentration </=2.0 multiples of the median. The odds ratios were 9.4 (95% confidence interval 4.6-19.3) for development of preeclampsia and 18.2 (95% confidence interval 6. 0-54.8) for preeclampsia necessitating delivery at <37 weeks' gestation. The association remained statistically significant for nulliparous women. CONCLUSION: Elevated maternal inhibin A concentration in the second trimester was strongly associated with a subsequent risk of preeclampsia. The potential role of second trimester inhibin A measurement in a screening strategy for preeclampsia needs to be investigated further.

Biomarkers↗
PubMed1999

Visualizing and characterizing white matter fiber structure and architecture in the human pyramidal tract using diffusion tensor MRI.

We used diffusion tensor imaging to assess diffusion anisotropy in the pyramidal tract in ten young, and ten elderly subjects (five males and five females in each group). The purpose of this study was to define normative values for anisotropy at different anatomic levels of the brainstem as well as to assess differences due to age, gender, and laterality. In all subjects, anisotropy was highest in the cerebral peduncle, lowest in the caudal pons, and intermediate in the medulla. In the pons and medulla the regional variability was high, with significant differences in anisotropy even between contiguous slices. Multifactorial ANOVA (performed using the average value of anisotropy within each region of interest) revealed that elderly subjects had significantly lower values than young subjects in the cerebral peduncle, with no differences in the pons and medulla. No significant differences in anisotropy due to gender and side were found. The differences in anisotropy at different levels of the brainstem reflect differences in the local architecture of white matter fibers. Anisotropy is high in the cerebral peduncle because fibers have a highly ordered arrangement, while in the pons and medulla, anisotropy is lower because the local fiber architecture is less coherent due to the presence of other fibers and nuclei. The biologic meaning of the intergroup differences in anisotropy is discussed in light of the structure and architecture of the tissue under investigation. We also consider potential sources of artifacts, such as noise and motion, partial volume contamination, anatomic mismatching, and the use of inappropriate statistical tests. We conclude that the age-related decrease in anisotropy in the cerebral peduncle is not artifactual but rather reflects subtle structural changes of the aging white matter. Our study however shows that caution must be exercised in interpreting diffusion anisotropy data.

Adult↗
PubMed1999

Molecular cloning, expression, localisation and functional characterisation of a rabbit SULT1C2 sulfotransferase.

The importance of sulfotransferases in xenobiotic metabolism is gaining recognition. The gastrointestinal (GI) tract is a major portal of entry for many xenobiotics, yet little is known about the contribution of sulfotransferases to detoxication or bioactivation metabolism in these tissues. To this end, isolation and characterisation of sulfotransferases expressed in the stomach of rabbits was undertaken. A unique sulfotransferase cDNA (GenBank Accession No. AF026304) was isolated from a rabbit stomach cDNA library. This cDNA was 1439 base pairs (bp) long and has an open reading frame of 888 bp. On expression of the cDNA in both COS cells and E. coli, a protein molecular weight of 34 kDa was detected on SDS-PAGE. Immunoblotting using an antibody raised in goats against the bacterially expressed protein detected expression of the protein in GI tract tissues. The 34 kDa immunoreactive band was detected in rabbit GI tract tissues (stomach, duodenum, jejunum, ileum, colon, caecum and rectum), liver and kidneys, but not in the lungs (n = 3). The human ortholog (GenBank Accession No AF026303) of the rabbit enzyme was cloned from a human stomach cDNA library. These two enzymes share 84% amino acid sequence identity and have been termed 1C2 sulfotransferases. When functional and kinetic characterisation of the recombinant rabbit and human proteins was carried out using 16 known ST substrates, detectable sulfonation activity was observed only with p-nitrophenol (with Km values of 2.2 mM and 13.3 mM, respectively). In conclusion, we have identified a rabbit GI tract sulfotransferase belonging to a newly defined sulfotransferase subfamily.

Amino Acid Sequence↗
PubMed1999

Simultaneous rupturing heterotopic pregnancy and acute appendicitis in an in-vitro fertilization twin pregnancy.

The presentation of acute abdominal pain in young women is not an unusual occurrence in casualty and gynaecology departments. Both acute appendicitis and ectopic pregnancy have to be considered and investigated, as these two conditions are accepted as the most common surgical causes of an acute abdomen. Difficulties in correctly identifying the cause of the pain can be hazardous to the patient and care needs to be taken in obtaining a prompt and accurate diagnosis enabling the most appropriate management. The case report presented here describes the extremely unusual occurrence of both these acute conditions happening simultaneously with the added complication of an ongoing twin pregnancy and it highlights the need to look beyond the most obvious diagnosis and always to expect the unexpected.

Abdominal Pain↗
PubMed1999

Expression of mouse mammary tumor virus superantigen mRNA in the thymus correlates with kinetics of self-reactive T-cell loss.

Mouse mammary tumor virus (MMTV) encodes a superantigen (Sag) that is expressed at the surface of antigen-presenting cells in conjunction with major histocompatibility complex (MHC) type II molecules. The Sag-MHC complex is recognized by entire subsets of T cells, leading to cytokine release and amplification of infected B and T cells that carry milk-borne MMTV to the mammary gland. Expression of Sag proteins from endogenous MMTV proviruses carried in the mouse germ line usually results in the deletion of self-reactive T cells during negative selection in the thymus and the elimination of T cells required for infection by specific milk-borne MMTVs. However, other endogenous MMTVs are unable to eliminate Sag-reactive T cells in newborn mice and cause partial loss of reactive T cells in adults. To investigate the kinetics of Sag-reactive T-cell deletion, backcross mice that contain single or multiple MMTVs were screened by a novel PCR assay designed to distinguish among highly related MMTV strains. Mice that contained Mtv-17 alone showed slow kinetics of reactive T-cell loss that involved the CD4(+), but not the CD8(+), subset. Deletion of CD4(+) or CD8(+) T cells reactive with Mtv-17 Sag was not detected in thymocytes. Slow kinetics of peripheral T-cell deletion by Mtv-17 Sag also was accompanied by failure to detect Mtv-17 sag-specific mRNA in the thymus, despite detectable expression in other tissues, such as spleen. Together, these data suggest that Mtv-17 Sag causes peripheral, rather than intrathymic, deletion of T cells. Interestingly, the Mtv-8 provirus caused partial deletion of CD4(+)Vbeta12(+) cells in the thymus, but other T-cell subsets appeared to be deleted only in the periphery. Our data have important implications for the level of antigen expression required for elimination of self-reactive T cells. Moreover, these experiments suggest that mice expressing endogenous MMTVs that lead to slow kinetics of T-cell deletion will be susceptible to infection by milk-borne MMTVs with the same Sag specificity.

Animals↗
PubMed1999

Homeoproteins CDP and SATB1 interact: potential for tissue-specific regulation.

Homeoproteins are known to participate in development and cell type specification. The homeoproteins CCAAT displacement protein (CDP) and special AT-rich sequence binding protein 1 (SATB1) have been shown to bind to nuclear matrix-associated regions and to act as repressors of many cellular genes. Moreover, binding of SATB1 to the mouse mammary tumor virus (MMTV) promoter region dramatically affects the tissue-specific transcription of this retrovirus. Because protein-protein interactions are a common means of regulating homeoprotein function, we tested whether SATB1 and CDP interact in vivo and in vitro. SATB1 interacted with CDP through its DNA-binding domain, as demonstrated by glutathione S-transferase (GST) pull-down assays. GST pull-down assays also showed that CDP associated with SATB1 through three of its four DNA-binding domains (CR1, CR2, and the homeodomain). SATB1-specific antisera, but not preimmune sera, precipitated CDP from nuclear extracts, and CDP-specific antisera precipitated SATB1 from the same extracts. Far-Western blotting detected interaction of SATB1 and CDP in several different tissue extracts. Association of purified SATB1 and CDP in vitro resulted in the inability of each protein to bind to DNA in gel retardation assays. CDP overexpression in cultured T cells led to a loss of detectable SATB1 binding to the MMTV promoter region, as measured by gel shift experiments. CDP overexpression also elevated MMTV long terminal repeat reporter gene activity in transient-transfection assays, a result consistent with neutralization of the SATB1 repressor function in T cells. SATB1 is very abundant in certain tissues, particularly thymus, whereas CDP is relatively ubiquitous, except in certain terminally differentiated cell types. Because of the tissue and cell type distribution of SATB1 and CDP, we propose that the SATB1-to-CDP ratio in different tissues is a novel mechanism for homeoproteins to control gene expression and differentiation in mammals.

Animals↗
PubMed1998

Anxiety and depression in mothers related to severe malformation of the heart of the child and foetus.

The aim of the study was to assess levels of anxiety and depression in three groups: pregnant mothers referred to foetal cardiology, subdivided into those with a confirmed diagnosis and those for which no abnormality was detected, and mothers who had a child with a heart malformation. Psychological status was measured between 6 and 10 months after diagnosis using the Hospital Anxiety and Depression scale in 108 females. Levels of anxiety were higher in the two groups with a confirmed diagnosis in the antenatal period or after birth (62%) than in those who were screened positively but in whom no abnormality was found (30%) (p = 0.0055). Anxiety was the highest in young females who had a foetus with a heart malformation. Depression scores were higher in those who had a child with heart malformation (18%) than in the other two groups (5%). Mothers who terminated a pregnancy after diagnosis remained depressed long after the event. Younger mothers may be especially vulnerable to mood problems associated with a traumatic obstetric experience.

Adult↗
PubMed1998

Acute deleterious effects of cocaine on cardiac conduction, hemodynamics, and ventricular fibrillation threshold: effects of interaction with a selective dopamine D1 antagonist SCH 39166.

Cocaine has demonstrated cardiotoxicity that has led to sudden death by unknown mechanisms. SCH 39166, a selective dopaminergic D1-receptor antagonist, suppresses the compulsive drug-intake actions of cocaine in primates. This study examined the cumulative toxic effects of cocaine after the long-term administration of SCH 39166. After pretreatment with oral placebo/SCH 39166 for 5 days, an i.v. infusion of 0.25 mg/kg/min of cocaine HCl was delivered to 14 anesthetized dogs, and cardiac conduction, arterial blood pressure, ventricular refractoriness, and arrhythmogenesis were examined. The cocaine infusion was stopped when QRS width increased by 20% from baseline (QRS20). In Coc + Placebo regimen, the QRS and His-Ventricular (HV) intervals showed a dose-dependent lengthening. Initially, the mean blood pressure (MBP) increased followed by a precipitate decrease at a mean dose of 2.03 +/- 0.5 mg/kg of cocaine. At QRS20, the ventricular effective refractory period (ERP) increased significantly, whereas the ventricular fibrillation threshold (VFT) showed a significant reduction from the baseline. In Coc + SCH, the QRS, HV intervals, and ERP increased similarly, but the decrease in MBP was attenuated, and the VFT was increased. A relatively small infusion of cocaine causes a hemodynamic compromise. The His-ventricular conduction delay and lengthened ERP suggest a predominant direct local anesthetic effect. Cocaine additionally decreased the VFT, suggesting an increased susceptibility to VF. SCH 39166 did not potentiate the cardiotoxic effects of cocaine. It displayed a protective trend by suppressing the arrhythmogenic effects and the hemodynamic compromise caused by cocaine.

Animals↗
PubMed1998

Cluster randomization: a trap for the unwary.

Controlled trials that randomize by practice can provide robust evidence to inform patient care. However, compared with randomizing by each individual patient, this approach may have substantial implications for sample size calculations and the interpretation of results. An increased awareness of these effects will improve the quality of research based on randomization by practice.

Cluster Analysis↗