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Biomedical subjects

D C Fisher

Publications and source records attributed to D C Fisher.

At least 19 recordsLinked to original sources
PubMed1998

Reduced mortality following bone marrow transplantation for breast cancer with the addition of peripheral blood progenitor cells is due to a marked reduction in veno-occlusive disease of the liver.

Clinical trials involving breast cancer in the Duke University Bone Marrow Transplant Program were evaluated to assess the association between type of hematopoietic support and treatment-related morbidity/mortality. Case histories of patients treated with high-dose chemotherapy and hematopoietic rescue on three separate protocols between 1986 and 1994 were reviewed. This included 307 patients with stage IV disease and 85 patients with high-risk (10 or more positive axillary lymph nodes) stage II or III disease. One hundred and twenty-eight of these patients were rescued with autologous bone marrow (BM) alone and 264 additionally received autologous peripheral blood progenitor cells (PBPC). The 100 day transplant-related mortality rate in those patients who received BM alone was 20.3%, with an overall mortality rate due to the high-dose chemotherapy procedure of 24.2%. The PBPC-treated group experienced a 100 day transplant-related mortality of only 6.1% and an overall trans-plant- related mortality of 10.2%. Sixteen of 31 deaths were attributed to veno-occlusive disease (VOD) in the group that received BM alone compared to only one VOD-related death in the PBPC group. These data demonstrate a marked improvement in transplant-related mortality which is related to the use of PBPC. This effect has been almost entirely due to a reduction in mortality from hepatic veno-occlusive disease.

Adult↗
PubMed1998

CD6+ T cell-depleted allogeneic bone marrow transplantation for non-Hodgkin's lymphoma.

For patients with non-Hodgkin's lymphoma (NHL) undergoing blood or bone marrow transplantation (BMT), the use of autologous grafts has often been preferred to that of allogeneic stem cells because of a significantly lower incidence of non-relapse mortality. If complications associated with allo-BMT could be minimized without compromising efficacy, then it might become a preferred strategy for certain subsets of patients. In this report, we describe the toxicity and long-term efficacy of T cell-depleted allogeneic BMT using anti-CD6 monoclonal antibody and complement alone to reduce the risk of GVHD and its sequelae. Twenty-two patients, aged 18-60 years, with high (n = 10), intermediate (n = 9), or low (n = 3) grade NHL underwent HLA-identical allogeneic BMT from siblings. Patients had either relapsed after at least one remission or never achieved a full remission with chemotherapy. Twenty patients had a history of marrow involvement. Bone marrow was depleted of CD6+ T cells with T12 monoclonal antibody and complement as the sole form of GVHD prophylaxis. Stable hematopoietic engraftment occurred in all 22 patients. Four patients developed grade 2 and 1 patient grade 3 GVHD (23% grades 2-4 GVHD). Chronic GVHD has occurred in three patients. Treatment-related mortality was very low. Only one patient died while in remission. Thirteen patients are alive and free of disease with a median follow-up of 30 months. Estimated event-free and overall survivals are 54 and 59%, respectively. CD6 allogeneic marrow transplantation is associated with a low risk of transplant-related complications and may offer advantages for certain patients with recurrent NHL felt to be at high risk for relapse after autologous transplantation.

Adolescent↗
PubMed1998

Identification of bacterial isolates obtained from intestinal contents associated with 12,000-year-old mastodon remains.

Mastodon (Mammut americanum) remains unearthed during excavation of ancient sediments usually consist only of skeletal material, due to postmortem decomposition of soft tissues by microorganisms. Two recent excavations of skeletal remains in anoxic sediments in Ohio and Michigan, however, have uncovered organic masses which appear to be remnants of the small and large intestines, respectively. Macrobotanical examinations of the composition of these masses revealed assemblages of plant material radiocarbon dated to approximately 11,500 years before the present and thought to be incompletely digested food remains from this extinct mammal. We attempted to cultivate and identify bacteria from the intestinal contents, bone-associated sediments, and sediments not in proximity to the remains using a variety of general and selective media. In all, 295 isolates were cultivated, and 38 individual taxa were identified by fatty acid-methyl ester (FAME) profiles and biochemical characteristics (API-20E). The taxonomic positions of selected enteric and obligately anaerobic bacteria were confirmed by 16S ribosomal DNA (rDNA) sequencing. Results indicate that the intestinal and bone-associated samples contained the greatest diversity of bacterial taxa and that members of the family Enterobacteriaceae represented 41% of all isolates and were predominant in the intestinal masses and sediments in proximity to the skeleton but were uncommon in the background sediments. Enterobacter cloacae was the most commonly identified isolate, and partial rDNA sequencing revealed that Rahnella aquatilis was the correct identity of strains suggested by FAME profiles to be Yersinia enterocolitica. No Bacteroides spp. or expected intestinal anaerobes were recovered. The only obligate anaerobes recovered were clostridia, and these were not recovered from the small intestinal masses. Microbiological evidence from this study supports other, macrobotanical data indicating the intestinal origin of these masses. Whether these organisms are direct descendants of the original intestinal microbiota, however, cannot be established.

Animals↗
PubMed1998

High-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation in mantle-cell lymphoma: no evidence for long-term remission.

PURPOSE: The role for high-dose therapy and autologous stem-cell transplantation in mantle-cell lymphoma (MCL) is unknown. We retrospectively analyzed patients with chemosensitive disease who underwent high-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation (ABMT) for MCL in first remission, as well as following relapse from conventional therapy. PATIENTS AND METHODS: Between August 1985 and April 1996, 28 patients underwent ABMT using a uniform ablative regimen with cyclophosphamide and total-body irradiation (TBI) and a bone marrow-purging regimen. Re-review of original tissue demonstrated that all patients had morphologic, phenotypic, and genotypic characteristics of MCL. MCL was the original diagnosis in 21 patients, whereas seven patients had a prior diagnosis of diffuse small cleaved-cell lymphoma. RESULTS: Twenty patients received multiple regimens before ABMT, while eight underwent ABMT in first complete remission (CR)/partial remission (PR) following CHOP induction. At bone marrow harvest, only 18% of patients were in CR and overt BM infiltration was present in 57%. Following cyclophosphamide/TBI, no treatment-related deaths were seen. Nineteen of 28 patients have relapsed at a median time of 21 months (range, 3 to 70). Of eight patients transplanted in first CR/PR, five have relapsed. Nine patients are in continuous CR with a median follow-up time of 24 months (range, 10 to 135). Disease-free survival (DFS) and overall survival (OS) are estimated to be 31% and 62% at 4 years, respectively. CONCLUSION: ABMT using cyclophosphamide/TBI conditioning may at best be effective in only a small fraction of patients with relapsed MCL. The lack of plateau with a median follow-up time of 24 months suggests cure may not be achievable. The role of this therapy in patients in first remission requires more study using better induction therapy to enhance the CR rate before ABMT.

Adult↗
PubMed1997

Cyclophosphamide, doxorubicin, vincristine, prednisone dose intensification with granulocyte colony-stimulating factor markedly depletes stem cell reserve for autologous bone marrow transplantation.

Hematopoietic growth factors allow dose escalation of chemotherapy. This approach may potentially reduce the quality and quantity of hematopoietic stem cells. The capacity of stem cells recovered after dose intensification to support myeloablative therapy is unknown. In patients with previously untreated advanced follicular lymphoma, trilineage hematopoietic engraftment was compared in two sequential trials of induction therapy (standard dose cyclophosphamide, doxorubicin, vincristine, prednisone [CHOP] without growth factors or dose intensification CHOP supported by granulocyte colony-stimulating factor [G-CSF ]) followed by identical myeloablative therapy and autologous stem cell support. Neutrophil, platelet, and red blood cell (RBC) engraftment were compared on days 100, 180, and 360 after stem cell reinfusion. Despite similar patient characteristics including reinfusion of comparable numbers of marrow mononuclear cells, after stem cell transplantation, a highly significant prolongation of neutrophil and platelet engraftment was seen in patients who received high dose CHOP and G-CSF in comparison to standard dose CHOP. These findings suggest that dose intensified chemotherapy and G-CSF recruited stem cells into a proliferative phase and that G-CSF allowed retreatment at a time when stem cells were susceptible to damage by cytotoxic therapy. Such inadequate hematologic engraftment after myeloablative therapy might be avoided by either shortening the time that growth factor support is administered, lengthening the interval between cycles, or attempting to repetitively harvest additional stem cells either from the marrow or peripheral blood. Therefore, intensification of chemotherapy with growth factor support must be used with caution if stem cells are to be used to support myeloablative therapy.

Adult↗
PubMed1996

Thrombotic microangiopathy as a complication of high-dose chemotherapy for breast cancer.

Five hundred and eighty-one patients with stage II-IV breast cancer were treated at Duke University Medical Center with high-dose chemotherapy, followed by hematopoietic support. All patients received a conditioning regimen of cyclophosphamide, cisplatin and carmustine. Of these patients, 15 (2.6%) developed symptoms similar to the hemolytic-uremic syndrome with evidence of thrombotic microangiopathy (TMA). The time of onset ranged from 75 days to 281 days post-transplant, with a median of 143 days. Hemolytic anemia and thrombocytopenia, without alternative cause, were required for diagnosis. All patients were treated with steroid therapy. In addition, 12 patients were treated primarily with plasmapheresis, and received a median of 46 treatments. Additional therapy included staphylococcal protein A column apheresis (eight patients), vincristine (three patients) and danazol (one patient). The mortality rate was 11 of 15 patients (73%). These patients had a median survival of 41 days from diagnosis of TMA (range 2-76 days). The four survivors are alive at 76, 186, 1837 and 2387 days from diagnosis of TMA. Three of these patients received twice daily plasmapheresis and protein A column apheresis therapy. One patient recovered without specific therapy. TMA is an infrequent complication of high-dose chemotherapy, but is associated with a high mortality. It frequently follows significant pulmonary drug toxicity. Survival may be improved with early diagnosis and aggressive plasmapheresis therapy.

Anemia, Hemolytic↗
PubMed1996

Central nervous system lymphoma not detectable on single-photon emission CT with thallium 201.

A 33-year-old man with acquired immunodeficiency syndrome had an erosive supraglottic mass visible on CT scans of the neck; biopsy was postponed because of the patient's debilitated condition. Two weeks later, he was admitted with altered mental status; an MR image of the brain obtained at that time showed multiple bilateral mass lesions, the largest of which was 5 cm. Findings on a thallium-201 single-photon emission CT (SPECT) scan of the brain were normal. Ten days later, the patient died and autopsy showed both the neck and the brain lesions to be large-cell lymphoma. This case is counterevidence to the reported 100% sensitivity of thallium-201 brain SPECT for demonstrating lymphoma of the central nervous system.

Adult↗
PubMed1995

The incidence of patent foramen ovale in 1,000 consecutive patients. A contrast transesophageal echocardiography study.

STUDY OBJECTIVE: Patent foramen ovale (PFO) is present in 10 to 35% of people and has been reported to be an important risk factor for cardioembolic cerebrovascular accidents (CVAs) and transient ischemic attacks (TIAs), especially in younger patients. While contrast transthoracic echocardiography has been used to detect PFO, contrast transesophageal echocardiography (TEE) has a greater sensitivity. Prior studies reported the incidence of PFO in patients presenting with a CVA or TIA. DESIGN: To determine the incidence of PFO in a more general population, we reviewed 1,000 consecutive TEEs performed with contrast and color Doppler for the presence of PFO and other cardioembolic risk factors, including atrial septal aneurysm (ASA), aortic plaque, atrial fibrillation (AFib), and atrial thrombi. While imaging with monoplane or biplane TEE, multiple injections of agitated saline solution were injected during cough or Valsalva maneuver to detect flow through a PFO. PATIENTS: There were 482 male and 518 female patients with mean age of 60 +/- 17 years (range 11 to 93 years). RESULTS: Patent foramen ovale was found in 9.2% of all patients and, though seen in all age groups divided by decade, the incidence in patients aged 40 to 49 years was greater than those aged 70 to 79 years (12.96% vs 6.15%, p = 0.03). Contrast TEE had a much higher detection rate than color Doppler alone. Importantly, there was no greater incidence of PFO in patients with CVA vs those without CVA, or in male vs female patients. Also, there was a very strong correlation between the presence of ASA and PFO (p < .001). CONCLUSION: Thus, PFO detected by TEE, frequently seen with ASA, is seen in all age groups and does not in itself present a risk factor for CVA. The association of PFO with peripheral thrombosis and CVA needs further study.

Adolescent↗
PubMed1995

How well do family physicians manage sexually transmitted diseases?

OBJECTIVE: To identify gaps in knowledge about sexually transmitted diseases (STDs) and evaluate practice. DESIGN: We compared how 49 family physicians managed 249 episodes of STDs with the recommendations of the 1988-1989 Canadian STD management guidelines. (The study took place before revised guidelines were distributed in late 1992.) SETTING: Family physicians' practices throughout Canada. PARTICIPANTS: Physicians recruited by the National Research System from among the members of the College of Family Physicians of Canada. These physicians had been in practice for a mean of 9 years; 43 were Certificants of the College. MAIN OUTCOME MEASURES: Family physicians' self-reported episodes of sexually transmitted disease evaluated in light of current Canadian guidelines. RESULTS: Of the 249 episodes studied, 215 (86.3%) were treated effectively, and 34 (13.7%) were judged to have been treated ineffectively. Of the 215 effective treatments, 67 (31.2%) were not completely in agreement with current guidelines. CONCLUSION: Experienced family physicians with postgraduate training usually manage STDs well. The number of ineffective treatments and effective treatments not following the 1988-1989 guidelines, especially for pelvic inflammatory disease, indicates that information on managing certain STDs and syndromes should be made available to all family physicians in a format that is easy to read and use.

Adolescent↗
PubMed1994

Advances in the clinical use of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor to intensify cancer chemotherapy.

The majority of human malignancies remain refractory to current therapeutic regimens. Several animal and human models provide evidence of a dose-response effect of many chemotherapeutic agents in a variety of malignancies. In recent years dose escalation with bone marrow transplant support has provided encouraging evidence that increased doses of antineoplastic agents may overcome clinical drug resistance. However, this approach has been limited by hematologic toxicity. This problem has been abrogated by the development and use of hematopoietic growth factors. These agents now offer the oncologist new treatment opportunities.

Chemotherapy, Adjuvant↗
PubMed1987

Preexposure of resting B cells to interferon-gamma enhances their proliferative response to subsequent activation signals.

In this report we demonstrate that pretreatment of resting splenic B cells with IFN-gamma increases their mitogenic response to subsequent activating stimuli. This effect is completely blocked by neutralizing anti-IFN-gamma antibodies. By contrast, a similar effect induced by partially purified BCGF is not completely inhibited by anti-IFN-gamma antibody, inferring that as in the mouse, a B-cell-specific factor may also induce increased responsiveness to mitogens in resting B cells. The mechanism of this response was analyzed. Phenotypic and cell cycle analyses of the IFN-gamma-treated cells following activation were not significantly different from control cells with respect to kinetics, although as expected from thymidine uptake, more cells were actively cycling. Even when a very early manifestation of cell activation, Ca2+ flux was examined, no response to IFN-gamma alone was evoked, and the response to subsequent activation was identical to that of control cells. These data show that IFN-gamma did not directly activate B cells, but primed B cells in a manner which amplified subsequent mitogenesis.

Antibodies, Anti-Idiotypic↗
PubMed1986

Studies of the in vitro activation and differentiation of human B lymphocytes. II. Optimization of activation by anti-immunoglobulin antibody bound to beads: analysis of the role of autocrine effects on B-cell proliferation and of T-cell help in B-cell differentiation.

We report experiments attempting to optimize the proliferative response of human B cells to rabbit anti-immunoglobulin antibody (RAHIg)-linked beads (anti-Ig beads). By choosing polyacrylamide beads of small size (3 micron) and coupling anti-Ig to them at high concentrations, beads were obtained which were both B-cell specific and more highly mitogenic than other than anti-Ig reagents and B-cell mitogens (SAC, protein A). Using these beads to activate B cells, the augmentation of the anti-Ig-induced proliferative response by added T-cell-derived growth factors was largely eliminated at high cell densities although the effect of these factors was still evident at low cell densities. However, when cultures were performed in round-bottom vessels which crowded the B cells together, the response to anti-Ig beads was independent of T-cell factors even at low B-cell densities, suggesting that normal B cells triggered by anti-Ig beads are able to maintain their own proliferation. In contrast to the proliferative response, even with the most potent anti-Ig bead preparations, no differentiation (Ig production or expression of terminal differentiation markers) was evident unless T-cell help was provided.

Antibodies, Anti-Idiotypic↗
PubMed1986

Social reinforcement: a treatment component in verbal self-instructional training.

This study investigated the effects of noncontingent social reinforcement on social and academic behaviors in grade school children. Twenty-four children in the second through fifth grades were selected on the basis of teacher ratings of disruptive behavior. Subjects were divided into a high social reinforcement verbal self-instructional (VSI) training group, a low social reinforcement VSI group, and a no-contact control group. Children in VSI groups were removed from their classrooms during four 40-minute periods and given VSI training. Significant between-groups differences on measures of social reinforcement were found indicating its successful manipulation. While none of the dependent measures indicated significant differences between experimental groups, a consistent pattern of difference scores emerged giving limited support to the hypothesis that noncontingent social reinforcement contributed to behavioral gains. Results are discussed in terms of the need for future research on the effects of rapport on treatment outcome.

Behavior Therapy↗
PubMed1985

Doppler ultrasound in noninvasive cardiac evaluation. The growing range of applications.

Ultrasound is of proven clinical utility for imaging cardiac structures. Doppler ultrasonic techniques can be used with or without echocardiography for noninvasive hemodynamic studies. The usefulness of Doppler ultrasonic techniques in the noninvasive laboratory has been shown recently at the Massachusetts General Hospital, Boston. In 61 of 100 consecutive patients in a prospective study, Doppler ultrasound provided clinical information that could not be obtained with echocardiographic studies alone. The advantages of this technique for noninvasive cardiac studies are now being recognized in the general medical community. The results of ongoing clinical investigations will help define the role of Doppler echocardiography as a clinically useful diagnostic tool for cardiac evaluation.

Cardiovascular Physiological Phenomena↗
PubMed1985

B5, a new B cell-restricted activation antigen.

The characterization of a new human B cell-restricted activation antigen (B5) is described in this report. With the use of a monoclonal antibody to B5, we show that B5 can be detected on peripheral blood or splenic B cells after 1 day of stimulation with either anti-immunoglobulin, protein A, Epstein Barr virus, or pokeweed mitogen. In contrast, B5 was not expressed on resting B, T, or myeloid cells. More important, B5 could not be detected on activated T cells or monocytes. The B5 antigen was expressed on some lymphoblastoid B cell lines and B cell neoplasms but was not expressed on leukemias or lymphomas of T or myeloid origin. The B5 antigen is distinct from previously reported B cell activation antigens by its m.w. and pattern of cellular expression. These studies suggest that B5 is a novel B cell-restricted activation antigen, which may be useful to study the events of early human B cell activation.

Animals↗
PubMed1985

Studies of in vitro activation and differentiation of human B lymphocytes. I. Phenotypic and functional characterization of the B cell population responding to anti-Ig antibody.

Investigation of the activation of splenic B cells by anti-immunoglobulin (Ig) antibody has enabled us to characterize the anti-Ig-responsive B cell and to analyze the phenotypic changes which accompany proliferation and differentiation. The anti-Ig antibody-responsive B cell population was characterized by the expression of high levels of the B2 antigen and represented approximately 40% of splenic B cells. Brisk mitogenesis which peaked at 3 to 4 days was induced by anti-Ig antibody. The proliferative phase was characterized phenotypically by a dramatic decline in B2 antigen expression, with most cells showing no detectable B2 by 4 days post-activation. The other hallmark of this phase was de novo expression of a group of "activation antigens." These included the B cell-restricted antigens B-LAST 1, BB1, and B5, and the T cell-associated interleukin 2 receptor and T12 antigens. Concomitantly, B1, B4, and Ia expression increased, the increase being roughly proportional to the increase in cell size. After day 4, the mitogenic response progressively diminished, while Ig synthesis increased. During this differentiation phase, cell surface antigens again displayed a distinct sequence of changes. The five activation antigens and the B1, B4, and Ia antigens began to decrease. However, two markers, T10 and PCA-1, which are found on plasmacytomas, appeared and their level of expression steadily increased. These changes and the appearance of morphologically identifiable plasma cells required the presence of T cells in this system. T cell supernatants alone induced Ig secretion but did not induce expression of PCA-1 or the appearance of cells with plasma cell morphology. The culture system developed in this study has allowed us to analyze the antigenic changes following activation by anti-Ig antibody. This sequence of changes has not only permitted the identification of antigens which, by their appearance at distinct stages may have an important role in proliferation and differentiation of B cells, but also provides us with the means of studying the function of each antigen.

Animals↗