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Biomedical subjects

Robert P Nelson

Publications and source records attributed to Robert P Nelson.

10 recordsLinked to original sources
PubMed2006

Serial transplantation resulting in tolerance to an unrelated cord blood graft.

Unrelated cord blood (UCB) hematopoietic stem cells were serially transplanted into two human leukocyte antigen (HLA)-identical siblings with T cell, B cell, natural killer cell severe combined immunodeficiency. Brother A received a 4/6-matched, HLA DRbeta1-identical but class I-disparate UCB graft after myeloablative dosages of busulfan, melphalan, and antithymocyte globulin. He experienced complete donor chimerism, severe acute gastrointestinal graft-versus-host disease (GVHD), and limited chronic skin GVHD that resolved with treatment. Two years later, brother B received unfractionated marrow from brother A after reduced-intensity conditioning with cyclophosphamide and antithymocyte globulin. Brother B experienced mixed-donor (i.e. original UCB) chimerism and no histologically documented GVHD. Both brothers are clinically well; brother A is in a fully immunologically reconstituted state. The uneventful course and progressive increase in donor chimerism after the second transplantation indicates that hematopoietic cells derived from the older brother's marrow engrafted without causing GVHD, suggesting that acquired tolerance to disparate unrelated HLA antigens was achieved.

Antilymphocyte Serum↗
PubMed2006

Use of intravenous immunoglobulin in human disease: a review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology.

Human immunoglobulin prepared for intravenous administration (IGIV) has a number of important uses in the treatment of disease. Some of these are in diseases for which acceptable treatment alternatives do not exist. In this review we have evaluated the evidence underlying a wide variety of IGIV uses and make specific recommendations on the basis of these data. Given the potential risks and inherent scarcity of IGIV, careful consideration of the indications for and administration of IGIV is warranted.

Asthma↗
PubMed2006

Desensitization to imatinib in patients with leukemia.

BACKGROUND: Imatinib mesylate is a tyrosine kinase inhibitor used for the treatment of chronic myeloid leukemia and hypereosinophilic syndrome. Imatinib is associated with a variety of adverse cutaneous reactions, including urticaria, maculopapular exanthem, generalized exanthematous pustulosis, exfoliative dermatitis, and Stevens-Johnson syndrome. OBJECTIVE: To evaluate the safety and efficacy of oral desensitization by administering incremental dosages of imatinib mesylate to patients with leukemia who have had rashes associated with prior exposure. METHODS: Ten patients with leukemia and imatinib-associated recurrent rash underwent a 4-hour outpatient oral desensitization procedure. Beginning with 10 ng, we administered oral imatinib elixir in increasing dosages every 15 minutes. Patient outcomes were monitored by a return clinic visit and by telephone follow-up for a median of approximately 3 years. RESULTS: No episodes of anaphylaxis or serious adverse effects occurred during or immediately after desensitization. Four patients (all with urticaria) had no recurrence of rash after desensitization, and 4 had recurrent rash that resolved after temporary glucocorticosteroid and antihistamine administration. Two patients developed a recurrent rash 5 hours and several days after the procedure and were unable to resume therapy. CONCLUSION: This oral desensitization protocol appears to help some leukemic patients with recurrent rash tolerate imatinib mesylate, thus permitting continuation of this life-prolonging therapy. These findings suggest that some adverse cutaneous reactions to imatinib may be due to a hypersensitivity mechanism rather than a pharmacologic effect.

Administration, Oral↗
PubMed2006

Bacterial meningitis and inflammation.

PURPOSE OF REVIEW: Bacterial meningitis is a condition in which inflammation plays a role in disease resolution and also contributes to morbidity. Markers of inflammation may be used to aid in establishing diagnoses and prognoses. Medical management aimed at modulating the inflammatory response with broadly active, potent glucocorticosteroids has proved useful as an adjunct to antimicrobial therapy in selected patient populations. Basic immunobiologists, in describing components of the immune response that define its features of specificity, recognition, activation, regulation and tolerance induction have opened the door for the development of agents with focused activity that permit selective immunomodulation. New insights regarding management may result from a better understanding of the role of inflammation in bacterial meningitis. RECENT FINDINGS: Insights have been gained from recent basic and clinical scientific investigations that examine the components and consequences of inflammation in animal models and patients with bacterial meningitis. SUMMARY: This issue of Current Opinion in Neurology addresses recent reports that illustrate aspects of the inflammatory responses associated with bacterial meningitis that emphasize the need for early diagnosis, and contribute to prognosis assessment, and reviews the investigations that may predict the next steps in the evolution of clinical management.

Biomarkers↗
PubMed2005

Does linezolid cause lactic acidosis by inhibiting mitochondrial protein synthesis?

Linezolid, an oxazolidinone antibiotic, inhibits bacterial protein synthesis by binding to 23S ribosomal RNA (rRNA). We studied 3 patients who experienced lactic acidosis while receiving linezolid therapy. The toxicity may have been caused by linezolid binding to mitochondrial 16S rRNA. Genetic polymorphisms may have contributed to the toxicity in 2 patients.

Acetamides↗
PubMed2005

Newly diagnosed chronic granulomatous disease in a 53-year-old woman with Crohn disease.

BACKGROUND: Chronic granulomatous disease (CGD) is characterized by defective bactericidal activity of white blood cells, specifically, a defect in superoxide production. Patients experience infections, predominantly caused by catalase-positive bacteria and fungal organisms, that may be severe and life-threatening. Most cases of CGD are diagnosed in children; however, it may rarely go undiagnosed until adulthood in individuals with unexplained infections and granulomatous inflammation. OBJECTIVE: To describe an adult with Crohn disease and recurrent infections who was newly diagnosed as having CGD. METHODS: A 53-year-old woman with a history of liver abscesses and Crohn disease presented with Burkholderia cepacia pneumonia and required a right middle lobe resection. Nitroblue tetrazolium test results confirmed the diagnosis of CGD, and Western blot analysis revealed the absence of the 47-phagocyte oxidase protein. Levels of Crohn-associated specific antibodies to Saccharomyces cerevisiae and Escherichia coli outer membrane porin C were elevated. RESULTS: The patient, newly diagnosed as having CGD, was given intravenous trimethoprim-sulfamethoxazole, after which she improved clinically and was discharged from the hospital in stable condition to receive daily oral trimethoprim-sulfamethoxazole treatment. CONCLUSIONS: The concomitant occurrence of Crohn disease and CGD, both characterized by granulomatous inflammation, is noteworthy. This case study demonstrates that CGD should be considered in adults with recurrent infections, especially those caused by catalase-positive organisms, such as B cepacia.

Anti-Infective Agents↗
PubMed2005

Augmented high-dose regimen of cyclophosphamide, carmustine, and etoposide with autologous hematopoietic stem cell transplantation for relapsed and refractory aggressive non-Hodgkin's lymphoma.

Progressive disease is the major cause of treatment failure after autologous hematopoietic stem cell transplantation for relapsed or refractory non-Hodgkin's lymphoma. An augmented high-dose regimen of cyclophosphamide 7,200 mg/m2, carmustine 300 - 400 mg/m2, and etoposide 2,400 mg/m2 (CBV) was developed in an attempt to improve disease control post-transplant. Sixty-seven adult patients received augmented CBV followed by infusion of unpurged autologous peripheral blood stem cells. Thirty seven patients had relapsed after standard chemotherapy, 28 patients had primary refractory disease, and 2 patients had transformed lymphoma in first partial response. Treatment-related mortality was 4%. Actuarial four year overall survival and progression-free survival were 46+/-8% and 36+/-6%, respectively. Risk factors for disease progression were histologic involvement of marrow by lymphoma and infusion of increased numbers of CD34 + cells per kg in the stem cell autograft. The outcome for patients with relatively chemorefractory disease (defined as 25 - 49% reduction in tumor volume after salvage chemotherapy) was no different than that for patients with chemosensitive disease. Compared to standard high-dose CBV regimens, augmented CBV does not appear to have substantially improved disease control. Prospective study of the association between inferior progression-free survival and infusion of higher CD34 + cell doses in stem cell autografts is warranted.

Adult↗
PubMed2003

26. Immunomodulation and immunotherapy: drugs, cytokines, cytokine receptors, and antibodies.

The preceding chapters in this primer have provided an overview of the immune response that serves as a background for understanding potential sites for immune modulation and immunotherapy. A number of soluble growth and activation factors are released from various cell populations involved in the immune response. They play vital roles in the initiation, propagation, and regulation of immunologic responses. Pharmacologic immunomodulators include suppressive and stimulatory agents. Immunosuppressive therapies include antimetabolites, cytotoxic drugs, radiation, adrenocortical glucocorticosteroids, immunophilins, and therapeutic antibodies. The field of clinical immunostimulation is emerging as an important therapeutic modality for a number of immunodeficiency diseases, chronic viral infections, and cancer. These compounds will be discussed in terms of general principles, molecular targets, major indications, and adverse effects.

Adjuvants, Immunologic↗
PubMed2002

Interleukin 12 immunotherapy after autologous stem cell transplantation for hematological malignancies.

PURPOSE: To determine the safety, maximum tolerated dose,and biological effects of recombinant human IL-12 after autologous stem cell transplantation for cancer. EXPERIMENTAL DESIGN: Twelve patients with hematological malignancies (8 non-Hodgkin's lymphoma, 2 Hodgkin's disease, and 2 plasma cell myeloma) began interleukin (IL)-12 therapy at a median of 66 days after transplantation. Recombinant human IL-12 was given by bolus i.v. injection in doses of 30, 100, or 250 ng/kg once as an inpatient and then, after a 2-week hiatus, once daily for 5 consecutive days every 3 weeks on an outpatient basis. RESULTS: Common side effects included fever, chills, fatigue, nausea or vomiting, and asymptomatic elevation in serum liver function tests. Transient neutropenia and thrombocytopenia were also common, but no patient required platelet transfusion or had a neutropenic fever. Dose-limiting toxicities (diarrhea and elevated liver function tests) occurred in 2 of 3 patients treated in the 250 ng/kg cohort. Biological effects, including increases in serum IFN-gamma levels and transient lymphopenia involving CD4 T cells, CD8 T cells, B cells, and NK cells, were seen at all three dose levels. CONCLUSIONS: Biologically active doses of IL-12 can be given safely to patients after autologous stem cell transplantation for high-risk hematological malignancies. Further studies are indicated to assess the efficacy of IL-12 in this setting.

Adult↗