Culture and loss: a project of self-reflection.
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Cultural Characteristics↗
Biomedical subjects
M L Lewis
Publications and source records attributed to M L Lewis.
Prolonged weightlessness affects promyelocytic multidrug resistance.
An immortalized promyelocytic cell line was studied to detect how doxorubicin uptake is affected by microgravity. The purpose of this experiment was to identify the effect that microgravity may have on multidrug resistance in leukocytes. HL60 cells and HL60 cells resistant to anthracycline (HL60/AR) were grown in RPMI and 10% FBS. Upon reaching orbit in the Space Shuttle Endeavour, the cells were robotically mixed with doxorubicin. Three days after mixing, cells were fixed with paraformaldehyde/glutaraldehyde. Ground control experiments were conducted concurrently using a robot identical to the one used on the Shuttle. Fixed cells were analyzed within 2 weeks of launch. Confocal micrographs identified changes in cell structure (transmittance), drug distribution (fluorescence), and microtubule polymerization (fluorescence). Flight cells showed a lack of cytoskeletal polymerization resulting in an overall amorphic globular shape. Doxorubicin distribution in ground cells included a large numbers of vesicles relative to flight cells. There was a greater amount of doxorubicin present in flight cells (85% +/- 9.7) than in ground control cells (43% +/- 26) as determined by image analysis. Differences in microtubule formation between flight cells and ground cells could be partially responsible for the differences in drug distribution. Cytoskeletal interactions are critical to the function of P-glycoprotein as a drug efflux pump responsible for multidrug resistance.
Biological Transport↗
In vitro studies of activities of the antifungal triazoles SCH56592 and itraconazole against Candida albicans, Cryptococcus neoformans, and other pathogenic yeasts.
We investigated the effects of various assay conditions on the activities of two antifungal drugs, SCH56592 and itraconazole, against seven species of fungi by the broth macrodilution testing procedure proposed by the National Committee for Clinical Laboratory Standards (NCCLS). For both drugs, which are insoluble in water, the concentration and type of solubilizing agent produced differences in drug activity. Starting inoculum size differences from 10(2) to 10(5) yeast cells per ml resulted in approximately a fourfold effect on the MIC of both drugs, but other significant differences were not observed with variations in synthetic medium composition, pH, buffering reagent, or incubation temperature. Under standardized conditions of reference method M27-T with 1% polyethylene glycol as the solubilizing agent, median MICs of SCH56592 and itraconazole of 60 and 125 mg/ml, respectively, were demonstrated for 110 strains (12 to 23 strains for each of seven species). Broth microdilution results were typically severalfold higher than broth macrodilution results. We conclude that the NCCLS standard reference method can be applied without modification to the testing of SCH56592 and itraconazole, but particular attention to solubilizing the agents is critical to obtaining consistent results.
Antifungal Agents↗
Decision-making task complexity: model development and initial testing.
Preparing skilled decision-makers requires an understanding of the decision-making tasks nurses face. This article presents the development and initial testing of a model of decision-making task complexity in nursing. The Decision-Making Task Complexity Model has its roots in Newell and Simon's (1972) Information Processing Theory. The Model includes two components, content and context, along with five characteristics in each component. The content component of the model was initially tested using a single sample repeated measures design. Case study examples of a weaning task in critical care were developed to include all combinations of the four independent variables: irrelevance, ambiguity, conflict, and change. Forty-one registered critical care nurses rated each case study example on a scale from 1 (least complex) to 7 (most complex). Results indicated that when conflict was manipulated the ratings were consistently higher. Implications for nursing education and the development of decision-making skills are described.
Decision Making↗
Effects of microgravity on osteoblast growth activation.
Space flight is an environmental condition where astronauts can lose up to 19% of weight-bearing bone during long duration missions. We used the MC3T3-E1 osteoblast to investigate bone cell growth in microgravity (10(-6) to 10(-9)g). Osteoblasts were launched on the STS-56 shuttle flight in a quiescent state with 0.5% fetal calf serum (FCS) medium and growth activation was initiated by adding fresh medium with 10% FCS during microgravity exposure. Four days after serum activation, the cells were fixed before return to normal Earth gravity. Ground controls were treated in parallel with the flight samples in identical equipment. On landing, cell number, cell cytoskeleton, glucose utilization, and prostaglandin synthesis in flight (n = 4) and ground controls (n = 4) were examined. The flown osteoblasts grew slowly in microgravity with total cell number significantly reduced (55 +/- 6 vs 141 +/- 8 cells per microscopic field). The cytoskeleton of the flight osteoblasts had a reduced number of stress fibers and a unique abnormal morphology. Nuclei in the ground controls were large and round with punctate Hoechst staining of the DNA nucleosomes. The flight nuclei were 30% smaller than the controls (P < 0.0001) and oblong in shape, with fewer punctate areas. Due to their reduced numbers, the cells activated in microgravity used significantly less glucose than ground controls (80.2 +/- 0.7 vs 50.3 +/- 3.7 mg of glucose/dl remaining in the medium) and had reduced prostaglandin E2 (PGE2) synthesis when compared to controls (57.3 +/- 17 vs 138.3 +/- 41 pmol/ml). Cell viability was normal since, on a per-cell basis, glucose use and prostaglandin synthesis were comparable for flight and ground samples. Taken together, these data suggest that growth activation in microgravity results in reduced growth, causing reduced glucose utilization and reduced prostaglandin synthesis, with significantly altered actin cytoskeleton in osteoblasts.
Animals↗
Bilaterality of idiopathic macular holes.
BACKGROUND: There has been wide variation in estimates of the incidence of bilateral idiopathic macular holes in the literature. This report of a large series of patients with macular holes provides further information regarding incidence of bilaterality, interval between onset in the first and the second eye, and visual outcome. METHODS: A retrospective chart review was done of 550 patients with idiopathic macular holes examined at the Bascom Palmer Eye Institute between 1968 and 1994. The incidence of bilaterality was estimated from 365 patients in whom the fellow eye was normal at the initial examination. The rate of onset in the fellow eye was evaluated by survival analysis. Mean follow-up was 31 months (median 17 months). RESULTS: Patients with incomplete macular holes (stage 1, aborted stage 1, lamellar) or full-thickness holes had a 19% incidence of bilaterality at 48 months follow-up. In the subset of 32 patients with full-thickness macular holes in the first eye, 13% developed full-thickness holes in the fellow eye within 48 months. The median interval between the onset in the first and in the second eye was 17.5 months. Visual acuity was excellent and stable in eyes with aborted stage 1 and lamellar holes. The visual acuity in the first eye with full-thickness macular hole decreased to 20/200 or worse in 79% of cases within 36 months' follow-up. CONCLUSION: The incidence of bilaterality and poor visual function in the majority of full-thickness idiopathic macular holes by 3 years' duration should be considered when advising patients and planning management.
Aged↗
Variations in the clinical course of submacular hemorrhage.
PURPOSE: To assess variations in the clinical course of submacular hemorrhages. METHODS: We reviewed fundus photography charts taken of patients during a 27-month period. Thirty-one eyes of 31 patients with submacular hemorrhages under the foveal avascular zone were reviewed. RESULTS: In 20 of the eyes, the underlying etiology was age-related macular degeneration (ARMD). The other 11 eyes had various underlying conditions, including macroaneurysms (two), presumed ocular histoplasmosis syndrome (two), trauma (one), Valsalva's retinopathy (one), idiopathic central serous choroidopathy (one), diabetic retinopathy (two), central retinal vein occlusion (one), and choroidal rupture (one). Of the eyes with ARMD (mean follow-up, 29 months), eight (40%) of 20 showed an improvement in visual acuity (> or = 2 Snellen lines), six (30%) of 20 had a final visual acuity of 20/80 or better, and three (15%) had a final visual acuity of 20/40 or better (range, 20/25 to 20/80). Of the eyes without ARMD (mean follow-up, 29 months), five (45) of 11 had an improvement in visual acuity and five (45%) of 11 attained a final visual acuity of 20/40 or better (range, 20/20 to 20/40). The best predictive factor for poor final visual acuity was the presence of a subretinal neovascular membrane. CONCLUSIONS: Patients with submacular hemorrhage may have spontaneous improvement in visual acuity without surgery. Patients without subretinal neovascular membranes had a better visual improvement rate.
Adult↗
Cerebrospinal fluid antibodies detected by ELISA against a 33-kDa antigen from spherules of Coccidioides immitis in patients with coccidioidal meningitis. The National Institute of Allergy and Infectious Diseases Mycoses Study Group.
Antibodies against a 33-kDa antigen from Coccidioides immitis were detected by ELISA in patients' cerebrospinal fluid (CSF). Anti-33-kDa antibodies were detected at dilutions > 1:80 in only 1 (1.4%) of 73 patients without coccidioidal meningitis but in 74 (71.8%) of 103 with meningitis. Anti-33-kDa antibodies were detected in 53 (91.4%) of 58 patients whose anti-coccidioidal complement-fixing (CF) antibodies were detectable and in 21 (46.7%) of 45 patients whose CSF was negative by CF test (positive predictive value, 99%; negative predictive value, 71%; sensitivity, 72%; specificity, 99%). Anti-33-kDa antibodies, among which IgG1 was the dominant subclass, increased when infections worsened and decreased when patients' conditions improved. Antibody concentration appeared to be independent of most baseline findings, although only 1 of 5 patients coinfected with human immunodeficiency virus had initially detectable antibodies. Measurement of anti-33-kDa antibodies is a sensitive indicator of coccidioidal meningitis and of its clinical course.
Antibodies, Fungal↗
Purification and photoaffinity labeling of herpes simplex virus type-1 thymidine kinase.
The molecular basis for the treatment of human herpesviruses with nucleoside drugs is the phosphorylation of these drugs by the viral-encoded thymidine kinases. In order to better understand the structural and enzymatic mechanisms by which herpesviral thymidine kinases recognize their substrates, photoaffinity labeling with [alpha-32P]5-azido-2'-deoxyuridine-5'-monophosphate and [ gamma-32P]8-azidoadenosine-5'-triphosphate was used to characterize the thymidine, thymidylate, and ATP active sites of the herpes simplex virus-1 (HSV-1) thymidine kinase. For this study, HSV-1 thymidine kinase and a site-specific mutant enzyme (C336Y, known to confer acyclovir resistance) were expressed in bacteria and purified by a rapid, two-step protocol. The specificity of photoaffinity labeling of these HSV-1 thymidine kinases was demonstrated by the ability of site-directed substrates such as thymidine, thymidylate, acyclovir, 5-bromovinyl-2'-deoxyuridine, and ATP to inhibit photoinsertion. Differences in inhibition patterns of photoaffinity labeling correlated with kinetic differences between the wild-type and C336Y HSV-1 thymidine kinases. Cumulative results suggest that the acyclovir-resistant cysteine 336 mutation primarily affects the ATP binding site; yet it also leads to alteration in the binding affinity of nucleoside drugs in the thymidine site. In this study, azidonucleotide photoaffinity analogs are shown to be effective tools for studying the active-site environment of HSV-1 thymidine kinase and related site-specific mutants.
Adenosine Triphosphate↗
Production and action of cytokines in space.
B6MP102 cells, a continuously cultured murine bone marrow macrophage cell line, were tested for secretion of tumor necrosis factor-alpha and Interleukin-1 during space flight. We found that B6MP102 cells secreted more tumor necrosis factor-alpha and interleukin-1 when stimulated in space with lipopolysaccharide than controls similarly stimulated on earth. This compared to increased secretion of interferon-beta and -gamma by lymphocytes that was measured on the same shuttle flights. Although space flight enhanced B6MP102 secretion of tumor necrosis factor-alpha, an experiment on a subsequent space flight (STS-50) found that cellular cytotoxicity, mediated by tumor necrosis factor-alpha, was inhibited.
Animals↗
Distribution function of transit times in the human pulmonary circulation.
The distribution function of pulmonary transit times (fPTT) defines contact time between blood and vascular bed, which affects gas exchange and endothelial metabolic functions. This study was undertaken to assess effects of abnormal pulmonary inflow (PPA) and outflow pressures (PLA) on fPTT. Three groups were studied: five patients with elevated PLA and passive pulmonary hypertension (LVD-Ab), eight with normal PLA (LVD-Nl), and six with pulmonary disease and various levels of PPA (PD). Empirical complex exponential functions were convoluted on right and left ventricular indicator-dilution curves to derive fPTT; mean transit time (Mo1), standard deviation (Sm2), and cube root of the third moment about Mo1 (Sm3) were calculated by standard equations. A single linear regression of Sm3 and Sm2 on Mo1 was observed for all patients, regardless of disease process. Inverse relations between Mo1, Sm2, and Sm3 and blood flow were highly significant, but dispersion volumes (DV = Mo1 x flow) were higher in patients with elevated PPA. Significant linear regressions of fPTT parameters on PPA, derived in LVD-Nl and LVD-Ab patients, failed to predict Mo1, Sm2, and Sm3 for the PD group, whereas linear regressions on PLA accurately predicted Mo1, Sm2, and Sm3 in the PD group. Relations between fPTT parameters and PLA were equally well fit by exponential equations in all 19 patients, consistent with an asymptotic pressure-volume relation of distensible vessels. Microvascular pressure (PMV), combining PPA and PLA, was not a better predictor of fPTT parameters in LVD-NL and LVD-Ab patients but provided a slightly closer estimate of relative dispersion and skewness in PD patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Reparative cell granuloma of the temporal bone.
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Adult↗
Choroidal neovascularization associated with choroidal nevi.
OBJECTIVE: We undertook a retrospective study of all choroidal nevi with overlying neovascularization seen at Bascom Palmer Eye Institute, Miami, Fla, to determine long-term effects on vision and whether the presence of neovascularization represented increased malignant potential of the lesion. DESIGN: A computer search of patients with a coded diagnosis of both a choroidal nevus and choroidal neovascularization was performed. Cases in which the neovascularization was directly overlying the nevus were used for the study. RESULTS: The records of 23 patients followed up for a mean of 6.5 years were reviewed for visual acuity, effect of treatment, and change in the size of the choroidal lesion. Fifteen of the 23 patients had a final visual acuity in the affected eye of 20/200 or better. Five of six patients treated with laser had visual improvement of 2 or more lines. Only one of these lesions showed any growth, and this was after 17 years of no growth. CONCLUSIONS: Choroidal neovascularization associated with choroidal nevi can have profound effects on vision. Laser treatment, when indicated, is effective and may be safely performed. The clinical course of these lesions, to date, does not indicate any clinically significant malignant transformation.
Adult↗
Use of microgravity bioreactors for development of an in vitro rat salivary gland cell culture model.
During development, salivary gland (SG) cells both secrete factors which modulate cellular behavior and express specific hormone receptors. Whether SG cell growth is modulated by an autocrine epidermal growth factor (EGF) receptor-mediated signal transduction pathway is not clearly understood. SG tissue is the synthesis site for functionally distinct products including growth factors, digestive enzymes, and homeostasis maintaining factors. Historically, SG cells have proven difficult to grow and may be only maintained as limited three-dimensional ductal-type structures in collagen gels or on reconstituted basement membrane gels. A novel approach to establishing primary rat SG cultures is use of microgravity bioreactors originally designed by NASA as low-shear culture systems for predicting cell growth and differentiation in the microgravity environment of space. These completely fluid-filled bioreactors, which are oriented horizontally and rotate, have proven advantageous for Earth-based culture of three-dimensional cell assemblies, tissue-like aggregates, and glandular structures. Use of microgravity bioreactors for establishing in vitro models to investigate steroid-mediated secretion of EGF by normal SG cells may also prove useful for the investigation of cancer and other salivary gland disorders. These microgravity bioreactors promise challenging opportunities for future applications in basic and applied cell research.
Animals↗
Interferon alfa-2a in the treatment of exudative age-related macular degeneration.
Nineteen patients (20 eyes) with the exudative form of macular degeneration were treated with parenteral interferon alfa-2a. Fifteen patients (16 eyes) had adequate follow-up for evaluation of outcome of the exudative macular lesion. The average follow-up was 8 months (range 5-11 months). Color photographs and fluorescein angiograms were evaluated independently by two masked readers for change in size, presence of fibrosis, and leakage of the neovascular lesion. During the follow-up, none of the exudative lesions resolved: one lesion became smaller, four remained the same, nine enlarged, and two could not be graded based on the photographs. Visual acuity remained 20/40 or better in four eyes. The proportion of eyes with visual acuity of 20/200 or worse increased from 35% at the initial visit to 59% at the final visit. Ten patients experienced significant but reversible side effects, including weight loss, depression, and/or hematopoietic suppression. The data from these cases do not support any significant treatment benefit from interferon alfa-2a at the doses used in exudative macular degeneration.
Aged↗
Low-dose recombinant alfa-2a-interferon: a feasible maintenance therapy in acute myeloid leukaemia in the older patient.
Eleven patients with acute myeloid leukaemia (AML) in first complete remission (CR) were treated with alfa-2a-interferon (for short 'interferon') maintenance therapy, at a dose of 3 MU twice to thrice weekly subcutaneously. Adjustments were made to maintain neutrophil counts > 1 x 10(9)/l and platelet counts > 100 x 10(9)/l. A transient fall in haemoglobin, neutrophil and platelet counts was noted in all 9 evaluable patients. Median time to nadir was 7 weeks. Initial dosage reductions were necessary in 5 patients, 3 of whom were later able to tolerate the starting dose. No episodes of infection or bleeding were documented during therapy and no red cell or platelet transfusions were necessary. At the time of writing (median follow-up of 31 weeks), 7 patients continue in CR, 6 of whom remain on interferon. One patient discontinued interferon on developing sicca syndrome. Other than in this patient, side effects were minor. Mean dose administered was 6.7 MU/patient/week. We conclude that low-dose IFN maintenance therapy is well tolerated in older patients with AML in first CR.
Aged↗
Quality improvement of the prophylactic antibiotic function.
Wound infection poses a volatile threat to the surgical patient. Perioperative nurses have a direct responsibility for prevention. As prophylactic antibiotics have become a practice standard, the perioperative nurse must assist the operating team in their administration. Quality Improvement staff can coordinate a multidisciplinary effort to improve this process. The systematic approach to prescribing, administering, and evaluating this function will be discussed.
Anti-Bacterial Agents↗
Wound healing in lower extremity amputation and a system for amputation prevention.
As our population ages, a potential exists for increase in lower extremity amputation related to diabetes mellitus and peripheral vascular disease. Besides the financial impact, amputations impose serious consequences on those affected. This article discusses the problem, its effects, care of the amputation sites, and offers support for prevention programs.
Algorithms↗