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Biomedical subjects

L Webb

Publications and source records attributed to L Webb.

At least 19 recordsLinked to original sources

Effect of uncertainty on the time course for selection of verbal name codes.

Response selection takes time. Hick's law (Hick, 1952) predicts that the time course of response selection is a logarithmic function of the number of equally likely response alternatives. However, recent work has shown that oculomotor responses constitute noteworthy exceptions in that the latencies of saccades (Kveraga, Boucher, & Hughes, 2002) and smooth pursuit movements (Berryhill, Kveraga, Boucher, & Hughes, 2004) are completely independent of response uncertainty. This finding extends to the case in which the required response was known in advance (i.e., simple reaction times [RTs] were equivalent to choice RTs). In view of these results, we reevaluated reports that latencies to name visually presented digits (Experiment 1) and/or repeat aurally presented digits (Experiment 2) are similarly independent of the size of the response set. We found that naming latencies were equivalent for response set sizes from one to eight, but simple RTs (response set of one) were faster. Thus, the overlearned task of digit naming is indeed highly automatic but has not reached the level of automaticity characteristic of the oculomotor system.

Adolescent↗

Nurse staffing levels and budgeted expenditure in acute mental health wards: a benchmarking study.

This paper describes benchmarking research undertaken within one former National Health Service Executive region examining acute ward funded and actual staffing establishments and funded expenditure for mental health nursing staff. Staffing establishment data were obtained for all 73 acute wards within the region. Of the established posts for trained mental health nurses across these wards, it was identified that there were 12% vacancies (117.99 whole time equivalent) at the time of the study. While some of the shortfall was dealt with by recruiting untrained nursing staff above funded establishments, there remained an overall shortfall in the total nursing workforce across the system of acute wards in the region. Although most of the provider trusts in the region were in development or experiencing major organizational change at the time of the study, considerable variation existed within and between trusts. Variations were identified in funded and actual nursing establishments and cost per bed, raising significant issues for trusts and their local mental health economies. Variations based on mixed- and single-sex wards were also noted. Findings are discussed in respect of the issues raised for the development of wards, provider trusts and their local systems. The utility of the methodology developed in this work is also discussed.

Acute Disease↗

Intracellular Staphylococcus aureus. A mechanism for the indolence of osteomyelitis.

Staphylococcus aureus is the bacterial pathogen which is responsible for approximately 80% of all cases of human osteomyelitis. It can invade and remain within osteoblasts. The fate of intracellular Staph. aureus after the death of the osteoblast has not been documented. We exposed human osteoblasts to Staph. aureus. After infection, the osteoblasts were either lysed with Triton X-100 or trypsinised. The bacteria released from both the trypsinised and lysed osteoblasts were cultured and counted. Colonies of the recovered bacteria were then introduced to additional cultures of human osteoblasts. The number of intracellular Staph. aureus recovered from the two techniques was equivalent. Staph. aureus recovered from time zero and 24 hours after infection, followed by lysis/trypsinisation, were capable of invading a second culture of human osteoblasts. Our findings indicate that dead or dying osteoblasts are capable of releasing viable Staph. aureus and that Staph. aureus released from dying or dead osteoblasts is capable of reinfecting human osteoblasts in culture.

Cell Death↗

Male sterility and enhanced radiation sensitivity in TLS(-/-) mice.

TLS (also known as FUS) is an RNA-binding protein that contributes the N-terminal half of fusion oncoproteins implicated in the development of human liposarcomas and leukemias. Here we report that male mice homozygous for an induced mutation in TLS are sterile with a marked increase in the number of unpaired and mispaired chromosomal axes in pre-meiotic spermatocytes. Nuclear extracts from TLS(-/-) testes lack an activity capable of promoting pairing between homologous DNA sequences in vitro, and TLS(-/-) mice and embryonic fibroblasts exhibit increased sensitivity to ionizing irradiation. These results are consistent with a role for TLS in homologous DNA pairing and recombination.

Animals↗

Use of mean platelet component to measure platelet activation on the ADVIA 120 haematology system.

Platelet activation results in changes in a number of cell surface molecules including an increase in P-Selectin (CD62P) that may be rapidly and conveniently measured by immunofluorescent flow cytometry. The ADVIA 120 (Bayer) is a new system that facilitates more accurate measurement of platelet volume and in addition provides an approximate measure of the mean refractive index (RI) of the platelets reported as mean platelet component (MPC) concentration. We were interested to determine whether changes in MPC might reflect changes in platelet activation status. To investigate this, the platelet CD62P expression, determined by flow cytometry, and change in MPC, measured on the ADVIA 120 system, was first examined in vitro after stimulation of EDTA anticoagulated whole blood with submaximal concentrations of bovine thrombin in the presence or absence of the thromboxane synthase inhibitor, Ridogrel. Thrombin produced a dose-dependent increase in platelet CD62P expression and a decrease in MPC that could be inhibited by Ridogrel at physiological concentrations. In the second set of experiments, blood from 20 normal controls was collected into both EDTA and sodium citrate (SC) anticoagulants. Within 30 min of venesection and again at 3 h post-venesection after storage at room temperature, the platelet MPC and CD62P expression were determined. Platelets in all samples with both anticoagulants showed very low levels of CD62P expression when first analysed. At 3 h there was a small increase in CD62P expression on platelets in whole blood anticoagulated with SC, but a significant (P < 0.001) increase was observed on platelets anti-coagulated with EDTA. A negative correlation was found between the change in MPC of the platelets and the increase in the mean fluorescence intensity (MFI) (r = -0.69, P < 0.001, n = 20) and the percentage (r = -0.72, P < 0.001, n = 20) of CD62P positive platelets at 3 h in blood anticoagulated with EDTA. We conclude that a reduction in MPC as measured by the ADVIA 120 may be used to detect anticoagulant induced, as well as thrombin stimulated, in vitro platelet activation in blood anticoagulated with EDTA. Further, we conclude that platelet activation is negligible for up to 3 h in sodium citrate anticoagulated whole blood.

Adult↗

Atiprimod (SK&F 106615), a novel macrophage targeting agent, enhances alveolar macrophage candidacidal activity and is not immunosuppressive in Candida-infected mice.

Azaspiranes are novel macrophage-targeting agents with activity in preclinical animal models of autoimmune disease and transplantation. The purpose of this work was to determine the effects of atiprimod (SK&F 106615), an azaspirane being developed for the treatment of rheumatoid arthritis, on rat pulmonary alveolar macrophage (AM) function and immunocompetance in Candida-infected mice. AM from rats treated with 20 mg/kg/day of atiprimod for 15 days demonstrated enhanced killing of Candida albicans ex vivo. Concentration-dependent increases in candidacidal activity were also observed as early as one hour after exposure in vitro in AM from untreated normal rats. Treatment of AM with atiprimod in vitro did not increase particulate-stimulated superoxide production or phagocytosis of Candida but decreased their ability to concentrate acridine orange, indicating an increase in lysosomal pH. Increased candidacidal activity was inhibited by superoxide dismutase and catalase, suggesting a role for reactive oxygen intermediates (ROI). Atiprimod also increased free radical-mediated killing of Candida in the presence of H2O2, iron and iodide in a cell-free system. These findings indicated that treatment with atiprimod increased the candidacidal activity of rat AM in a free radical-dependent manner. The data also suggested that atiprimod did not increase ROI production by AM, but rather increased the efficiency of radical-mediated killing. This increase may be caused by cyclization of atiprimod, facilitating electron transfer and peroxidation of lipid membranes. In vivo studies in Candida-infected CBA mice showed that atiprimod (10 mg/kg/day), did not compromise immune function in the infected mice and could be differentiated from prototypical immunosuppressive compounds used for treatment of autoimmune diseases.

Acridine Orange↗

Hepatic artery chemoembolization for management of patients with advanced metastatic carcinoid tumors.

BACKGROUND: Patients with advanced metastatic carcinoid tumors who have disease progression despite conventional therapy are left with few therapeutic options. Hepatic artery chemoembolization (HACE) may play a role in palliating these patients' symptoms. METHODS: Fifteen patients with biopsy-proven advanced bilobar hepatic carcinoid metastases who demonstrated progression of symptoms and/or tumor size despite treatment with somatostatin analogues were treated with intra-arterial chemotherapy and HACE to determine efficacy and safety. Five days of intra-arterial 5-fluorouracil (1 g/m2) were followed by HACE with adriamycin (60 mg), cisplatin (100 mg), mitomycin C (30 mg), and polyvinyl alcohol (Ivalon); 200 micron to 710 micron). Patients were continued on octreotide at the same dose (150 to 2000 microg subcutaneous q 8 hours) before, during, and after the procedure. RESULTS: Efficacy of treatment was assessed by comparing pretreatment and 3-month clinical, laboratory, radiographic, and quality of life parameters. Symptoms were improved in 8 of 12 patients who had diarrhea, 7 of 12 who had flushing, 9 of 12 who had abdominal pain, and in 4 of 7 who had malaise. Elevated tumor markers decreased in all patients. Biochemical markers (mean +/- SE) at 3 months decreased by 60% +/- 6% for 5-HIAA, 75% +/- 10% for chromogranin A and 50% +/- 7% for neuron-specific enolase. Tomographic assessment revealed tumor liquefaction in 10 of 13 patients. The Karnofsky performance status improved from a mean of 66 +/- 2 to 84 +/- 2 (P <0.001). Median follow-up was 16 months, with 13 deaths occurring from 1 week to 71 months after treatment. CONCLUSIONS: Hepatic artery chemoembolization improves symptoms of carcinoid syndrome, has a high tumor response rate, and improves short-term quality of life in this group of patients with advanced hepatic carcinoid disease.

Adult↗

Underprediction of pain in children undergoing ear piercing.

Ear piercing is a brief, standard, painful stimulus which is submitted to voluntarily, offering a unique opportunity for research on children's anticipation of pain in a naturalistic context. Self-ratings on visual analogue scales of fear, predicted pain, and experienced pain were collected, as each ear was pierced in turn, from 32 girls aged 5-11 yr. Of these, 69% underpredicted their pain on the first ear. These underpredictors of pain on the first ear expected and reported significantly greater pain when the second ear was pierced than did overpredictors or children who accurately predicted the pain for the first ear. Fear scores taken before the first ear was pierced did not significantly predict pain for the second ear. Younger children made less accurate predictions and were more likely to use the extremes of the scale. The results, which are consistent with those of previous studies of prediction of pain and anxiety, have implications for preparation of children for brief procedural pain: they support recommendations to encourage children to expect realistic rather than minimal amounts of pain.

Analysis of Variance↗

Influence of phytogenic surfactants (quillaya saponin and soya lecithin) on bio-elimination of phenanthrene and fluoranthene by three bacteria.

The influence of two phytogenic surfactants on the elimination of polycyclic aromatic hydrocarbons (PAH) was studied in shaken-batch cultures of three soil bacteria under axenic conditions. At sufficiently high concentrations, quillaya saponin and soybean lecithin solubilized phenanthrene or fluoranthene efficiently. However, complete solubilization of the PAH by lecithin only doubled the maximal rate of elimination of the two PAH compounds by Pseudomonas 0259, strain MKm (Rhizomonas ?) and Mycobacterium EMI 2. By contrast, quillaya saponin did not improve PAH bioavailability, and in strain MKm it caused significant growth lags above 2.5 g/l. Simultaneously with the elimination of the PAH the bacteria utilized the surfactants as substrates for growth. Intermediate formation of PAH metabolites was noted. The results suggest that some phytogenic surfactants might improve PAH bioavailability in rhizospheres.

Bacteria↗

Rupture and hemorrhage of hepatic focal nodular hyperplasia.

Although adenoma and focal nodular hyperplasia (FNH) are both benign liver lesions, adenomas are associated with a risk of rupture and malignant degeneration. This had led to the general recommendation of resection of adenomas. However, FNH rarely ruptures or becomes malignant, and a nonoperative approach has been adopted by most hepatobiliary centers when the diagnosis of FNH can be made with reasonable certainty. There are only two previous reports of rupture of FNH in the English literature; we present a third case of FNH with spontaneous rupture and hemorrhage. An 18-year-old healthy Caucasian woman presented with sudden onset of severe RUQ pain. She had never been pregnant, nor used oral contraceptive agents, and had not sustained major trauma. Her abdominal exam revealed RUQ tenderness on palpation. Hepatic biochemical tests, CBC, and coagulation tests were normal. Her hematocrit of 44% fell to 31% over 48 hours. CT scan revealed right anterior lobe and left medial segment hypodense liver lesions (4-5 cm) as well as hemoperitoneum and angiography revealed hypervascular lesions. At laparotomy, two tan fibrous subcapsular masses were excised. Pathology showed a central stellate scar in both lesions with several nodules surrounding the central scar on microscopic section, characteristic of FNH. There was evidence of hemorrhage in one lesion. Significant symptoms are an indication for resection of FNH lesions. However, most patients with FNH are asymptomatic and have a normal physical exam. The natural history of these lesions is enigmatic, and the indications for surgery are still evolving. This report emphasizes that a small risk of rupture clearly exists.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Liver Cell↗

Lack of ras mutations and prediction of long-term survival in carcinoma of the colon.

Ras oncogene mutations are found in a significant number of human colonic carcinomas. Correlation between patient survival and ras mutations was explored and compared with other clinical parameters. Colonic carcinoma embedded in paraffin was subjected to the polymerase chain reaction using primers to amplify codon 12 of the K-ras oncogene. Oligonucleotide probes to six mutations were used to identify mutated genes. A total of 71 cases were successfully amplified. Some 54% of the cases had mutations. There was no correlation between presence of a mutation and age. Patients in Stage D, patients with a family history of carcinoma, and males have a greater incidence of ras mutations. Patients in Stage C had a lower incidence of mutations. Presence of the mutation did not correlate with decreased survival except in Stage D. Some 61% of long-term survivors with colon carcinoma living for more than 6 yr had ras mutations. The absence of K-ras mutations did not identify long-term survivors.

Adult↗