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Biomedical subjects

R Allman

Publications and source records attributed to R Allman.

At least 19 recordsLinked to original sources
PubMed2004

Investigation of sequential mitomycin C and photodynamic therapy in a mitomycin-resistant bladder cancer cell-line model.

OBJECTIVES: To investigate the hypothesis that sequential mitomycin C and 5-aminolaevulinic acid (ALA)-mediated photodynamic therapy (PDT) interact additively in both the J82 bladder cancer cell line and its mitomycin-C-resistant derivative, J82/MMC, and to assess the theoretical basis of this interaction by measuring the relative mitochondrial density of the respective cell lines, on the basis that the mitochondria are the intracellular site where ALA is metabolized to the active photosensitizer, protoporphyrin IX. MATERIALS AND METHODS: Cell survival was assayed in J82 cell line and the J82/MMC derivative after treating them with sequential ALA-mediated PDT and mitomycin C, and with the sequence of treatments reversed. Cell survival was estimated using the tetrazolium assay. The relative mitochondrial density of the two cell lines was estimated using flow cytometry to measure 123rhodamine fluorescence. RESULTS: The effect of sequential mitomycin C followed by ALA-mediated PDT enhanced the effect of PDT in both cell lines. In J82/MMC this effect was marginally supra-additive. When ALA-mediated PDT was administered before mitomycin C, the combined effect was 'sub-additive'. 123Rhodamine fluorescence was > 10 times greater in J82/MMC than J82, suggesting a significantly higher mitochondrial density in the former than the latter. CONCLUSION: Mitomycin C appears to enhance ALA-mediated PDT when administered first. This appears to be particularly so in J82/MMC. This phenomenon may have clinical significance in recurrent superficial bladder cancer.

Aminolevulinic Acid↗
PubMed2003

Delayed expression of apoptosis in human lymphoma cells undergoing low-dose taxol-induced mitotic stress.

The links between low-dose range taxol-induced mitotic arrest and the subsequent engagement of apoptosis are important for identifying the routes to therapeutic action. Here we have investigated the timing of cell-cycle perturbation and cell death responses following continuous exposure to clinically relevant drug concentrations (1-20 nM). Following 8 h of exposure to taxol, the cell line DoHH2 (p53 wild type) exhibited mitotic arrest and engagement of apoptosis, whereas the cell line SU-DHL-4 (p53 mutant) breached cell-cycle arrest with progression to an abnormal cycle and a 24 h delay in the engagement of apoptosis. Imaging showed equivalent dysfunction of mitotic spindles in both cell lines. The results of kinetic analyses indicated that although cell death may occur at different stages of progression through mitosis and subsequent cell cycles, the overall kinetics of cell death relate to the rate of arrival at a critical event window in the cell cycle. We propose a simple model of low-dose taxol-induced cell death for cycling populations in which mitotic stress acts as a primary trigger for apoptosis with equivalent but potentially delayed outcomes. This view provides a rationale for the clinical effectiveness of this agent, independent of the initial capacity of the tumour cell to engage apoptosis due, for example, to mutant p53 expression. The results provide a perspective for the design of combination regimens that include low-dose taxol and a component that may disturb mitotic delivery.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Quality of care for hospitalized medicare patients at risk for pressure ulcers.

BACKGROUND: No state peer review organization has attempted to identify processes of care related to pressure ulcer prediction and prevention in US hospitals. OBJECTIVE: To profile and evaluate the processes of care for Medicare patients hospitalized at risk for pressure ulcer development by means of the Medicare Quality Indicator System pressure ulcer prediction and prevention module. METHODS: A multicenter retrospective cohort study with medical record abstraction was used to obtain a total of 2425 patients aged 65 years and older discharged from acute care hospitals after treatment for pneumonia, cerebrovascular disease, or congestive heart failure. Six processes of care for prevention of pressure ulcers were evaluated: use of daily skin assessment; use of a pressure-reducing device; documentation of being at risk; repositioning for a minimum of 2 hours; nutritional consultation initiated for patients with nutritional risk factors; and staging of pressure ulcer. The associations between processes of care and incidence of pressure ulcer were determined with Kaplan-Meier survival analyses. RESULTS: National estimates of compliance with process of care were as follows: use of daily skin assessment, 94%; use of pressure-reducing device, 7.5%; documentation of being at risk, 22.6%; repositioning for a minimum of 2 hours, 66.2%; nutritional consultation, 34.3%; stage 1 pressure ulcer staged, 20.2%; and stage 2 or greater ulcer staged, 30.9%. CONCLUSION: These results suggest that US hospitals and physicians have numerous opportunities to improve care related to pressure ulcer prediction and prevention.

Age Distribution↗
PubMed2000

Understanding racial variation in the use of coronary revascularization procedures: the role of clinical factors.

BACKGROUND: Black patients undergo coronary artery bypass grafting and percutaneous transluminal coronary angioplasty less often than white patients. It is unclear how racial differences in clinical factors contribute to this variation. METHODS: A retrospective cohort study was performed of 666 male patients (326 blacks and 340 whites), admitted to 1 of 6 Veterans Affairs hospitals from October 1, 1989, to September 30, 1995, with acute myocardial infarction or unstable angina who underwent cardiac catheterization. The primary comparison was whether racial differences in percutaneous transluminal coronary angioplasty and coronary artery bypass grafting rates persisted after stratifying by clinical appropriateness of the procedure, measured by the appropriateness scale developed by the RAND Corporation, Santa Monica, Calif. RESULTS: Whites more often than blacks underwent a revascularization procedure (47% vs 28%). There was substantial variation in black-white odds ratios within different appropriateness categories. Blacks were significantly less likely to undergo percutaneous transluminal coronary angioplasty (odds ratio, 0.30; 95% confidence interval, 0.14-0.63 [P<.01]) when the indication was rated "equivocal." Similarly, blacks were less likely to undergo coronary artery bypass grafting (odds ratio, 0.44; 95% confidence interval, 0.23-0.86 [P<.01]) when only coronary artery bypass grafting was indicated as "appropriate and necessary." Differences in comorbidity or use of cigarettes or alcohol did not explain these variations. Using administrative data from the Veterans Health Administration, we found no differences in 1-year (5.2% vs 7.4%) and 5-year (23.3% vs 26.2%) mortality for blacks vs whites. CONCLUSION: Among patients with acute myocardial infarction or unstable angina, variation in clinical factors using RAND appropriateness criteria for procedures explained some, but not all, racial differences in coronary revascularization use.

Adult↗
PubMed2000

In vitro and in vivo effects of a cyclic peptide with affinity for the alpha(nu)beta3 integrin in human melanoma cells.

Expression of the integrin alpha(nu)beta3 has been shown to be associated with increasing metastatic potential in malignant melanoma. It also has a functional role on vascular endothelial cells during angiogenesis. The cyclic oligopeptide cRGDfV is known to bind with high affinity to alpha(nu)beta3. We have investigated the cellular effects of cRGDfV on a panel of human melanoma cell lines in vitro and also on the A375 melanoma cell line growing as xenografts in nude mice. cRGDfV is a potent inhibitor of alpha(nu)beta3-mediated cell adhesion, however, we have found no convincing evidence that integrin ligation by cRGDfV induces apoptosis in melanoma cell lines. However, cRGDfV when administered subcutaneously into nude mice did inhibit the growth of A375 melanoma xenografts. Histological examination of the tumours indicated that this effect was primarily one of angiogenesis inhibition. The results suggest that agents which target the alpha(nu)beta3 integrin may have a useful role as anti-angiogenesis agents in clinical oncology, but that they may not exert a direct effect on alphavbeta3-expressing tumour cells.

Animals↗
PubMed2000

Awareness and unawareness of thought disorder.

OBJECTIVE: There is little systematic evidence to determine if patients with thought disorder are aware of their impaired communication. Awareness versus unawareness of deficit has important implications for neurocognitive models of thought disorder. The aims of this study were to assess awareness of impaired communication in patients prone to thought disorder, and to explore associations between degree of awareness of thought disorder, objective measurement of thought disorder and performance on tests sensitive to impaired executive ability. METHOD: Thirty-one patients with schizophrenia, 16 patients with mania and 20 well controls were included. Subjects completed a new instrument to assess awareness of thought disorder, the Communication Awareness Scale (CAS). Thought disorder was rated from free speech samples scored with Andreasen's Scale for the Assessment of Thought Language and Communication. Four tests sensitive to impaired executive ability were administered. RESULTS: Subjects with higher levels of positive thought disorder had significantly higher CAS scores. Unexpectedly, those with lower scores on executive ability had significantly higher scores on the CAS. CONCLUSIONS: The significant correlation between objective levels of positive thought disorder and higher scores on the CAS suggests that, overall, patients with thought disorder are aware of their deficit. A neurocognitive model of thought disorder is described that involves a dissociation between the ability to monitor errors (required for accurate awareness of deficit) and the ability to correct errors (required for the production of efficient communication).

Adolescent↗
PubMed2000

Effect of photodynamic therapy in combination with ionizing radiation on human squamous cell carcinoma cell lines of the head and neck.

Photodynamic therapy (PDT) is a promising treatment modality for head and neck, and other tumours, using drugs activated by light. A second generation drug, 5-aminolaevulinic acid (5-ALA), is a precursor of the active photosensitizer protoporphyrin IX (PpIX) and has fewer side-effects and much more transient phototoxicity than previous photosensitizers. We have investigated the effect of 5-ALA mediated PDT in combination with gamma-irradiation on the colony forming ability of several human head and neck tumour cell lines. The effect of treatments on the DNA cell cycle kinetics was also investigated. Our results indicate that the combination of 5-ALA mediated PDT and gamma-irradiation results in a level of cytotoxicity which is additive and not synergistic. 5-ALA mediated PDT had no discernible effect on DNA cell cycle distributions. gamma-irradiation-induced cell cycle arrest in G2 did not enhance the phototoxicity of 5-ALA.

Aminolevulinic Acid↗
PubMed1998

Strategies for the promotion of computer applications in radiology in healthcare delivery.

The objective of this paper is to identify current trends in the development and implementation of computer applications in today's ever-changing healthcare environment. Marketing strategies are discussed with the goal of promoting computer applications in radiology as a means to advance future healthcare acceptance of technologic developments from the medical imaging field. With the rapid evolution of imaging and and information technologies along with the transition to filmless imaging, radiologists must assume a proactive role in the development and application of these advancements. This expansion can be accomplished in a number of ways including internet based educational programs, research partnerships, and professional membership in societies such as the Society of Computer Applications in Radiology (SCAR). Professional societies such as SCAR, in turn, should reach out to include other professionals from the healthcare community. These would include financial, administrative, and information systems disciplines to promote these technologies in a cost conscious and value added manner.

Costs and Cost Analysis↗
PubMed1997

Ganglioside expression in lung cancer cell lines.

Gangliosides are complex glycolipid constituents of cell membranes. They are involved in many biological functions including cell-cell recognition, cell-matrix attachment, cell growth and cell differentiation. Analysis of tumor associated gangliosides may aid in the characterisation of tumour cells and their degree of malignant transformation. We have characterised a total of eight lung cancer cell lines (four small cell and four non-small cell lung cancer) with respect to ganglioside and alpha v integrin receptor expression. Ganglioside GD3 was detected using the monoclonal antibody R24. Ganglioside GM1 was detected using the beta-subunit of cholera toxin. Ganglioside 9-O-acetyl GD3 and the alpha v integrin receptor were measured using commercially available monoclonal antibodies. Our results indicate that small cell lung cancer cell lines express significant levels of GD3 and 9-O-acetyl GD3. Ganglioside GM1 and alpha v integrin receptor were not specific to any histological subtype. The expression of ganglioside GM1 and GD3 was independent of cell-cycle phase. We conclude that GD3 and 9-O-acetyl GD3 expression may be additional markers of the Small Cell Lung Cancer phenotype, but their significance is unknown. Therefore a characteristic ganglioside pattern cannot be defined according to histological subtype. alpha v integrin receptor expression is not unique to cells expressing GD3.

Antibodies, Monoclonal↗
PubMed1997

Effect of photodynamic therapy in combination with mitomycin C on a mitomycin-resistant bladder cancer cell line.

Photodynamic therapy is a method for treating cancer using drugs activated by light. A new compound, 5-aminolaevulinic acid (ALA), is a precursor of the active photosensitizer protoporphyrin IX (PpIX) and has fewer side-effects and much more transient phototoxicity than previous photosensitizers. Cell survival of ALA-mediated photodynamic therapy was measured in the J82 bladder cancer cell line, along with its mitomycin C-resistant counterpart J82/MMC. This demonstrated that mitomycin resistance is not cross-resistant to photodynamic therapy. There was also a suggestion that the mitomycin-resistant cells were more susceptible to photodynamic therapy than the parent cell line. Photodynamic therapy appeared to enhance the effect of mitomycin C, when mitomycin C was given first. This phenomenon was apparent for both drug-resistant and drug-sensitive cell lines. This suggests a possible role for combined mitomycin C and photodynamic therapy in superficial bladder tumours that have recurred despite intravesical cytotoxic drug treatment.

Aminolevulinic Acid↗
PubMed1997

Photodynamic therapy of bladder cancer cell lines.

OBJECTIVE: To determine the effect of photodynamic therapy mediated by 5-aminolevulinic acid (ALA) on a range of bladder cancer cell lines, including a squamous cancer cell line and a multi-drug resistant cell line. MATERIALS AND METHODS: Experiments were performed on cells growing in culture: the cell lines studied were the transitional cell cancer lines RT112, T24 and EJ138, the squamous cancer cell line, SCaBER, and the multi-drug resistant transitional cancer cell line, MGH-U1(R), together with its non-resistant parent line, MGH-U1. The kinetics of the ALA-mediated generation of fluorescent photosensitizer were determined using flow cytometry. Photodynamic therapy was performed by incubating cells in ALA followed by exposure to various doses of white light. RESULTS: The response of the various transitional cancer cell lines to photodynamic therapy depended on dose. The squamous cell line was relatively resistant to photodynamic therapy. There was some cross-resistance of the MGH-U1(R) cell line to photodynamic therapy, although the mechanism of cross-resistance appeared not to be necessarily a property of the drug-resistant phenotype. CONCLUSION: This study suggests that ALA-mediated photodynamic therapy may be effective in transitional cell carcinoma of the bladder. Based on these findings, this therapeutic method should be further evaluated clinically.

Aminolevulinic Acid↗
PubMed1996

Adhesion molecules in melanoma--more than just superglue?

Malignant melanoma is increasing in incidence, and, though early lesions are readily treatable, systemic therapy for metastatic disease remains disappointing. Integrins are a family of cell-surface molecules that mediate adhesion between the cell and the extracellular matrix. One member of the integrin family, the alpha v beta 3 integrin, is associated with progression of melanomas, in that the most malignant cells express the highest levels of alpha v beta 3. Like many members of the integrin family, alpha v beta 3 recognizes the sequence Arg-Gly-Asp (RGD) in its ligands, and other molecules that contain this sequence will complete with the natural ligands (such as vitronectin) for binding. There is growing evidence that integrins function as receptors for signal transduction, and that integrin-mediated signalling can affect cell behaviour and even cell survival. Under certain circumstances, loss of integrin-mediated signalling will induce apoptosis, or programmed cell death, and we have demonstrated that melanoma cells treated with a cyclic peptide with high affinity for the alpha v beta 3 integrin will undergo apoptosis within three days. This mechanism might be exploited therapeutically.

Cell Adhesion↗
PubMed1996

Evaluation of soft-tissue foreign bodies: comparing conventional plain film radiography, computed radiography printed on film, and computed radiography displayed on a computer workstation.

OBJECTIVE: The study was performed to evaluate detection of soft-tissue foreign bodies using conventional radiography (film-screen radiography), computed radiography printed on films (computed radiography-hard copy), and computed radiography displayed on a computer workstation (computed radiography-soft copy). SUBJECTS AND METHODS: Fifteen foreign bodies of different size, shape, and composition were implanted at different locations in a fresh cadaveric hand, and images were obtained using three radiographic techniques. Images were evaluated by four board-certified radiologists to ascertain the conspicuity of the foreign bodies with the different techniques. A subjective grade was assigned to each image in an attempt to identify the relative conspicuity of foreign bodies when imaged with the three techniques. RESULTS: Computed radiography-soft copy is the preferred imaging technique for the detection of wood and plastic foreign bodies in soft tissue regardless of the size of the wood or the plastic. No significant differences in conspicuity among the three techniques were demonstrated with glass foreign bodies. CONCLUSION: Detection of soft-tissue foreign bodies is best done using computed radiography-soft copy instead of film-screen radiography and computed radiography-hard copy imaging.

Cadaver↗
PubMed1995

The ability of membrane potential dyes and calcafluor white to distinguish between viable and non-viable bacteria.

Various dyes were assessed for their ability to discriminate between viable and non-viable bacteria. Two methods of killing were employed: by heat treatment or by gramicidin treatment. Staining was carried out in two ways; by staining directly in the medium or by washing cells prior to staining in buffer. Carbocyanine and rhodamine 123 dyes only exhibited small changes in fluorescence between viable and non-viable populations of bacteria. Both oxonol dye (bis 1,3-dibutylbarbituric acid trimethine oxonol) and calcafluor white proved much more useful.

Bacterial Physiological Phenomena↗
PubMed1994

Determination of the viability of Trichomonas vaginalis using flow cytometry.

In clinical laboratories, viability of Trichomonas vaginalis is determined by using light microscopy (differential count of motile to nonmotile organisms). Alternative methods are proposed that utilise flow cytometry. Under an epifluorescence microscope, live organisms fluorescence intensely green with fluorescein diacetate (FDA), whereas dead cells fluoresce orange with propidium iodide (PI). Flow cytometric histograms of green versus red fluorescence reveal distinct populations for live and dead cells. The anionic oxonal probe DiBAC4(3) is a membrane potential sensitive dye that distributes between the inside of the cell and the medium. Live organisms are less fluorescent than dead organisms when stained with the oxonol probe. Valinomycin, dicyclohexylcarbodiimide, and vanadate all give significant changes in the fluorescence intensities of cultures stained with the oxonol probe compared with control cultures, indicating that this probe is detecting changes in plasma membrane potential. Both FDA/PI and oxonol staining protocols allow good discrimination between populations and permit counts that are more statistically significant than those obtained by light microscopy. These methods remove the subjectiveness of microscopic counts and would increase the accuracy of susceptibility assays.

Animals↗