Search PubMed⌕ Search

Biomedical subjects

W Miller

Publications and source records attributed to W Miller.

At least 109 records · Page 6Linked to original sources
PubMed1996

BCR/ABL-negative primitive progenitors suitable for transplantation can be selected from the marrow of most early-chronic phase but not accelerated-phase chronic myelogenous leukemia patients.

We have previously reported that selection of marrow cells on the basis of the CD34+HLA-DR- phenotype (34+DR-) may result in the recovery of Philadelphia chromosome (Ph)- and BCR/ABL-negative long-term culture-initiating cells (LTC-IC) in selected patients with chronic myelogenous leukemia (CML). We now present data on 27 early chronic-phase ([ECP] studied within 1 year after diagnosis) and 23 advanced-phase ([AP] late chronic phase, ie, studied >1 year from diagnosis, or accelerated phase) CML patients. Fluorescence-activated call-sorting (FACS)-selected 34+DR- and 34+DR+ cells were subjected to reverse transcriptase-polymerase chain reaction and fluorescence in situ hybridization. These cells were also cultured in long-term bone marrow culture for 1 to 5 weeks to examine the number of LTC-IC and the presence or absence of the BCR/ABL gene rearrangement in progeny of primitive LTC-IC. The number of 34+DR- cells and LTC-IC present in ECP CML marrow was similar to that in normal (NL) marrow, whereas the numbers were reduced in AP CML. Furthermore, 34+DR- cells from more than 80% of ECP CML patients were BCR/ABL mRNA- and Ph-negative and contained only BCR/ABL mRNA- and Ph-negative LTC-IC, whereas 34+DR- cells and LTC-IC from less than 40% of AP CML patients were BCR/ABL mRNA- and Ph-negative. In contrast to NL marrow, 34+DR+ cells from CML marrow, irrespective of clinical stage, contained large numbers of LTC-IC. CML 34+DR+ cells and LTC-IC were BCR/ABL mRNA- and Ph-positive. Since these studies suggested that a population of primitive progenitors that are Ph-negative can be selected from steady-state marrow in some ECP CML patients, we determined if similar results could be obtained when large quantities of marrow sufficient for transplantation are processed. We demonstrate that 1 to 3 x 10(5) BCR/ABL mRNA-negative 34+DR- cells/kg recipient body weight, containing only BCR/ABL mRNA-negative LTC-IC, can be obtained from a 2- to 2.5-L marrow collection by sequential COBE Spectra apheresis (COBE BCT, Lakewood, CO), CD34+ enrichment using the CEPRATE SC Cell-Concentrator (CellPro, Bothell, WA), and high-speed FACS. Thus, large-scale selection of a BCR/ABL mRNA- and Ph-negative 34+DR- cell population is possible in a fraction of chronic-phase CML patients, in whom these cells could be used to reconstitute the hematopoietic compartment following autologous transplantation.

Antigens, CD34↗
PubMed1996

Role of DNA sequences outside the cores of DNase hypersensitive sites (HSs) in functions of the beta-globin locus control region. Domain opening and synergism between HS2 and HS3.

The roles of each DNase hypersensitive site (HS), and the DNA sequences between them, in the activity of the locus control region of the mammalian beta-globin gene domain were examined by placing human and rabbit restriction fragments containing the cores of HS2, HS3, HS4, and HS5, along with varying amounts of flanking DNA, upstream of a hybrid epsilon-globin-luciferase reporter gene and testing for effects on expression both prior to and after integration into the chromosomes of K562 cells, a human erythroid cell line. Prior to integration, fragments containing HS2 enhanced expression to the greatest extent, and the modest enhancement by some fragments containing HS3 correlated with the presence of a well-conserved binding site for AP1/NFE2. The stronger effects of larger locus control region DNA fragments in clones of stably transfected cells indicates a role for sequences outside the HS cores after integration into the genome. The strong effect of a 1.9-kilobase HindIII fragment containing HS3 after, but not prior to, integration argues for the presence of a chromatin domain-opening activity. Use of a rabbit DNA fragment containing both HS2 and HS3 demonstrated a synergistic interaction between the two HSs when their natural context and spacing are preserved.

Animals↗
PubMed1996

HLA DRB1*DQB1* haplotype in HTLV-I-associated familial infective dermatitis may predict development of HTLV-I-associated myelopathy/tropical spastic paraparesis.

A possible causal association between infective dermatitis and HTLV-I infection was reported in 1990 and confirmed in 1992. We now report familial infective dermatitis (ID) occurring in a 26-year-old mother and her 9-year-old son. The mother was first diagnosed with ID in 1969 at the age of 2 years in the Dermatology Unit at the University Hospital of the West Indies (U.H.W.I.) in Jamaica. The elder of her 2 sons was diagnosed with ID at the age of 3 years, also at U.H.W.I. Both mother and son are HTLV-I-seropositive. A second, younger son, currently age 2 years, is also HTLV-I-seropositive, but without clinical evidence of ID. Major histocompatibility complex (MHC), class II, human leucocyte antigen (HLA) genotyping documented a shared class II haplotype, DRB1*DQB1* (1101-0301), in the mother and her 2 sons. This same haplotype has been described among Japanese patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and has been associated with a possible pathologically heightened immune response to HTLV-I infection. The presence of this haplotype in these familial ID cases with clinical signs of HAM/TSP may have contributed to their risk for development of HAM/TSP. The unaffected, HTLV-I-seropositive younger son requires close clinical follow-up.

Adult↗
PubMed1996

Prophylactic antibiotics eliminate bacteremia and allow safe outpatient management following high-dose chemotherapy and autologous stem cell rescue.

This study examines the effectiveness of prophylactic ciprofloxacin and rifampin following high-dose chemotherapy and autologous stem cell rescue (HDC/ ASCR). Specific endpoints included the incidence of fever, clinically documented infection, bacteremia, and readmission rates from an outpatient bone marrow transplant setting following infection or fever. A group of 97 patients receiving 134 cycles of HDC/ASCR were studied. Patients were given ciprofloxacin 750 mg p.o. twice daily and rifampin 300 mg p.o. twice daily beginning on the day of stem cell reinfusion (24-48 h after completion of high-dose chemotherapy). Most patients were either discharged to an outpatient setting following completion of their chemotherapy or received all of their chemotherapy in an outpatient setting. Febrile neutropenia was treated with empirical antibiotics in an outpatient setting unless it was complicated by hypotension, renal failure, severe mucositis or other problems. The median duration of neutropenia (absolute neutrophil count below 500/mm3) was 7 days. Neutropenic fever occurred in 62% of patients but clinically documented bacterial infection occurred in only 2 (1.5%) patients during their neutropenic period. No bacteremia was noted. Readmission to the hospital following fever or infection occurred in 26% of patients maintained in the outpatient setting. There were no deaths from a bacterial infection in this study although 1 patient (0.7%) died from aspergillosis. Prophylactic ciprofloxacin and rifampin is a well-tolerated and highly effective combination that effectively decreases the risk of both gram-positive and gram-negative bacterial infection following HDC/ASCR. It facilitates outpatient management of myelosuppressed patients receiving autologous stem cell rescue.

Ambulatory Care↗
PubMed1996

High-dose chemotherapy supported by peripheral blood progenitor cells in poor prognosis metastatic breast cancer--phase I/II study. Edinburgh Breast Group.

Current treatments for metastatic breast cancer are not associated with significant survival benefits despite response rates of over 50%. High-dose therapy with autologous bone marrow transplantation (ABMT) has been investigated, particularly in North America, and prolonged survival in up to 25% of women has been reported, but with a significant treatment-related mortality. However, in patients with haematological malignancies undergoing autologous transplantation, haematopoietic reconstruction is significantly quicker and mortality lower than with ABMT, when peripheral blood progenitor cells (PBPCs) are used. In 32 women with metastatic breast cancer, we investigated the feasibility of PBPC mobilisation with high-dose cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) after 12 weeks' infusional induction chemotherapy and the subsequent efficacy of the haematopoietic reconstitution after conditioning with melphalan and either etoposide or thiotepa. PBPC mobilisation was successful in 28/32 (88%) patients, and there was a rapid post-transplantation haematopoietic recovery: median time to neutrophils > 0.5 x 10(9) l-1 was 14 days and to platelets > 20 x 10(9) l-1 was 10 days. There was no procedure-related mortality, and the major morbidity was mucositis (WHO grade 3-4) in 18/32 patients (56%). In a patient group of which the majority had very poor prognostic features, the median survival from start of induction chemotherapy was 15 months. Thus, PBPC mobilisation and support of high-dose chemotherapy is feasible after infusional induction chemotherapy for patients with metastatic breast cancer, although the optimum drug combination has not yet been determined.

Adult↗
PubMed1996

Progressive multiple alignment with constraints.

A progressive alignment algorithm produces a multialignment of a set of sequences by repeatedly aligning pairs of sequences and/or previously generated alignments. We describe a method for guaranteeing that the alignment generated by a progressive alignment strategy satisfies a user-specified collection of constraints about where certain sequence positions should appear relative to others. Our main result is an algorithm to compute just the "prime" constraints that are implied by the user-given constraints; these are shown to be precisely the constraints that the alignment algorithm must obey. In practice, the time required to handle constraints is negligible and frequently much less than the time saved because the constraints permit searching a restricted region of the dynamic-programming grid. An alignment of the beta-like globin gene cluster of several mammals illustrates the practicality of the method.

Algorithms↗
PubMed1996

Clinical ladder to professional advancement program. An evolutionary process.

Since the early 1970s, clinical ladder programs have been a method of defining, recognizing, and rewarding nursing practice. As clinical practice in an institution grows and evolves, so must the program that supports the development of the practitioner. An in-depth evaluation of one clinical ladder program was conducted to determine if it was reflective of current practice. The authors discuss the method of evaluation, findings, and the revised program.

Career Mobility↗
PubMed1996

Phase II trial of all-trans retinoic acid in metastatic non-small cell lung cancer.

The toxicity and marginal effectiveness of cytotoxic chemotherapy in metastatic non-small cell lung cancer (NSCLC) necessitates the search for new agents. Preliminary data in lung cancer and other malignant and premalignant disorders have identified retinoid compounds as potentially useful antitumor agents. Twenty-eight patients with metastatic NSCLC were treated with oral all-trans retinoic acid in a phase II trial. The study population consisted of patients with excellent performance status and minimal weight loss. Toxicities were generally mild and included cutaneous effects, headache, and myalgia. A significant number of patients developed elevations of hepatic transaminases or hyperlipidemia and 3 patients had treatment-related leukocytosis. Two patients (8%) achieved a partial response, and 1 had a mixed response. The duration of remission in the 2 responders was 7 and 13 months and the median survival of all patients 7 months. Therefore, all-trans retinoic acid has minimal activity as a single agent in NSCLC but warrants further study in combination with biological agents and chemotherapy.

Adult↗
PubMed1996

Outcome of second bone marrow transplantation following a uniform conditioning regimen as therapy for malignant relapse.

Twenty-three second bone marrow transplants (BMT) were performed between October 1987 and January 1994 for patients with malignant relapse following initial BMT. For first BMT, twenty-one of 23 (91%) were conditioned with cyclophosphamide plus total body irradiation. For second BMT, a uniform conditioning regimen consisting of busulfan and cyclophosphamide was used. Eleven patients had chronic myelogenous leukemia, seven acute leukemia, four lymphoma, and one myelodysplastic syndrome. Median patient age at second BMT was 32 years, the median time between first BMT and relapse was 22 months, and the median time to second BMT after relapse was 5 months. The second BMT marrow source included: autologous marrow (1), unrelated donors (4), new matched sibling donors (5) and same matched sibling donors as the first BMT (13). The Kaplan-Meier disease-free survival and survival rates at 3 years were 38 and 43%, respectively (median follow-up of survivors was 45 and 48 months, respectively), and five patients survive disease-free at 4-6 years. Nine of the 13 deaths occurred within 100 days after second BMT; eight had relapsed within 1 year of the first BMT. We conclude that: (1) second BMT can offer durable long-term survival in certain patients, especially those who relapse late after first transplant; (2) busulfan and cyclophosphamide is a suitable conditioning regimen for second BMT.

Adolescent↗
PubMed1995

Late infections after allogeneic bone marrow transplantations: comparison of incidence in related and unrelated donor transplant recipients.

Infectious complications are a major cause of morbidity and mortality after allogeneic bone marrow transplantation (BMT). We have evaluated the incidence of late infections (beyond day +50) in recipients of related (RD) and unrelated donor (URD) allogeneic BMT, factors associated with increased risks of infection, and the impact of the late infections on survival. Between 1989 and 1991, 249 patients received an RD (n = 151) or URD (n = 98) allogeneic BMT at the University of Minnesota and all late infections were investigated. Three hundred sixty-seven late infectious events developed in 162 patients between 50 days and 2 years after BMT. The incidence of any late infection was greater in URD versus RD recipients (84.7% v 68.2%, respectively; P = .009). In multivariate analysis, advanced graft-versus-host disease (GVHD) was significantly associated with late infections. The effect of GVHD was apparent only in RD recipients (relative risk [RR], 2.29; P = .003), whereas URD recipients, with or without GVHD, had more late infections compared with RD recipients without GVHD. Multivariate analysis showed that late posttransplantation infections were the dominant independent factor associated with increased nonrelapse mortality (RR, 5.5; P = .0001), resulting in improved 3-year survival for RD versus URD recipients (49.9% +/- 8% v 34.4% +/- 10%; P = .004). In this study, we observed that late infections are more frequent in URD recipients, resulting in substantially higher nonrelapse mortality. This prolonged period of increased infectious risk in URD recipients suggests the need for aggressive surveillance and therapy of late infections and perhaps prolonged antibiotic prophylaxis for all URD BMT recipients.

Adolescent↗
PubMed1995

A comparison of filtered leukocyte-reduced and cytomegalovirus (CMV) seronegative blood products for the prevention of transfusion-associated CMV infection after marrow transplant.

We performed a prospective, randomized trial in CMV seronegative marrow recipients to determine if filtered blood products were as effective as CMV-seronegative blood products for the prevention of transfusion-transmitted CMV infection after marrow transplant. Before transplant, 502 patients were randomized to receive either filtered or seronegative blood products. Patients were monitored for the development of CMV infection and tissue-documented CMV disease between days 21 and 100 after transplant. Infections occurring after day 21 from transplant were considered related to the transfusion of study blood products and, thus, were considered evaluable infections for the purpose of this trial. In the primary analysis of evaluable infections, there were no significant differences between the probability of CMV infection (1.3% v 2.4%, P = 1.00) or disease (0% v 2.4%, P = 1.00) between the seronegative and filtered arms, respectively, or probability of survival (P = .6). In a secondary analysis of all infections occurring from day 0 to 100 post-transplant, although the infection rates were similar, the probability of CMV disease in the filtered arm was greater (2.4% v 0% in the seronegative arm, P = .03). However, the disease rate was still within the prestudy clinically defined acceptable rate of < or = 5%. We conclude that filtration is an effective alternative to the use of seronegative blood products for prevention of transfusion-associated CMV infection in marrow transplant patients.

Adolescent↗
PubMed1995

Allogeneic transplantation combining mobilized blood and bone marrow in patients with refractory hematologic malignancies.

BACKGROUND: Mobilized blood stem cells have been used successfully in autologous transplant recipients to reduce the complications of pancytopenia due to dose-intensive chemotherapy. Reports of cytokine-mobilized blood progenitor cells in allogeneic transplant recipients are rare. STUDY DESIGN AND METHODS: This is a pilot trial of six patients. Patients with advanced hematologic malignancy received bone marrow (median total 2.6 x 10(8) mononuclear cells/kg) followed by four daily transfusions of blood (median total 9.5 x 10(8) mononuclear cells/kg) from HLA-matched sibling donors who were mobilized with recombinant human granulocyte-colony-stimulating factor (5 micrograms/kg/day subcutaneously for 5 days). All patients received cyclosporine and prednisone for graft-versus-host disease (GVHD) prophylaxis. RESULTS: An absolute neutrophil count greater than 500 per mm3 was achieved on Day 12, and platelet transfusion independence was achieved on Day 16. The median day of hospital discharge was Day 23 after transplant. All patients achieved 100-percent donor cell engraftment. Acute > or = Grade III GVHD did not develop in any patients, but all patients developed Grade I (n = 4) or Grade II (n = 2) acute GVHD. Chronic extensive GVHD developed in four of six patients. One patient died of pneumonia 263 days after transplant while undergoing immune-suppressive therapy for chronic GVHD. CONCLUSION: The transfusion of blood stem cells in patients undergoing allogeneic bone marrow transplant is well tolerated soon after transplant, but the development of chronic GVHD may limit the general usage of unmanipulated blood stem cells.

Adult↗
PubMed1995

A local alignment tool for very long DNA sequences.

This paper presents a practical program, called sim2, for building local alignments of two sequences, each of which may be hundreds of kilobases long. sim2 first constructs n best non-intersecting chains of 'fragments', such as all occurrences of identical 5-tuples in each of two DNA sequences, for any specified n > or = 1. Each chain is then refined by delivering an optimal alignment in a region delimited by the chain. sim2 requires only space proportional to the size of the input sequences and the output alignments, and the same source code runs on Unix machines, on Macintoshes, on PCs, and on DEC Alpha PCs. We also describe an application of sim2 for aligning long DNA sequences from Escherichia coli. sim2 facilitates contig-building by providing a complete view of the related sequences, so differences can be analyzed and inconsistencies resolved. Examples are shown using the alignment display and editing functions from the software tool ChromoScope.

Amino Acid Sequence↗
PubMed1995

Saliva and serum as diagnostic media for antibody to hepatitis A virus in adults and in individuals who have received an inactivated hepatitis A vaccine.

Saliva was evaluated as a diagnostic fluid for screening individuals for evidence of previous hepatitis A virus (HAV) infection and for evidence of seroconversion after vaccination with inactivated hepatitis A vaccine. A new and simple saliva collection method and an assay for detection of HAV antibody were used; the assay used an antibody capture format. There was complete concordance between the results of saliva-based assays and those of serum-based assays, both of which were used for determining previous natural HAV exposure. However, for vaccine recipients, 100% concordance for saliva-based and serum-based assays occurred only at serum titers of > 9,000 mIU/mL, which were determined with use of the modified HAVAB assay. Saliva provides adequate sensitivity and specificity for determining naturally acquired HAV infection, although it is not useful in clinical trials for determining seroconversion after HAV vaccination.

Adult↗
PubMed1995

Paraneoplastic autoimmune phenomena in patients with myelodysplastic syndromes: response to immunosuppressive therapy.

We analysed the clinical features, course and response to immunosuppressive therapy in 30 patients with autoimmune disorders associated with myelodysplastic syndromes (MDS). 18 patients with MDS developed acute systemic autoimmune disorders. Common manifestations were skin vasculitis (n = 15) and arthritis (n = 11). Seven patients had an acute clinical syndrome of vasculitic skin rash, fever and arthritis with peripheral oedema in three and pulmonary infiltrates in five of these seven patients. Other acute manifestations included pericarditis, pleural effusions, skin ulceration, seizures, myositis and peripheral neuropathy. Chronic or isolated autoimmune manifestations (n = 11) included glomerulonephritis, polyneuropathy, pyoderma gangrenosum, ulcerative colitis and polyarthritis. Classic connective tissue disorders recognized included relapsing polychondritis, polymyalgia rheumatica, Raynaud's syndrome and Sjögren's syndrome. Autoimmune manifestations responded to immunosuppressive therapy (primarily prednisone) in 26/27 patients treated. Furthermore, cytopenias improved substantially in six patients, including complete normalization of peripheral blood counts in two patients with cytogenetic remission in one. Patients with a haematological response to immunosuppressive therapy had improved survival compared with non-responding patients. The autoimmune syndrome was implicated as a primary cause of death in 8/17 patients who died. Autoimmune manifestations may be more common than previously recognized in patients with MDS. Aggressive therapy with immunosuppressive agents in selected patients often controls autoimmune phenomena associated with MDS and may lead to haematological responses in some patients.

Adolescent↗
PubMed1995

A successful field-based pharmacy program.

Once physicians are aware of the trends and of how pharmacy utilization methods such as therapeutic interchange and formulary management can control costs, they are better able and more willing to provide patients with effective, lower-cost treatment. As the majority of pharmacy benefit managers (PBMs) today stress quality in addition to greater cost efficiencies, quantitative results defining quality and highlighting improved compliance and increased patient knowledge should also be initiated by PBMs. The author describes a pilot field-based pharmacy program, which indicates that active intervention and cooperation between the medical group and pharmacy benefit manager works.

Aged↗
PubMed1995

[Surgical and drug therapy of metastatic gastrinoma. Successful palliation over the course of 2 1/2 years].

A midaged lady suffering from ulcer disease for about seven years had undergone several surgical and drug therapies without any satisfying success. Then the diagnosis of a gastrinoma was made. By this time there were already multiple liver metastases. First the large supposed primary tumor of the pancreas was resected and within six months later the resection of the progressing liver metastases became necessary because of local tumor complications. The additional drug therapy with octreotide (Sandostatin) given three times daily subcutaneously prevented further tumor progress. Until now this combination of surgical and medical treatment has proved to be a successful palliative method of treating the malignant gastrinoma for 2.5 years.

Combined Modality Therapy↗