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Biomedical subjects

S Gillis

Publications and source records attributed to S Gillis.

At least 37 records · Page 2Linked to original sources
PubMed1998

Rhinocerebral mucormycosis treated with amphotericin B colloidal dispersion in three patients.

Rhinocerebral mucormycosis (zygomycosis) primarily affects diabetic or immunosuppressed patients and typically progresses rapidly, necessitating surgical excision and antifungal therapy with amphotericin B. Large doses of amphotericin B are required for cure, causing significant renal toxicity. Amphotericin B colloidal dispersion (ABCD; Amphocil, Sequus Pharmaceuticals, Menlo Park, CA) is a 1:1 complex of cholesteryl sulfate and amphotericin B, which results in significant reduction of toxicity, especially nephrotoxicity. We describe three patients with life-threatening rhinocerebral mucormycosis treated with ABCD. All patients had high serum creatinine levels due to prior treatment with amphotericin B; these levels reverted to normal during treatment with ABCD. Two patients with diabetes mellitus were cured after receiving a combination of surgery and ABCD therapy. The third patient, who had myelodysplastic syndrome, had an initial good response, with cure of the fungal infection; however, he eventually died of his primary illness. To the best of our knowledge, this is the first detailed clinical description of the treatment of mucormycosis with ABCD.

Adult↗
PubMed1997

Intensive plasmapheresis for severe thrombotic thrombocytopenic purpura: long-term clinical outcome.

Plasma exchange is of proven efficacy in the treatment of thrombotic thrombocytopenic purpura (TTP). In most series, less than 40 plasma exchanges (PE) were required for treatment and as many as two thirds of patients had permanent residual organ damage. We report on 4 patients who required very intensive PE for the resolution of TTP (37, 68, 102 and 108 procedures, respectively). The maximum number of PE procedures per attack was 102. None of these patients has any permanent sequellae of TTP (other than those associated with splenectomy, which was performed on all patients). Two of the female patients had uncomplicated pregnancies since resolution of the disease. We conclude that even highly refractory cases of TTP can have an excellent clinical outcome with intense PE therapy.

Adult↗
PubMed1997

gamma-Carboxyglutamic acids 36 and 40 do not contribute to human factor IX function.

The gamma-carboxyglutamic acid (Gla) domains of the vitamin K-dependent blood coagulation proteins contain 10 highly conserved Gla residues within the first 33 residues, but factor IX is unique in possessing 2 additional Gla residues at positions 36 and 40. To determine their importance, factor IX species lacking these Gla residues were isolated from heterologously expressed human factor IX. Using ion-exchange chromatography, peptide mapping, mass spectrometry, and N-terminal sequencing, we have purified and identified two partially carboxylated recombinant factor IX species; factor IX/gamma 40E is uncarboxylated at residue 40 and factor IX/gamma 36,40E is uncarboxylated at both residues 36 and 40. These species were compared with the fully gamma-carboxylated recombinant factor IX, unfractionated recombinant factor IX, and plasma-derived factor IX. As monitored by anti-factor IX:Ca (II)-specific antibodies and by the quenching of intrinsic fluorescence, all these factor IX species underwent the Ca(II)-induced conformational transition required for phospholipid membrane binding and bound equivalently to phospholipid vesicles composed of phosphatidylserine, phosphatidylcholine, and phosphatidylethanolamine. Endothelial cell binding was also similar in all species, with half-maximal inhibition of the binding of 125I-labeled plasma-derived factor IX at concentrations of 2-6 nM. Functionally, factor IX/gamma 36,40E and factor IX/gamma 40E were similar to fully gamma-carboxylated recombinant factor IX and plasma-derived factor IX in their coagulant activity and in their ability to participate in the activation of factor X in the tenase complex both with synthetic phospholipid vesicles and activated platelets. However, Gla 36 and Gla 40 represent part of the epitope targeted by anti-factor IX:Mg(II)-specific antibodies because these antibodies bound factor IX preferentially to factor IX/gamma 36,40E and factor IX/gamma 40E. These results demonstrate that the gamma-carboxylation of glutamic acid residues 36 and 40 in human factor IX is not required for any function of factor IX examined.

1-Carboxyglutamic Acid↗
PubMed1997

Danaparoid for cardiopulmonary bypass in patients with previous heparin-induced thrombocytopenia.

Anticoagulation for cardiopulmonary bypass in patients with heparin-induced thrombocytopenia requires the use of other anticoagulants. We report a case in whom this was achieved using the heparinoid danaparoid (Orgaran). Based on our experience and a review of the literature, we provide guidelines for managing these rare patients. A danaparoid dose substantially lower than that recommended by the manufacturer may minimize bleeding complications.

Anticoagulants↗
PubMed1997

Interactions of neutrophils and coagulation proteins.

Some of the interactions between coagulation factors and neutrophils are described. Proteins of the contact system, FXa, thrombin, and fibrinogen all bind to various sites on the neutrophil. This binding has a dual purpose: the assembly of coagulation complexes such as the prothrombinase complex and the contact system on the neutrophil membrane and influencing the various neutrophil functions including chemotaxis, aggregation, degranulation, and transendothelial migration. In addition, neutrophil elastase degrades many coagulation proteins, thus modulating both the thrombotic and the fibrinolytic systems. These interactions should be viewed in a wider context as part of the links between the coagulation and inflammation pathways.

Blood Coagulation Factors↗
PubMed1996

Granulocyte-macrophage colony-stimulating factor: an effective adjuvant for protein and peptide-based vaccines.

The current studies evaluate granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant. An important issue for developing vaccine therapy for human malignancy is identifying adjuvants that can elicit T-cell responses to proteins and peptides derived from "self" tumor antigens. GM-CSF, in vitro, stimulates the growth of antigen-presenting cells such as dendritic cells and macrophages. Initial experiments examined whether GM-CSF injected into the skin of rats could affect the number or character of antigen presenting cells, measured as class II major histocompatability complex expressing cells, in lymph nodes draining the injection site. Intradermal (id) inoculation of GM-CSF every 24 hours for a total of five inoculations resulted in an increase of class II+ fluorescing cells that peaked at the fourth inoculation. Subcutaneous (sq) inoculation resulted in an increase of class II+ fluorescing cells that peaked following the second inoculation, then decreased over time. Using this schema for "conditioning" the inoculation site, GM-CSF was administered id or sq for five injections and a foreign antigen, tetanus toxoid (tt), was given at the beginning or the end of the immunization cycle. Id immunization was more effective than sq at eliciting tt specific immunity. In addition, GM-CSF id, administered as a single dose with antigen, compared favorably with complete Freund's adjuvant (CFA) and alum in eliciting tt specific antibody and cellular immunity. We have shown that immunity to rat neu (c-erbB-2) protein, an oncogenic self protein, can be generated in rats by immunization with peptides derived from the normal rat neu sequence plus CFA. The current study demonstrates that rat neu peptides inoculated with GM-CSF could elicit a strong delayed type hypersensitivity reaction (DTH) response, whereas peptides alone were non-immunogenic. GM-CSF was as effective as CFA in generating rat neu specific DTH responses after immunization with a neu peptide based vaccine. Soluble GM-CSF is a potent adjuvant for the generation of immune responses to foreign proteins as well as peptides derived from a self tumor antigen.

Adjuvants, Immunologic↗
PubMed1996

Low molecular weight heparin for the prevention of veno-occlusive disease of the liver in bone marrow transplantation patients.

Hepatic veno-occlusive disease (VOD), a common complication of bone marrow transplantation (BMT), is a result of intensive conditioning by chemo-radiotherapy. Endometrial injury causes fibrin deposition in the affected hepatic venules, leading to abnormal laboratory parameters followed by lethal full-blown disease. Previous studies have shown that unfractionated heparin can prevent VOD in BMT patients. Since low molecular weight heparin (LMWH) preserves the antithrombotic, but not the anticoagulant, activity of unfractionated heparin, we initiated a pilot study to determine the safety of LMWH for the prevention of VOD. Sixty-one patients undergoing BMT (allogeneic, n=24; autologous, n=37) were randomized to receive subcutaneous injection of enoxaparin (40 mg/day x 1) or a placebo prior to BMT conditioning and until day 40 after transplantation or discharge from the hospital. LMWH administration did not influence marrow engraftment, nor was it associated with bleeding tendency. Hemorrhagic events occurred significantly less frequently (P=0.025) were shorter duration (P=0.006) in the LMWH group than in the placebo group. Time to platelet recovery was significantly shorter (16.5 vs 29.6 days, (P=0.0075), and platelet transfusion requirements were lower (p=0.05) in the LMWH patients. VOD parameters occurred less frequently in the experimental group, including duration of elevated bilirubin levels (P=0.01) and incidence of hepatomegaly (P=0.04). LMWH, which seems to enhance platelet recovery, may be safely administrated to BMT patients in an attempt to prevent VOD of the liver.

Adult↗
PubMed1996

Selective discharge of patients with acute myeloid leukemia during chemotherapy-induced neutropenia.

PURPOSE: It is common practice for patients with acute myeloid leukemia (AML) to be observed in hospital during the entire nadir after intensive chemotherapy. In an attempt to lessen the likelihood of developing infections with hospital acquired pathogens, we usually discharge patients upon completion of chemotherapy and follow them as outpatients. They are readmitted if fever develops. We evaluated the feasibility and safety of this practice. PATIENTS AND METHODS: We studied 29 patients with AML (median age 40 years, range 16-63) who were treated with intensive remission-induction and consolidation chemotherapy. Afebrile patients not receiving antibiotics were discharged immediately following chemotherapy and were followed every 3-4 days at the day care unit. Patients were instructed to return immediately if fever rose to 38.2 degrees C or a fever of 38 degrees C persisted for 2 hr. The 29 patients received a total of 86 courses. Following 50 courses, patients were discharged. These 50 ambulatory nadir periods (ANPs) were monitored. RESULTS: Median WBC and platelet counts on discharge were 2,900 per cubic millimeter (range 300-8,300) and 137,000 per cubic millimeter (range 17,000-618,000), respectively. Mean traveling time from the hospital by car was 1.6 hr (range 15 min-3 hr). In three of the 50 ANPs (6%), patients were not readmitted during their entire nadir. During 47 of the ANPs, patients returned to the hospital (because of fever in 44 cases), a mean of 7.2 days (range 1.0-12.7 days) after discharge. In 45 ANPs, patients were readmitted in good general condition. Four patients had life-threatening complications. Two patients were admitted in septic shock due to delay in seeking admission, but rapidly recovered. Two other patients died, one of cardiogenic shock within 24 hr of readmission and one 24 days later. Only one of the 11 gram negative bacteria cultured was resistant to mezlocillin and gentamicin. After 45 ANPs, patients were discharged a mean of 12.2 days (range 5-42 days) following readmission. We estimate that approximately 383 hospital days were saved by this policy, a mean of 7.6 days per patient, representing 16% of total inpatient hospital days. CONCLUSIONS: For AML patients who are reliable and without complicating medical conditions, selected discharge following chemotherapy is a low-risk practice and may reduce the incidence of infection with resistant hospital-acquired pathogens.

Acute Disease↗
PubMed1996

The thrombocytopenic purpuras. Recognition and management.

Idiopathic thrombocytopenic purpura (ITP) and thrombotic thrombocytopenic purpura (TTP), are distinct entities. ITP is a relatively common autoimmune disorder typically manifesting with isolated thrombocytopenia. The acute form, more common in children, is a self-limiting, often post-viral disease. Therapy, if indicated, usually consists of a brief course of steroids or intravenous IgG. Chronic ITP, more common in adults, rarely remits spontaneously. Most patients respond initially to steroids, but generally the disease relapses when steroids are tapered. Splenectomy offers a 70% chance of cure. A variety of treatment options exist for patients not responding to splenectomy. The treating physician must choose the most effective and least toxic treatment for the individual patient. TTP is a rare, often life-threatening, multisystem disease of unknown aetiology. Its hallmark is widespread occlusion of the microcirculation by platelet aggregates. The clinical symptoms usually respond dramatically to plasma exchange therapy. Steroids, antiplatelet agents and vincristine may also be useful. Splenectomy should be considered in patients with multiple relapses. More specific therapy awaits a fuller understanding of the pathogenesis of this disease.

Anti-Bacterial Agents↗
PubMed1995

Acute promyelocytic leukaemia with t(15;17) following treatment of Hodgkin's disease--a report of 4 cases.

BACKGROUND: Therapy-related acute myeloid leukemia (t-AML) is a recognized entity complicating successful therapy for Hodgkin's disease (HD) and other neoplasias after many years. This risk appears to be related to cumulative exposure to alkylating agents and procarbazine, while drugs affecting DNA--topoisomerase II, such as epipodophyllotoxins and anthracyclines, are also associated with t-AML developing after a much shorter latent period. PATIENTS AND METHODS: Of 56 patients with t-AML or myelodysplasia seen in our institutes during the period 1980-1994 we encountered 5 patients with acute promyelocytic leukemia (APL) all of whom had t(15;17). Four of these had been treated for HD with both chemotherapy and radiotherapy, and one with radiotherapy alone. RESULTS: To the best of our knowledge these appear to be the first cases of t-AML in HD with cytogenetically proven t(15;17). Similarly to other cases of t-APL reported after therapy for neoplasias other than HD, these patients also have a relatively favorable prognosis as seen in de-novo APL. CONCLUSIONS: Although rare, t-APL should be added to the list of late complications of therapy for HD.

Adult↗
PubMed1995

Late relapse following autologous bone marrow transplantation for acute myelogenous leukemia: case report and review of the literature.

Most relapses following autologous bone marrow transplantation (BMT) for acute myelogenous leukemia (AML) occur within 18 months. A patient is presented who relapsed 4 years after successful autologous BMT for AML. A review of the literature confirms this to be a rare event and may have been associated with extramedullary relapse of the leukemia.

Adult↗
PubMed1995

Effect of in vivo administration of IL-3 and IL-6, alone and in combination with G-CSF, GM-CSF or IL-1, on haematopoiesis, graft-versus-host disease and survival after murine haematopoietic stem cell transplantation.

We have explored the effect of IL-3 and IL-6, each alone and in combination with G-CSF, GM-CSF or IL-1, on neutrophil and platelet recovery in BALB/c mice (H-2d) given 10 Gy total body irradiation followed by 10(7) bone marrow cells and 10(6) spleen cells from C57BL6 donors (H-2b), as well as the effect of IL-3 alone and IL-6 alone on graft-versus-host disease (GVHD) and survival. Neither IL-3 alone nor IL-6 alone significantly increased the circulating absolute neutrophil count (ANC) at day 6 post transplant when compared with mice given saline injections (ANC 0.31 x 10(9)/l). G-CSF and IL-1, each alone, significantly raised the day-6 ANC (0.58 x 10(9)/l, p = 0.02; 0.67 x 10(9)/l, p = 0.007 respectively). However, IL-3, 200 ng twice daily, significantly increased the day-6 ANC when used in combination with GM-CSF (0.49 x 10(9)/l, p = 0.003) or with IL-6 (0.66 x 10(9)/l, p = 0.004), as well as with G-CSF (0.62 x 10(9)/l, p = 0.007) or with IL-1 (0.49 x 10(9)/l, p = 0.003). Apart from the combination with IL-3, IL-6 significantly raised the day-6 ANC only in combination with G-CSF (0.79 x 10(9)/l, p = 0.007). When used alone, both IL-6 and G-CSF raised the day-6 platelet count (312 x 10(9)/l, p = 0.02 and 309 x 10(9)/l, p = 0.01 respectively) compared with control mice (216 x 19(9)/l). IL-3 alone resulted in a platelet count of 303 x 10(9)/l (p = 0.06). In combination, only IL-3 with G-CSF significantly increased the value over that of saline control mice (328 x 10(9)/l, p = 0.02). IL-3 200 ng alone twice daily and IL-6 200 ng alone twice daily for 14 days post transplant resulted in survival not different from that of mice given saline injections. However, IL-3 500 ng twice daily for 14 days resulted in impaired survival and accelerated weight loss. In summary, while neither IL-3 nor IL-6 (nor GM-CSF) used alone accelerated neutrophil recovery post transplant, the combinations of IL-3 plus IL-6 and IL-3 plus GM-CSF did so. IL-6 (and G-CSF) accelerated platelet recovery post transplant, but combining IL-3 or IL-6 with the other cytokines was generally unsuccessful in this regard. Higher-dosage IL-3 appeared to accelerate graft-versus-host disease and impair survival, thus providing indirect evidence of the involvement of this cytokine in the mediation of GVHD.

Animals↗
PubMed1994

Understanding the dendritic cell lineage through a study of cytokine receptors.

Dendritic cells form a system of antigen presenting cells that are specialized to stimulate T lymphocytes, including quiescent T cells. The lineage of dendritic cells is not fully characterized, although prior studies have shown that growth and differentiation are controlled by cytokines, particularly granulocyte/macrophage colony-stimulating factor (GM-CSF). To further elucidate the nature and control of the dendritic cell lineage, we have studied the expression of specific cytokine receptors. Sufficient numbers of dendritic cells were purified from spleen and skin to do quantitative binding studies with radiolabeled M-CSF, GM-CSF, and interleukin 1 (IL-1). To verify the nonlymphoid nature of dendritic cells, we made an initial search for rearrangements in T cell receptor and immunoglobulin genes and none were found. M-CSF binding sites, a property of mononuclear phagocytes, also were absent. In contrast, GM-CSF receptors were abundant on mature dendritic cells, with approximately 3,000 binding sites/cell with a single Kd of 500-1,000 pM. Substantial numbers of high affinity (< 100 pM) IL-1 binding sites were identified as well; cultured epidermal dendritic cells (i.e., epidermal Langerhans cells) had 500/cell and spleen dendritic cells approximately 70/cell. Cross-linking approaches showed the 80-kD species that is expected of high-affinity type 1 IL-1 receptor. Anti-type 1 IL-1 receptor (R) mAbs also visualized these receptors by flow cytometry on freshly isolated epidermal dendritic cells. These results provide new evidence that dendritic cells represent a differentiation pathway distinct from lymphocytes and monocytes. Together with recent findings on the effects of IL-1 and GM-CSF on epidermal dendritic cells in situ (see Results and Discussion), the data lead to a proposal whereby IL-1 signals IL-1R to upregulate GM-CSF receptors and thereby, the observed responsiveness of dendritic cells to GM-CSF for growth, viability, and function.

Animals↗
PubMed1994

Bacterial laryngotracheitis associated with toxic shock syndrome in an adult.

Nonmenstrual toxic shock syndrome (TSS) in adults has been associated with various staphylococcal respiratory tract infections, including pharyngitis, tonsillitis, pneumonia, and postinfluenza respiratory tract infections. In children, nonmenstrual TSS has also been described as a complication of bacterial tracheitis. We describe the case of a 40-year-old woman who presented with laryngotracheitis as well as clinical and laboratory evidence of TSS. Culture of her sputum samples yielded pure growth of Staphylococcus aureus, which was shown to produce TSS toxin 1 (TSST-1). The patient responded promptly to therapy with iv clindamycin. We discuss the association of TSS with staphylococcal laryngotracheitis and the role of clindamycin in the treatment of TSS. To our knowledge, there are no previous reports of TSS complicating laryngotracheitis in adults.

Adult↗
PubMed1994

Increased levels of interleukin-1 are detected in nasal secretions of volunteers during experimental rhinovirus colds.

The potential involvement of interleukin-1 (IL-1) in the pathogenesis of experimental rhinovirus colds was examined. Nasal lavages were recovered before and for 5 days after rhinovirus infection from 44 subjects, 22 of whom were randomized to receive prophylaxis with glucocorticoids, while the rest received placebo. Immunoreactive IL-1 beta was significantly increased in subjects who were infected and symptomatic compared with noninfected volunteers or subjects who were infected but asymptomatic. Concentrations of immunoreactive IL-1 beta correlated with levels of kinins and albumin in lavage fluids. Studies of IL-1 bioactivity established that most activity in lavages from infected subjects was IL-1 beta. Glucocorticoid prophylaxis did not inhibit IL-1 production, nor did it significantly affect the symptomatic response to infection or, in a subset of patients, neutrophil infiltration. These data are consistent with the hypothesis that IL-1 could contribute to the pathogenesis of rhinovirus infections.

Adolescent↗