Bacterial translocation in cardiopenic shock: the gastrointestinal tract as the motor of sepsis?
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Biomedical subjects
Publications and source records attributed to S Price.
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Interferometric RADARSAT data are used to map ice motion in the source areas of four West Antarctic ice streams. The data reveal that tributaries, coincident with subglacial valleys, provide a spatially extensive transition between slow inland flow and rapid ice stream flow and that adjacent ice streams draw from shared source regions. Two tributaries flow into the stagnant ice stream C, creating an extensive region that is thickening at an average rate of 0.49 meters per year. This is one of the largest rates of thickening ever reported in Antarctica.
Erythropoietin (Epo), a glycoprotein hormone produced principally in the fetal kidney and in the adult liver in response to hypoxia, is the prime regulator of growth and differentiation in erythroid progenitor cells. The regulation of Epo gene expression is not fully understood, but two mechanisms have been proposed. One involves the participation of a heme protein capable of reversible oxygenation and the other depends on the intracellular concentration of reactive oxygen species (ROS), assumed to be a function of pO2. We have investigated the production of Epo in response to three stimuli, hypoxia, cobalt chloride, and the iron chelator desferrioxamine, in Hep3B cells. As expected, hypoxia caused a marked rise in Epo production. When the cells were exposed to the paired stimuli of hypoxia and cobalt no further increase was found. In contrast, chelation of iron under hypoxic conditions markedly enhanced Epo production, suggesting that the two stimuli act by separate pathways. The addition of carbon monoxide inhibited hypoxia-induced Epo production, independent of desferrioxamine concentration. Taken together these data support the concept that pO2 and ROS are sensed independently.
The knowledge, skills and attitudes which institutions expected of applicants for pre-registration Diploma programmes in children's nursing were investigated. Criteria were derived through an examination of nursing literature related to activities undertaken to meet the needs of children, when they are ill. Specific qualities, such as observational, psychomotor and interpersonal skills, combined with a desire to work with children and their families, were considered as being important in the selection of potential children's nurses. These criteria were compared with the expectations of those involved in the selection of students for children's nursing. Surprisingly, psychomotor skills were not mentioned by respondents and only around one-third of institutions clearly stated that they expected some understanding of children and their families. There was no mention of observational skills. These data supported the notion that there are a number of inherent qualities which selectors might look for in candidates; however, not all respondents have the same expectations of their candidates for the Child Branch. This raises the question of whether those offering programmes which leads to a qualification, acceptable throughout the UK, should be encouraged to work towards greater agreement on the qualities of those suitable to be taken into education as a children's nurse.
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The motor thalamic areas receiving input from the globus pallidus (VA) and the cerebellar nuclei (VL) appear to have different roles in the generation and guidance of movements. In order to further test these differences, we used electrical stimulation to map the ventro-anterior and ventro-lateral nuclei of the thalamus in three ketamine anaesthetised monkeys. Movements were readily evoked from VL at currents of down to 10 microA. The movements were typically multijoint, and stimulation could evoke arm and trunk or arm and facial movement at the same current threshold. Evoked arm movements often involved multiple joints, with or without finger movements. Facial movements included the lips, tongue, jaw, eyebrows and, occasionally, the eyes. The thalamic map was topographic, but complex with at least two separate regions related to arm movement. Very few sites within the VA could stimulate movement, even at high currents. We therefore suggest that the cerebellar projections to motor regions of the cortex, which pass through the VL thalamic nuclei, have a different relationship and are closer to movement execution than the projections from basal ganglia via the ventro-anterior nucleus.
As the use of aromatherapy within a health care setting has grown so rapidly in recent years, and will continue to do so, the need for suitable training has become apparent. No health service can afford the risk of having staff who are inadequately trained in the practice of aromatherapy using essential oils incorrectly on those in a state of ill-health, especially if the essential oils used are not to a standard suitable for therapeutic use. Training to an acceptable level in aromatic therapy is essential for safety and effectiveness. Knowledge of the nature and make-up of essential oils, their effect on the body and the emotions, and how, when, and where to apply them is imperative in order for them to be beneficial to a patient's health. Contraindications to certain oils, patients, or treatment have also to be thoroughly understood, and the dosage employed is related to some extent to the standard of training undertaken.
Allogeneic peripheral blood progenitor cell (PBPC) transplants are an alternative to BMT, although G-CSF mobilization dose, timing of pheresis and risk of GVHD are not well defined. We compared harvest characteristics, donor and recipient outcomes and costs of two PBPC transplant strategies with historical controls who received BMT. Twenty donors mobilized with four daily s.c. G-CSF doses (5 microg/kg/day) (group 1) and 20 mobilized with 10 microg/kg/day G-CSF (group 2) were compared with 20 BM controls (group 3). G-CSF and phereses were well tolerated. Four of 40 PBPC donors required femoral catheter placement. At least 2.5 x 10(6) CD34+/kg recipient weight were collected with two phereses in 19/20 donors (group 1) and 18/20 donors (group 2). Time to neutrophil (18 vs 20 vs 22 days, P = 0.02) and platelet (21 vs 24 vs 27 days, P = 0.005) engraftment was shorter in the PBPC groups (group 2 vs group 1 vs group 3) but secondary engraftment outcomes were not different. The incidence of grade 2-4 aGVHD was higher in the low-dose G-CSF group (group 1) but there was no difference in cGVHD, 100-day or 1-year survival. The mean PBPC transplant cost (group 1) at first hospital discharge was less than BM (group 3) ($34,643 vs $37,354) but the mean overall cost for both groups was similar at 100 days ($46,334 vs $46,083). Allogeneic PBPC transplant with short course, low-dose G-CSF mobilization is safe, feasible and cost equivalent to allogeneic BMT.
Activation of CDK4 is regulated, in part, by its association with a D-type cyclin. Conversely, CDK4 activity is inhibited when it is bound to the cyclin-dependent kinase inhibitor, p16(INK4A). To investigate the molecular basis of the interactions between CDK4 and cyclin D1 or p16(INK4A) we performed site-directed mutagenesis of CDK4. The interaction was examined using in vitro translated wild type and mutant CDK4 proteins and bacterially expressed cyclin D1 and p16 fusion proteins. As mutational analysis of CDC2 suggests that its cyclin binding domain is primarily located near its amino terminus, the majority of the mutations constructed in CDK4 were located near its amino terminus. In addition, CDK4 residues homologous to CDC2 sites involved in Suc1 binding were also mutated. Our analysis indicates that cyclin D1 and p16 binding sites are overlapping and located primarily near the amino terminus. All CDK4 mutations that resulted in decreased p16 binding capability also diminished cyclin D1 binding. In contrast, amino-terminal sequences were identified, including the PSTAIRE region, that are important for cyclin D1 binding but are not involved in p16 binding.
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A quantitative analysis of peripheral blood stem cell (PBSC) yield, measuring absolute numbers of CD34+ cells x 10(6)/kg and CFU-C x 10(4)/kg was performed in 74 consecutive patients. The interval or 'gap' from the end of previous chemotherapy to the date of priming was recorded in weeks. Geometric mean CD34 and CFU-C values were significantly higher in patients with a score of < or = 60 compared to those with score > 60 (P = 0.003 and 0.02, respectively) and a significant difference in CD34 values was also found when scores of < or = 38 were compared with scores > 38 (P = 0.003), with the difference in CFU-C values approaching significance (P = 0.08). Patients exposed to toxicity factor 4 drugs had significant lowering of both CD34 and CFU-C values (P < 0.001 and P = 0.038) and this emerged as the only independent factor when analysed using linear regression. No significant difference in the geometric mean CD34 or CFU-C values of patients was found in any of the gap categories analysed. Prior exposure to toxicity factor 4 drugs had a significant adverse effect on stem cell yield and should be avoided or minimized prior to stem cell harvesting.
The structure of a domain of the group I intron, the largest structure of an RNA to date, reveals structural details of tertiary interactions required for the folding of a large RNA.
General dental practitioners (GDPs) in the UK may wish additional education on relevant aspects of human immunodeficiency virus (HIV) disease. The aim of the present study was to develop and assess a computer assisted learning package on the oral manifestations of HIV disease of relevance to GDPs. A package was developed using a commercially-available software development tool and assessed by a group of 75 GDPs interested in education and computers. Fifty-four (72%) of the GDPs completed a self-administered questionnaire of their opinions of the package. The majority reported the package to be easy to load and run, that it provided clear instructions and displays, and that it was a more effective educational tool than videotapes, audiotapes, professional journals and textbooks, and of similar benefit as post-graduate courses. The GDPs often commented favourably on the effectiveness of the clinical images and use of questions and answers, although some had criticisms of these and other aspects of the package. As a consequence of this investigation the package has been modified and distributed to GDPs in England and Wales.
Monoclonal hybrid cell lines derived from either mesencephalic or striatal neuronal parents were screened for the effects of glial-derived neurotrophic factor (GDNF) on morphological differentiation. The mesencephalic dopaminergic MN9D cell line responded to GDNF with a 3- to 4-fold increase in the number of differentiated solitary cells and provides an unlimited source of monoclonal cells for studies on the mechanism of action of GDNF and the nature of its receptor.
Oxadiazon [5-ter-butyl-3-(2,4-dichloro-5-isopropoxyphenyl)- 1,3,4-oxadiazol-2(3H)-one] was administered orally at 20-500 mg/ kg body wt/day to male Sprague-Dawley CD rats for 14 days, at 20-200 mg/kg body wt/day to male CD1 [CR1/CD-1(1GR)BR] mice for 28 days, and at 500 mg/kg body wt/day to male beagle dogs for 28 days. Although liver enlargement was observed in the three species, morphological studies indicated that peroxisome proliferation only occurred in rats and mice. Parallel biochemical investigations showed that there was a dose-dependent increase in the peroxisomal cyanide-insensitive palmitoyl CoA oxidase and acetyl carnitine transferase activities in treated rats and mice. Acetyl carnitine activity appeared to correlate well with the number and volume of peroxisomes as determined histologically. The increases in enzyme activities at 200 mg/kg body wt/day oxadiazon were comparable in rats and mice indicating that both rodent species were equally sensitive to oxadiazon-induced peroxisome proliferation. When added in vitro to cultured rat hepatocytes at concentrations ranging from 2.5 to 10 x 10(-5) M, oxadiazon induced a dose-dependent increase in the activities of palmitoyl CoA oxidase and acetyl carnitine transferase. The ratio obtained by comparing oxadiazon and clofibric acid on acetyl carnitine transferase activity at 5 x 10(-5) M in the present in vitro study on rat hepatocytes are equivalent to those that can be calculated from the results on this enzyme activity obtained in vivo in the rat with 500 mg/ kg body wt/day oxadiazon (this study) and clofibric acid (literature values), indicating that the rat hepatocyte cultures gave satisfactory results regarding peroxisome proliferation. Neither oxadiazon nor clofibric acid modified the activities of palmitoyl CoA oxidase and acetyl carnitine transferase in cultured human hepatocytes. The results presented here demonstrate clearly that oxadiazon induces peroxisome proliferation in rodents in vivo and in vitro, as determined both biochemically and morphologically, whereas dogs in vivo and human hepatocytes in vitro were refractory to peroxisome proliferation. This observation extends to the herbicide oxadiazon, which is structurally unrelated to other known peroxisome proliferators, the generally observed marked species difference in sensitivity to peroxisome proliferation, and has important implications in the human safety evaluation of this herbicide.
Growth of Listeria monocytogenes was inhibited in culture media and in certain foods by four hop extracts (I-IV) containing varying concentrations of alpha-and beta-acids. Extracts (II and III) containing the highest concentrations of beta-acids were inhibitory at 0.01 mg/l in trypticase soy broth. In food, these hop extracts showed varying magnitudes of inhibition. In coleslaw, hop extract III at 1 mg/g enhanced the rate of inactivation of L. monocytogenes Scott A. Hop extract II was inhibitory at 0.1 and 1 mg/ml in skim and 2% milk, and was inhibitory at 1 mg/ml in whole milk. Hop extract II was listericidal in cottage cheese at 0.1 to 3 g/kg. No inhibition of L. monocytogenes by hop extract III was observed in Camembert cheese. Overall, the antimicrobial activity of hop extracts in food appeared to increase with acidity and lower fat content. Our results indicate that hop extracts could be used to control L. monocytogenes in minimally processed food with low fat content.
A case-control study was undertaken to investigate the possibility of an association between stressful life events and the development of breast cancer. Ninety-nine breast cancer cases, and 99 controls matched by age and area of residence, completed a life events inventory to measure life change and distress scores over a 2-year and a 10-year period. Study subjects were also interviewed to establish potential breast cancer risk factors; their height and weight were measured; they completed a food frequency questionnaire and provided a fasting blood sample for hormonal assay. After adjusting for potential confounders, women with a 10-year life change score greater than 210 (i.e. the highest quartile) had 4.67 times the risk of developing breast cancer, compared with those in the lowest quartile (P < 0.05).