PubMed Health⌕ Search

Biomedical subjects

R P Nelson

Publications and source records attributed to R P Nelson.

At least 19 recordsLinked to original sources
PubMed2006

Macrophage activation syndrome and other systemic inflammatory conditions after BMT.

Autologous hematopoietic cell transplantation (HCT) is being used to treat autoimmune diseases refractory to conventional therapy, including rheumatoid arthritis. Macrophage activation syndrome (MAS) is a descriptive term for a systemic inflammatory disorder that has been described in patients with juvenile rheumatoid arthritis (JRA). This case report describes a young adult with systemic JRA (sJRA) who developed MAS on day # 12 post-autologous transplantation. The patient developed high fever, laboratory evidence of disseminated intravascular coagulation (DIC), hepatocellular injury, pancytopenia and hyper-ferritinemia. All viral, bacterial and fungal studies were negative and the patient improved with high-dose glucocorticosteroid and cyclosporine therapy. Extreme elevation of serum ferritin was documented and helpful in monitoring response to therapy. A number of systemic inflammatory syndromes have been described in association with HCT. These include DIC, 'engraftment syndrome,' infection-associated hemophagocytic syndrome and familial hemophagocytic lymphohistiocytosis. Macrophage activation syndrome presents with features of DIC and is closely related or identical to infection-associated hemophagocytic syndrome. The diagnosis needs to be established in a timely fashion because early and appropriate treatment may improve outcome.

Adult↗
PubMed2006

Skin cancer after nonmyeloablative hematopoietic cell transplantation.

Squamous cell carcinoma (SCC) is the most common skin cancer in patients receiving immunosuppressive therapy, and is well documented to occur in patients that have undergone either solid organ transplantation or conventional myeloablative bone marrow transplantation. Nonmyeloablative hematopoietic cell transplantation (NMAT) provides transient, intensive immunosuppression, permitting allogeneic engraftment without ablating the marrow. The purpose of this report is to describe six patients that developed SCC (n=3), basal cell carcinoma (n=2), or malignant melanoma (n=2) over a period of 2-26 months following NMAT. All patients had myelodysplasia or acute myelogenous leukemia prior to transplantation. The authors demonstrate for the first time that patients who undergo NMAT are at risk for developing skin cancers and emphasize the need for close surveillance in the post transplantation period.

Basal Cell Carcinoma↗
PubMed2002

Nonablative hematopoietic cell transplantation for the treatment of metastatic renal cell carcinoma.

Nonablative hematopoietic cell transplantation (HCT) is becoming a preferred treatment for those recipients in whom the potential toxicity risk of standard ablative allogeneic therapy may be unacceptable. Graft-versus-malignancy effects may be generated against epithelial malignancies which are similar to the graft-versus-leukemia activity that is well documented in human hematological malignancies. Renal cell carcinoma has been shown to be responsive to immunotherapy with recombinant human cytokines and may be an ideal model for exploring this novel therapy. Clinical investigations have demonstrated regression of metastatic renal cell carcinoma occurs in some patients following nonablative allogeneic HCT. However, graft-versus-host disease remains a significant toxicity of nonablative transplantation, and further investigations are warranted to further evaluate this promising approach and to improve its safety.

Antineoplastic Agents↗
PubMed2001

Long-term virologic and immunologic responses in human immunodeficiency virus type 1-infected children treated with indinavir, zidovudine, and lamivudine.

Virologic and immunologic responses were examined for 33 human immunodeficiency virus (HIV)-infected children who participated for > or = 96 weeks in a phase 1/2 protocol of 16 weeks of indinavir monotherapy, followed by the addition of zidovudine and lamivudine. At week 96, a median increase of 199 CD4+ T cells/microL and a median decrease of 0.74 log(10) HIV RNA copies/mL were observed. The relationship between control of viral replication and CD4) T cell count was examined. Patients were categorized into 3 response groups on the basis of duration and extent of control of viral replication. Of 21 children with a transient decrease in virus load of > or = 0.7 log(10) HIV RNA copies/mL from baseline, 7 experienced sustained increases in CD4+, CD4+ CD45RA+, and CD4+ CD45RO+ T cell counts. CD4+ CD45RA+ (naive) T cells were the major contributor to CD4+ T cell expansion. Continued long-term immunologic benefit may be experienced by a subset of children, despite only transient virologic suppression.

Adolescent↗
PubMed2001

Immunologic reconstitution following bone marrow transplantation for X-linked hyper IgM syndrome.

X-linked hyper IgM syndrome (XHIM), caused by mutations of the CD40 ligand (CD40L) gene, is characterized by recurrent bacterial and opportunistic infections, an increased incidence of autoimmunity and malignancies, and immunodeficiency due to abnormal T/B cell interaction. Because of poor long-term prognosis, bone marrow transplantation (BMT) has been proposed as an alternative treatment. An 8-month-old boy with XHIM and a splice site mutation of CD40L underwent BMT using a fully matched sibling donor. Markers of engraftment and immunologic reconstitution were measured serially. After BMT, activated T cells expressed functional CD40L, and genomic DNA obtained from circulating white cells contained predominantly wild-type CD40L sequences. Serum immunoglobulin levels including IgE and antibody responses to recall antigens normalized, and immunization with the T-cell-dependent neoantigen, bacteriophage φX174, demonstrated amplification of the response and isotope switching. BMT provides a permanent cure for XHIM if a fully matched sibling donor is available and the procedure is performed before complications have occurred.

Bone Marrow Transplantation↗
PubMed2001

Lymphocytic interstitial pneumonitis, elevated IgM concentration, and hepatosplenomegaly in ataxia-telangiectasia.

An 8-year-old girl developed ataxia-telangiectasia. Western blotting of lysate revealed absence of the ATM protein, and 2 mutations in the ATM gene were found. Subsequently, the patient developed increased respiratory symptoms. Open lung biopsy revealed lymphocytic interstitial pneumonitis, which is not characteristic of ataxia-telangiectasia. There was a therapeutic response to glucocorticosteroid treatment.

Ataxia Telangiectasia↗
PubMed2001

Bone metabolism in children with human immunodeficiency virus infection receiving highly active anti-retroviral therapy including a protease inhibitor.

We measured serum osteocalcin levels in prepubertal children with human immunodeficiency virus (HIV) infection receiving highly active antiretroviral therapy including a protease inhibitor and uninfected control children. Osteocalcin values were significantly elevated in the HIV-infected patients. Though osteocalcin serves as an index of bone formation, it likely functions as a negative regulator of bone formation. Further study is necessary to determine whether protease inhibitors normalize bone physiology or decrease bone formation and reduce bone mineral density in children receiving these therapies.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Effects of bupropion sustained-release on sexual functioning and nocturnal erections in healthy men.

Many antidepressants are known to cause adverse sexual effects. Bupropion is an antidepressant with fewer reported adverse sexual effects. Studies of sexual side effects are often confounded by psychiatric and medical conditions affecting sexual function. In this study, the effects of bupropion on subjective and objective sexual functioning were measured in healthy men. Thirteen men without psychiatric or medical illness completed a 2-week, placebo-controlled, double-blind, crossover trial of bupropion sustained-release 300 mg/day. Subjects had a 1-week washout period between trials. Sexual function was measured using a validated, self-administered questionnaire and the RigiScan, an instrument measuring nocturnal penile tumescence and rigidity. No differences were found in self-reported sexual function, number of erections, total erection time, or penile rigidity in subjects taking bupropion compared with those taking placebo or baseline. These findings support that bupropion does not have subjective adverse sexual side effects and does not affect nocturnal erections in healthy men.

Adult↗
PubMed2001

A randomized, double-blind study of triple nucleoside therapy of abacavir, lamivudine, and zidovudine versus lamivudine and zidovudine in previously treated human immunodeficiency virus type 1-infected children. The CNAA3006 Study Team.

OBJECTIVES: Abacavir (ABC) is a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. We compared the efficacy, safety, and tolerability of combination therapy with ABC, lamivudine (3TC), and zidovudine (ZDV) versus 3TC and ZDV in antiretroviral experienced HIV-1-infected children over 48 weeks. METHODS: Two hundred five HIV-1-infected children who had received previous antiretroviral therapy and had CD4(+) cell counts >/=100 cells/mm(3) were stratified by age and by previous treatment. Participants were randomly assigned to receive ABC (8 mg/kg twice daily [BID]) plus 3TC (4 mg/kg BID) and ZDV (180 mg/m(2) BID; ABC/3TC/ZDV group) or ABC placebo plus 3TC (4 mg/kg BID) and ZDV (180 mg/m(2); 3TC/ZDV group). Participants who met a protocol-defined switch criteria (plasma HIV-1 RNA >0.5 log(10) copies/mL above baseline at week 8 or >10 000 copies/mL after week 16) had the option to switch to open-label ABC plus any antiretroviral combination or continue randomized therapy or withdraw from the study. RESULTS: The Kaplan-Meier estimates (95% confidence interval) of the proportion of participants who maintained HIV-1 RNA levels </=10 000 copies/mL for 48 weeks or more was significantly better in the ABC/3TC/ZDV group compared with the 3TC/ZDV group: 33% (23%-42%) versus 21% (13%-29%). At week 48, the proportions of participants with HIV-1 RNA </=10 000 copies/mL were 36% versus 26% for the ABC/3TC/ZDV and 3TC/ZDV groups, respectively, by intent-to-treat analysis. For the subgroup of participants with baseline HIV-1 RNA >10 000 copies/mL, a significantly higher proportion of participants in the ABC/3TC/ZDV group had HIV-1 RNA </=10 000 copies/mL compared with the 3TC/ZDV group (29% vs 12%) but no difference was observed in the subgroup of participants with baseline HIV-1 RNA </=10 000 copies/mL (78% vs 72%). The median changes from baseline in CD4(+) cell counts were greater in the ABC/3TC/ZDV group than in the 3TC/ZDV group. Few participants (3%) experienced abacavir-related hypersensitivity reaction. CONCLUSIONS: ABC, in combination with 3TC and ZDV, provides additional antiretroviral activity over 48 weeks, compared with combination therapy with 3TC and ZDV in antiretroviral experienced HIV-1-infected children. ABC was safe and generally well-tolerated and should be considered an active component of combination antiretroviral therapy in this pediatric population.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Immunoreconstitution after ritonavir therapy in children with human immunodeficiency virus infection involves multiple lymphocyte lineages.

OBJECTIVE: To evaluate lymphocyte reconstitution after protease inhibitor therapy in children with human immunodeficiency virus (HIV) infection. STUDY DESIGN: Forty-four HIV-infected children receiving ritonavir monotherapy followed by the addition of zidovudine and didanosine were evaluated during a phase I/II clinical trial. The cohort had a median age of 6.8 years and advanced disease (57% Centers for Disease Control and Prevention stage C, 73% immune stage 3) and was naive to protease inhibitor therapy. RESULTS: After 4 weeks of therapy, there was a significant increase in CD4(+) and CD8(+) T cells. CD4(+) T cells continued to increase, whereas CD8(+) T cells returned to baseline by 24 weeks. Unexpectedly, there was a significant increase in B cells. Changes in CD4(+) T-cell subsets revealed an initial increase in CD4(+) CD45RO T cells followed by a sustained increase in CD4(+) CD45RA T cells. Children <6 years of age had the highest increase in all lymphocyte populations. Significant improvement in CD4(+) T-cell counts was observed even in those children whose viral burden returned to pre-therapy levels. CONCLUSIONS: Early increases in lymphocytes after ritonavir therapy are a result of recirculation, as shown by increases in B cells and CD4(+) CD45RO and CD8(+) T cells. Children exhibited a high potential to reconstitute CD4(+) CD45RA T cells even with advanced disease and incomplete viral suppression.

Adolescent↗
PubMed1999

Glucocorticosteroid treatment for cerebrospinal fluid eosinophilia in a patient with ventriculoperitonial shunt.

BACKGROUND: Cerebrospinal fluid (CSF) eosinophilia commonly occurs in patients with ventriculoperitoneal (VP) shunts and is associated with shunt complications such as obstruction or infection. Glucocorticosteroids (GCS) are effective in reducing eosinophilia and eosinophils in skin, nasal mucosa, and airway epithelium. Effects of GCS on CSF eosinophils has not been reported. OBJECTIVE: To demonstrate glucocorticosteroid effects on the CSF eosinophil levels and to propose that GCS may be used as a therapeutic agent for CSF eosinophilia. RESULT: A case report of a patient with congenital hydrocephalus and a VP shunt developed CSF eosinophilia associated with latex allergy and shunt malfunction. Daily treatment with 2 mg/kg of methylprednisolone was associated with reduced peripheral eosinophilia and slightly reduced CSF eosinophil counts. Pulse methylprednisolone, 15 mg/kg, was associated with complete reduction of CSF eosinophils and prolonged VP shunt survival. CONCLUSION: Systemic glucocorticosteroids effectively reduce CSF eosinophils. Glucocorticosteroids may be beneficial for treatment of CSF eosinophilia associated with VP shunt malfunction.

Anti-Inflammatory Agents↗
PubMed1999

Persistent Sweet's syndrome occurring in a child with a primary immunodeficiency.

Sweet's syndrome (SS) occurs most commonly in association with inflammatory or neoplastic disorders. Only rarely has it been associated with immunodeficiency disorders. We describe a child with a T-cell immunodeficiency who had a persistent neutrophilic dermatosis that was histologically and clinically consistent with SS. SS associated with immunodeficiencies may occur as a reaction to an underlying infection or a defect in immunoregulation. Such patients, however, may not be able to produce the classic fever and neutrophilia associated with SS. They may fail to respond to standard treatment for SS and may suffer a prolonged and persistent course.

B-Lymphocytes↗
PubMed1999

Genetic linkage of hyper-IgE syndrome to chromosome 4.

The hyper-IgE syndrome (HIES) is a rare primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated levels of serum IgE. HIES is now recognized as a multisystem disorder, with nonimmunologic abnormalities of the dentition, bones, and connective tissue. HIES can be transmitted as an autosomal dominant trait with variable expressivity. Nineteen kindreds with multiple cases of HIES were scored for clinical and laboratory findings and were genotyped with polymorphic markers in a candidate region on human chromosome 4. Linkage analysis showed a maximum two-point LOD score of 3.61 at recombination fraction of 0 with marker D4S428. Multipoint analysis and simulation testing confirmed that the proximal 4q region contains a disease locus for HIES.

Chromosome Deletion↗
PubMed1998

Interleukin 12 deficiency associated with recurrent infections.

A 3-yr-old female patient exhibited interleukin 12 (IL-12) deficiency that was associated with recurrent episodes of pneumococcal pneumonia with sepsis and other infections in the absence of fevers. The patient's peripheral blood mononuclear cells (PBMCs) exhibited normal proliferative responses to antigens. Immune responses, including in vivo production of antibodies to diphtheria, tetanus, or pneumococcal antigens, were normal. Ig levels and B cell and T cell phenotypes were also normal. In contrast, IL-12 p70 heterodimer production was undetectable by using supernatants of the patient's stimulated PBMCs when compared with control cells treated similarly. Although present, interferon gamma (IFN-gamma) was reduced. The addition of recombinant IFN-gamma to control cells enhanced the production of IL-12 by up to sixfold. By contrast, IL-12 was undetectable in supernatants of the patient's cells in the presence of recombinant IFN-gamma. IL-12 p40 subunit mRNA by using the patient's PBMCs after stimulation with Staphylococcus aureus Cowan strain 1 or lipopolysaccharide was also undetectable by reverse transcription-PCR when compared with control cells. Production of IL-2, IL-6, tumor necrosis factor alpha, or IFN-gamma of the patient's PBMCs after appropriate stimulation was observed. This patient has either a defect in Staphylococcus aureus Cowan strain 1-lipopolysaccharide- or staphylococcal enterotoxin A-induced signaling pathways for the activation of IL-12 p40 gene expression, or an abnormality in the IL-12 p40 gene itself.

Adolescent↗
PubMed1998

Characterization of natural suppressor cells in human bone marrow.

Natural suppressor (NS) cells, which exert nonspecific suppressive activity in an unprimed manner, have been found in mouse, rabbit and monkey bone marrow (BM). In the present study, we characterize NS cells in human BM. NS activity was found in a fraction of low density (1.055-1.065 g/ml) BM cells that had been depleted of T cells, B cells, and monocytes. The NS activity was significantly decreased by the depletion of CD34+ or CD33+ cells but not CD56+ cells. The NS activity was indeed detected in isolated CD34+ cells and further enriched in CD34+CD33+ cells. Hematopoietic progenitor cells committed to the myeloid lineage were also enriched in the CD34+CD33+ cells, which significantly correlated to the NS activity. From these findings, it is strongly suggested that NS activity in human BM is exerted by the myeloid hematopoietic progenitors. Since cell-to-cell contact was not necessary for the action, NS cells seemed to secrete soluble mediator(s). Transforming growth factor-beta 1 and leukemia inhibitory factor were, however, not the candidates, based on experiments using neutralizing antibodies.

Antigens, CD↗
PubMed1998

Disturbances in biotin metabolism in children undergoing long-term anticonvulsant therapy.

BACKGROUND: In subjects undergoing long-term therapy with carbamazepine and/or phenytoin, reduced plasma concentrations of biotin have been reported. However, the diagnostic value of plasma biotin is unclear, in part because of the presence of significant plasma concentrations of biotin metabolites. Pathologic organic aciduria has also been reported with long-term anticonvulsant therapy, suggesting biotin deficiency, but no mechanism leading to deficiency has yet been determined. METHODS: In the current study, we sought to determine whether biotin catabolism was accelerated in children receiving long-term treatment with certain anticonvulsants and to assess biotin status as judged by urinary excretion of biotin and 3-hydroxyisovaleric acid, an organic acid that is an indicator of deficiency of a biotin-dependent enzyme. Seven children treated with carbamazepine and/or phenytoin and six treated with phenobarbital provided untimed urine samples. Sixteen healthy children receiving no anticonvulsants served as controls. Biotin and biotin metabolites were determined by high-performance liquid chromatography/avidin-binding assay. Urinary excretion of 3-hydroxyisovaleric acid was determined using gas chromatography/mass spectrometry. RESULTS: Bisnorbiotin excretion was increased significantly in the carbamazepine/phenytoin group and in the phenobarbital group. Biotin sulfoxide excretion was significantly increased in the carbamazepine/phenytoin group but not in the phenobarbital group. 3-Hydroxyisovaleric acid excretion was increased significantly in the carbamazepine/phenytoin group. However, only one child (carbamazepine/phenytoin group) had a decreased urinary excretion of biotin. CONCLUSION: These data provide evidence that long-term administration of some anticonvulsants can accelerate biotin catabolism, but the indicators of biotin status conflict.

Anticonvulsants↗