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Biomedical subjects

K Anderson

Publications and source records attributed to K Anderson.

At least 109 records · Page 6Linked to original sources
PubMed1999

Multicenter phase III trial to evaluate CD34(+) selected versus unselected autologous peripheral blood progenitor cell transplantation in multiple myeloma.

High-dose chemotherapy followed by autologous transplantation has been shown to improve response rates and survival in multiple myeloma and other malignancies. However, autografts frequently contain detectable tumor cells. Enrichment for stem cells using anti-CD34 antibodies has been shown to reduce autograft tumor contamination in phase I/II studies. To more definitively assess the safety and efficacy of CD34 selection, a phase III study was completed in 131 multiple myeloma patients randomized to receive an autologous transplant with either CD34-selected or unselected peripheral blood progenitor cells after myeloablative therapy. Tumor contamination in the autografts was assessed by a quantitative polymerase chain reaction detection assay using patient-specific, complementarity-determining region (CDR) Ig gene primers before and after CD34 selection. A median 3.1 log reduction in contaminating tumor cells was achieved in the CD34 selected product using the CEPRATE SC System (CellPro, Inc, Bothell, WA). Successful neutrophil engraftment was achieved in all patients by day 15 and no significant between-arm difference for time to platelet engraftment occurred in patients who received an infused dose of at least 2.0 x 10(6) CD34(+) cells/kg. In conclusion, this phase III trial demonstrates that CD34-selection of peripheral blood progenitor cells significantly reduces tumor cell contamination yet provides safe and rapid hematologic recovery for patients receiving myeloablative therapy.

Adolescent↗
PubMed1999

Effects of spaceflight conditions on fertilization and embryogenesis in the sea urchin Lytechinus pictus.

Calcium loss and muscle atrophy are two of the main metabolic changes experienced by astronauts and crew members during exposure to microgravity in space. Calcium and cytoskeletal events were investigated within sea urchin embryos which were cultured in space under both microgravity and 1 g conditions. Embryos were fixed at time-points ranging from 3 h to 8 days after fertilization. Investigative emphasis was placed upon: (1) sperm-induced calcium-dependent exocytosis and cortical granule secretion, (2) membrane fusion of cortical granule and plasma membranes; (3) microfilament polymerization and microvilli elongation; and (5) embryonic development into morula, blastula, gastrula, and pluteus stages. For embryos cultured under microgravity conditions, the processes of cortical granule discharge, fusion of cortical granule membranes with the plasma membrane, elongation of microvilli and elevation of the fertilization coat were reduced in comparison with embryos cultured at 1 g in space and under normal conditions on Earth. Also, 4% of all cells undergoing division in microgravity showed abnormalities in the centrosome-centriole complex. These abnormalities were not observed within the 1 g flight and ground control specimens, indicating that significant alterations in sea urchin development processes occur under microgravity conditions.

Animals↗
PubMed1999

Spaceflight hardware allowing unilateral irradiation and chemical fixation in petri dishes.

To accommodate a spaceflight experiment with moss (SPM), experiment-unique equipment (EUE) was developed by engineers at Kennedy Space Center. The hardware allows sterile culture for an extended period of time in commercial petri dishes, lateral illumination of each culture with light of a specific wavelength (660 nm; other wavelengths are possible) and a range of intensities (0.05-5 micromoles photons m-2 s-1), incubation in complete darkness, and chemical fixation to terminate the experiment under conditions of microgravity. The use of a fixative required triple containment to protect the astronaut crew. An external panel on the experiment container allowed the timing of illumination and fixation to be controlled by the crew. Light quality is provided by light emitting diodes (LEDs) that are located in the lid of the outer container, the BRIC (Biological Research In Canisters)-LED. Each canister accommodates 6 Petri Dish Fixation Units (PDFUs), and each PDFU holds one 6 cm petri dish. All components are autoclavable. LED illumination is piped through a transparent glass rod. Each PDFU contains fixative in a reservoir that is released by the depression of an actuator. This hardware performed well during its first flight, the 16-day STS-87 mission in Nov./Dec., 1997 as part of the Collaborative USA and Ukrainian Experiment (CUE). It supported vigorous and sterile moss growth, cells were maintained in position and were well-fixed, and there was a vigorous and consistent response to light. Although here used for moss, in future flight experiments this unique new hardware can be used for many types of organisms normally grown in petri dishes, with or without a requirement for illumination.

Bryopsida↗
PubMed1999

Spur reformation after arthroscopic acromioplasty.

Rotator cuff pathology has been associated with a hooked acromial morphology. Impingement syndrome has traditionally been considered to be the result of bony encroachment into the subacromial space. This report of a spur recurrence after acromioplasty presents evidence that acromial morphology may be a reactive change attributable to primary rotator cuff insufficiency.

Acromion↗
PubMed1999

Hormone replacement therapy and improved survival among postmenopausal women diagnosed with colon cancer (USA).

OBJECTIVES: Hormone replacement therapy (HRT) has been inversely associated with colon cancer incidence in several epidemiologic studies. In this study we used data from a population-based incident case-control study of colon cancer to evaluate the role of HRT use in survival after diagnosis with colon cancer. METHODS: Data from 815 postmenopausal women living in Utah, California, and Minnesota diagnosed between 1 September 1991 and 30 September 1994 were used to examine associations between HRT and survival. RESULTS: After adjusting for age at time of diagnosis, stage of disease at time of diagnosis, study center, and body mass index (BMI), we observed that women who had ever used HRT had a 30% lesser probability of dying of any cause and a 40% lower probability of dying from colon cancer specifically during the follow-up period. Further evaluation by years of HRT use showed that those who had used HRT for 4 or more years had the lowest risk of dying of colon cancer (hazard rate ratio 0.5, 95% confidence interval 0.3-0.9). Evaluation of other lifestyle variables with HRT use did not show significant confounding or effect modification. CONCLUSIONS: These findings suggest that HRT use may improve short-term survival after diagnosis with colon cancer; there is no suggestion that HRT use is detrimental to survival.

Adult↗
PubMed1999

Reexamining the value of hematuria testing in patients with acute flank pain.

PURPOSE: Hematuria testing is routinely performed in patients with acute flank pain to screen for ureterolithiasis and to help determine the need for excretory urography. Unenhanced helical computerized tomography (CT) has recently been shown to be superior to excretory urography in diagnosing ureteral obstruction and can evaluate many other causes of flank pain. Given the speed, accuracy and safety of CT the value of hematuria testing for acute flank pain should be reexamined. MATERIALS AND METHODS: We reviewed the medical records of 267 consecutive patients with acute flank pain referred for unenhanced helical CT. Microscopic and dipstick urinalysis data were obtained in 195 patients. Using helical CT as the gold standard, we calculated the sensitivity, specificity, predictive value and accuracy of hematuria for diagnosing ureterolithiasis. RESULTS: Of the patients with ureterolithiasis 33% had 5 or less, 19% had 1 or less and 11% had no red blood cells (RBCs) per high power field. Of the patients without ureterolithiasis 24% had greater than 5 and 51% had greater than 1 RBC per high power field. Of the patients with ureterolithiasis 14% had a negative dipstick test and 1 RBC or less per high power field. There were 25 patients without ureterolithiasis who had CT abnormalities unrelated to the urinary tract, of whom 8 had greater than 1 RBC per high power field. CONCLUSIONS: Absence of hematuria in the setting of acute flank pain cannot exclude a diagnosis of ureterolithiasis and should not obviate other diagnostic testing. Even when strongly positive on microscopy, hematuria has insufficient positive predictive value for diagnosing ureterolithiasis and may be misleading as other serious conditions resulting in acute flank pain may yield a positive test.

Acute Disease↗
PubMed1999

Stable electrical performance of high efficiency pacing leads having small surface, steroid-eluting pacing electrodes.

Previous experience with steroid-eluting small electrode designs have described their increased pacing efficiency, yet some reports have questioned their electrical stability. We report our experience with a new pacing lead design incorporating small surface (i.e. 1.2 mm2), high impedance pacing electrodes. Medtronic Model 5034 ventricular pacing leads were implanted by a single physician in 167 patients. Of those, 96 patients had an additional Model 5534 atrial lead implanted. All patients were followed for at least 9 months. Microdislodgment, as defined by a sudden increase in pacing threshold accompanied by radiographic stability, was observed in 6 of 263 (2.3%) leads implanted. Of the 4/167 (2.4%) ventricular leads that exhibited electrical instability, only 2 were sustained. Importantly, neither was significant enough to result in loss of capture. The other two cases of ventricular electrode instability manifested as a transient threshold rise with eventual return to near the original values. By comparison, the atrial lead model exhibited a sudden and sustained pacing threshold rise 5 which was evident in two patients (2.1%) with neither requiring invasive intervention. For all remaining chronic leads, clinically acceptable electrical performance profiles were demonstrated. We conclude that low microdislodgment rates and stable electrical performance profiles can be achieved with the small electrode steroid-eluting pacing electrodes as long as careful lead positioning and securing techniques are followed during implantation. We further suggest that successful high impedance lead design is critically dependent on its stiffness and mass characteristics.

Aged↗
PubMed1999

ERK activation protects against DNA damage and apoptosis in hyperoxic rat AEC2.

The survival of type 2 alveolar epithelial cells (AEC2) in the lung after hyperoxic injury is regulated by signals from the cellular environment. Keratinocyte growth factor and Matrigel can ameliorate the hallmarks of apoptosis seen in hyperoxic AEC2 after 24-h culture on plastic [S. Buckley, L. Barsky, B. Driscoll, K. Weinberg, K. D. Anderson, and D. Warburton. Am. J. Physiol. 274 (Lung Cell. Mol. Physiol. 18): L714-L720, 1998]. We used the same model of in vivo short-term hyperoxia to characterize the protective effects of substrate attachment. Culture of hyperoxic AEC2 on various biological adhesion substrates showed reduced DNA end labeling in cells grown on all biological substrates compared with growth on plastic. In contrast, the synthetic substrate poly-D-lysine conferred no protection. Hyperoxic AEC2 cultured on laminin showed an increased ratio of expression of Bcl-2 to interleukin-1beta-converting enzyme compared with culture on plastic. Laminin also partially restored hyperoxia-depleted glutathione levels and conferred improved optimal mitochondrial viability as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Conversely, attachment to the nonphysiological substrate poly-D-lysine afforded no such protection, suggesting that protection against hyperoxia-induced damage may be associated with integrin signaling. Increased activation of extracellular signal-regulated kinase (ERK), as detected by increased ERK tyrosine phosphorylation, was seen in hyperoxic AEC2 as soon as the cells started to attach to laminin and was sustained after 24 h of culture in contrast to that in control AEC2. To confirm that protection against DNA strand breakage and apoptosis was being conferred by ERK activation, the cells were also plated in the presence of 50 microM PD-98059, an inhibitor of the ERK-activating mitogen-activating kinase. Culture for 24 h with PD-98059 abolished the protective effect of laminin. We speculate that after hyperoxic lung injury, signals through the basement membrane confer specific protection against oxygen-induced DNA strand breakage and apoptosis through an ERK activation-dependent pathway.

Animals↗
PubMed1999

Vasopressin treats the persistent feeling of coldness after brain injury.

In this pilot study, 6 patients who complained of persisting coldness after brain injury were treated with intranasal vasopressin (DDAVP) twice daily for 1 month. Response was assessed after 1 month of treatment, DDAVP was discontinued, and response was reassessed 1 month later. Five of the 6 patients had a dramatic response to DDAVP, as soon as 1 week after initiating treatment, and no longer complained of feeling cold. Response persisted even after discontinuation of treatment. Patients denied any side effects from treatment with DDAVP. The experience of persisting coldness can respond dramatically to brief treatment with intranasal DDAVP. The authors discuss possible mechanisms of action to explain this phenomenon.

Adolescent↗
PubMed1999

Sensitivity and value of digital CT scout radiography for detecting ureteral stones in patients with ureterolithiasis diagnosed on unenhanced CT.

OBJECTIVE: When unenhanced CT reveals ureterolithiasis, some patients will require baseline or follow-up conventional radiography to help guide clinical management. We sought to determine the sensitivity of routinely obtained scout radiographs for revealing stones to determine if the scout view can be used in place of baseline conventional radiography. MATERIALS AND METHODS: We retrospectively reviewed the CT scout radiographs in conjunction with axial CT images in a series of 215 consecutive patients in whom CT revealed a single ureteral stone. On the scout radiographs, stones were classified as definitely visible, definitely not visible, or indeterminate. In addition, a phantom was constructed using fragments of kidney stones to evaluate the effect of the digital scout kilovoltage settings on stone visualization. RESULTS: Forty-nine percent of stones were definitely visible on scout radiography, 47% were definitely not visible, and 4% were indeterminate. Four stones larger than 10 mm that were not visible on scout radiography were composed of uric acid (n = 2) or xanthine (n = 2). Scout radiographs of the phantom determined an optimal kilovoltage setting of 80-100 kVp to visualize stones less than 3 mm, whereas stones greater than or equal to 3 mm were visible at all kilovoltage settings. CONCLUSION: In our series, 49% of ureteral stones were visible on the often-overlooked routine CT scout radiograph. Imaging of phantoms showed that stone visualization can be optimized by using the lowest kilovoltage settings. Therefore, the CT scout view can be used as a baseline study in patients requiring follow-up radiography and for planning treatment of patients requiring lithotripsy or other intervention. Finally, large stones not visible on scout radiographs are likely composed of uric acid or xanthine.

Abdominal Pain↗
PubMed1999

Active heroin injectors' perceptions and use of methadone maintenance treatment: cynical performance or self-prescribed risk reduction?

In addition to the numerous heroin users who voluntarily enter methadone treatment as a way to free themselves from illicit drug addiction and those ordered to do so by the courts, there are a large number of opioid users who enter methadone treatment with other objectives in mind. These include shorter-term goals that users do not necessarily equate with complete heroin abstinence. In this paper we report the results of a qualitative study designed to identify and describe the motivations active heroin users have for entering methadone treatment, and to suggest that many of these short-term methadone episodes may operate as self-prescribed attempts at risk reduction, and act as pilot tests for users considering or anticipating entering treatment to quit the use of illicit drugs. We argue that heroin users' motivations, perceptions about methadone, and the strategies they devise for adapting methadone treatment for their own needs should be recognized for their value in reducing the multiple risks associated with drug use.

Colorado↗
PubMed1999

Advances in the biology of multiple myeloma: therapeutic applications.

Recent advances in the biology of multiple myeloma cell growth and survival have suggested new avenues for treatment and potential cure of this disease. Adhesion molecules on the myeloma cell surface mediate their localization in the bone marrow via binding to extracellular matrix proteins and stromal cells. Stromal cell to tumor cell contact and the secretion of transforming growth factor by tumor cells triggers interleukin-6 secretion from stromal cells and paracrine tumor cell growth. CD40 activation of myeloma cells changes their cell surface phenotype, triggers autocrine interleukin-6 secretion, and can regulate myeloma cell cycle in a p53-dependent fashion. Interleukin-6 is both a growth and survival factor for myeloma cells, and delineation of the signaling cascades mediating its effects permits the development of novel therapies either to interrupt growth or trigger apoptosis. New immune therapies offer the opportunity to treat minimal residual disease after stem cell transplantation, thereby improving outcome. Selected donor lymphocyte infusions after allografting and infusion of activated autologous T cells following autografting are examples of adoptive immunotherapy. Myeloma cell to dendritic cell fusions have been used in a vaccination strategy both to prevent and treat myeloma in an animal model, providing the rationale for similar clinical trials in humans. For the first time, a variety of novel treatment strategies derived from advances in understanding the disease pathogenesis offer the potential to achieve long-term disease-free survival in patients with multiple myeloma.

Bone Marrow Cells↗
PubMed1999

Selective in vivo mobilization with granulocyte macrophage colony-stimulating factor (GM-CSF)/granulocyte-CSF as compared to G-CSF alone of dendritic cell progenitors from peripheral blood progenitor cells in patients with advanced breast cancer undergoing autologous transplantation.

Dendritic cells (DCs) are potent antigen-presenting cells that are essential for the initiation of T cell-mediated immunity. DCs develop from myeloid progenitor populations under the influence of granulocyte macrophage colony-stimulating factor (GM-CSF) and pass through an intermediate stage of maturation that is characterized by CD14 expression. Interest has focused on generating human-derived DCs for antigen-specific tumor vaccines to be used as adjuvant immunotherapy in minimal disease settings, such as after autologous transplantation. In the present study, mobilized peripheral blood progenitor cells (PBPCs) were obtained from 18 patients with locally advanced or metastatic breast cancer preparing to undergo autologous stem cell transplantation. PBPCs mobilized in 10 patients with GM-CSF for 1 week, followed by the combination of GM-CSF and G-CSF, were compared with those obtained from patients receiving G-CSF alone with respect to the presence of DC progenitors and the capacity to generate functionally active mature DCs. PBPCs mobilized with GM-CSF/G-CSF were markedly enriched for CD14+ DC progenitor cells as compared with those mobilized with G-CSF alone. Consistent with an immature progenitor population, the CD14+ cells express Ki-67 antigen but not nonspecific esterase. CD14+ cells purified by fluorescence-activated cell sorting from PBPCs mobilized with either regimen and cultured for 1 week in GM-CSF and interleukin-4 generated nearly pure populations of cells with characteristic DC phenotype and function. The addition of GM-CSF to the mobilization regimen resulted in greater yields of functionally active DCs for potential use in posttransplant immunotherapy.

Breast Neoplasms↗
PubMed1999

Topical diclofenac versus placebo: a double blind, randomized clinical trial in patients with osteoarthritis of the knee.

OBJECTIVE: To assess the efficacy and safety of a topical formulation of 2% diclofenac in lecithin organogel in the treatment of pain associated with mild to moderate osteoarthritis (OA) of the knee. METHODS: Seventy patients completed a double blind, randomized, placebo controlled, parallel group design 2 week clinical trial. Patient responses to disease-specific (WOMAC VA3.0) and quality of life (Medical Outcome Survey SF-36) health status measures were assessed. Global assessments were also made at baseline and post-treatment. The physician conducted a global assessment and range of motion of the knee at baseline and post-treatment. RESULTS: T tests on the aggregated WOMAC total score and aggregated subscale scores revealed significant improvement (p<0.05) on the aggregated total score and the pain, stiffness, and physical function subscales from baseline to post-treatment for the active treatment group versus the placebo group. Analysis of gain scores from the aggregated WOMAC total score and aggregated subscale scores also revealed that this improvement was significantly greater than the improvement recorded by the placebo treatment group on the aggregated total and the pain and physical function subscale scores. Other efficacy measures exhibited no significant differences between or within treatment groups. CONCLUSION: A topical formulation of 2% diclofenac in a lecithin organogel appears to have therapeutic value in patients with mild to moderate OA of the knee as determined by responses from the WOMAC (VA3.0) osteoarthritis health status measure.

Administration, Topical↗
PubMed1999

Distribution and concordance of N-acetyltransferase genotype and phenotype in an American population.

Polymorphic arylamine N-acetyltransferase 2 (NAT2) status varies widely between individuals and ethnic groups and has been associated with susceptibility to several cancers. Few studies have reported the distribution of NAT2 status for Caucasian-American populations or evaluated the concordance between methods of assessment for cancer cases and controls. In our study, distribution of NAT2 status was classified by genotype and phenotype measurements in PANCAN, a population-based case-control study of pancreatic cancer, and concordance between measurements was evaluated for 33 cases and 222 controls. Major genotypes and alleles among controls were *5B/*6A, *5B/*5B, *4/*6A, and *5B/*4. One putative new allele was found in a single individual. Genotypes and phenotypes were classified as rapid or slow, according to a bimodal model. Presence of the *4 (wild-type) allele defined a NAT2 genotype as rapid. The NAT2 phenotype was analyzed by the caffeine assay. Ratios of 5-acetylamino-6-formylamino-3-methyluracil to 1-methylxanthine were determined, and individuals with values of > or =0.66 were identified as having a rapid phenotype. In our population, 58.1 and 59.5% of control subjects were classified as slow acetylators by phenotype and genotype, respectively. Concordance of NAT2 genotype and phenotype classification was 97.8% in the bimodal model. A similar analysis was completed for a trimodal model. Concordance of genotype and phenotype was high in cases (90.9%) and similar to controls; genotyping alone provided an efficient, accurate method of analysis for acetylator status. A comparison with two previous reports revealed subtle differences in genotype and allele distribution but exhibited overall similarity with other Caucasian-American populations.

Aged↗