Targeting drug-eluting stents to lesions at high risk of restenosis: a flawed approach?
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Angioplasty, Balloon, Coronary↗
Biomedical subjects
C Newman
Publications and source records attributed to C Newman.
Is Mycobacterium bovis in the environment important for the persistence of bovine tuberculosis?
Mycobacterium bovis is the causative agent of bovine tuberculosis (bTB) in cattle and wildlife. Direct aerosol contact is thought to be the primary route of infection between conspecifics, whereas indirect transmission via an environmental reservoir of M. bovis is generally perceived not to be a significant source for infection. Here, we report on the application of molecular technology (PCR) to quantify the prevalence of M. bovis in the environment and to explore its epidemiological significance. We show that the detectability of viable M. bovis at badger setts and latrines is strongly linked to the frequency of M. bovis excretion by infected badgers, and that putative M. bovis in the environment is prevalent on a large proportion of endemic cattle farms in Britain. These results raise important questions about the role of an environmental reservoir in bTB persistence.
Animals↗
Differentiating among prefrontal substrates in psychopathy: neuropsychological test findings.
Frontal lobe and consequent executive dysfunction have long been related to psychopathy. More recently, there have been suggestions that specific regions of frontal cortex, rather than all of frontal cortex, may be implicated in psychopathy. To examine this issue, the authors presented 25 individuals with psychopathy and 30 comparison individuals with measures preferentially indexing the orbitofrontal cortex (OFC; object alternation task), dorsolateral prefrontal cortex (DLPFC; spatial alternation task), and anterior cingulate cortex (ACC; number-Stroop reading and counting tasks). The individuals with psychopathy showed significant impairment on the measure preferentially sensitive to OFC functioning. In contrast, the 2 groups did not show impairment on the measures preferentially sensitive to the functioning of the DLPFC or ACC. These results are interpreted with reference to executive dysfunction accounts of the disorder.
Antisocial Personality Disorder↗
Instrumental learning and relearning in individuals with psychopathy and in patients with lesions involving the amygdala or orbitofrontal cortex.
Previous work has shown that individuals with psychopathy are impaired on some forms of associative learning, particularly stimulus-reinforcement learning (Blair et al., 2004; Newman & Kosson, 1986). Animal work suggests that the acquisition of stimulus-reinforcement associations requires the amygdala (Baxter & Murray, 2002). Individuals with psychopathy also show impoverished reversal learning (Mitchell, Colledge, Leonard, & Blair, 2002). Reversal learning is supported by the ventrolateral and orbitofrontal cortex (Rolls, 2004). In this paper we present experiments investigating stimulus-reinforcement learning and relearning in patients with lesions of the orbitofrontal cortex or amygdala, and individuals with developmental psychopathy without known trauma. The results are interpreted with reference to current neurocognitive models of stimulus-reinforcement learning, relearning, and developmental psychopathy.
Adult↗
Historical and other patterns of monomethyl and inorganic mercury in the Florida panther (Puma concolor coryi).
Since the late 1980s, elevated levels of mercury have been reported in the tissues of the Florida panther (Puma concolor coryi) from the Florida Everglades. The extent, degree, and length of time of mercury contamination in the Florida panther are unknown. The objective of this study was to determine the historical and other patterns of monomethyl and inorganic mercury in the Florida panther by analysis of mercury in panther hair from museum collections. In addition, this study evaluated the effects of preservation of skins on mercury concentrations in hair and the representativeness of museum collections for evaluating historical trends of contamination in the Florida panther. Hair from 42 Florida panther specimens collected from 1896 to 1995 was analyzed for both monomethyl and inorganic mercury. Monomethyl mercury (MMHg) and inorganic mercury (IHg) were found in all specimens. Monomethyl mercury in hair from untanned skins was significantly higher than MMHg in hair from tanned skins. For untanned specimens, the mean MMHg concentration in hair was 1.62 +/- 1.87 mug/g (range 0.11 to 6.68 mug/g, n = 16). Monomethyl mercury accounted for 88% of the total mercury in untanned Florida panther hair. No sexual or geographical differences were found. Although MMHg is generally stable in hair, the tanning process appears to reduce the amount of MMHg in hair. In addition, exogenous IHg contamination of the panther hair was found in museum specimens, especially in older specimens. The implication of these and other factors in interpreting results of museum studies is discussed. The presence of MMHg in panther hair since the 1890s indicates long-term and widespread exposure of the Florida panther to mercury. Levels of MMHg are significantly greater in the 1990s than the 1890s. When combined with field studies of mercury in the Florida panther, considerable individual variability is observed, reflecting short-term changes in exposure of individual panthers to mercury. Although museum specimens showed a significant increase in MMHg over the last 100 years, they did not show the magnitude of increase that field populations of Florida panthers did. A number of Florida panthers appeared to be at risk from mercury over their lifetimes, especially individuals from the early 1990s.
Animals↗
Neonatal diabetes, with hypoplastic pancreas, intestinal atresia and gall bladder hypoplasia: search for the aetiology of a new autosomal recessive syndrome.
AIMS/HYPOTHESIS: Neonatal diabetes is a rare disease with several identified molecular aetiologies. Despite associations with other malformations, neonatal diabetes with intestinal and biliary anomalies has not been described. The current study aims to describe a new syndrome, and to examine a possible link with one of three genes known to cause neonatal diabetes. METHODS: Five clinical cases are described. Immunohistochemical staining for pancreatic islet hormones was performed on three of the infants. DNA from one infant was analysed for abnormalities of the PLAGL-1 (ZAC), glucokinase and PDX-1 (IPF-1) genes. RESULTS: Five infants (two sibling pairs from two families, and an isolated case) presented with neonatal diabetes, hypoplastic or annular pancreas, jejunal atresia, duodenal atresia and gall bladder aplasia or hypoaplasia. One sibling pair was born to consanguineous parents. One patient with a milder form is surviving free of insulin. Four children died in the first year of life despite aggressive medical management. Pancreatic immunohistochemistry revealed few scattered chromogranin-A-positive cell clusters but complete absence of insulin, glucagon and somatostatin. Exocrine histology was variable. In one case from the consanguineous family, molecular analysis showed no duplication or uniparental isodisomy of PLAGL-1 at 6q24, no contiguous gene deletion involving the glucokinase gene, and no mutation in the coding sequences or splice sites of PDX-1. CONCLUSIONS/INTERPRETATION: This combination of multiple congenital abnormalities has not been previously described and probably represents a new autosomal recessive syndrome involving a genetic abnormality that interferes with normal islet development and whose aetiology is as yet unknown.
Abnormalities, Multiple↗
First report of Cheyletiella parasitovorax infestation in the Eurasian badger (Meles meles).
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Animals↗
Potential tenfold drug overdoses on a neonatal unit.
Nearly one third of intravenous drug prescriptions on a neonatal unit were for doses less than one tenth of a single drug vial. Tenfold drug errors in prescribing are well documented and with the continued use of vials containing adult size doses, great potential exists for serious administration errors.
Drug Overdose↗
Theory of mind and psychopathy: can psychopathic individuals read the 'language of the eyes'?
There have been suggestions that Theory of Mind (ToM) impairment might lead to aggressive behaviour and psychopathy. Psychopathic and matched non-psychopathic individuals, as defined by the Hare Psychopathy Checklist [The Hare Psychopath Checklist-Revised, 1991] completed the 'Reading the Mind in the Eyes' ToM Test [Journal of Child Psychology and Psychiatry, 1997;38:813]. This test requires the self-paced identification of mental states from photographs of the eye region alone. Results indicated that the psychopathic individuals did not present with any generalised impairment in ToM. The data are discussed with reference to the putative neural system mediating performance on this task and models of psychopathy.
Adult↗
Unlicensed and off label drug use in acute lymphoblastic leukaemia and other malignancies in children.
BACKGROUND: The need to use unlicensed and off label drugs in children due to the lack of suitable, licensed formulations with appropriate prescribing information creates many problems on an everyday basis for healthcare professionals, carers and children. PATIENTS AND METHODS: This prospective study was designed to examine the incidence and nature of unlicensed and off label prescribing, in paediatric oncology patients with acute lymphoblastic leukaemia and other malignancies. Inpatient and outpatient prescriptions were analysed for a 4-week period. RESULTS: All patients received at least one unlicensed or off label drug. Fifty-five per cent of prescriptions were licensed, 19% were unlicensed and 26% were licensed drugs used in an off label manner. Unlicensed preparations were used in 40% of prescriptions for cytotoxic agents, due to a lack of commercially available formulations suitable for the paediatric patient. These drugs included mercaptopurine and methotrexate which have been used in the treatment of paediatric leukaemia for many years, their efficacy having been demonstrated by on-going Medical Research Council trials. CONCLUSIONS: It is disappointing that drugs, which are the mainstay of therapy for paediatric leukaemia and other malignancies, are unavailable in appropriate licensed formulations to facilitate their administration to children. This needs to be urgently addressed.
Adolescent↗
Leukocyte coping capacity: a novel technique for measuring the stress response in vertebrates.
Methods used to quantify the stress response in animals are vital tools in many areas of biology. Here we describe a new method of measuring the stress response, which provides rapid results and can be used in the field or laboratory. After a stressful event, we measure the capacity of circulating leukocytes to produce a respiratory burst in vitro in response to challenge by phorbol myristate acetate (PMA). During the respiratory burst leukocytes produce oxygen free radicals, and the level of production can be measured directly as chemiluminescence. When in vitro PMA-stimulated whole blood chemiluminescence is measured directly after a stressful event, we define the response as the leukocyte coping capacity (LCC). In an experiment badgers (Meles meles), which were caught as part of an on-going population study, were either transported to a central site prior to blood sampling or blood was collected at their site of capture. Transported animals had a significantly lower LCC and showed changes in leukocyte composition that were indicative of stress. We conclude that the stress of transport reduced LCC in badgers and that LCC serves as a quantitative measure of stress. Potential applications of this method are discussed.
Animal Welfare↗
Randomized, controlled, dose-range study of Ro 25-8315 given before and after a high-dose combination chemotherapy regimen in patients with metastatic or recurrent breast cancer patients.
PURPOSE: To evaluate the safety, pharmacokinetics, and efficacy of three different dose levels of pegylated granulocyte colony-stimulating factor (Ro 25-8315) on progenitor cell mobilization and hematologic recovery in cancer patients. PATIENTS AND METHODS: Breast cancer patients (n = 36) were randomly assigned to receive before (part I) and after (part II) chemotherapy either a single-dose injection of Ro 25-8315 (20 microg/kg, n = 9; 60 microg/kg, n = 9; 100 microg/kg, n = 10) or a standard daily dose of filgrastim (part I, 10 microg/kg/d; part II, 5 microg/kg/d) (control group, n = 8). RESULTS: Overall, Ro 25-8315 was well tolerated. In part I, more progenitor cell mobilization was observed with Ro 25-8315 100 microg/kg. The peak of circulating CD34(+) cells was obtained at day +5 in the four groups, and the absolute neutrophil count (ANC) returned to less than 20 x 10(9)/L by day +15. In part II, high levels of circulating CD34(+) cells (> 20 cells/microL) were obtained in all four groups. The chemotherapy-induced neutropenia (< 1 x 10(9)/L) was similar in the four groups. Ro 25-8315 100 microg/kg was more effective than filgrastim in reducing the number of patients with an ANC less than 0.5 x 10(9)/L on day +12 after chemotherapy. CONCLUSION: A single injection of Ro 25-8315 100 microg/kg might be the optimal dose for steady-state peripheral-blood progenitor cell mobilization. A single injection of 20, 60, or 100 microg/kg could be as efficient as daily administration of filgrastim to correct chemotherapy-induced cytopenia. The optimal dose of Ro 25-8315 should be determined according to the planned chemotherapy regimen.
Adult↗
E. coli O157 phage type 21/28 outbreak in North Cumbria associated with pasteurized milk.
In March 1999, a large community outbreak of Escherichia coli O157 infection occurred in North Cumbria. A total of 114 individuals were reported to the Outbreak Control Team (OCT); 88 had laboratory confirmed E. coli O157. Twenty-eight (32%) of the confirmed cases were admitted to hospital, including three children (3.4%) with haemolytic uraemic syndrome. There were no deaths. A case-control study found that illness was strongly associated with drinking pasteurized milk from a local farm (P = <0.0001) on single variable analysis. Microbiological investigations at the farm revealed E. coli O157 phage type (PT) 21/28 VT 2 which was indistinguishable from the human isolates by pulsed field gel electrophoresis. At the time of occurrence this was the largest E. coli O157 outbreak in England and Wales and the first E. coli O157 PT 21/28 VT 2 outbreak associated with pasteurized milk. This outbreak highlights lessons to be learnt regarding on-farm pasteurization.
Adolescent↗
Immunomodulation by exogenous surfactant: effect on TNF-alpha secretion and luminol-enhanced chemiluminescence activity by murine macrophages stimulated with group B streptococci.
Group B streptococci (GBS) are important pathogens in neonatal sepsis and pneumonia. GBS stimulate alveolar macrophages to produce inflammatory cytokines and free oxygen radicals, which can damage the lungs. In several studies, use of exogenous surfactant in term babies has improved outcome related to sepsis and respiratory failure. The role(s) of exogenous surfactant in modulating the inflammatory response produced by this microbe was examined. Tumor necrosis factor alpha (TNF-alpha) production and luminol-enhanced chemiluminescence (LCL), a measure of respiratory burst, were investigated. For measuring TNF-alpha release, RAW 264.7 murine macrophages were pre-incubated with bovine surfactant and stimulated with either lipopolysaccharide, live or heat-killed GBS type Ia. LCL was measured after macrophages were pre-incubated with or without surfactant overnight, then stimulated with GBS or phorbol myristate acetate. Lipopolysaccharide and GBS stimulated TNF-alpha secretion from macrophages that was suppressed by exogenous surfactant in a dose-dependent fashion. GBS and phorbol myristate acetate also increased LCL from macrophages, which was significantly suppressed by pre-incubation of macrophages with exogenous surfactant. We conclude that GBS type Ia stimulates TNF-alpha release and LCL from RAW 264.7 cells and that these responses are suppressed by surfactant. Suppression of inflammatory mediators by exogenous surfactant might improve respiratory disease associated with GBS.
Animals↗
Coccidiosis in the European badger, Meles meles in Wytham Woods: infection and consequences for growth and survival.
In total 1502 faecal samples were collected from a population of European badgers (Meles meles) between 1992 and 1995 at Wytham Woods, Oxfordshire, UK. Two coccidia species, Eimeria melis and Isospora melis, were identified. Cubs showed a marked seasonal pattern of infection with E. melis, with infection occurring at significantly higher intensity and prevalence than in adults. There was preliminary evidence to suggest that infantile coccidiosis in badgers may be associated with impaired growth and increased mortality.
Age Factors↗
The development of reaching and looking preferences in infants to objects of different sizes.
Reaching and looking preferences and movement kinematics were recorded in 5-15-month-old infants, who were divided into 3 age groups. Infants were presented with pairs of cylinders of 3 different diameters: small (1-cm diameter), medium (2.5-cm diameter), and large (6-cm diameter). Whereas infants between 5 and 12 months of age showed a preference for looking first at the large object, a significant preference for reaching to smaller (graspable) objects was observed in 81/2-12-month-old infants. Kinematic measures suggest that the onset of object-oriented action requires a slowing down of the reach and an extended "homing-in" phase. The divergent looking and reaching preferences in infants at different ages may reflect a dissociation during development of visual processing streams subserving object-related action from those related to visual orienting.
Choice Behavior↗
Endovascular stent-grafts for the repair of infrarenal abdominal aortic aneurysms: a brief review.
In the United States nearly 1.5 million people have abdominal aortic aneurysms (AAAs). The natural history of AAAs is to enlarge and rupture. Rupture of an AAA results in an estimated 15,000 deaths per year. The major objective in the treatment of AAAs is to prevent aneurysm rupture and death. Endoluminal grafting for the treatment of aortic aneurysms is the most exciting topic in vascular surgery today. It is anticipated that approximately half of all aneurysms in the infrarenal abdominal and descending thoracic aorta will be repaired endovascularly in the future. Despite the enthusiasm for this technology, there are unanswered questions like the long-term fate of the device, management of endoleaks, and the ability to protect the patient from subsequent rupture. This article describes the two FDA approved devices in clinical use today and the indications, techniques, and potential pitfalls of endoluminal stent-grafting for the treatment of AAAs.
Aortic Aneurysm, Abdominal↗
Matching identities of familiar and unfamiliar faces caught on CCTV images.
People can be inaccurate at matching unfamiliar faces shown in high-quality video images, even when viewpoint and facial expressions are closely matched. However, identification of highly familiar faces appears good, even when video quality is poor. Experiment 1 reported a direct comparison between familiar and unfamiliar faces. Participants who were personally familiar with target items appearing on video were highly accurate at a verification task. Unfamiliar participants doing the same task performed very inaccurately. Familiarity affected discriminability, but not bias. Experiments 2 and 3 showed that brief periods of familiarization have little beneficial effect unless "deep" or "social" processing is encouraged. The results show that video evidence can be used effectively as a probe to identity when the faces shown are highly familiar to observers, but caution should be used where images of unfamiliar people are being compared.
Adult↗