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Biomedical subjects

A Baker

Publications and source records attributed to A Baker.

At least 37 records · Page 2Linked to original sources
PubMed2001

Catalytic oligodeoxynucleotides define a key regulatory role for early growth response factor-1 in the porcine model of coronary in-stent restenosis.

Early growth response factor-1 (Egr-1) controls the expression of a growing number of genes involved in the pathogenesis of atherosclerosis and postangioplasty restenosis. Egr-1 is activated by diverse proatherogenic stimuli. As such, this transcription factor represents a key molecular target in efforts to control vascular lesion formation in humans. In this study, we have generated DNAzymes targeting specific sequences in human EGR-1 mRNA. These molecules cleave in vitro transcribed EGR-1 mRNA efficiently at preselected sites, inhibit EGR-1 protein expression in human aortic smooth muscle cells, block serum-inducible cell proliferation, and abrogate cellular regrowth after mechanical injury in vitro. These DNAzymes also selectively inhibit EGR-1 expression and proliferation of porcine arterial smooth muscle cells and reduce intimal thickening after stenting pig coronary arteries in vivo. These findings demonstrate that endoluminally delivered DNAzymes targeting EGR-1 may serve as inhibitors of in-stent restenosis.

Animals↗
PubMed2001

Hemodynamic response to continuous infusion of dobutamine in Alagille's syndrome.

BACKGROUND: Alagille's syndrome is a rare condition that is characterized by paucity of interlobular bile ducts and peripheral pulmonary artery stenosis. Liver transplantation in the setting of peripheral pulmonary stenosis and right ventricular hypertension seems to be associated with a higher mortality, which raises the concern that these patients are unable to increase their cardiac output in the immediate posttransplantation period to meet the demands of reperfusion and early graft dysfunction and cope with further increases in pulmonary vascular resistance. METHOD: Cardiac catheterization was performed in 15 children with Alagille's syndrome and peripheral pulmonary artery stenosis to measure the cardiac output response to dobutamine infusion. The cardiac output was measured before and during each increment of infusion of dobutamine at 10 microg/kg/min and 20 microg/kg/min by using a thermodilution catheter placed in the pulmonary artery. RESULTS: There was a significant change in the baseline cardiac index (P<0.001) with an infusion of 20 microg/kg/min of dobutamine with an increase from 4.4(1.0) L/min/m2 to 6.4(1.5) L/min/m2. There was, however, a wide variation between individuals in the increase in cardiac index, ranging from 7.3-95%. There was no correlation between the baseline systolic right ventricular/aortic pressure ratios and the increase in cardiac index (r=0.1086). CONCLUSION: The increase in cardiac index, in response to dobutamine in patients with Alagille's syndrome, is independent of the more conventional measurement of the right ventricular pressure. This method of producing a hemodynamic response is closer to the response that results after liver transplantation, and thus, it may be a better way of predicting the outcome of liver transplantation in these patients.

Adolescent↗
PubMed2001

Perforin-low memory CD8+ cells are the predominant T cells in normal humans that synthesize the beta -chemokine macrophage inflammatory protein-1beta.

The synthesis of antiviral beta-chemokines has joined cytolysis as a potential mechanism for the control of HIV-1 infection by CD8(+) T cells. Recent evidence suggests that these two effector functions can diverge in some individuals infected with HIV-1; however, little is known about the CD8(+) T cell subsets in normal individuals that synthesize antiviral beta-chemokines. In this report, we have used mutliparameter flow cytometry to characterize the T cell subsets that secrete the antiviral beta-chemokine macrophage inflammatory protein (MIP)-1beta. These studies have shown: (i) CD8(+) cells are the predominant T cell subset that synthesizes MIP-1beta; (ii) MIP-1beta and IFN-gamma are synthesized congruently in most CD8(+) T cells; however, significant numbers of these cells synthesize only one of these effector molecules; (iii) approximately 60% of the CD8(+) T cells that synthesize MIP-1beta lack perforin; (iv) MIP-1beta is synthesized with approximately equal frequency by CD28(+) and CD28(-) subpopulations of CD8(+) T cells; (v) MIP-1beta is synthesized by three distinct CD8(+) T cell subsets defined by the expression of CD45R0 and CD62L; and (vi) MIP-1beta is not synthesized in short-term cultures of naive CD8(+) T cells. These results demonstrate substantial subset heterogeneity of MIP-1beta synthesis among CD8(+) T cells and suggest that these subsets should be evaluated as correlates of protective immunity against HIV-1.

CD28 Antigens↗
PubMed2001

Identification and characterisation of PEX6 orthologues from plants.

The sunflower (Helianthus annuus) orthologue of PEX6, an AAA ATPase essential for the biogenesis of peroxisomes in yeasts and mammals, was isolated. HaPex6p is immunologically related to Pichia pastoris Pex6p. Like other genes involved in peroxisome biogenesis and function HaPEX6 mRNA and protein levels peak in early post-germinative growth and mRNA levels also increase in senescent tissue. HaPEX6 identifies probable orthologues in Arabidopsis and rice.

ATPases Associated with Diverse Cellular Activitie↗
PubMed2001

Fluorescence excitation-emission matrix characterization of some sewage-impacted rivers.

Fluorescence excitation-emission matrix (EEM) spectrophotometry was applied to 10 sample sites in six rivers in northeastern England, some of which were adversely impacted by sewage treatment works (STW) discharges, with the aim to investigate whether STW discharge has a significantly distinct fluorescence signature. Upstream, downstream, and STW discharge samples for two STWs demonstrated that treated sewage has a distinct fluorescence EEM, with high tryptophan and fulvic-like fluorescence intensities that are of approximately equal ratio. This signature could be seen in downstream samples. When all 10 sample locations were compared, two trend lines were apparent where STW impacted rivers plotted separately from the other sample locations. Fluorescence EEM signatures were compared to absorption at 254 nm and demonstrated to provide a better fingerprint of sewage-impacted water. It is suggested that fluorescence EEM spectrophotometry can provide a useful tool for the analysis of grab samples taken for both routine and investigative monitoring and has the potential for on-line monitoring of STW impacts on river systems.

Environmental Monitoring↗
PubMed2001

Veno-occlusive disease with multi-organ involvement following actinomycin-D.

Actinomycin-D (Act-D) is a rare cause of veno-occlusive disease (VOD). Between 1993 and 1998, we managed 6 patients, all male, median age 19 months (range 6-48 months) who received Act-D for Wilms' tumour (n=4), clear cell sarcoma (n=1) or rhabdomyosarcoma (n=1). VOD presented with a median platelet count of 12 x 10(9)/l, INR 3.8, fibrinogen 16 mg/l, fibrinogen degradation products (FDPs) > or =80 microg/l, aspartate aminotransferase (AST) 6922 IU/l, bilirubin 47 micromol/l. In 3 cases, transient liver dysfunction and thrombocytopenia without neutropenia had been observed after a previous course of Act-D. All six children developed encephalopathy, hepatomegaly, ascites, reversed portal flow and renal impairment. All received mechanical ventilation and two required haemofiltration. The treatment was supportive. Severe Adult Respiratory Distress Syndrome developed in 3 patients, all of whom died. 3 patients recovered. The outcome of VOD with multi-organ failure is poor. Intravascular coagulopathy precedes and characterises severe VOD during Act-D treatment.

Antibiotics, Antineoplastic↗
PubMed2001

Deaths from antidepressants in England and Wales 1993-1997: analysis of a new national database.

BACKGROUND: The prescription of antidepressants has increased substantially over the last 10 years. It is therefore timely to examine trends in mortality associated with overdoses of antidepressants and to compare the relative mortality associated with different antidepressants. METHODS: Data were derived from a newly developed national database of deaths from overdose and poisoning in England and Wales between 1993 and 1997. Age and sex specific death rates associated with overdose and poisoning with antidepressants were calculated together with numbers of deaths per 100,000 prescriptions of individual antidepressants. RESULTS: Twenty per cent (2,503) of all deaths from overdose or poisoning were antidepressant related. The number of deaths increased by 18% between 1993 and 1997. Ninety-five per cent of deaths from antidepressants were associated with tricyclic antidepressants, particularly dothiepin and amitriptyline. Tricyclic antidepressants were associated with 5.3 deaths per 100,000 prescriptions, 4.4 for monoamine oxidase inhibitors and 0.4 for selective serotonin reuptake inhibitors. Annual death rates were highest in men aged 30-44 years (18.2 per million) and women aged 45-59 years (14.8). Death rates from antidepressants were 2.5 times higher in the most deprived fifth than in the least deprived fifth of enumeration districts. CONCLUSIONS: Antidepressants are an important cause of death from poisoning and overdose. SSRIs and newer antidepressants are associated with <10% of the risk of death than the older antidepressants. There is a strong association between area deprivation and deaths from antidepressants.

Aged↗
PubMed2001

No effect of copper supplementation on biochemical markers of bone metabolism in healthy young adult females despite apparently improved copper status.

OBJECTIVE: To investigate the effects of increasing Cu intakes, above the usual dietary intake, on biomarkers of bone metabolism in healthy young adult females (aged 21-28 y) over a 4 week period. DESIGN: A double-blind, placebo-controlled randomised repeat crossover Cu supplementation trial. SETTING: The study was conducted at the Royal Veterinary and Agricultural University (RVAU), Copenhagen, Denmark. SUBJECTS: Sixteen healthy young adult females aged 20-28 y were recruited from among students at the RVAU. INTERVENTION: During the 4 week intervention periods in this randomised, crossover trial (3x4 weeks with a minimum 3 week wash-out period), each subject received, in addition to their usual diet, either 3 or 6 mg elemental Cu/day as CuSO4 or a matching placebo. On the last 3 days of each dietary period 24 h urines were collected. In addition, blood was collected on the last day of each dietary period. RESULTS: Serum Cu and erythrocyte superoxide dismutase (but not caeruloplasmin protein concentration or activity (putative indices of Cu status)) were significantly increased (P<0.05) after daily Cu supplementation with 3 and 6 mg/day for 4 weeks. Serum osteocalcin (biomarker of bone formation), urinary creatinine (Cr) concentration, urinary pyridinoline (Pyr)/Cr or deoxypyridinoline (Dpyr)/Cr excretion, or daily urinary Pyr or Dpyr excretion (biomarkers of bone resorption) were unaffected by Cu supplementation. CONCLUSION: Copper supplementation of the usual diet in healthy young adult females, while apparently improving Cu status, had no effect on biochemical markers of bone formation or bone resorption over 4 week periods. SPONSORSHIP: Funding from the European Commission.

Adult↗
PubMed2001

Randomized controlled trial of brief cognitive-behavioural interventions among regular users of amphetamine.

AIMS: To identify whether brief cognitive-behavioural interventions are feasible among regular users of amphetamine, to assess the effectiveness of intervention overall and to pilot two- and four-session interventions. DESIGN: Subjects were assigned randomly to individually receive a cognitive-behavioural intervention (n = 32) of either two or four sessions' duration or a self-help booklet (control condition; n = 32). SETTING: Subjects were volunteers recruited from needle exchange schemes and treatment centres in Newcastle, Australia. PARTICIPANTS: Regular (at least monthly) users of amphetamine were recruited. INTERVENTION: Either four sessions of cognitive-behaviour therapy, consisting of a motivational interview and skills training in avoidance of high-risk situations, coping with craving and relapse prevention, or two sessions consisting of a motivational interview and discussion of skills. MEASUREMENTS: The Opiate Treatment Index was the main measure at pre-treatment and 6-month follow-up. FINDINGS: There was a significant reduction in amphetamine use among the sample as a whole, with inconclusive differences between intervention subgroups. There was a moderate overall intervention effect, with the intervention group reporting over twice the reduction in daily amphetamine use as the control group. Significantly more people in the cognitive-behavioural intervention condition abstained from amphetamine at 6-month follow-up compared to the control condition. CONCLUSION: Brief cognitive-behavioural interventions appear feasible among regular users of amphetamine. A larger randomised controlled trial of the effectiveness of such interventions appears warranted.

Adult↗
PubMed2001

Perceptions of labour pain by mothers and their attending midwives.

AIMS: The aim of the current study was to examine the perception of pain by labouring women and their attendant midwife, from the onset of labour to delivery. RATIONALE: Accurate measurement and appropriate management of pain is a significant problem for attendant medical and nursing personnel. Both the experience and perception of pain are regarded as subjective and are therefore difficult to measure objectively. Indeed, much of the literature reports that pain is often under- or over-estimated by nursing staff who as a consequence consistently fail to administer adequate analgesia. Few studies have specifically examined the ability of midwives to assess the pain of labouring women. DESIGN: The short form McGill Pain Questionnaire (SF-MPQ), routinely used to assess pain in obstetric environments, was used to determine pain perception. Thirteen labouring women and nine midwives completed the SF-MPQ every 15 minutes beginning at the time of admittance to the delivery suite. Peak pain ratings for the preceding 15 minutes were obtained without reference to prior ratings or each other's scores. Further, midwives in the maternity unit of The Queen Elizabeth Hospital (TQEH), Adelaide, South Australia completed a survey investigating the cues they use to assess pain during labour. RESULTS: On each measure of pain on the SF-MPQ, the midwives scores correlated with the mothers' scores across the entire pain range. Further analysis showed that mothers' and midwives' pain scores were similar at mild-moderate pain levels, but midwives significantly underestimated pain intensity at levels that mothers described as severe. The survey responses indicated that midwives rely on both verbal and nonverbal cues to assess pain levels. CONCLUSIONS: The cues used by midwives to differentiate pain intensities and qualities are similar to those used in other clinical settings, but may have limited discriminatory value as pain levels become severe.

Adult↗
PubMed2001

A multicenter study of lamivudine treatment in 33 patients with hepatitis B after liver transplantation.

Hepatitis B virus (HBV) infection after liver transplantation (LT) may lead to severe and rapidly progressive graft failure. Antiviral treatment may be of benefit in selected patients with recurrent hepatitis B post-LT. The aim of this prospective open-label study is to determine the safety and efficacy of lamivudine in 33 liver transplant recipients with active HBV infection. The median time from LT to study enrollment was 51 months, all patients were hepatitis B surface antigen positive, and 75% and 94% of subjects had detectable hepatitis B e antigen (HBeAg) and HBV DNA at entry, respectively. The median duration of lamivudine treatment on study was 85 weeks, during which time median HBV DNA levels became undetectable by 16 weeks and 9% of patients lost previously detectable HBeAg. Serum alanine aminotransferase (ALT) levels improved in most patients and normalized in 27% of patients with elevated values pretreatment. Serum bilirubin and albumin levels significantly improved in patients with abnormal values at entry (P <.05). Virological breakthrough was detected in 13 subjects after a median of 61 weeks of lamivudine treatment and was confirmed to be caused by YMDD mutants in all patients tested. None of the patients with virological breakthrough showed a complete loss of clinical response to lamivudine. Serum ALT and bilirubin levels in patients with and without virological breakthrough were not significantly different at last study follow-up. Study results show that lamivudine is safe and effective in liver transplant recipients with recurrent hepatitis B. However, the high rate of virological breakthrough with prolonged therapy indicates the need for further studies of combination antiviral therapy in this patient population. Our results and others further establish the improving long-term outcomes with LT for patients with hepatitis B through advances in prevention of reinfection, as well as the availability of safe and effective antiviral therapies to treat patients with HBV recurrence.

Adult↗
PubMed2001

Predictor index of mortality in dementia patients upon entry into long-term care.

BACKGROUND: The purpose of this study was to develop an algorithm that predicts survival in patients with dementia upon entry into long-term care. There are, as yet, no predictive equations developed for those in the late stages of Alzheimer's disease (AD). METHODS: This was a prospective, observational study of 132 patients with dementia (61% with AD) followed for up to 5.0 years (median of 41.0 months) after admission to a long-term care facility for dementia patients. Information on demographic characteristics, physical health, and cognitive, emotional, and behavioral characteristics was collected shortly after admission and entered as predictors of time until death in Cox regressions. Findings were used to derive an index predicting mortality. RESULTS: There were 60 deaths among the 132 patients (45.4% mortality), with an average survival of 22.4 months in those who died. Better physical health and the presence of delusions were associated with longer survival. These two variables were aggregated into the Copper Ridge Index (CRI). Each one-point increase on the CRI was associated with a four-fold greater likelihood of death over 5 years. CONCLUSIONS: A predictive equation incorporating measures of general physical health and delusions accurately predicted time to death in dementia patients in long-term care.

Aged↗
PubMed2001

Trends in deaths from drug overdose and poisoning in England and Wales 1993-1998.

BACKGROUND: The study examines time trends and sociodemographic aspects of drug poisoning deaths in England and Wales. METHODS: Socio-demographic data from the four drug groups most commonly used in poisoning were extracted, and annual age- and sex-specific mortality rates calculated. Enumeration districts were ranked into five groups on the basis of their Carstairs scores, and the number of deaths in each of the five groups was calculated. RESULTS: There were 15720 deaths from drug poisoning between 1993 and 1998. More deaths occurred in men than in women (10 223 versus 5497). Opiates were the most commonly used drugs in deaths from drug poisoning (32 per cent of deaths); mortality rates increased twofold for these drugs. Males had higher number of deaths from opiate poisoning than females (4523 versus 1221). Highest mortality rates from opiate poisoning (77.4 per million) occurred in men aged 24-35 years. Deaths from drug poisoning were strongly associated with deprivation. CONCLUSION: There are substantial socio-demographic differences in mortality rates from drug poisoning.

Acetaminophen↗
PubMed2001

Microtubule-independent motility and nuclear targeting of adenoviruses with fluorescently labeled genomes.

A novel adenovirus system for analyzing the adenovirus entry pathway has been developed that contains green fluorescent protein bound to the encapsidated viral DNA (AdLite viruses). AdLite viruses enter host cells and accumulate around the nuclei and near the microtubule organizing centers (MTOC). In live cells, individual AdLite particles were observed trafficking both toward and away from the nucleus. Depolymerization of microtubules during infection prevented AdLite accumulation around the MTOC; however, it did not abolish perinuclear localization of AdLite particles. Furthermore, depolymerization of microtubules did not affect AdLite motility and did not affect gene expression from wild-type adenovirus and adenovirus-derived vectors. These data revealed that adenovirus intracellular motility and nuclear targeting can be supported by a mechanism that does not rely on the microtubule network.

Adenovirus Infections, Human↗
PubMed2001

Portal vein thrombosis and pancreatic failure.

We report a case of a child with portal vein thrombosis presenting with protein losing enteropathy. He later developed exocrine and endocrine pancreatic failure. This association has not been reported before.

Abdomen↗