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Biomedical subjects

R H Giller

Publications and source records attributed to R H Giller.

At least 19 recordsLinked to original sources
PubMed2007

Effect of myeloablative bone marrow transplantation on growth in children with sickle cell anaemia: results of the multicenter study of haematopoietic cell transplantation for sickle cell anaemia.

Although haematopoietic cell transplantation (HCT) is curative for sickle cell anaemia (SCA), concerns about its short- and long-term toxicities limit its application. A potential toxicity is an adverse effect on growth. To identify an HCT growth effect, serial height and weight measurements from 53 children and adolescents with SCA after receiving a transplant were compared to historical controls. Hierarchical Linear Models for longitudinal data were used for analysis. In general growth was not impaired by HCT for SCA in young children; however, diminished growth may occur if HCT is carried out near or during the adolescent growth spurt.

Age Factors↗
PubMed2005

Monosomy 7 associated with pediatric acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS): successful management by allogeneic hematopoietic stem cell transplant (HSCT).

Pediatric acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) with monosomy 7 is associated with poor disease-free survival when treated by conventional chemotherapy, immunosuppression or supportive measures. Hematopoietic stem cell transplant (HSCT) may improve outcomes; however, data to support this are limited. To better understand the curative potential of HSCT in these patients, all cases of AML and MDS with monosomy 7 treated by two transplant programs (1992 to present) were reviewed. A total of 16 patients were treated, all by allogeneic HSCT. Primary diagnoses were MDS (N = 5), therapy-related MDS (N = 3), AML (N = 5) and therapy-related AML (N = 3). In all, 11 patients (69%) survive event-free at 2 years with median follow-up of 986 days (range 330-2011 days). Toxicity caused deaths of the five nonsurviving patients, four of whom were transplanted with active leukemia. Allogeneic HSCT is effective therapy for childhood AML and MDS associated with monosomy 7, particularly for patients with AML in complete remission and MDS.

Acute Disease↗
PubMed2001

Peripheral placement of apheresis catheters in children: feasibility, safety, and efficacy in the collection of blood stem cells--initial experience.

An 8-F 24-cm-long apheresis catheter was placed in the basilic vein with imaging-guided percutaneous technique in 15 children undergoing leukapheresis for collection of autologous peripheral blood stem cells. There were no immediate or long-term complications. This is a low-morbidity procedure requiring minimal sedation that results in successful collection of peripheral blood stem cells and allows flow rates comparable to those with surgically placed central catheters.

Adolescent↗
PubMed1997

Successful program to prevent aspergillus infections in children undergoing marrow transplantation: use of nasal amphotericin.

Aspergillus infections in the pediatric bone marrow transplant (BMT) patients are usually fatal. We began the use of a prophylactic nasal spray of amphotericin in 1990. This nasal spray was provided in addition to low-dose intravenous amphotericin. During the time of this study, the number of fatal cases of aspergillus in the pediatric BMT population was reduced significantly from 13.8% to 1.8% (P < 0.0025) thereby suggesting that the use of nasal amphotericin in this population helps to prevent fatal aspergillus infections. The lack of significant side-effects and the ease of administration make this a very helpful preventive measure in the supportive care of pediatric bone marrow transplant patients.

Administration, Intranasal↗
PubMed1993

Cutaneous vasculitis in the newborn of a mother with cutaneous polyarteritis nodosa.

Vasculitis in an infant of a woman who had a long history of cutaneous polyarteritis nodosa is reported. During the neonatal period the child developed cutaneous vasculitis manifested by livedo reticularis, cutaneous nodules, and acral necrosis. The infant's vasculitis remitted by age 7 months. This is the third such report and strongly suggests the presence of a circulating factor that is capable of crossing the placenta and inducing cutaneous polyarteritis nodosa.

Adult↗
PubMed1992

Pulmonary resection for fungal infection in children undergoing bone marrow transplantation.

Recipients of bone marrow transplants for hematologic malignancies are at risk for a variety of infectious complications. We have reviewed our experience with six patients 2 to 15 years of age who developed significant fungal infections of the lungs before or after bone marrow transplant. No patient was known to have active fungal or bacterial infection at the time bone marrow transplant was performed. In two patients fungal infections were diagnosed before bone marrow transplant, and operations were performed to permit bone marrow transplant under optimal conditions. Four patients had pulmonary mycoses discovered after bone marrow transplant, and underwent operation 12 to 24 days following transplant. Operations consisted of lobectomy (three), multiple unilateral wedge resections (one), staged segmentectomy and contralateral wedge resection (one), and staged bilateral wedge resection (one). Survival following bone marrow transplant was achieved for 6 months and 11 months in patients undergoing lung resection before transplant, and for 24, 30, 39, and 60 days in patients undergoing lung resections after transplant. Bone marrow transplant recipients are at high risk of pulmonary mycoses, and a vigorous search for occult fungal infections should be carried out before transplant. Aggressive operative treatment of fungal infections of the lungs combined with antifungal chemotherapy before transplant may offer the best hope of extended survival.

Adolescent↗
PubMed1990

Operative treatment of Fusarium fungal infection of the lung.

Systemic fungal infections with Fusarium occur predominantly in immunocompromised patients and are usually fatal. We report a patient with acute lymphocytic leukemia and fusariosis involving the skin and lungs. This patient underwent antifungal chemotherapy and bilateral pulmonary resections. She subsequently had successful bone marrow transplantation. The results of this treatment suggest that this aggressive management of pulmonary fusariosis offers the best chance of survival.

Adolescent↗
PubMed1990

Bone marrow transplantation improves survival for acute lymphoblastic leukemia in relapse: a preliminary report.

Acute lymphoblastic leukemia of childhood is the most common malignant disease in children greater than 1 year of age. Chemotherapy has improved the survival of children with this disorder. More than 95% of children will achieve a remission with chemotherapy. However, 30% of children with acute lymphoblastic leukemia who achieved a remission will have a relapse sometime after successful remission-inducing chemotherapy. Although a second remission can be induced in most of these children, in 10-40% a remission cannot be induced or they relapse shortly thereafter and develop refractory leukemia. We present in this preliminary report the early results of therapy for refractory leukemia with an intensive preparative regimen for bone marrow transplantation including etoposide, cytosine arabinoside, cyclophosphamide, and fractionated total body irradiation. Transplantation was done in twenty-three patients with refractory leukemia. Projected survival at 917 days after transplantation in these patients is 43.4% +/- 11%. The survival of these patients so far is similar to the survival of children with acute lymphoblastic leukemia transplanted in second remission. All patients treated with this regimen who had transplantation in relapse were free of leukemia 27 days after transplantation. The results of this preliminary report suggest that an intensive preparative regimen can improve the outlook of refractory leukemia and may rescue some patients who otherwise would have died of their disease.

Adolescent↗
PubMed1989

Epstein-Barr virus: the hematologic and oncologic consequences of virus-host interaction.

Varicella-zoster virus (VZV) and Epstein-Barr virus (EBV) are two of the human herpesviruses. The others include herpes simplex virus (HSV) type 1, HSV type 2, and cytomegalovirus (CMV). In a series of two articles, we review the clinical diseases caused by VZV and EBV infections; we pay particular attention to the manifestations of these two viral infections in immunosuppressed and immunocompromised patients. In addition to the clinical reviews, each of the two articles begins with a brief discussion of the molecular aspects of VZV and EBV, respectively; this introduction describes features of the genome and immunogenic viral proteins which have clinical relevance. A model for pathogenesis is included. The first review concerns VZV infections. Recent data about the DNA sequence of the entire VZV genome are included, as well as a review of the VZV glycoproteins. Primary VZV infection (chickenpox) and VZV reactivation (zoster) are described in detail in both healthy individuals and people with cancer. The decade-long VZV vaccine trials in children with leukemia receive special emphasis because they have engendered considerable interest and debate. The second review (published here) covers EBV infections. This virus has been implicated in the causation of a wide variety of human hematological and oncological disorders, besides classical infectious mononucleosis. In particular, Burkitt's lymphoma, nasopharyngeal carcinoma, and lymphoproliferative disorders are strongly associated with EBV infection of the transformed cells. In addition, immunologically mediated cytopenias occasionally follow EBV infection. Finally, treatment regimens with antiviral chemotherapy and other agents are discussed for both VZV and EBV infections.

Burkitt Lymphoma↗
PubMed1989

Cellular and humoral immunity to varicella zoster virus glycoproteins in immune and susceptible human subjects.

To further delineate the immune responses that protect against serious primary varicella zoster virus (VZV) infection and inhibit viral reactivation, antibody responses and T lymphocyte reactivity to three major VZV glycoproteins, gpI, gpII, and gpIII, were studied. Individual viral glycoproteins were purified using murine monoclonal antibodies. Cellular immunity was measured by lymphocyte proliferation. Antibody responses were tested in enzyme-linked immunosorbent assays. Individual glycoproteins induced VZV-specific proliferation by mononuclear cells from 15 of 20 immune subjects. Serologic responses to the VZV glycoproteins occurred in 16 of 20 immune subjects. Of note, gpII served as a potent T and B cell antigen during both acute infection and convalescence. Cell-mediated responses to the glycoprotein antigens represented proliferation by T lymphocytes and required antigen presentation by adherent mononuclear cells. These findings indicate that virally encoded glycoproteins contain epitopes that stimulate VZV-specific cellular and humoral immune responses.

Antibodies, Viral↗
PubMed1988

Xanthoma disseminatum. An unusual histiocytosis syndrome.

The histiocytoses are a diverse group of illnesses that present a variety of diagnostic and therapeutic dilemmas. In this article, we describe the case of an 8-year-old boy with xanthoma disseminatum, a histiocytic disorder involving the skin, eyes, and brain. In our discussion, we have emphasized the clinical, pathologic, and radiographic features that distinguish this entity from clinically similar juvenile xanthogranuloma and Langerhans' cell histiocytoses (histiocytosis X) such as the Hand-Schuller-Christian syndrome. The importance of differentiating the various histiocytoses, in view of their varying natural histories and therapeutic responsiveness, is reviewed in relation to the new classification system for these disorders proposed by the Histiocyte Society.

Brain Diseases↗
PubMed1986

Reduced cellular immunity to varicella zoster virus during treatment for acute lymphoblastic leukemia of childhood: in vitro studies of possible mechanisms.

To determine the effect of antileukemic therapy on preexisting immunity to varicella zoster virus, we studied 20 children with acute lymphoblastic leukemia maintained in complete continuous remission for greater than 1 year. Cellular immunity was tested by lymphocyte proliferation in response to varicella antigen. Antiviral antibody was measured using the fluorescent antibody to membrane antigen technique. Reduced lymphocyte proliferation was found in 9 of 16 seropositive patients when compared to an age-related control group. On the other hand, antibody titers in patients receiving chemotherapy remained positive and were essentially unchanged from pretreatment values. Shingles occurred in two of nine children with diminished and none of seven patients with normal cellular immunity, suggesting that proliferative responses to varicella antigen may have predicative value in identifying patients at risk for viral reactivation. Additional studies were done to determine if defective antigen presentation or reduced lymphocyte responder-cell frequency could account for the subnormal proliferative responses. Intact presentation of varicella antigens by patient mononuclear cells to parental, virus-specific T-cell blasts suggested that antigen processing was not defective. However, varicella-specific responder-cell frequencies measured by limiting dilution analysis were found to be depressed in most patients, including some with normal proliferative responses. Our findings indicate that therapy for acute lymphoblastic leukemia in children can be associated with depressed cell-mediated immunity to varicella zoster virus even though patients remain seropositive. Further studies suggest that while monocyte-mediated antigen presentation remains intact, virus-specific lymphocyte numbers decline and probably contribute to decreased cellular immunity to varicella zoster virus in children being treated for leukemia.

Adult↗
PubMed1985

T-lymphocyte subpopulations and function during murine cytomegalovirus infection.

To study the effects of cytomegalovirus infection on T-lymphocyte subpopulations, we determined helper (Lyt 1.2) and suppressor (Lyt 2.2) T-lymphocyte subset numbers using monoclonal antibodies and measured lymphocyte responsiveness to mitogen during sublethal murine cytomegalovirus (MCMV) infection of 3-wk-old Balb/c mice. MCMV-infected mice had reduced Lyt 1.2 to Lyt 2.2 T-lymphocyte ratios on days 1, 3, 5, and 9 of infection. Alterations in T-lymphocyte subsets were accompanied by diminished lymphocyte response to concanavalin A. Lymphocyte responsiveness and Lyt 1.2 to Lyt 2.2 ratios were maximally reduced on day 5 of MCMV infection and correlated strongly with peak virus recovery from spleen, bone marrow, and peripheral blood leukocytes. These results indicate that acute MCMV infection of mice causes abnormalities in T-lymphocyte subset ratios and responsiveness to mitogen similar to the abnormalities observed in human cytomegalovirus infections. MCMV infection of mice is a useful model to study the mechanism by which cytomegalovirus infections induce altered T-lymphocyte subpopulations.

Animals↗
PubMed1985

Lysis of varicella zoster virus infected cells by lymphocytes from normal humans and immunosuppressed pediatric leukaemic patients.

Varicella zoster virus (VZV) is an important cause of morbidity and mortality in immunosuppressed children but little is known of the cellular mechanisms of VZV immunity. We therefore developed a clinically applicable system to study responses to VZV infected cells. Fresh blood mononuclear cells (MNC) from VZV immune donors killed VZV infected fibroblasts in an 18 h 51Cr release assay. The specificity for virus was confirmed by cold target inhibition. An enhancing role for HLA matching was demonstrated using targets mismatched for HLA, and blocking by antibodies to HLA framework and T cell subsets. Cytotoxicity was not blocked with anti-Ia or anti-VZV antibodies. Killing of VZV infected target cells was reduced in seven out of nine VZV antibody positive patients in remission who were receiving maintenance treatment for acute lymphocytic leukaemia. Three of these patients had normal lymphocyte proliferative responses to VZV. Of the two patients with normal cytotoxic responses to VZV, one had reduced proliferation. It therefore appears that presence of VZV antibody, T cell proliferative responses, and cytotoxicity are independently variable. Cytotoxicity may be more susceptible to immunosuppression than either antibody or T cell proliferation.

Antibodies, Viral↗
PubMed1984

Dissociation among Ia antigen expression, accessory cell function, and antigen processing in two acute monoblastic leukemia lines.

To better understand the role of Ia antigen expression, accessory cell function, and antigen ingestion in antigen presentation and the initiation of T cell proliferation, we studied these events in two acute monoblastic leukemia (AMoL) lines. The cell lines were positive for surface Ia antigen; one stimulated proliferation of the allogeneic mononuclear cells in mixed lymphocyte culture and culture supernatants from the other line contained interleukin 1 (IL-1) when tested for comitogen activity in a standard mouse thymocyte assay. The AMoL cells also contributed accessory factors for mitogen-induced proliferative responses by T cells. High numbers of cells of one of the lines tended to suppress mitogen induced T cell proliferation. Irradiated trinitrophenylated AMoL cells were able to stimulate TNP-specific HLA-DR matched T cell blasts to proliferate. However, when irradiated AMoL cells were cultured with a protein antigen (tetanus toxoid or varicella zoster) plus antigen-specific parental T cell blasts, antigen presentation failed to occur. Diminished phagocytosis by the AMoL cells, together with reduced catabolism of labelled antigen, is a likely explanation for this finding. Our results demonstrate that the concurrent presence of a complex protein antigen and Ia-positive monocytic leukemia cells capable of accessory function is alone insufficient to maintain antigen-specific T cell proliferation. Moreover, these findings suggest that antigen processing, involving ingestion and reexpression of antigenic determinants, is an essential aspect of antigen presentation not tightly linked to Ia antigen expression or IL-1 production in these AMoL lines.

Antigen-Presenting Cells↗