Biomedical subjects

John Klein

Publications and source records attributed to John Klein.

7 recordsLinked to original sources

PubMed2007

HLA mismatching within or outside of cross-reactive groups (CREGs) is associated with similar outcomes after unrelated hematopoietic stem cell transplantation.

The National Marrow Donor Program maintains a registry of volunteer donors for patients in need of a hematopoietic stem cell transplantation. Strategies for selecting a partially HLA-mismatched donor vary when a full match cannot be identified. Some transplantation centers limit the selection of mismatched donors to those sharing mismatched antigens within HLA-A and HLA-B cross-reactive groups (CREGs). To assess whether an HLA mismatch within a CREG group ("minor") may result in better outcome than a mismatch outside CREG groups ("major"), we analyzed validated outcomes data from 2709 bone marrow and peripheral blood stem cell transplantations. Three-hundred and ninety-six pairs (15%) were HLA-DRB1 allele matched but had an antigen-level mismatch at HLA-A or HLA-B. Univariate and multivariate analyses of engraftment, graft-versus-host disease, and survival showed that outcome is not significantly different between minor and major mismatches (P = .47, from the log-rank test for Kaplan-Meier survival). However, HLA-A, HLA-B, and HLA-DRB1 allele-matched cases had significantly better outcome than mismatched cases (P < .001). For patients without an HLA match, the selection of a CREG-compatible donor as tested does not improve outcome.

Alleles↗

PubMed2004

Added value of new acute coronary syndrome computer algorithm for interpretation of prehospital electrocardiograms.

A new computerized acute coronary syndrome (ACS) computer algorithm has been developed with the aim of improving the electrocardiographic detection of acute myocardial ischemia and infarction in the emergency department (ED). The purpose of this study was to determine the added value of the new ACS algorithm in assisting ED physicians to obtain a more accurate diagnosis in patients with ACS. The new algorithm combines a rule-based decision tree, which uses well-known clinical criteria and a data-centered neural network model for more robust pattern recognition. Input parameters of the neural network model consist of morphology features of derived Frank X, Y, Z waveforms and the patient's gender and age. The neural network model was trained with electrocardiograms obtained from documented acute myocardial infarction patients at the Mayo Clinic who were a part of a research ACS database, which includes electrocardiograms (ECGs) of more than 5,000 individuals at hospital admission (1st ECG in the ED). The test set portion of the study was conducted in 2 steps: 1) One emergency physician and 1 cardiologist classified 1,902 clinically correlated out-of-hospital ECGs without seeing the interpretation statement from the algorithm into 1 of the following categories: 1) acute myocardial infarction, acute ischemia, or nonischemic; 2) After 9 months, the same 2 physicians classified the same group of ECGs but with the interpretation statement of the algorithm printed on the tracing. The results demonstrated that with the assistance of the new algorithm, the emergency physician and cardiologist improved their sensitivity of interpreting acute myocardial infarction by 50% and 26%, respectively, without a loss of specificity. The new algorithm also improved the emergency physician's acute ischemia interpretation sensitivity by 53% and still maintained a reasonable specificity (91%). The new ACS algorithm provides added value for improving acute ischemia and infarction detection in the ED.

Age Factors↗

PubMed2004

Effect of rocker soles on plantar pressures.

OBJECTIVE: To examine the effect of different types of rocker soles on plantar pressures. DESIGN: In-shoe plantar pressures were measured in subjects without deformity with baseline shoes and 3 types of rockers: toe-only, negative heel, and double. SETTING: Medical college. PARTICIPANTS: Forty healthy patients (20 men, 20 women) without foot deformity. INTERVENTIONS: Plantar pressures were recorded over a 2 1/2-hour test period with over 400 steps analyzed for each type of rocker sole. Peak pressures, pressure-time integral (PTI), and sensor contact duration were computed for each step. MAIN OUTCOME MEASURES: Peak plantar pressure PTI, and contact duration were compared for each rocker with a baseline shoe. RESULTS: Significant reduction (P<.01) in peak pressure and PTI were recorded across the forefoot for all 3 rockers. The reduction of pressure at the forefoot was balanced by shifting pressure to the midfoot with the negative heel and toe-only rockers. CONCLUSION: This study lends scientific credence to the prescription of rocker soles for patients who need forefoot pressure reduction, such as in diabetic neuropathy and possible ulceration.

Diabetic Neuropathies↗

PubMed2003

Modulation of bone ingrowth and tissue differentiation by local infusion of interleukin-10 in the presence of ultra-high molecular weight polyethylene (UHMWPE) wear particles.

Interleukin-10 (IL-10) is a cytokine that plays a major role in suppressing the inflammatory response, particularly cell-mediated immunity that is characteristic of the TH1 response. The purpose of this study was to determine whether local infusion of IL-10 could mitigate the suppression of bone ingrowth associated with polyethylene wear particles. Drug test chambers were implanted in the proximal tibia of 20 mature New Zealand White rabbits. The DTC provided a continuous 1 x 1 x 5-mm canal for tissue ingrowth. After a 6-week period for osseointegration, the DTC was then connected to an osmotic diffusion pump. IL-10 at doses of 0.1-100 ng/mL (0.25 microL/h) was infused with or without ultra-high molecular weight polyethylene particles (0.5 +/- 0.2 microm diameter, 10(12) particles/mL) present in the chamber for a 3- or 6-week period. The tissue in the chamber was harvested after each treatment; sections were stained with hematoxylin and eosin for morphometric analysis. Osteoclast-like cells were identified by immunohistochemical staining using a monoclonal antibody directed against the alpha chain of the vitronectin receptor, CD51. Osteoblasts were identified using alkaline phosphatase staining. In dose-response studies, infusion of 1 ng/mL IL-10 yielded the greatest bone ingrowth in the presence of particles. The addition of polyethylene particles evoked a marked foreign body reaction and fibrosis; bone ingrowth was significantly suppressed (p = 0.0003). Bone ingrowth was increased by over 48% with infusion of IL-10 for the final 3 weeks of a 6-week ultra-high molecular weight polyethylene particle exposure compared with particles alone (p = 0.027). IL-10 is a cytokine that plays a major role in suppressing the inflammatory response, especially cell-mediated immunity that is characteristic of the TH1 response. Local infusion of immune-modulating cytokines such as IL-10 may prove to be useful in abating particle-induced periprosthetic osteolysis.

Alkaline Phosphatase↗

PubMed2003

Modeling minimal residual disease (MRD)-testing.

There is considerable effort to develop more sensitive methods to detect minimal residual disease (MRD) in bone marrow and blood samples of persons with cancer. Results of MRD-testing are used to predict clinical outcome and determine if more anti-cancer therapy is needed. Mathematical models were developed to assess factors affecting sensitivity and specificity of MRD-testing at diverse cancer cell prevalences. Modeling results and predictions were compared to results of large published studies.Accuracy of MRD-testing depends on cancer cell prevalence and distribution in the blood or bone marrow of the subject, sensitivity and specificity of the MRD-test and sample size. In subjects with low cancer cell prevalences (< or = 10(-4)) results of MRD testing are likely inaccurate. Increasingly sensitive MRD-tests are only marginally useful; the major obstacle to accuracy is inadequate sampling. Increasing sensitivity of methods to detect MRD is unlikely sufficient to increase accuracy of MRD-testing. In contrast, increased sampling (size and frequency) and assigning a high cut-off value (for example, > or = 10(-3)) to declare a MRD-test positive will increase sensitivity and specificity, respectively.

Biomarkers↗

PubMed2002

Superior survival associated with transplantation of matched unrelated versus one-antigen-mismatched unrelated or highly human leukocyte antigen-disparate haploidentical family donor marrow grafts for the treatment of hematologic malignancies: establishing a treatment algorithm for recipients of alternative donor grafts.

The purpose of this study was to compare transplantation outcomes in patients with hematologic malignancies who received marrow grafts from either phenotypically matched unrelated, one-antigen-mismatched unrelated, or highly human leukocyte antigen (HLA)-disparate family donors. Between 1993 and 2000, 139 patients underwent transplantation from unrelated donors (81 matched and 58 mismatched) and 48 patients received marrow grafts from family donors that were mismatched at 2, 3, or 4 of 8 HLA loci. All patients received a standardized conditioning regimen and a graft-versus-host disease (GVHD) prophylaxis schedule with the exception of recipients of haploidentical marrow grafts, who received antithymocyte globulin after bone marrow transplantation as additional immunosuppression. There was no statistically significant difference in the rate of engraftment, or the cumulative incidences of acute and chronic GVHD between any of the 3 groups. The 2-year cumulative incidence of relapse was lower in matched unrelated patients (25%, P =.01) and mismatched unrelated patients (26%, P =.014) than in haploidentical patients (42%). Transplant-related mortality was significantly higher in recipients of mismatched unrelated grafts (45%, P =.01) and haploidentical grafts (42%, P =.001) compared with recipients of matched unrelated marrow grafts (23%). This resulted in a significantly higher probability of overall survival for matched unrelated patients (58%) versus either mismatched unrelated (34%, P =.01) or haploidentical (21%, P =.002) patients. There was no statistically significant difference in survival between patients who received mismatched unrelated grafts versus those who received haploidentical grafts. This study supports a donor selection algorithm whereby patients who lack a closely matched family donor be offered a phenotypically matched unrelated donor if available. There is no apparent advantage to using a mismatched unrelated versus a highly HLA-disparate family donor.

Adolescent↗

PubMed2002

Autologous versus allogeneic unrelated donor transplantation for acute lymphoblastic leukemia: comparative toxicity and outcomes.

For patients with high-risk or relapsed acute lymphoblastic leukemia (ALL) lacking a related histocompatible donor, autologous (Auto) and unrelated donor (URD) transplantation are available options. We compared outcomes and toxicities in 712 patients with ALL (517 URD, 195 Auto) in first complete remission (CR1) or second complete remission (CR2) who underwent transplantation. All patients were <50 years old, although URD patientswere younger (median age, 14 versus 18 years, P < .002). The proportion of patients in CR1 versus CR2 was similar (36% versus 38%, P = .57), but more URD recipients than Auto recipients had high-risk karyotypes (25% versus 13%, P = .003) and white blood cell (WBC) counts > or =50 x 10(9)/L (33% versus 14%, P < .001). Engraftment was similar in URD and Auto recipients. Ex vivo purging delayed but did not prevent engraftment after Auto transplantation. Transplantation-related mortality was higher after URD transplantation (42%+/-8%) than after Auto transplantation (20%+/-12%) in CR1 (P = .004) and also in CR2. Conversely, relapse was more frequent after Auto transplantation in CR1 (Auto, 49%+/-12% versus URD, 14%+/-5%) and CR2 (64%+/-8% versus 25%+/-5%) (P < .0001). These findings showed net similar outcomes for these 2 transplantation choices. Transplantation in CR1 yielded similar 3-year survival rates for URD (51%+/-7%) and Auto (44%+/-12%), as did transplantation in CR2 (40%+/-6% versus 32%+/-9%, respectively). Multivariate regression analysis identified significantly better disease-free survival after the first 6 months in matched URD versus Auto in younger patients, in those in CR2 with CR1 >1year, WBC <50 x 10(9)/L, performance status > or =90%, and in those who have undergone transplantation since 1995. These comparative data suggest that both matched URD and Auto transplantation can yield extended survival. Although URD transplantation offers substantially better protection against leukemic relapse, improvements in allotransplantation safety and refinements in patient selection are required to better aid treatment decision making for the best overall survival.

Adolescent↗