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Biomedical subjects

J O Moore

Publications and source records attributed to J O Moore.

At least 37 records · Page 2Linked to original sources
PubMed1995

Predictors of outcome of tricuspid valve replacement in carcinoid heart disease.

The cardiac valvular surgical experience of patients in the Duke Carcinoid Database was reviewed to assess operative outcome. Of the 604 patients in the database, 19 patients with carcinoid heart disease were identified by cardiac catheterization or echocardiography, or both. Eight of these underwent tricuspid valve replacement surgery with bioprostheses (2 also had open pulmonic valvuloplasty). Compared with patients medically managed, surgically treated patients were similar with the exception that they had higher right atrial mean (17 +/- 6 vs 9 +/- 4 mm Hg, p = 0.03) and v-wave (27 +/- 6 vs 17 +/- 7 mm Hg, p = 0.04) pressures. Of the 8 surgical patients, 5 (63%) died within 30 days. Causes of death included tricuspid valve thrombosis, cerebral vascular accident, coagulopathy, renal failure, and intractable right heart failure. High comorbidity was present in all 8 patients. There was a weak trend (p = 0.17) toward lower Charlson comorbidity indexes in survivors (6.7 +/- 0.6) compared with nonsurvivors (7.6 +/- 0.9). Age was significantly lower (p = 0.036) in survivors (46 +/- 13 years) compared with nonsurvivors (69 +/- 4 years). Extended follow-up revealed 2 patients who survived beyond a decade. Review of 47 carcinoid valve replacement cases (Duke Carcinoid Database and 39 published cases) revealed a 30-day mortality of 56% for patients > 60 years of age, and 0% for those < or = 60 years of age (p < 0.0001). Although valve replacement surgery can afford prolonged palliation from carcinoid heart disease, it is associated with a significant mortality risk. Careful preoperative risk stratification by age and comorbidity may provide a means for optimal selection of surgical candidates.

Adult↗
PubMed1995

Nitric oxide modulation of the growth and differentiation of freshly isolated acute non-lymphocytic leukemia cells.

Freshly isolated acute non-lymphocytic leukemia (ANLL) cells were treated with the nitric oxide (NO)-liberating compounds sodium nitroprusside or S-nitrosoacetyl penicillamine and analyzed for viability, growth, and differentiation at 3-5 days. NO decreased the viability and the growth of freshly isolated ANLL cells in vitro. NO treatment significantly increased expression of CD14 in blast cells from patients with M5 ANLL, and increased at least one differentiation parameter in M4 or M5 cells. It had little or no effect on parameters of differentiation in other ANLL cells. We conclude that in vitro culture with NO decreases the growth and viability of most freshly isolated ANLL cells. NO also induces the differentiation of ANLL cells with a monocytic phenotype.

Cell Differentiation↗
PubMed1995

Long-term follow-up of a randomized post-induction therapy trial in acute myelogenous leukemia (a Southeastern Cancer Study Group trial).

A phase III clinical trial was designed to determine if more intensive induction and consolidation therapy for acute myeloblastic leukemia increases the remission rate and prolongs survival. A minor objective was to determine if the use of non-cross resistant drugs was more effective than the same drugs used for induction. Patients with untreated leukemia between the ages of 15 and 50 were given daunorubicin 45 mg/m2 for the first 3 days of a 10-day continuous infusion of cytosine arabinoside, initially at a dose of 2000 mg/m2 but reduced to 100 mg/m2 because of toxicity. Those under 36 achieving a complete remission and with an histocompatible donor were assigned to a transplant arm. The rest were randomized to receive one of three consolidation arms: A, cytosine arabinoside, 200 mg/m2 daily for 7 days and daunorubicin 45 mg/m2 daily for 3 days for three courses; B, one course as in Arm A followed by amsacrine, 120 mg/m2 daily for 5 days followed by a 5-day continuous infusion of azacytidine, 150 mg/m2/day; C, thioguanine and cytosine arabinoside, 100 mg/m2 every 12 h and daunorubicin 10 mg/m2 daily for 5 days for three courses followed by four maintenance courses of cytosine arabinoside, 100 mg/m2 daily for 5 days and daunorubicin, 45 mg/m2 for 2 days every 13 weeks. From 1981 to 1986, 398 eligible patients were enrolled and 219 achieved a complete remission. The initial induction dose of cytosine arabinoside was reduced after five of 29 patients exhibited fatal gastrointestinal toxicity. Only 11 patients were assigned to the transplant arm. There were no significant differences in the consolidation arms. The 5 year disease-free survivals were 38, 31 and 27% in arms A, B, and C respectively. Intensive consolidation therapy with the same or different drugs used in induction was as effective as lower dose consolidation followed by maintenance therapy.

Adolescent↗
PubMed1994

Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B.

BACKGROUND: About 65 percent of previously untreated adults with primary acute myeloid leukemia (AML) enter complete remission when treated with cytarabine and an anthracycline. However, such responses are rarely durable when conventional postremission therapy is administered. Uncontrolled trials have suggested that intensive postremission therapy may prolong these complete remissions. METHODS: We treated 1088 adults with newly diagnosed AML with three days of daunorubicin and seven days of cytarabine and randomly assigned patients who had a complete remission to receive four courses of cytarabine at one of three doses: 100 mg per square meter of body-surface area per day for five days by continuous infusion, 400 mg per square meter per day for five days by continuous infusion, or 3 g per square meter in a 3-hour infusion every 12 hours (twice daily) on days 1, 3, and 5. All patients then received four courses of monthly maintenance treatment. RESULTS: Of the 693 patients who had a complete remission, 596 were randomly assigned to receive postremission cytarabine. After a median follow-up of 52 months, the disease-free survival rates in the three treatment groups were significantly different (P = 0.003). Relative to the 100-mg group, the hazard ratios were 0.67 for the 3-g group (95 percent confidence interval, 0.53 to 0.86) and 0.75 for the 400-mg group (95 percent confidence interval, 0.60 to 0.94). The probability of remaining in continuous complete remission after four years for patients 60 years of age or younger was 24 percent in the 100-mg group, 29 percent in the 400-mg group, and 44 percent in the 3-g group (P = 0.002). In contrast, for patients older than 60, the probability of remaining disease-free after four years was 16 percent or less in each of the three postremission cytarabine groups. CONCLUSIONS: These data support the concept of a dose-response effect for cytarabine in patients with AML who are 60 years of age or younger. The results with the high-dose schedule in this age group are comparable to those reported in similar patients who have undergone allogeneic bone marrow transplantation during a first remission.

Acute Disease↗
PubMed1994

A pilot study of etoposide, vinblastine, and doxorubicin plus involved field irradiation in advanced, previously untreated Hodgkin's disease.

BACKGROUND: Advanced stage Hodgkin's disease (HD) usually is treated with combination chemotherapy with or without supplemental irradiation. The risk of significant acute and long term toxicity when the chemotherapy regimen contains alkylating agents has provided the impetus for the development of systemic combinations that do not include alkylating agents. This trial was designed to assess the toxicity and efficacy of a regimen of etoposide, vinblastine, and doxorubicin (EVA) as part of a combined modality approach in patients with moderate to high risk HD. METHODS: This was a prospective pilot study that included 26 previously untreated patients. They received 6 cycles of EVA, and complete responders received low dose (1500-2500 cGy) involved field radiation. RESULTS: Four patients were hospitalized for sepsis during chemotherapy. Complete response was achieved in 54% of patients, and 46% patients experienced induction failures. Two year failure-free survival is 44%, while 2 year overall survival is 86%. Median follow-up is 27 months. CONCLUSIONS: The EVA regimen is no more efficacious than other programs already in use and may be less so. It also is potentially leukemogenic because of the presence of etoposide. New combinations that do not contain etoposide should be explored in therapy programs for advanced HD in the hopes of discovering an efficacious treatment program that has minimal long term side effects.

Adolescent↗
PubMed1994

Hepatosplenic T-cell lymphoma: an unusual case of a gamma delta T-cell lymphoma with a blast-like terminal transformation.

We describe a case of a middle-aged women who presented with anemia and mild hepatosplenomegaly and who was found to have an unusual peripheral T-cell lymphoma with only subtle morphologically abnormal but mature-appearing cells noted in the blood and bone marrow. Less than 2 years after diagnosis the patient presented with an increasing white blood cell count to 26 x 10(9)/L, and numerous blasts were noted in the periphery. Flow cytometry studies showed cells with an unusual T-cell phenotype expressing the gamma delta T-cell receptor and restricted expression of the V delta 1 but not the V delta 2 protein, indicating the clonal nature of the proliferation. A clonal T-cell receptor gene rearrangement was seen with a V delta 1 probe. The patient died and was found at autopsy to have extensive hepatic sinusoidal infiltration by abnormal cells. The histopathologic, immunophenotypic, and molecular findings are those of "hepatosplenic T-cell lymphoma." In spite of the striking morphologic change during the course of the patient's disease the same phenotype and clonal rearrangement were found both at initial diagnosis and during terminal phase, indicating that this change represented a blast-like transformation of the patient's original lymphoproliferative disorder.

Female↗
PubMed1993

Cigarette smoking and risk of acute leukemia: associations with morphology and cytogenetic abnormalities in bone marrow.

BACKGROUND: Cigarette smoking may be a risk factor for leukemia. No detailed biological mechanism has been proposed, but a causal link is made plausible by evidence of systemic effects of cigarette smoke and the presence in cigarette smoke of chemicals that have been associated with leukemia risk. PURPOSE: Our purpose was to investigate the leukemia risk associated with cigarette smoking in a multicenter case-control study of acute leukemias in adults. METHODS: Adults aged 18-79 with newly diagnosed leukemia were contacted to participate in this epidemiologic study when they entered a clinical trial to be treated under protocols sponsored by Cancer and Leukemia Group B. Smoking histories for 610 patients with acute leukemia and 618 population control subjects were obtained by telephone interviews. We examined bone marrow samples and classified patients by morphology of leukocyte precursor cells according to the French-American-British (FAB) classification system and, for 378 patients, by the presence or absence of specific clonal chromosome abnormalities. We calculated odds ratios (ORs) for risk of leukemia associated with smoking cigarettes. ORs were adjusted for age, race, and sex. RESULTS: Smoking was associated with only a modest increase in risk for leukemia overall (adjusted OR = 1.13; 95% confidence interval [CI] = 0.89-1.44). However, among participants aged 60 and older, smoking was associated with a twofold increase in risk for acute myeloid leukemia (AML) (OR = 1.96; 95% CI = 1.17-3.28) and a threefold increase in risk for acute lymphocytic leukemia (ALL) (OR = 3.40; 95% CI = 0.97-11.9). Among older persons, risks increased with amount and duration of smoking. Smoking was associated with increased risk for AML classified as FAB type M2 at all ages, with ORs of 1.70 (95% CI = 1.00-2.90) for those younger than 60 and 3.50 (95% CI = 1.53-8.03) for those aged 60 and older. Smoking was also associated with ALL type L2 at all ages, with ORs of 1.72 (95% CI = 0.90-3.27) for those younger than 60 and 5.34 (95% CI = 1.03-27.6) for those who were older. Smoking was more common among patients with specific chromosome abnormalities in AML [-7 or 7q-, -Y, +13] and in ALL [t(9;22)(q34;q11)]. CONCLUSIONS: Cigarette smoking is associated with increased risk for leukemia and may lead to leukemias of specific morphologic and chromosomal types. The association varies with age. IMPLICATION: Examining discrete subtypes of disease may permit more accurate assessment of risk. As standardized morphologic classification and cytogenetic and molecular evaluation of leukemia patients becomes more common, epidemiologic studies that take advantage of these advances will begin to contribute to the identification of additional risk factors and mechanisms in acute leukemia.

Acute Disease↗
PubMed1993

The syndrome of 5-fluorouracil cardiotoxicity. An elusive cardiopathy.

BACKGROUND: A case of reversible cardiogenic shock linked to 5-fluorouracil (5-FU) was observed. Recognizing the increasing use of 5-FU, the authors tried to map this syndrome. METHODS: They reviewed 134 additional case reports, retrieved information from literature searches, focused on clinical features, and discussed possible pathophysiologic findings and prevention of this syndrome. RESULTS: Although angina and electrocardiographic changes were common and reproducible (approximately 90% each), coronary artery disease was found in a few patients. A total of 33 patients had severe left ventricular dysfunction, 28 without evidence of myocardial infarction. The symptoms were responsive to conservative management (90%). CONCLUSIONS: Cardiac toxicity is a little known complication of 5-FU therapy, with an unknown but significant incidence. It is highly treatable.

Female↗
PubMed1991

The erythrocytes in paroxysmal nocturnal haemoglobinuria of intermediate sensitivity to complement lysis.

The sensitivity to lysis by complement of the erythrocytes of 56 patients with paroxysmal nocturnal haemoglobinuria (PNH) was compared to the membrane expression of decay accelerating factor (DAF, CD55), membrane inhibitor of reactive lysis (MIRL, CD59) and acetylcholinesterase (AChE). Most patients (36/50 72% in whom the analysis could be made) appeared to have erythrocytes of intermediate sensitivity to complement in the blood. These cells appeared as a discrete population of cells (PNH II cells), as a 'tail' of cells slightly less sensitive than the predominant PNH III cells (previously called PNH IIIb cells), or as a continuous spectrum of cells sensitive to complement. The PNH III cells totally lacked all three proteins (DAF, MIRL, AChE) by flow cytometric analysis whereas PNH I cells appeared to have normal or nearly normal amounts of each. The cells of intermediate sensitivity (PNH II) had coordinately decreased expression of all three proteins; the level of expression of DAF and MIRL paralleled the sensitivity of the cells to the haemolytic action of complement.

Acetylcholinesterase↗
PubMed1990

Improved survival in advanced Hodgkin's disease with the use of combined modality therapy.

To compare the effectiveness of combined modality therapy and chemotherapy alone for the treatment of advanced Hodgkin's disease (Stages IIB-IV), records of 154 patients who achieved a complete or partial response to induction combination chemotherapy were analyzed. Sixty-seven patients received consolidation radiotherapy and 87 patients received no further treatment. Thirty of 154 patients participated in a prospective randomized trial of the Southeastern Cancer Study Group (SEG). Ten-year actuarial survival (Hodgkin's disease deaths only) was 93% for the combined modality therapy patients compared with 59% for the chemotherapy alone patients (p less than 0.0005). Combined modality therapy patients had an 87% 10-year actuarial freedom from relapse as opposed to 56% for the chemotherapy alone patients (p less than 0.0005). Relapse occurred in 33 of the chemotherapy alone patients, 28 (85%) being in sites involved at initial diagnosis. Seven combined modality therapy patients recurred with only two true in-field failures. Multi-variate analysis demonstrated treatment (combined modality) as the only variable affecting outcome. Patients prospectively treated with combined modality therapy in the Southeastern Cancer Study Group trial also showed a statistically significant improvement in both survival and freedom from relapse compared with patients receiving chemotherapy only. There was no apparent increase in toxicity from using combined modality therapy compared with chemotherapy. Three chemotherapy patients and one combined modality therapy patients developed acute leukemia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Treatment of patients with recurrent gliomas with cyclophosphamide and vincristine.

Seventeen patients with recurrent gliomas were treated with the combination of cyclophosphamide and vincristine. All but one had previously received and failed chemotherapy. Cyclophosphamide was administered at doses ranging from 250 to 1000 mg/sq m by intravenous infusion on Days 1 and 2, and vincristine was given at a dose of 1.0 mg/sq m (2 mg maximal dose) intravenously on Day 1; cycles were repeated every 4 weeks. Clinical and radiographic improvement was observed in eight of 16 evaluable patients, and four other patients had stabilization of previously progressive disease. Four patients are alive and off treatment without evidence of recurrence for a median period of 37 months; these included an adult with a cerebral anaplastic astrocytoma now more than 51 months after therapy. Toxicity included moderately severe myelosuppression that required hospitalization in seven patients. These results indicate that the combination of cyclophosphamide and vincristine has activity in the treatment of recurrent gliomas, and warrant the use of these drugs in larger controlled studies, particularly if they can be used in conjunction with hematopoietic growth factors.

Adolescent↗
PubMed1989

Hodgkin's disease presenting as myelofibrosis.

Four patients with Hodgkin's disease and bone marrow fibrosis are presented in whom the clinical presentation was dominated by cytopenias; this was associated with a delayed diagnosis for an average of 20 months. Despite marrow involvement, chemotherapy resulted in complete remissions and two patients appear to have been cured. Marrow fibrosis resolved at least partially after chemotherapy. The medical literature relevant to bone marrow involvement by Hodgkin's disease is reviewed. Hodgkin's disease should be considered in the differential diagnosis of idiopathic myelofibrosis.

Adult↗
PubMed1989

High-dose combination cyclophosphamide, cisplatin, and melphalan with autologous bone marrow support. A clinical and pharmacologic study.

A total of 23 patients were treated at five dose escalations with high-dose combination cyclophosphamide, cisplatin, and melphalan with autologous bone marrow support. The maximum tolerated doses of cyclophosphamide, cisplatin, and melphalan were 5,625, 180, and 80 mg/m2, respectively. The dose-limiting toxicity was cardiac toxicity. Objective tumor regression occurred in 14 of 18 evaluable cases, with a median duration of 3.5 months. Pharmacokinetic evaluation of melphalan in 20 patients revealed a dose-related increase in maximum plasma concentration (Cmax) and area under the curve (AUC). Perturbation of the melphalan plasma half-life and AUC, associated with severe toxicity, resulted when renal insufficiency occurred. The results suggest that high-dose combination cyclophosphamide, cisplatin, and melphalan produces frequent, rapid responses in breast cancer, melanoma, and sarcoma, although with significant extramedullary toxicity. The pharmacokinetics suggest that modification of the treatment schedule may result in a reduction of treatment-related toxicity.

Adult↗
PubMed1989

Clinicopathologic and cytogenic features of CD34 (My 10)-positive acute nonlymphocytic leukemia.

The authors performed membrane antigen phenotyping on 75 patients with acute nonlymphocytic leukemia with a panel of myeloid-associated monoclonal antibodies. The 34 patients (45%) with CD34-positive leukemia were not significantly different from the 41 with CD34-negative leukemia with respect to age, hemoglobin, white blood cell count, or platelet count at presentation, but their blasts were more likely to lack the CD15 or CD33 antigens and to have FAB M1 or M2 morphologic characteristics. CD34-positive leukemia was more likely to arise after chemotherapy. Patients with CD34-positive leukemia were less likely to enter a complete remission even when analysis was limited to those patients receiving a high-dose induction-type chemotherapy regimen. Giemsa-banding karyotyping studies were obtained in 55 of the cases. In 30 of these cases (56%) clonal karyotypic abnormalities were demonstrated. Although the karyotypic abnormalities and phenotypes were varied, there was a high degree of association between the karyotypic abnormalities monosomy 7/del (7q) and the CD34-positive phenotype; this antigen was expressed on blasts from eight of the nine patients displaying this abnormality. Monoclonal antibody phenotyping of myeloid leukemia with reagents such as anti-CD34 may help to define biologically interesting subsets of ANLL with distinct clinicopathologic expression.

Antigens, Differentiation↗
PubMed1989

Familial aggregation of multiple myeloma and central nervous system diseases.

Degenerative central nervous system diseases such as Alzheimer's disease and lymphoreticular malignancies such as multiple myeloma occur with increased frequency with advancing age. Relatives of early-onset Alzheimer's disease patients may have an increased risk of lymphoreticular malignancies. This led us to evaluate the family history of central nervous system diseases in a case-control study of multiple myeloma. Thirteen of 439 multiple myeloma cases had one or more first-degree relatives with degenerative or demyelinating central nervous system disease. In comparison, there were nine "positive" family histories in 1,317 matched hospital controls (relative risk = 4.4, 95% confidence interval = 1.9-10.3). Relative risks for the component categories of Parkinson's disease, multiple sclerosis, and miscellaneous degenerative central nervous system diseases were 3.0, 4.0 and 11.9, respectively. Our findings suggest that the degenerative and demyelinating central nervous system diseases and the lymphoreticular malignancies may comprise an etiologically related group of "protean diseases." These diseases may have a shared genetic susceptibility, possibly an immunologic abnormality. The varied disease manifestation in family members suggests a second necessary etiologic step of a variable and possibly environmental nature.

Aged↗
PubMed1989

Carcinoid tumors: iodine-131 MIBG scintigraphy.

Eighty-two patients with pathologically proved carcinoid tumors were examined with iodine-131 metaio-dobenzylguanidine (MIBG) scintigraphy. Localization scores of I-131 MIBG accumulation in the primary tumor or metastatic site ranged from 0 to 3+ on the basis of comparison with normal liver. I-131 MIBG uptake varied greatly in different patients with carcinoid tumors. The localization scores in known tumor sites were related to the location of the primary tumor in the stomach (1-3+ in two of five patients), pancreas (1-3+ in four of five patients), cecum (3+ in two of two patients), appendix (0 in one of one patient), jejunum (0 in one of one patient), Meckel diverticulum (3+ in one of one patient), terminal ileum (2-3+ in 19 of 28 patients), bronchus (3+ in one of nine patients), thymus (1+ in one of two patients), and unknown (2-3+ in 18 of 28 patients). Tumors of midgut origin concentrated I-131 MIBG more frequently than those of foregut origin. Uptake of I-131 MIBG was more likely if neurohumor levels, particularly serum serotonin, were elevated. There was no relationship of I-131 MIBG uptake to carcinoid syndrome. I-131 MIBG is useful in the determination of the location and extent of some carcinoid tumors, particularly those of midgut origin.

3-Iodobenzylguanidine↗
PubMed1989

CD7+, CD4-, CD8- acute leukemia: a syndrome of malignant pluripotent lymphohematopoietic cells.

Following our initial observation of in vivo conversion of CD7+, CD4-, CD8- acute lymphoblastic leukemia (ALL) cells from lymphoid to myeloid lineages (Proc Natl Acad Sci (USA) 81:253, 1984) we have studied eight additional cases of ALL with this leukemic cell phenotype. The CD7+, CD4-, CD8- phenotype was associated with a distinct clinical entity with those affected predominantly male (either less than 35 years or greater than 65 years of age), with frequent mediastinal and/or thymic masses, skin and CNS disease, high peripheral WBC counts, and bone marrow blasts that were morphologically L1 or not ascribable to a specific lineage. These patients did not respond to conventional chemotherapeutic regimens for either acute lymphoid or myeloid leukemias. No common karyotype or T-cell gene rearrangement pattern could be defined. Importantly, seven of eight patient's leukemic cells studied were capable of multilineage (myeloid, erythroid, monocytoid, megakaryocytoid, and lymphoid) differentiation in vitro. Data is presented suggesting that CD7+, CD4-, CD8- leukemias, in many instances, are leukemias of immature hematopoietic cells. The development of novel therapeutic approaches to this form of leukemia will be necessary to alter its poor prognosis.

Adolescent↗