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Biomedical subjects

D Wuest

Publications and source records attributed to D Wuest.

18 recordsLinked to original sources
PubMed2001

N7: a novel multi-modality therapy of high risk neuroblastoma (NB) in children diagnosed over 1 year of age.

BACKGROUND: The N7 protocol for poor-risk neuroblastoma uses dose-intensive chemotherapy (as in N6 protocol [Kushner et al.: J Clin Oncol 12:2607-2613, 1994] but with lower dosing of vincristine) for induction, surgical resection and 2100 cGy hyperfractionated radiotherapy for local control, and for consolidation, targeted radioimmunotherapy with 131I-labeled anti-GD2 3F8 monoclonal antibody and immunotherapy with unlabeled/unmodified 3F8 (400 mg/m2). PROCEDURE: The chemotherapy consists of: cyclophosphamide 70 mg/kg/d x 2 and a 72-hr infusion of doxorubicin 75 mg/m2 plus vincristine 2 mg/m2, for courses 1, 2, 4, and 6; and cisplatin 50 mg/m2/d x 4 and etoposide 200 mg/m2/d x 3, for courses 3, 5, and 7. 131I-3F8 is dosed at 20 mCi/kg, which is myeloablative and therefore necessitates stem-cell support. RESULTS: Of the first 24 consecutive previously untreated patients more than 1 year old at diagnosis, 22 were stage 4 and two were unresectable stage 3 with MYCN amplification. Chemotherapy achieved CR/VGPR in 21 of 24 patients. Twenty patients to date have completed treatment with 131I-3F8, and 15 patients have completed all treatment. With a median follow-up of 19 months, 18 of 24 patients remain progression-free. CONCLUSIONS: Major toxicities were grade 4 myelosuppression and mucositis during chemotherapy, and self-limited pain and urticaria during antibody treatment. Late effects include hearing deficits and hypothyroidism.

Antibodies, Monoclonal↗
PubMed1998

Perioperative outcomes of major hepatic resections under low central venous pressure anesthesia: blood loss, blood transfusion, and the risk of postoperative renal dysfunction.

BACKGROUND: We have previously demonstrated that maintenance of a low central venous pressure (LCVP) combined with extrahepatic control of venous outflow reduced the overall blood loss during major hepatic resections. This study examined the overall outcomes and, in particular, renal morbidity associated with a large series of consecutive major liver resections performed with this approach. In addition, the rationale for the anesthetic management to maintain LCVP was carefully reviewed. STUDY DESIGN: All major hepatectomies performed between December 1991 and April 1997 were reviewed. The prospective Hepatobiliary Surgical Service database was merged with the Memorial Hospital Laboratory and Blood Bank databases to yield the nature of the operation, blood loss, blood product transfusions, outcomes, and levels of preoperative, postoperative, and discharge serum creatinine and blood urea nitrogen. RESULTS: A total of 496 LCVP-assisted major liver resections were performed, with no intraoperative deaths and an in-hospital mortality rate of 3.8%. The median blood loss was 645 mL. Sixty-seven percent of the patients did not require perioperative blood transfusion during surgery and the immediate 12 hours after surgery. The median number of blood transfusions was 2. Only 3% of the patients experienced a persistent and clinically significant increase in serum creatinine possibly attributable to the anesthetic technique. Renal failure directly attributable to the anesthetic technique did not occur. CONCLUSIONS: Major resection with LCVP allowed easy control of the hepatic veins before and during parenchymal transection. The anesthetic technique, designed to maintain LCVP during the critical stages of hepatic resection, not only helped to minimize blood loss and mortality but also preserved renal function.

Blood Loss, Surgical↗
PubMed1998

Phase II study of "dose-dense" high-dose chemotherapy treatment with peripheral-blood progenitor-cell support as primary treatment for patients with advanced ovarian cancer.

PURPOSE: We performed a pilot phase II study to evaluate the potential for delivery of rapidly sequenced high-dose chemotherapy treatments rescued with autologous peripheral-blood progenitor cells (PBP) in patients with previously untreated, advanced ovarian cancer. PATIENTS AND METHODS: A single cycle of mobilization was used, primed with cyclophosphamide (CPA)/paclitaxel (Txl) and filgrastim (granulocyte colony-stimulating factor [G-CSF]), followed by three cycles of high-dose carboplatin (CBDCA)/Txl and one cycle of high-dose melphalan (MEL), each rescued by PBP. We then analyzed the outcome for a total of 56 consecutive patients treated with high-dose chemotherapy as part of this program. RESULTS: In the phase II pilot, 21 patients were enrolled. There were no treatment-related deaths through 98 high-dose treatments, although 34 treatments were complicated by hospitalization, primarily for neutropenic fever. Seventy-six percent of patients experienced grade 3 to 4 gastrointestinal toxicity and 62% experienced grade 2 to 3 neuropathy. Five of 15 (33%) patients who underwent second-look surgery attained a pathologic complete response. In the overall analysis, 56 patients were reviewed. Forty-four patients were assessable for response by second-look surgery or clinical progression. Fifteen of 44 patients achieved a pathologic complete response (34%). The pathologic complete response rate in optimal-disease patients was 12 of 22 (55%), while only three of 22 (13%) suboptimal stage III and IV patients achieved a pathologic complete response. CONCLUSION: The Gynecologic Oncology Group has initiated a pilot phase II trial of this approach in patients with optimally debulked stage III ovarian cancer. There is no evidence to support the use of this or other aggressive regimens outside of a clinical trial.

Adult↗
PubMed1998

Factors affecting mobilization of peripheral blood progenitor cells in patients with lymphoma.

The objective of this study was to identify factors associated with poor mobilization of peripheral blood progenitor cells (PBPCs) or delayed platelet engraftment after high-dose therapy and autologous stem cell transplantation in patients with lymphoma. Fifty-eight patients with Hodgkin's disease or non-Hodgkin's lymphoma underwent PBPC transplantation as the "best available therapy" at Memorial Sloan-Kettering Cancer Center (New York, NY) between 1993 and 1995. PBPCs were mobilized with either granulocyte colony-stimulating factor (G-CSF) alone (n = 19) or G-CSF following combination chemotherapy (n = 39). Forty-eight of these patients underwent a PBPC transplant, receiving a conditioning regimen containing cyclophosphamide, etoposide, and either total body irradiation, total lymphoid irradiation, or carmustine. A median number of 4.6 x 10(6) CD34+ cells/kg were obtained with a median of three leukapheresis procedures. Mobilization of PBPCs using chemotherapy plus G-CSF was superior to G-CSF alone (6.7 x 10(6) versus 1.5 x 10(6) CD34+ cells/kg; P = 0.0002). Poorer mobilization of progenitor cells was observed in patients who had previously received stem cell-toxic chemotherapy, including (a) nitrogen mustard, procarbazine, melphalan, carmustine or > 7.5 g of cytarabine chemotherapy premobilization (2.0 x 10(6) versus 6.0 x 10(6) CD34+ cells/kg; P = 0.005), or (b) > or = 11 cycles of any previous chemotherapy (2.6 x 10(6) versus 6.7 x 10(6) CD34+ cells/kg; P = 0.02). Platelet recovery to > 20,000/microliter was delayed in patients who received < 2.0 x 10(6) CD34+ cells (median, 13 versus 22 days; P = 0.06). Patients who received > or = 11 cycles of chemotherapy prior to PBPC mobilization tended to have delayed platelet recovery to > 20,000/microliter and to require more platelet transfusions than less extensively pretreated patients (median, 13.5 versus 23.5 days; P = 0.15; median number of platelet transfusion episodes, 13 versus 9; P = 0.17). These data suggest that current strategies to mobilize PBPCs may be suboptimal in patients who have received either stem cell-toxic chemotherapy or > or = 11 cycles of chemotherapy prior to PBPC mobilization. Alternative approaches, such as ex vivo expansion or the use of other growth factors in addition to G-CSF, may improve mobilization of progenitor cells for PBPC transplantation.

Analysis of Variance↗
PubMed1995

Seroprevalence of human immunodeficiency virus-1, hepatitis B virus, and hepatitis C virus in patients having major surgery.

OBJECTIVE: To determine the proportion of major surgical procedures that involve patients having serologic evidence of infection with human immunodeficiency virus-1 (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) in a single center in Westchester County, New York. METHODS: Blood samples sent for transfusion screening or cross-match were tested blindly for HIV antibody (anti-HIV), HBV core antibody, HBV surface antigen (HBsAg), and HCV antibody (anti-HCV). Demographic characteristics and operation category were correlated with serologic results by univariate and regression analyses. RESULTS: Of 1,062 operations evaluated, 71 (6.7%, 95% confidence interval [CI95], 5.2% to 8.4%) were performed on patients with either anti-HIV, HBsAg, or anti-HCV. In 17 (1.6%, CI95, .93% to 2.5%) of these operations, the patient evidenced anti-HIV; in 15 (1.4%; CI95, .79% to 2.3%), HBsAg; and in 55 (5.2%, CI95, 3.9% to 6.7%), anti-HCV. Anti-HCV was detected significantly more often than anti-HIV (5.2% versus 1.6%, P < .001) or HBsAg (5.2% versus 1.4%, P < .001). Operations involving women aged 25 to 44 years had the highest proportion with serologic evidence of at least one of the three viruses (17.2%); of anti-HCV (15.3%); and of anti-HIV (6.7%). Logistic regression analysis found that being in the 25- to 44-year age group was associated significantly with infection with any virus (P < .001) and with anti-HCV (P < .001). The strongest logistic predictors of anti-HIV seropositivity were having anti-HCV seropositivity (P < .001), being age 25 to 44 years (P < .001), and having a general surgery operation (P = .002). CONCLUSION: The prevalences of serologic evidence of at least one of the three viruses (16.7%), of anti-HCV (14.5%), and of anti-HIV (5.6%) are high in patients aged 25 to 44 years undergoing major surgery at a tertiary-care medical center located in Westchester County, New York. Anti-HCV is more prevalent than anti-HIV or HBsAg and is predictive of anti-HIV seropositivity. Testing for anti-HIV alone would have detected only 24% of patients infected with a bloodborne pathogen. These data strongly underscore the importance of universal precautions.

Adult↗
PubMed1993

Treatment of cancer chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome by protein A immunoadsorption of plasma.

BACKGROUND: Chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (C-TTP/HUS) is a condition involving thrombocytopenia, microangiopathic hemolytic anemia, and progressive renal dysfunction that develops in 2-10% of patients with a history of malignant neoplasms treated with certain chemotherapeutic agents. Pathogenesis of the disease may depend on the following: (1) generation of endothelial lesions in the kidney microvasculature, resulting from drug toxic effects and/or generation of small soluble circulating immune complexes (CIC), and (2) generation of autoantibodies and/or CIC that trigger aggregation and deposition of platelets around the lesions. METHODS: Extracorporeal immunoadsorption treatment of plasma (PROSORBA columns, IMRE Corporation, Seattle, WA) to remove immunoglobulin G and CIC was evaluated in 55 patients for the potential to induce significant clinical benefits (increase in platelet count, decrease in hemolysis, stabilization of renal function) and longer survival. RESULTS: Response to therapy was achieved in 25 of 55 patients examined. Response was associated with an estimated 1-year survival rate of 61%, as compared with an estimated survival rate of only 22% in those who did not respond (P = 0.0001). Patients whose malignant neoplasms were in complete or partial remission at the time of development of C-TTP/HUS had a significantly higher estimated 1-year survival rate (74%) as compared with a historic control group of patients receiving other treatments (22%, P = 0.0161). Clinical responses were correlated with normalization of serum levels of CIC and complement components C3c and C4. There were no side effects associated with 75% of treatments. Immunoadsorption therapy was associated with generally mild to moderate manageable side effects, such as fever, chills, nausea/vomiting, respiratory symptoms, pain, hypertension, and hypotension, which were reported in 25% of procedures. CONCLUSIONS: This multicenter study establishes protein A immunoadsorption as an effective and safe treatment for cancer chemotherapy-associated TTP/HUS, an otherwise fatal disease.

Adult↗
PubMed1993

Transfusion therapy for severe anemia.

PURPOSE: We evaluated the safety and efficacy of a new transfusion regimen for children with severe anemia. PATIENTS AND METHODS: Twenty-two consecutive patients with severe anemia (hemoglobin < 5 g/dl) of gradual onset requiring transfusion of packed red blood cells (PRBC) were studied. The transfusion regimen consisted of continuous infusion of PRBC at the rate of 2 cc/kg/h until the desired volume was given. Throughout the transfusion, the patients were closely monitored for any clinical signs of heart failure. The rise in hematocrit per 1 cc of PRBC/kg transfused was computed for each patient. RESULTS: No patient developed any signs of cardiac failure or increase in the heart rate during or after the completion of transfusion. All patients had a decrease in the heart rate by the completion of transfusion. The mean decrease in the heart rate was 28% of the pretransfusion heart rate (range 12-44%). Excluding the four patients with sickle cell anemia, the remaining 18 patients had a mean increase in the hematocrit of 1.04% per 1 cc/kg of PRBC (range 0.85-1.28). CONCLUSION: We conclude that for children with severe anemia of gradual onset requiring transfusion therapy, continuous transfusion of PRBC at the rate of 2 cc/kg/h is a safe and effective regimen resulting in an increase in the hematocrit of approximately 1% for each 1 cc/kg of PRBC transfused in all patients, except patients with sickle cell anemia.

Acute Disease↗
PubMed1992

Peripheral blood stem cell mobilization by cytokines.

Hematopoietic stem cells circulate in the peripheral blood. These cells can be collected by apheresis techniques either in the unperturbed state, after mobilization following the administration of cytokines like G-CSF or GM-CSF, or during the phase of early blood count recovery following chemotherapy-induced myelosuppression. The number of cells collected following mobilization is greater than that obtained after apheresis in the unperturbed state. There are, however, qualitative differences between unperturbed and mobilized cells. Chemotherapy related mobilization can be potentially dangerous in that severe myelosuppression necessary to achieve mobilization can have serious consequences. There are no controlled studies that evaluate the relative merits of each method of collection. Regardless of the techniques employed peripheral blood stem cells can reliably accelerate hematologic recovery after potentially myeloblative therapy and provide an alternative to bone marrow support.

Blood Cell Count↗
PubMed1992

Hemopoietic stem cell processing: comparison of progenitor cell recovery using the Cobe 2991 cell washer and the Haemonetics V50 apheresis system.

Using 24 bone marrow (BM) harvests intended for cryopreservation and transplantation, we compared the use of the Cobe 2991 cell washer (2991) and the Haemonetics V50 apheresis system (HV50) for automated BM processing. Our in vitro data indicate that while the mononuclear cell (MNC) concentration of the HV50 product was significantly greater than that of the 2991, the overall MNC recovery of the two products was equivalent. In addition, although the concentration of CFU-GM and BFU-E in the products was equivalent, recovery of these progenitors in the 2991 product was significantly greater than those of the HV50 product. There was no significant difference in either the final product concentration or the overall recovery of cells bearing the primitive myeloid antigens, CD33 or CD34, between the two methods. The HV50 product volume, the red cell and the granulocyte mass were significantly lower than those of the 2991. We conclude that the advantages gained through the use of each machine should be evaluated within the context of the specific intention for the graft. Future advances in the identification and understanding of the primitive stem cell will aid in attempts to evaluate the methods used to isolate these cells.

Adolescent↗
PubMed1991

Marrow storage techniques: a clinical comparison of refrigeration versus cryopreservation.

Fifty-three patients were evaluated for a comparison of the efficacy, safety, and cost efficiency of bone marrow (BM) transplanted after either refrigeration or cryopreservation. Thirty-eight patients had BM stored at 4 degrees C for an average of 3 days and 15 patients had cryopreserved BM stored for an average of 56 days. The average number of cells harvested was 3.8 x 10(8)/kg. The time to WBC recovery greater than 1 x 10(9)/l was 17 days refrigerated and 23 days for cryopreserved BM. The time to platelet recovery greater than 20 x 10(9)/l was 24 days for refrigeration storage and 51 days for cryopreserved BM. Four of 38 patients with refrigerated vs. 4/15 patients with cryopreserved BM experienced delayed engraftment (p less than 0.05). Refrigeration storage requires no special equipment, is cheaper than and presents a safe and viable alternative to cryopreserved BM in reconstituting hemopoiesis following high-dose chemo-radiotherapy.

Adolescent↗
PubMed1988

Plasmapheresis in the treatment of acute relapsing inflammatory demyelinating polyradiculoneuropathy associated with human immunodeficiency virus infection: a case report.

Neurologic complications, including both the acute and chronic forms of inflammatory demyelinating polyradiculoneuropathy (IDP) are becoming more prevalent among patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related-complex (ARC). Although the etiology of the above radiculoneuropathies is not known, an autoimmune process has been postulated. Plasmapheresis has been reported to be of benefit in both the acute and chronic forms of these neuropathies. In this report we describe the use of plasmapheresis in the treatment of a patient with ARC and the acute relapsing form of IDP. The treatment consisted of an intensive course of plasmapheresis following his initial presentation and after an acute relapse which occurred several weeks after his initial presentation. Both the initial presentation and relapse involved respiratory compromise necessitating intubation and mechanical ventilation. In both instances marked clinical improvement was achieved after initiation of plasmapheresis. Thus, plasmapheresis may have a role in the management of acute relapsing IDP associated with human immunodeficiency virus infection.

AIDS-Related Complex↗
PubMed1982

Corticosteroid alteration of human monocyte to macrophage differentiation.

Human monocyte to macrophage differentiation in vitro is associated morphologically with an increased cell size, an increased number of lysosomes, and rough endoplasmic reticulum. Functional changes associated with monocyte to macrophage differentiation include increased tumoricidal activity and increased cell protein, acid phosphatase, and 5'-nucleotidase. Hydrocortisone succinate (HCS) at 2.5 microM markedly altered monocyte to macrophage differentiation: HCS inhibited the development of tumoricidal activity and the increased levels of cell protein, acid phosphatase, and 5'-nucleotidase. By transmission electron microscopy, macrophages incubated with HCS failed to develop an increased complement of lysosomes and developed an increased number of membrane-bound electron lucent vacuoles. Dexamethasone inhibited the development of tumoricidal activity at a 10-fold lower concentration than HCS. HCS also markedly inhibited monocyte 3H-uridine incorporation. Mechanisms of HCS alteration of monocyte differentiation are discussed. These data suggest that corticosteroid alteration of monocyte differentiation may be a mechanism of HCS immunosuppression in vivo.

Adrenal Cortex Hormones↗