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Biomedical subjects

K A Nelson

Publications and source records attributed to K A Nelson.

At least 37 records · Page 2Linked to original sources

Wide-band acoustic spectroscopy of biological material based on a laser-induced grating technique.

A laser-induced transient grating technique enables fast noncontact acoustic measurements on transparent biological materials in a frequency range from tens of megahertz to 1 GHz. We have applied this method to the characterization of bovine vitreous and found high-frequency acoustic attenuation values to be close to those of water, with a quadratic dependence on frequency, in contrast to low-frequency data. The potential of the technique for studying other biological materials, such as human stratum corneum, is demonstrated.

Animals↗

In vitro susceptibility to pexiganan of bacteria isolated from infected diabetic foot ulcers.

During two clinical trials involving the treatment of 835 outpatients with infected diabetic foot ulcers, 2515 bacterial isolates, including 2337 aerobes and 178 anaerobes, were grown from cultures of the ulcers. The in vitro susceptibility of these isolates was determined to pexiganan, a peptide anti-infective evaluated in these clinical trials, and to other classes of antibiotics. Pexiganan demonstrated broad spectrum antimicrobial activity against Gram-positive and Gram-negative aerobes and anaerobes. The MIC90 values for the most common species among 1735 Gram-positive aerobes isolated, such as Staphylococcus aureus, coagulase-negative staphylococci, Group A streptococci, and Group B streptococci, were 16 micrograms/mL or less. Of 602 Gram-negative aerobes tested, the MIC90 values for pexiganan were 16 micrograms/mL or less for Acinetobacter, Pseudomonas, Stenotrophomonas, Citrobacter, Enterobacter, Escherichia, Klebsiella, and Flavobacterium species. Pexiganan had a MIC90 of 4 to 16 micrograms/mL against the anaerobic isolates of Bacteroides, Peptostreptococcus, Clostridium, and Prevotella species. Importantly, pexiganan did not exhibit cross-resistance with other commonly used antibiotics, including beta-lactams, quinolones, macrolides, and lincosamides. The broad spectrum in vitro antimicrobial activity of pexiganan against clinical isolates from infected diabetic foot ulcers supports its potential as a local therapy for infected diabetic foot ulcers.

Adult↗

The accuracy of hospital reports of organ donation eligibility, requests, and consent: a cross-validation study.

BACKGROUND: Many states require hospitals to complete a form for each patient who dies, reporting the patient's organ and tissue donation eligibility status, whether a request was made, and the outcome of the request. A study was conducted to determine the accuracy of state-required forms in documenting organ eligibility and procurement activities. METHODS: Four Level 1 trauma hospitals in northeast Ohio were sampled by using a weekly review of all deaths. Detailed chart reviews were conducted on a total of 2,270 deaths occurring during a six-month period in 1997, interviews with health care providers and staff members at organ procurement organizations were held, and records of the local Ohio Department of Health (ODH) were reviewed. Agreement between these data sources and the ODH form were compared to evaluate whether the ODH form correctly documented patients' eligibility status, occurrence of a donation request, and donation request outcome. Descriptive statistics and sensitivity and specificity analyses were completed. RESULTS: The quality of the information provided through these forms was variable. Problems included missing, inaccurate, and contradictory data. State reporting forms overrepresented the size of the organ donor pool by about four times, and requests for donation and consent to donation were inaccurately reported. Hospital form completion rates ranged from 12% to 82.6%. CONCLUSIONS: Basing the evaluation of hospital or statewide organ procurement performance on summary information provided by these forms would lead to an inaccurate picture of organ procurement activities in the state.

Brain Death↗

Attributions and affective reactions of family members and course of schizophrenia.

The authors tested an attribution-affect model of schizophrenic relapse attending to the role of families' positive affect (warmth) and negative affect (criticism). Coders listened to interviews of 40 family members taken from C. E. Vaughn, K. S. Synder, S. Jones, W. B. Freeman, and I. R. Falloon (1984) and rated their attributions of controllability for the symptoms and behaviors of their relatives with schizophrenia. For family members not designated as emotionally overinvolved, perceptions that their ill relatives' symptoms and behaviors were under the patients' control were related to family members' warmth and criticism and to patients' clinical outcomes. Of the affective reactions, only criticism predicted outcome. In addition, patients' use of street drugs was related to attributions, criticism, and outcome. Together these findings suggest that families' attributions and criticism are important in understanding the relationship between family factors and course of illness.

Adolescent↗

Donor-recipient sharing of HLA class II alleles predicts earlier recurrence and accelerated progression of hepatitis C following liver transplantation.

Both direct viral cytopathic effects and host immune responses appear to be important in the pathogenesis of hepatitis C virus (HCV) infection. Liver transplantation provides a means to explore the role of the immune system in the development of HCV-related liver damage through comparing the natural history of HCV in patients with different degrees of donor-recipient human leukocyte antigen (HLA) matching. We evaluated 36 patients with recurrent hepatitis C viremia following liver transplantation to determine whether hepatocellular injury or progression to bridging fibrosis occur more rapidly when donor and recipients share HLA alleles. HLA typing for the HLA-A and HLA-B loci was performed by serological techniques and PCR-based oligotyping was used to type alleles of the DRB1, DRB3, DQA1, and DQB1 loci. A median of eight liver biopsies, obtained during a median follow-up of 36 months, were reviewed per patient. Donor-recipient sharing of alleles of HLA-DQB1 or DRB1 was associated with more rapid development of recurrent hepatitis by univariate analysis (chi2=5.7, P=0.02 and chi2=5.54, P=0.02 respectively). However, only sharing of HLA-DRB1 alleles was identified as an independent predictor of reduced time to recurrent histologic injury by multivariate analysis (chi2 =5.74, P=0.02). Furthermore, sharing of HLA-DRB3 and histologic evidence of rejection were associated with more rapid progression to bridging fibrosis both by univariate methods (chi2=4.12, P=0.04 and chi2=4.66, P=0.03 respectively), and by multivariate analysis (chi2=13.01, P=0.001). These findings suggest that HLA class II-restricted immune responses may contribute to the pathogenesis of HCV-related liver injury in liver transplant recipients.

Adult↗

Prolonged allogeneic and xenogeneic microchimerism in unmatched primates without immunosuppression by intrathymic implantation of CD34+ donor marrow cells.

Engraftment of stem cell-enriched donor marrow implanted in the thymus of a foreign host might facilitate acceptance of donor-specific organ or tissue grafts. To test this hypothesis, allogeneic and xenogeneic CD34+ marrow cells from unrelated adult male baboons and humans were injected intrathymically in eight infant female baboons, both with and without standard cyclosporine-based immunosuppression. In allogeneic experiments, male (donor) cells, of both T- and B-cell lineages, were detected by PCR in the peripheral blood of all six recipients and persisted for at least 15 months in 2/4 recipients studied longtutudinally. Donor-derived skin grafts survived twice as long as third party grafts in unimmunosuppressed recipients. In xenogeneic protocols, human male (donor) cells were demonstrable for 7 and 15 months, respectively, in two baboon recipients with evidence that implanted human CD34+ cells had produced lymphoid progeny. Survival of donor-specific skin xenografts was prolonged in one of two recipients. These experiments demonstrate that the intrathymic injection of CD34+ marrow cells can result in long-lasting lymphohematopoietic microchimerism in unrelated primates even without immunosuppression and can alter donor-specific skin graft survival.

Animals↗

Results of a survey of infectious disease testing practices by organ procurement organizations in the United States.

BACKGROUND: Information related to infectious disease testing policies and practices of organ procurement organizations in the United States does not currently exist. METHODS: A total of 63 organ procurement organizations in the United States were surveyed during May 1996. Participants responded to a detailed questionnaire concerning infectious disease tests performed for tissue and solid organ donors and policies related to the reporting and notification of positive test results. RESULTS: The response rate was 77.8%. The majority of testing is performed by hospital laboratories with an expected turnaround time of 5 hr or less by 71% of organ procurement organizations. Almost all routinely perform screening tests for human immunodeficiency virus, hepatitis C virus, cytomegalovirus, syphilis, human T lymphocyte virus I, and hepatitis B surface antigen. Other tests are performed with greater variability. Although the majority of organ procurement organizations perform confirmatory tests when screening tests are positive, 35% do not perform confirmatory testing or do so only sporadically. There are a wide range of policies concerning the subsequent reporting of positive infectious disease tests and to whom results should be reported. CONCLUSIONS: Infectious disease testing policies of organ procurement organizations, particularly for solid organs, demonstrate variability in interpretation and perceived significance of positive test results, the initiation or need for reflex and confirmatory testing, the reporting of positive results, and to whom positive test results should be reported. There is a need for a consistent national policy for appropriate infectious disease testing and reporting of results.

AIDS Serodiagnosis↗

A prospective, within-patient, crossover study of continuous intravenous and subcutaneous morphine for chronic cancer pain.

The dose, efficacy, and side effects of continuous intravenous infusion (CIVI) of morphine were compared with continuous subcutaneous infusion (CSCI) of morphine in patients with chronic cancer pain. Eligible patients were referred to the Palliative Care Program and were receiving a stable dose of CIVI of morphine. The design was a within-patient, one-way crossover; in which each patient provided data before and after a switch from CIVI to CSCI of morphine. "Rescue" doses were 50% of the hourly dose given every 2 hours as needed. Morphine was infused intravenously (i.v.) and subcutaneously (s.c.) via a McGaw/AccuPro Volumetric Infusion Pump. After baseline data, including side effects and pain assessment, were obtained, patients were evaluated twice daily for toxicity and analgesic efficacy. Those who had a stable CIVI dose for 48 consecutive hr were crossed over to the CSCI at the same dose as the intravenous (i.v.) phase. A stable dose was defined as no dose change, four or less rescue doses in the previous 24 hr, and a pain rating of none or mild. CIVI was considered equal to CSCI if these criteria were maintained for 96 consecutive hr. Fifty-seven patients were entered, and 40 were evaluable (15 women and 25 men). The median age was 67 (range 30-83 years). All 40 participants, after maintaining a stable dose throughout the i.v. phase, crossed to the s.c. phase and remained on s.c. for at least 48 hr. Thirty-two patients maintained a stable dose throughout the i.v. and s.c. phases. The mean stable i.v. dose (day 2) was 5.05 mg/hr, and the mean stable s.c. dose (day 4) was 5.7 mg/hr (P = 0.01). The mean number of rescue doses on day 2 was 0.83 per 24 hr versus 0.80 per 24 hours on day 4 (P = 0.6). The mean categorical pain score on day 2 was 0.83, and on day 4, 0.85 (P = 0.7). The mean visual analogue scale (VAS) on day 2 was 22.9 mm versus 17.6 mm on day 4 (P = 0.1). The mean incidence of side effects on day 2 was 1.7, and on day 4, 2.0 (P = 0.2). No patient was withdrawn or had a dose reduction due to unacceptable toxicity. There were two reports of local toxicity (mild erythema) at the SC needle insertion point, which required a site change. All of our 40 patients had adequate pain control with CIVI and CSCI morphine. Of the eight participants who were not maintained on the same i.v. and s.c. dose, all had adequate pain control and a similar side-effect profile on a higher s.c. morphine dose. These data suggest that the i.v. and s.c. routes are equianalgesic for most patients when administered as a continuous infusion. Pain control and side-effect profiles are quite similar and acceptable. s.c. morphine is an excellent alternative to i.v. morphine in both inpatients and outpatients requiring parenteral morphine for pain.

Adult↗

High-dose oral dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic neuralgia.

N-methyl-D-aspartate (NMDA) receptor antagonists relieve neuropathic pain in animal models, but side effects of dissociative anesthetic channel blockers, such as ketamine, have discouraged clinical application. Based on the hypothesis that low-affinity NMDA channel blockers might have a better therapeutic ratio, we carried out two randomized, double-blind, crossover trials comparing six weeks of oral dextromethorphan to placebo in two groups, made up of 14 patients with painful distal symmetrical diabetic neuropathy and 18 with postherpetic neuralgia. Thirteen patients with each diagnosis completed the comparison. Dosage was titrated in each patient to the highest level reached without disrupting normal activities; mean doses were 381 mg/day in diabetics and 439 mg/day in postherpetic neuralgia patients. In diabetic neuropathy, dextromethorphan decreased pain by a mean of 24% (95% CI: 6% to 42%, p = 0.01), relative to placebo. In postherpetic neuralgia, dextromethorphan did not reduce pain (95% CI: 10% decrease in pain to 14% increase in pain, p = 0.72). Five of 31 patients who took dextromethorphan dropped out due to sedation or ataxia during dose escalation, but the remaining patients all reached a reasonably well-tolerated maintenance dose. We conclude that dextromethorphan or other low-affinity NMDA channel blockers may have promise in the treatment of painful diabetic neuropathy.

Administration, Oral↗

Human leukocyte antigen system and the immune response to it.

Immunologic rejection of tissue grafts follows recognition of donor alloantigens; either those resulting from ABO incompatibility of those encoded by the human major histocompatibility complex, HLA. Alloantigens encoded by HLA are present on membrane proteins that are expressed constitutively by tissues or whose expression can be induced by cytokines released during inflammation. Genes of the HLA complex are highly polymorphic resulting in variations in amino acid sequence that shape the peptide binding pocket of HLA molecules and define the complementary structure that interacts with the T lymphocyte receptor for antigen. Variants of HLA proteins expressed by the allografts that are not expressed by the recipient can stimulate the immune response to the allograft resulting in rejection both by humoral antibody and through attack by T lymphocytes. Class II HLA antigens on donor cells can stimulate these responses directly by contact with recipient T cells. However, rejection also may result when HLA antigens are released from the graft, processed to peptides, and presented to recipient T cells by cells expressing recipient HLA Class II molecules. Rejection can be avoided by preventing activation of T lymphocytes, by minimizing differences in HLA proteins between recipient and donor or by avoiding preexisting responses to donor HLA antigens.

Genes, MHC Class I↗

Thirty hours from referral to cross-clamp: a case study in organ procurement.

Families of potential organ donors might have requests that prolong the donation process. Organ procurement organizations therefore should be sensitive to these issues, or risk losing potential donors. This study focused on a case that in duration surpassed 30 hours from initial referral to cross-clamp in the operating room. This article examines the legal, family, and management issues involved in such a case.

Adolescent↗

A platelet monoclonal antibody inhibition assay for detection of glycoprotein IIb/IIIa-related platelet alloantibodies.

Post-transfusion purpura (PTP) and neonatal alloimmune thrombocytopenia (NAT) result from formation of alloantibodies to platelet membrane glycoprotein-associated antigens. The detection and identification of platelet-specific alloantibodies in patient sera is often complicated by the presence of co-existing HLA antibodies and/or more than one platelet specificity in the same serum. We describe a solid phase assay that specifically detects antibodies to platelet membrane associated alloantigens by measuring the ability of patient antisera to inhibit the binding of glycoprotein GPIIb or GPIIIa monoclonal antibodies to intact platelets. When tested in the GPIIIa assay against a panel of random platelet donors, the reactivities of two known PLAI antisera that also contained different HLA antibodies were highly correlated (r = 0.99) and allowed PLA phenotyping of the population. A standard direct binding platelet ELISA, on the other hand, was unable to accurately PLA phenotype the same population. The reactivities of two known Baka antisera (one containing additional anti-PLA2 and the other anti-Brb specificities) were highly correlated (r = 0.95) in the GPIIb assay, and Bak phenotype determination was similarly accomplished for a random platelet panel. Furthermore, a comparison of platelet phenotype results (using the monoclonal inhibition assay) and genotype results (using DNA analysis) for the PLA and Bak systems showed a concordance of 98% for 146 alleles tested. In conclusion, the platelet monoclonal antibody inhibition assay: (1) allows determination of platelet-specific alloantibodies in the presence of contaminating HLA antibodies and/or in sera containing multiple platelet alloantibodies; (2) allows accurate platelet phenotyping for the GPIIIa-associated PLA and GPIIb-associated Bak antigen systems; and (3) may be applicable to the detection of other known or even novel platelet glycoprotein-associated antigens.

Antibodies, Monoclonal↗

The cancer anorexia-cachexia syndrome.

PURPOSE: To review the research related to the anorexia-cachexia syndrome in patients with cancer, with attention to the etiology and symptomatic treatment. DESIGN: A comprehensive literature review using MEDLINE. RESULTS AND CONCLUSION: The anorexia-cachexia syndrome is a common problem in advanced cancer. Although many possible etiologies have been investigated, the cause has not been determined. Appropriate clinical evaluation is necessary to identify those patients who may respond to available, symptomatic treatments.

Animals↗

DNA cytometric and interphase cytogenetic analyses of paraffin-embedded hydatidiform moles and hydropic abortions.

The combined application of DNA cytometric and interphase cytogenetic analyses was used to find objective criteria for the differential diagnosis of complete hydatidiform mole, partial hydatidiform mole and hydropic abortion. DNA ploidy and G0/G1 exceeding rates were determined using image and flow cytometric analyses on paraffin-embedded tissues of 166 cases: 71 cases of complete mole, 20 cases of partial mole, and 75 cases of abortions. To determine the existence and histological distribution of cell subpopulations with numerical chromosome aberrations, interphase cytogenetic analysis using probes specific for chromosomes 1, X, and Y was applied to paraffin tissue sections of 23 cases: 12 cases of complete mole, 3 cases of partial mole, and 8 cases of abortions. In contrast to previously reported findings that complete moles are diploid, the results of this study showed that complete moles are DNA-polyploid (96 per cent), with high G0/G1 exceeding rates and a high frequency of numerical chromosomal aberrations in the trophoblast hyperplasia. The majority of the partial moles were DNA-triploid (55 per cent). This study, however, also showed the presence of DNA-polyploid partial moles (30 per cent). Abortions were DNA-diploid (60 per cent) or DNA-triploid (39 per cent). DNA cytometric analysis, especially image DNA cytometric analysis with determination of the G0/G1 exceeding rate, and interphase cytogenetic analysis provide objective measurements which are contributory in the differential diagnosis between complete mole, partial mole, and hydropic abortion.

DNA↗