Biomedical subjects
D Lane
Publications and source records attributed to D Lane.
Cost analysis of filgrastim for the prevention of neutropenia in pediatric T-cell leukemia and advanced lymphoblastic lymphoma: a case for prospective economic analysis in cooperative group trials.
BACKGROUND: Growth factor use has been shown to ameliorate chemotherapy-induced neutropenia, leading to shorter hospital stays and lower use of parenteral antibiotics, two costly areas of cancer treatment. Prior reports on pediatric patients have shown evidence of cost savings in some studies, but no such evidence in others. In this study a retrospective analysis compared the costs of inpatient supportive care for pediatric patients with T-cell leukemia and advanced lymphoblastic lymphoma enrolled in a Pediatric Oncology Group trial. PROCEDURE: Patients 1-22 years of age were randomized to receive either granulocyte colony-stimulating factor (G-CSF; n = 45) or no G-CSF (n = 43) following induction and two cycles of maintenance therapy. There were no significant differences in neutropenia-related outcomes during the induction phase. During maintenance therapy, G-CSF patients had significantly fewer days to an ANC >500 cells/microl and a trend towards fewer days of hospitalization. Data on resource utilization were tabulated from case report forms. Costs were imputed from national data on hospitalization costs, average wholesale prices of pharmaceuticals, and patient billing information from a single institution. RESULTS: Total median costs of supportive care were $34,190 for patients receiving G-CSF and $28,653 for patients not receiving G-CSF (P > 0. 05 for the cost difference). Sensitivity analyses demonstrated that the total cost difference was not statistically significant, even in scenarios that included reasonable variations in estimates of the range of the length of stay, antibiotic regimen, and dosage and cost of G-CSF. CONCLUSIONS: In the setting of pediatric leukemia, the cost of growth factor may offset potential savings from shorter hospital stays or lower antibiotic use, a finding consistent with that from the Children's Cancer Study Group.
The role of fluorescence in situ hybridization technologies in molecular diagnostics and disease management.
Large genomic changes, such as aneuploidy, deletions, and other chromosomal rearrangements, have long been associated with pregnancy loss, congenital abnormalities, and malignancy. These genomic changes are quantitative, unambiguous, and fundamental in the transition of normal cells to abnormal ones. Detection of these large genetic changes has an increasingly important role in determining patient diagnosis and care, including therapeutic selection. We have developed two major product platforms that assess genomic changes at various levels of resolution. Fluorescence in situ hybridization (FISH) techniques and the related technology of array-based comparative genomic hybridization (CGH) allow detection of genesized or larger alterations in the genome. FISH is a robust DNA probe technology that can measure both balanced and unbalanced genomic changes on a cell-by-cell basis. In most instances, it is not dependent on metaphase chromosomes, and it is widely used in clinical diagnostics. Array-based CGH has much greater multiplexing capabilities than FISH. This technology has the potential to examine many regions of the genome simultaneously for changes in DNA copy number and identify complex patterns of gains and losses within the genome. In this article, we review several of the current medical applications of FISH and discuss such advanced techniques as CGH and array-based CGH.
Effects of depression and anxiety on mortality and quality-of-life 4 months after myocardial infarction.
OBJECTIVE: The purpose of this study was to determine the impact of depression and anxiety on mortality and quality-of-life in patients hospitalized for an acute myocardial infarction (MI). METHODS: Questionnaire measures of depression and anxiety were completed during hospitalization by 288 MI patients. The main outcomes were mortality and quality-of-life, assessed by the Dartmouth COOP charts, at 4 months. RESULTS: A total of 25 patients died, 22 from cardiac causes, during the 4-month follow-up. Symptoms of depression and anxiety did not predict either cardiac or all-cause mortality. Severity of infarction, extent of heart failure, and a longer stay in hospital predicted mortality. Symptoms of depression and anxiety predicted 4-month quality-of-life among survivors, as did gender, partner status, occupational status, living alone, previous exercise behaviour, length of hospital admission, and Peel Index scores. In a multiple regression model, depression emerged as the strongest predictor of quality-of-life. State anxiety, severity of infarction, and partner status also entered the model. CONCLUSION: Neither depression nor anxiety predicted mortality 4 months after MI. Both depression and anxiety predicted quality-of-life at 4 months among survivors.
Effect of Healon and Viscoat on outflow facility in human cadaver eyes.
PURPOSE: To compare the acute effects of Healon (sodium hyaluronate) and Viscoat (sodium chondroitin sulfate-sodium hyaluronate) on outflow facility in human cadaver eyes and determine which viscoelastic agent is least likely to cause an intraocular pressure (IOP) spike after cataract surgery. SETTING: The Glaucoma Research Lab, University of Toronto, Ontario, Canada. METHODS: In this prospective paired study, 15 pairs of human cadaver eyes were used. Following the construction of a 3.0 mm scleral tunnel, 0.25 cc of Healon was injected into the anterior chamber of 1 eye and 0.25 cc of Viscoat was injected into the contralateral eye. The viscoelastic agents were removed from both eyes in a standardized fashion and the scleral tunnels closed. The eyes were then perfused at a constant IOP of 8.0 mm Hg, corresponding to 16.0 mm Hg in vivo. Outflow facility (microL/minute [min]/mm Hg) was recorded every 15 minutes for 24 hours using standard methods. RESULTS: Outflow facility in the Viscoat-treated eyes decreased appreciably for the first 3 hours, then recovered somewhat after 12 hours; facility in the Healon-treated eyes showed less of an overall decrease. Over the 24 hour perfusion period, mean outflow facility was 0.037 microL/min/mm Hg +/- 0.015 (SD) in the Viscoat-treated eyes and 0.060 +/- 0.012 microL/min/mm Hg in the Healon-treated eyes. Healon reduced outflow facility significantly less than Viscoat between 3.25 and 10.50 hours postoperatively (P < .05, 2-tailed t test). CONCLUSIONS: Healon reduced outflow facility less than Viscoat between 3.25 and 10.50 hours postoperatively.
Disruption of the F plasmid partition complex in vivo by partition protein SopA.
The SopA protein plays an essential, though so far undefined, role in partition of the mini-F plasmid but, when overproduced, it causes loss of mini-F from growing cells. Our investigation of this phenomenon has revealed that excess SopA protein reduces the linking number of mini-F. It appears to do so by disturbing the partition complex, in which SopB normally introduces local positive supercoiling upon binding to the sopC centromere, as it occurs only in plasmids carrying sopC and in the presence of SopB protein. SopA-induced reduction in linking number is not associated with altered sop promoter activity or levels of SopB protein and occurs in the absence of changes in overall supercoil density. SopA protein mutated in the ATPase nucleotide-binding site (K120Q) or lacking the presumed SopB interaction domain does not induce the reduction in linking number, suggesting that excess SopA disrupts the partition complex by interacting with SopB to remove positive supercoils in an ATP-dependent manner. Destabilization of mini-F also depends on sopC and SopB, but the K120Q mutant retains some capacity for destabilizing mini-F. SopA-induced destabilization thus appears to be complex and may involve more than one SopA activity. The results are interpreted in terms of a regulatory role for SopA in the oligomerization of SopB dimers bound to the centromere.
Do depression and anxiety predict recurrent coronary events 12 months after myocardial infarction?
We examined the association between depression and anxiety and recurrent coronary heart disease events during the first 12 months subsequent to myocardial infarction. The Beck Depression Inventory and the State-Trait Anxiety Inventory were completed during hospitalization by 288 myocardial infarction patients. Peel Index score and Killip class were used as indices of disease severity. The 12-month incidence of recurrent coronary heart disease events (fatal and non-fatal) was determined. Eighty-two patients experienced recurrent coronary heart disease events, including 27 cardiac fatalities, during follow-up. Whereas the Peel Index differentiated patients who experienced recurrent events from those who did not (OR 3.00, 95% CI 1.46-6.20), symptoms of depression (OR 0.97, 95% CI 0. 55-1.70) and anxiety (OR 1.00, 95% CI 0.98-1.02) were unrelated to outcome. Depression and anxiety did not predict subsequent coronary heart disease events and were not associated with either Peel Index scores or Killip class.
Interleukin-2 involvement in early acute respiratory distress syndrome: relationship with polymorphonuclear neutrophil apoptosis and patient survival.
OBJECTIVE: To determine blood and lung alveolar concentrations of interleukin (IL)-2 in acute respiratory distress syndrome (ARDS) and their relationship with polymorphonuclear neutrophil (PMN) apoptosis and patient survival. DESIGN: Prospective cohort study. SETTING: Medical and surgical intensive care units (ICUs; Canada) and the intensive care department (Belgium). PATIENTS: Nineteen consecutive patients with ARDS, 14 non-ARDS ICU patients, and 20 healthy volunteers. INTERVENTIONS: Blood samples and bronchoalveolar lavages (BAL) obtained via venous puncture and by fiberoptic bronchoscopy in the first 72 hrs after the onset of ARDS. MEASUREMENTS AND MAIN RESULTS: One early point concentration of IL-2 was measured in both blood and BAL fluids of the three groups. In vivo alveolar PMN apoptotic index in BAL fluids and the influence of BAL fluid exposure on normal blood PMN spontaneous apoptosis in vitro were evaluated. Blood IL-2 was significantly lower in patients with ARDS compared with non-ARDS ICU patients and controls. In contrast, IL-2 in BAL fluids of patients with ARDS was dramatically elevated compared with non-ARDS ICU patients and controls. ARDS survivors exhibited lower early IL-2 blood levels than nonsurvivors and generally had a higher IL-2 lung content Lung alveolar PMN apoptosis in vivo was lower in patients with ARDS in comparison with controls. This apoptotic index was correlated with corresponding IL-2 alveolar levels in patients with ARDS. Exposure of normal blood PMN to BAL fluids from patients with ARDS delayed apoptosis in vitro. Immunodepletions of IL-2, granulocyte-macrophage colony stimulating factor, and a combination of both cytokines from BAL fluids of ARDS patients significantly restored PMN apoptosis. The recovery of PMN apoptosis was more effective when IL-2 was depleted in BAL fluids from ARDS survivors compared with nonsurvivors. CONCLUSIONS: Opposite and disproportional concentrations of IL-2 are observed in blood and lung fluids of patients with early ARDS. IL-2 significantly contributes (with granulocyte-macrophage colony stimulating factor) to the inhibition of PMN apoptosis in BAL fluids of patients with ARDS. Early low blood IL-2 and high IL-2-driven inhibition of PMN apoptosis are beneficial to survivors. Thus, IL-2 is a new candidate for monitoring in early ARDS and an interesting indicator of prognosis.
Cultural differences in music chosen for pain relief.
Nurses use music therapeutically but often assume that all patients will equally appreciate the same type of music. Cultural differences in music preferences are compared across five pain studies. Music preferences for pain relief are described as the most frequently chosen type of music for each culture. Findings indicate that in four studies, musical choices were related to cultural background (p = .002 to .049). Although the majority in each group chose among the other types of music, Caucasians most frequently chose orchestra music, African Americans chose jazz, and Taiwanese chose harp music. For culturally congruent care, nurses should become aware of cultural differences in music preference and provide culturally specific selections among other music expected to have a therapeutic effect.
The F plasmid centromere, sopC, is required for full repression of the sopAB operon.
The SopB protein of the F plasmid has a dual role in the partition of F plasmid copies to daughter cells prior to division. It binds to the sopC centromere site to form the partition complex needed for stabilizing the plasmid, and it interacts with SopA to repress transcription of the sopAB operon, thus preventing the destabilization that results from excess SopB. We have isolated sop mutants by screening for unstable inheritance of mutagenized mini-F DNA. Four of the mutants resulted from different missense mutations in sopB. All four were deficient, to varying degrees, in autoregulation of Sop protein synthesis. The mutant proteins showed diminished capacity for reducing the linking number of mini-F and for destabilizing a plasmid carrying sopC, indicating that reduced ability to form a normal complex with sopC might underlie the autoregulation defect. Repression of the transcription of a sop promoter- lacZ fusion by SopA and SopB was strongly enhanced in the presence of sopC, in cis or in trans, and the enhancement was reduced or nullified when wild-type sopB was replaced by the mutant sopB alleles. A single 43 bp unit of sopC was almost as effective as sopC itself in enhancing repression. The results show that sopC is necessary for full repression of the sop promoter. They thus indicate a previously unsuspected role for this centromere site, and suggest that autoregulation and partition might normally be coordinated processes.
Cutaneous inflammatory cell infiltrate in chronic idiopathic urticaria: comparison of patients with and without anti-FcepsilonRI or anti-IgE autoantibodies.
BACKGROUND: Previous studies defining the histopathologic features of patients with chronic idiopathic urticaria (CIU) were performed on wheals of uncertain duration and before the identification of functional autoantibodies against FcepsilonRI and/or IgE, now known to be present in approximately 30% of patients with CIU. OBJECTIVE: We sought to determine the timing of the inflammatory infiltrate in the wheals of patients with CIU and to detect differences between patients with and without autoantibodies. METHODS: Immunohistochemistry was used to identify neutrophils (neutrophil elastase), T lymphocytes (CD3), and activated eosinophils (EG2) in biopsy specimens from uninvolved skin and wheals present for less than 4 hours and greater than 12 hours in 22 patients with CIU, as well as in biopsy specimens from the skin of 12 healthy control subjects. Patients were identified as having functional autoantibodies on the basis of their serum-evoked histamine release in vitro from the basophils of 2 healthy donors. RESULTS: EG2(+), neutrophil elastase+, and, to a lesser extent, CD3(+) cells were found in greater numbers in wheals undergoing biopsy at less than 4 and greater than 12 hours than in uninvolved skin (P <.05). Patients without autoantibodies (n = 12) had significantly more EG2(+) cells in wheals of greater than 12 hours' duration than patients with autoantibodies (n = 10; P =.02). There was no other difference between patients with and without autoantibodies in the cutaneous cellular infiltrate. CONCLUSION: Neutrophil and eosinophil accumulation occurs early in the evolution of a wheal in patients with CIU, but eosinophil activation may occur later or be more persistent in patients without autoantibodies.
Psychology in coronary care.
Psychological stress has been implicated in the onset and progression of coronary heart disease (CHD). Recent research has highlighted the importance of depression and anxiety as independent risk factors for mortality in cardiac patients. Accordingly, it is critical that clinically significant levels of distress are identified, both in-hospital and after discharge, to target patients who require specific psychological intervention, in addition to conventional cardiac rehabilitation. Ameliorating distress has been shown to improve adherence to treatment advice, such as modifying cardiac risk factors, compliance with medication regimens, and attendance at exercise programmes, which in turn should reduce cardiac morbidity and mortality. The emphasis within cardiac rehabilitation should be on tailoring provision to meet individual patients' needs.
Partition of the linear plasmid N15: interactions of N15 partition functions with the sop locus of the F plasmid.
A locus close to one end of the linear N15 prophage closely resembles the sop operon which governs partition of the F plasmid; the promoter region contains similar operator sites, and the two putative gene products have extensive amino acid identity with the SopA and -B proteins of F. Our aim was to ascertain whether the N15 sop homologue functions in partition, to identify the centromere site, and to examine possible interchangeability of function with the F Sop system. When expressed at a moderate level, N15 SopA and -B proteins partly stabilize mini-F which lacks its own sop operon but retains the sopC centromere. The stabilization does not depend on increased copy number. Likewise, an N15 mutant with most of its sop operon deleted is partly stabilized by F Sop proteins and fully stabilized by its own. Four inverted repeat sequences similar to those of sopC were located in N15. They are distant from the sop operon and from each other. Two of these were shown to stabilize a mini-F sop deletion mutant when N15 Sop proteins were provided. Provision of the SopA homologue to plasmids with a sopA deletion resulted in further destabilization of the plasmid. The N15 Sop proteins exert effective, but incomplete, repression at the F sop promoter. We conclude that the N15 sop locus determines stable inheritance of the prophage by using dispersed centromere sites. The SopB-centromere and SopA-operator interactions show partial functional overlap between N15 and F. SopA of each plasmid appears to interact with SopB of the other, but in a way that is detrimental to plasmid maintenance.
Transcription factor E2F-1 is upregulated in response to DNA damage in a manner analogous to that of p53.
The transcription factor E2F-1 directs the expression of genes that induce or regulate cell division, and a role for E2F-1 in driving cells into apoptosis is the subject of intense discussion. Recently it has been shown that E2F-1 binds and coprecipitates with the mouse double-minute chromosome 2 protein (Mdm2). A domain of E2F-1 (amino acids 390 to 406) shows striking similarity to the Mdm2 binding domain of the tumor suppressor protein p53. It is known that interaction of Mdm2 with p53 through this domain is required for Mdm2-dependent degradation of p53. We show here that E2F-1 protein is upregulated in response to DNA damage. The kinetics of induction are dependent upon the source of DNA damage, i.e., fast and transient after irradiation with X rays and delayed and stable after irradiation with UVC, and thus match the kinetics of p53 induction in response to DNA damage. We show further that E2F-1 is also upregulated by treatment with the transcription inhibitor actinomycin D and with the kinase inhibitor DRB, as well as by high concentrations of the kinase inhibitor H7, all conditions which also upregulate p53. In our experiments we were not able to see an increase in E2F-1 RNA production but did find an increase in protein stability in UVC-irradiated cells. Upregulation of E2F-1 in response to DNA damage seems to require the presence of wild-type p53, since we did not observe an increase in the level of E2F-1 protein in several cell lines which possess mutated p53. Previous experiments showed that p53 is upregulated after microinjection of an antibody which binds to a domain of Mdm2 that is required for the interaction of Mdm2 with p53. Microinjection of the same antibody also increases the expression of E2F-1 protein, while microinjection of a control antibody does not. Furthermore, microinjection of Mdm2 antisense oligonucleotides upregulates E2F-1 protein, while microinjection of an unrelated oligonucleotide does not. These data suggest that E2F-1 is upregulated in a similar way to p53 in response to DNA damage and that Mdm2 appears to play a major role in this pathway.
Preputial prolapse in an alpaca.
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Finasteride--an update and review.
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The promise of molecular oncology.
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