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Biomedical subjects

K Anderson

Publications and source records attributed to K Anderson.

At least 37 records · Page 2Linked to original sources
PubMed2002

Thalidomide in multiple myeloma.

Thalidomide--removed from widespread clinical use by 1962 because of severe teratogenicity--has anti-angiogenic and immunomodulatory effects, including the inhibition of TNF alpha. It has returned to practice as an effective oral agent in the management of various disease states including erythema nodosum leprosum, for which it was FDA-approved in 1998, and more recently certain malignancies, including multiple myeloma. Whilst the mechanism of action of thalidomide remains incompletely understood, considerable insight has been generated by extensive preclinical studies in multiple myeloma. Moreover, clinical trials both as a single agent and in combination have confirmed benefit in relapsed and refractory disease. Thalidomide's role in treating newly diagnosed patients is currently under study and it is now established as an important therapeutic option in the treatment of multiple myeloma.

Adult↗
PubMed2002

Takes your breath away--the immunology of allergic alveolitis.

Extrinsic allergic alveolitis (synonym: hypersensitivity pneumonitis) is caused by inhaling antigenic aerosols which induce hypersensitivity responses in susceptible individuals. It is an interstitial inflammatory disease affecting the distal, gas-exchanging parts of the lung, in contrast to allergic asthma where the inflammation is more proximal, affecting the conducting airways. The aims of this review are to describe current concepts of the immunology of this model of lung inflammation, to describe some of the constitutional and environmental characteristics which affect disease susceptibility and development, and to describe topics for prospective study.

Alveolitis, Extrinsic Allergic↗
PubMed2002

The effects of bolus hardness on masticatory kinematics.

This study investigated how jaw kinematics, including cycle duration, three-dimensional (3-D) excursive ranges and velocities, and cycle shape, changed with increasing hardness of chewing gum. Twenty-six subjects (13 males and 13 females; mean age 23.6 +/- 2.5 years) with Class I normal occlusion were asked to chew two brands of gum with differing hardness. Jaw motion during chewing was tracked with an Optotrak camera at 100 Hz, and all movements were recorded as pure 3-D mandibular movements relative to Frankfort horizontal. Cycle duration did not change significantly with harder gum, but 3-D excursive ranges and velocities increased, except during the occlusal phases of the chewing. Cycle shape was similar for hard and soft gum, but the overall size of the cycle was larger with hard gum. These results suggest that greater muscular effort when chewing harder gum produces a greater acceleration of the mandible in all phases except when the harder gum slows the mandible during the occlusal phases.

Acceleration↗
PubMed2002

Effect of total body irradiation dose escalation on outcome following T-cell-depleted allogeneic bone marrow transplantation.

Prior studies of non-T-cell-depleted (TCD) transplantation have demonstrated a reduction in relapse in patients receiving escalated doses of TBI; however, overall survival in these studies was not significantly improved due to increased treatment-related toxicity seen at the higher doses of irradiation. Toxicity was in part related to an increased incidence of GVHD. Because T-cell depletion of donor bone marrow reduces the incidence of GVHD and other treatment-related complications after allogeneic bone marrow transplantation, it was postulated that TBI dose may be safely escalated in this setting and may decrease the risk of relapse following TCD BMT. Herein, we report the results of a trial assessing the safety and impact of escalated doses of TBI after TCD BMT. Two hundred adults with hematologic malignancies were treated in consecutive cohorts defined by increasing doses of TBI (1400, 1480, and 1560 cGy) in combination with cyclophosphamide. In vitro T-cell depletion using anti-CD6 monoclonal antibody was used for GVHD prophylaxis. The incidence of grade II or greater acute GVHD in patients receiving 1560 cGy (36%) was significantly higher than in patients receiving 1400 cGy (18%) (P = .04) or 1480 cGy (13%) (P = .01). Two-year treatment-related mortality was significantly higher in patients who received 1560 cGy of TBI (33%) than in those who received 1400 cGy (20%) (P = .04) or 1480 cGy (19%) (P = .05). The increased dose of TBI did not reduce the rates of relapse, with the estimated 2-year risk of relapse being 24% (1400 cGy), 24% (1480 cGy), and 31% (1560 cGy) for the 3 cohorts of patients. Overall survival at 2 years was inferior for patients receiving 1560 cGy of TBI (36%) compared with those who received 1400 cGy (55%) or 1480 cGy (58%) (P = .01). We conclude that dose escalation of TBI is associated with increased GVHD and inferior survival following TCD BMT. Future efforts to reduce the risk of relapse after TCD BMT should focus on immunologic methods to induce the graft-versus-leukemia effect after BMT rather than intensification of the ablative regimen by escalation of irradiation dose.

Adolescent↗
PubMed2002

Determinants of improvement in epicardial flow and myocardial perfusion for ST elevation myocardial infarction; insights from TIMI 14 and InTIME-II.

BACKGROUND: When evaluating new reperfusion regimens for ST elevation MI, it is important to adjust for factors that influence the likelihood of achieving normal epicardial flow and complete ST resolution. METHODS AND RESULTS: A total of 610 patients from TIMI 14 contributed to the angiographic analyses. The electrocardiographic analyses were based on 544 patients from TIMI 14 and 763 patients from InTIME-II. For each hour from onset of symptoms to initiation of pharmacological reperfusion, the odds of achieving TIMI 3 flow at 90 min or complete ST resolution at 60-90 min decreased significantly (P=0.03). Anterior location of infarction was associated with a reduction in the odds of achieving TIMI 3 flow or complete ST resolution. The use of abciximab as part of the reperfusion regimen significantly increased the odds of TIMI 3 flow (P=0.01) and ST resolution (P<0.001). The fibrinolytic administered (alteplase, reteplase, lanoteplase) did not influence the odds of TIMI 3 flow or ST resolution after adjusting for time to treatment, infarct location, and use of abciximab. CONCLUSIONS: The influence of time from symptoms on epicardial flow and STRES reinforces the need for increased efforts to reduce treatment delays in patients with ST elevation MI. The significant benefits of abciximab with respect to facilitation of epicardial and myocardial reperfusion are evident even after adjusting for time to treatment and infarct location. To adjust for determinants of success of reperfusion regimens, phase II trials evaluating new drug combinations should consider using a randomization scheme that stratifies patients based on infarct location and time from symptoms.

Abciximab↗
PubMed2002

Cocaine increases intracellular calcium in the interferon-gamma-primed macrophages but not in the LPS-primed-macrophages.

Calcium is required for antigen presentation. In the past study, we found that cocaine increased macrophage antigen-presenting activity. To investigate whether cocaine induces a calcium influx into macrophage cytosol, we used Fura2-AM to directly test the macrophage intracellular calcium concentration [Ca2+]i under the influence of different concentrations of cocaine after macrophages were primed by IFN-gamma or LPS. We report here that cocaine increases the IFN-gamma-primed macrophage [Ca2+]i, but it does not affect the LPS-primed macrophage [Ca2+]i. Furthermore, calcium blocker, nifedipine, blocks the effect of cocaine, suggesting that extracellular calcium enters the cytosol through the L-channel.

Animals↗
PubMed2001

Lifestyle factors and Ki-ras mutations in colon cancer tumors.

Heterogeneity in colon tumors implies that environmental, lifestyle, or genetic factors influence the type of mutations seen in tumors. In this study we evaluate the association between previously identified risk factors for colon cancer and Kirsten-ras (Ki-ras) mutations in tumors. The presence of Ki-ras mutations in codons 12 and 13 were determined in a population-based case-control study of colon cancer. Participants were between 30 and 79 years of age at time of diagnosis and include both men and women. Questionnaire data were used to obtain information on lifestyle factors. Valid study data and Ki-ras mutational status were available from 1428 cases of colon cancer, data from 2410 controls were available for comparative purposes. Participants with Ki-ras mutations were more likely to have proximal rather than distal tumors. Cigarette smoking, use of aspirin and/or NSAIDs, use of vitamin/mineral supplements, and consumption of caffeine were associated with both Ki-ras+ and Ki-ras- tumors; the associations were not confounded by dietary intake or other lifestyle factors. Among men, but not among women, those with low levels of physical activity were more likely to have a tumor with a Ki-ras mutation than one without a Ki-ras mutation. However, among women, those with a larger BMI were more likely to have a Ki-ras mutation in their tumor. Given the limited information available on what causes Ki-ras mutations, the information generated from this study indicates that these factors previously associated with colon cancer work through other disease pathways.

Adult↗
PubMed2001

Breath sounds, asthma, and the mobile phone.

The sounds generated by breathing in asthma are widely accepted as an indicator of disease activity. We have investigated the use of a mobile phone and electronic signal transfer by e-mail and voice mail to study tracheal breath sounds in individuals with normal lung function and patients with chronic or exercise-induced asthma. Spectrograms from patients with active asthma and impaired lung function were significantly different from people without asthma (p<0.0001). Our results suggest that mobile phone recordings clearly discriminate tracheal breath sounds in asthma and could be a non-invasive method of monitoring airway diseases.

Adolescent↗
PubMed2001

Dietary intake and microsatellite instability in colon tumors.

Microsatellite instability (MSI) occurs in approximately 15% of colon tumors. Other than relatively rare mutations in mismatch repair genes, the causes of MSI are not generally known. The purpose of this study was to determine if dietary intake of nutrients previously reported as being associated with colon cancer relate specifically to the MSI disease pathway. Data from a population-based case-control study of adenocarcinoma of the colon were used to evaluate associations between dietary intake and MSI. Participants were between 30 and 79 years of age at time of diagnosis and included both men and women. Dietary intake data were obtained from a computerized diet history questionnaire. MSI was evaluated in several ways: by a panel of 10 tetranucleotide repeats, and by 2 mononucleotide repeats, BAT-26 and TGFbetaRII. A total of 1,510 cases had valid study data and tumor DNA on which we were able to obtain MSI status. Cases with and without MSI were compared with dietary data reported by 2,410 population-based controls to determine dietary associations that may be different for these 2 subsets of cases. We compared dietary intake for cases with and without MSI to further determine associations that are specific to the MSI disease pathway. When comparing MSI+ to MSI- tumors we observed that long-term alcohol consumption, especially intake of liquor, increased the probability of having a tumor with MSI [odds ratio (OR) for MSI+ vs. MSI- tumors for alcohol 1.6, 95% confidence interval (CI) 1.0-2.5; OR for liquor 1.6, 95% CI 1.1-2.4]. The likelihood of having MSI in the tumor from the combined effects of high alcohol consumption and smoking cigarettes showed a 70% excess in risk from the additive model. There were some suggestions that high intakes of refined grain might also be associated with MSI+ tumors, although associations were less consistent. Risk estimates for most other dietary factors did not differ substantially by MSI status. Data from this large population-based case-control study of colon cancer indicate that alcohol consumption, especially consumption of liquor, may increase the odds of an MSI+ tumor. Most other dietary factors do not appear operate exclusively in the MSI+ disease pathway.

Adult↗
PubMed2001

T-cell--depleted allogeneic bone marrow transplantation followed by donor lymphocyte infusion in patients with multiple myeloma: induction of graft-versus-myeloma effect.

Previous trials of allogeneic bone marrow transplantation (BMT) in patients with multiple myeloma (MM) have demonstrated high response rates but also high transplantation-related mortality (TRM) and high relapse rates. Exploitation of this strategy remains of interest because donor lymphocyte infusions (DLIs) can induce a potent graft-versus-myeloma (GVM) effect. CD6 T-cell--depleted allogeneic BMT was combined with prophylactic CD4(+) DLI administered 6 to 9 months after BMT in an effort to reduce TRM and to induce a GVM response after BMT. Twenty-four patients with matched sibling donors and chemotherapy-sensitive disease underwent BMT. CD6 T-cell depletion of donor bone marrow was the sole method of graft-versus-host disease (GVHD) prophylaxis. GVHD after BMT was minimal, 1 (4%) grade III and 4 (17%) grade II GVHD. Fourteen patients received DLI, 3 in complete response and 11 with persistent disease after BMT. Significant GVM responses were noted after DLI in 10 patients with persistent disease, resulting in 6 complete responses and 4 partial responses. After DLI, 50% of patients developed acute (> or = II) or extensive chronic GVHD. Two-year estimated overall survival and current progression-free survival (PFS) for all 24 patients is 55% and 42%, respectively. The 14 patients receiving DLI had an improved 2-year current PFS (65%) when compared with a historical cohort of MM patients who underwent CD6-depleted BMT survived 6 months with no GVHD and did not receive DLI (41%) (P =.13). Although this study suggests that prophylactic DLI induces significant GVM responses after allogeneic BMT, only 58% of patients were able to receive DLI despite T-cell--depleted BMT. Therefore, less toxic transplantation strategies are needed to allow a higher proportion of patients to receive DLI and the benefit from the GVM effect after transplantation. (Blood. 2001;98:934-939)

Actuarial Analysis↗
PubMed2001

Risk of stroke associated with abciximab among patients undergoing percutaneous coronary intervention.

CONTEXT: Abciximab, a potent inhibitor of the platelet glycoprotein IIb/IIIa receptor, reduces thrombotic complications in patients undergoing percutaneous coronary intervention (PCI). Because of its potent inhibition of platelet aggregation, the effect of abciximab on risk of stroke is a concern. OBJECTIVE: To determine whether abciximab use among patients undergoing PCI is associated with an increased risk of stroke. DESIGN: Combined analysis of data from 4 double-blind, placebo-controlled, randomized trials (EPIC, CAPTURE, EPILOG, and EPISTENT) conducted between November 1991 and October 1997 at a total of 257 academic and community hospitals in the United States and Europe. PATIENTS: A total of 8555 patients undergoing PCI with or without stent deployment for a variety of indications were randomly assigned to receive a bolus and infusion of abciximab (n = 5476) or matching placebo (n = 3079). One treatment group in EPIC received a bolus of abciximab only. MAIN OUTCOME MEASURE: Risk of hemorrhagic and nonhemorrhagic stroke within 30 days of treatment among abciximab and placebo groups. RESULTS: No significant difference in stroke rate was observed between patients assigned abciximab (n = 22 [0.40%]) and those assigned placebo (n = 9 [0.29%]; P =.46). Excluding the EPIC abciximab bolus-only group, there were 9 strokes (0.30%) among 3023 patients who received placebo and 15 (0.32%) in 4680 patients treated with abciximab bolus plus infusion, a difference of 0.02% (95% confidence interval [CI], -0.23% to 0.28%). The rate of nonhemorrhagic stroke was 0.17% in patients treated with abciximab and 0.20% in patients treated with placebo (difference, -0.03%; 95% CI, -0.23% to 0.17%), and the rates of hemorrhagic stroke were 0.15% and 0.10%, respectively (difference, 0.05%; 95% CI, -0.11% to 0.21%). Among patients treated with abciximab, the rate of hemorrhagic stroke in patients receiving standard-dose heparin in EPIC, CAPTURE, and EPILOG was higher than in those receiving low-dose heparin in the EPILOG and EPISTENT trials (0.27% vs 0.04%; P =.057). CONCLUSIONS: Abciximab in addition to aspirin and heparin does not increase the risk of stroke in patients undergoing PCI. Patients undergoing PCI and treated with abciximab should receive low-dose, weight-adjusted heparin.

Abciximab↗
PubMed2001

A novel endo-beta-galactosidase from Clostridium perfringens that liberates the disaccharide GlcNAcalpha 1-->Gal from glycans specifically expressed in the gastric gland mucous cell-type mucin.

We found that commercially available sialidases prepared from Clostridium perfringens ATCC10543 were contaminated with an endoglycosidase capable of releasing the disaccharide GlcNAcalpha1-->4Gal from glycans expressed in the gastric gland mucous cell-type mucin. We have isolated this enzyme in electrophoretically homogeneous form from the culture supernatant of this organism by ammonium sulfate precipitation followed by affinity chromatography using a Sephacryl S-200 HR column. The enzyme was specifically retained by and eluted from the column with methyl-alpha-Glc. By NMR spectroscopy, the structure of the disaccharide released from porcine gastric mucin by this enzyme was established to be GlcNAcalpha1-->4Gal. The specificity of this enzyme as an endo-beta-galactosidase was established by analyzing the liberation of GlcNAcalpha1-->4Gal from GlcNAcalpha1-->4Galbeta1-->4GlcNAcbeta1-->6(GlcNAcalpha1--> 4Galbeta1-->3)GalNAc-ol by mass spectrometry. Because this novel endo-beta-galactosidase specifically releases the GlcNAcalpha1-->4Gal moiety from porcine gastric mucin, we propose to call this enzyme a GlcNAcalpha1-->4Gal-releasing endo-beta-galactosidase (Endo-beta-Gal(GnGa)). Endo-beta-Gal(GnGa) was found to remove the GlcNAcalpha1-->4Gal epitope expressed in gastric adenocarcinoma AGS cells transfected with alpha1,4-N-acetylglucosaminyltransferase cDNA. Endo-beta-Gal(GnGa) should become useful for studying the structure and function of glycoconjugates containing the terminal GlcNAcalpha1-->4Gal epitope.

Adenocarcinoma↗
PubMed2001

Estrogens reduce and withdrawal of estrogens increase risk of microsatellite instability-positive colon cancer.

There are sex differences in the occurrence of microsatellite instability (MSI) in colon tumors. Taken together with the epidemiological evidence that hormone replacement therapy (HRT) and, less consistently, parity, are inversely associated with colon cancer, it has been hypothesized that estrogens are associated with MSI. The purpose of this study was to evaluate sex-specific differences in the prevalence of MSI in colon tumors and to determine whether reproductive history and hormonal exposures are associated with MSI. Using data from a population-based case-control study of 1836 cases with MSI data and 2410 population-based controls, we evaluated sex, reproductive factors, and hormone exposure in relation to the presence or absence of MSI in tumors. MSI was evaluated by a panel of 10 tetranucleotide repeats, the noncoding mononucleotide repeat BAT-26, and the coding mononucleotide repeat in transforming growth factor beta receptor type II (TGFbetaRII). Exposure data on reproduction, hormone use, obesity, and physical activity were obtained from an interviewer-administered questionnaire. Women were less likely then men to have MSI+ tumors at a young age and more likely to have unstable tumors at an older age; we observed a significant interaction (P < 0.01) between age, sex, and MSI. Evaluation of reproductive factors showed that women who had ever been pregnant had half the risk of MSI+ tumors compared with women who had never been pregnant. In complementary fashion, total ovulatory months were associated with an increased risk of MSI+ tumors [odds ratio (OR), 2.1; 95% confidence interval (CI), 1.1-4.0 comparing MSI+ versus MSI- tumors]. Age at first and last pregnancy did not influence the association. The observed associations were strongest among women <60 years of age at the time of diagnosis. Having used oral contraceptives was associated with a lower risk of MSI+ tumors (OR, 0.7; 95% CI, 0.4-1.2); recent users of HRT were at a reduced risk of MSI+ tumors (OR, 0.8; 95% CI, 0.5-1.4); and women who were former HRT users were at an increased risk of MSI+ tumors (OR, 1.8; 95% CI, 1.1-3.0). Obesity and lack of physical activity were associated with an elevated risk of both MSI+ (OR, 1.7; 95% CI, 0.7-3.3) and MSI- (OR, 2.2; 95% CI, 1.7-3.) tumors in men, but only with MSI- (OR, 1.5; 95% CI, 1.1-2.2) tumors in women. The excess of MSI+ tumors in women is explained by the excess of MSI+ tumors at older ages. Our data suggest that estrogen exposure in women protects against MSI, whereas the lack of estrogen in older women increases risk of instability. HRT in these older women may, again, reduce the risk of unstable tumors. A model for the way in which estrogens (endogenous, exogenous, and obesity-associated) modify the risk of MSI+ tumors is proposed.

Adipose Tissue↗
PubMed2001

Factors associated with CPR certification within an elderly community.

OBJECTIVE: To determine the frequency of CPR certification amongst residents living within a predominantly elderly community and examine the perceived barriers to learning basic CPR and factors associated with intent to become certified. METHODS: A household survey was sent with a community newsletter to each home of a non-gated elderly community that requires one member of each household to be at least 55 years of age. The community consists of 2488 homes (approximately 4000 residents). Thirteen Yes/No questions were asked in a skip-pattern based upon the question: "Are you CPR certified?" Data analysis included univariate, bivariate, and logistic regression. RESULTS: 947 participants with a mean age of 69 completed and returned the survey. Forty-eight percent of the participants had received prior training in CPR. Eighty-four percent were not currently certified in CPR, and top reasons cited were: 'don't know why' (36%), 'lack of interest' (20%), 'concerned about health risks' (17%). Forty-six percent of those not certified desired certification. Increasing age was inversely associated with CPR certification status and the desire to be certified. CONCLUSION: Almost half of the residents in this predominantly elderly community had received prior training in CPR, although most were not currently certified and cite significant specific and non-specific reasons and obstacles. Improved survival requires targeted interventions to achieve higher proportions of CPR-competent individuals in such high-risk communities.

Aged↗
PubMed2001

Characterization of oligosaccharides from the chondroitin sulfates. (1)H-NMR and (13)C-NMR studies of reduced disaccharides and tetrasaccharides.

Chondroitin sulfates were fragmented using the enzymes chondroitin sulfate ABC endolyase and chondroitin ACII lyase; both disaccharide and tetrasaccharide fragments were isolated after reduction to the corresponding 2-deoxy-2-N-acetylamino-D-galactitol (GalNAc-ol) form. These have the structures: Delta UA(beta 1--3)GalNAc4S-ol, Delta UA(beta 1--3)GalNAc6S-ol, Delta UA2S(beta 1--3)GalNAc6S-ol, Delta UA(beta 1--3)GalNAc4S(beta 1--4)L-IdoA(alpha 1--3)GalNAc4S-ol, Delta UA(beta 1--3)GalNAc4S(beta 1--4)GlcA(beta 1--3)GalNAc4S-ol, Delta UA(beta 1--3)GalNAc6S(beta 1--4)GlcA(beta 1--3)GalNAc4S-ol, Delta UA(beta 1--3)GalNAc6S(beta 1--4)GlcA(beta 1--3)GalNAc6S-ol, Delta UA2S(beta 1--3)GalNAc6S(beta 1--4)GlcA(beta 1--3)GalNAc4S-ol and Delta UA2S(beta 1--3)GalNAc6S(beta 1--4)GlcA(beta 1--3)GalNAc6S-ol, where Delta UA represents a 4,5-unsaturated hexuronic acid (4-deoxy-alpha-Lthreo-hex-4-enepyranosyluronic acid) and 6S/4S/2S represent O-ester sulfate groups at C6/C4/C2 sites. Complete (1)H-NMR and (13)C-NMR data are derived for these species, which may help to alleviate some of the significant difficulties resulting from signal complexity that are currently hindering the characterization and assignment of major and minor structural components within chondroitin sulfate and dermatan sulfate polymers.

Animals↗
PubMed2001

A 30-month study of patient complaints at a major Australian hospital.

Health practitioners often regard complaints about the quality of patient care in a negative light. However, complaints can indicate strategies to improve care. Therefore, an audit was undertaken of all formal complaints about patient care at a major Australian hospital over a 30-month period. The profile of complainants, the reasons for complaints, and the outcome were analysed. A total of 1308 complaints, concerning the care of 1267 patients, were received. The complaint rate was 1.12 per 1000 occasions of service. In all, 57% of complaints were lodged by advocates and 71% of complaints related to poor communication or to the treatment provided. In 97% of occasions, an explanation and/or an apology resulted. To date, no complaint has proceeded to litigation. Complaints are potentially useful quality assurance tools and can identify remediable system flaws. Health professionals and employers should understand why patients complain and be able to respond appropriately.

Adult↗