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Biomedical subjects

D Amato

Publications and source records attributed to D Amato.

At least 73 records · Page 4Linked to original sources
PubMed1986

Doxorubicin chemotherapy in the treatment of soft-tissue sarcoma. Combined results of two randomized trials.

In 1978, there were initiated two independent randomized, prospective trials of adjuvant doxorubicin hydrochloride (Adriamycin) following primary therapy for soft-tissue sarcoma. The virtual identity of these two protocols permits their combination for analysis. A total of 75 patients (42 men, 33 women) with soft-tissue sarcoma (stages IIB to IVA) were randomized, after receiving optimal regional therapy, to receive either doxorubicin hydrochloride (450 mg/m2) (37 patients) or observation (38 patients). Follow-up has ranged from 16 to 80 months (median, 49 months). Twenty-five patients (33%) died, and two patients receiving doxorubicin developed cardiotoxicity. No significant differences in local control, metastasis-free survival, disease-free survival, and overall survival were observed for the two treatment arms. Despite temporary prolongation of disease-free survival with doxorubicin in some subgroups, we conclude that there is no advantage to the use of adjuvant doxorubicin in the treatment of soft-tissue sarcoma.

Clinical Trials as Topic↗
PubMed1985

Diffuse lymphomatous polyposis of the gastrointestinal tract. A case report with immunohistochemical studies.

A case of diffuse lymphomatous polyposis of the gastrointestinal tract is reported. The patient presented with abdominal pain and weight loss and x-rays revealed multiple polyps involving the entire gastrointestinal tract. Biopsies confirmed the diagnosis of lymphomatous polyposis. The patient also had involvement of the bone marrow and supraclavicular lymph node. Immunologically this lymphoma was characterized as a monoclonal proliferation of B lymphocytes bearing immunoglobulin M, type kappa. Diffuse lymphomatous polyposis of the gastrointestinal tract appears to be a generalized malignancy of uncommitted B cells of Peyer's patches. The migratory properties of these cells may account for the tendency to dissemination of lymphomatous polyposis. Diffuse lymphomatous polyposis of the gastrointestinal tract is a distinct entity, separate from the diffuse gastrointestinal lymphoma known as Mediterranean-type lymphoma.

Aged↗
PubMed1985

Selection bias in clinical trials.

Of 90 patients with intermediate or high-grade sarcoma eligible for a randomized trial of adjuvant doxorubicin (Adriamycin, Adria Laboratories, Columbus, Ohio), 48 were not entered: 24 (27%) by physician's choice and 24 refused randomization. Sixty-five percent of lower stage patients were randomized compared with 37% of those with higher stage (P = .02). Patients with extremity lesions were more frequently offered participation in the study (P = .07). Patients with lower stage lesions accepted randomization more readily than those with higher stage lesions (P = .01). As predicted by the higher stage and percentage of central lesions, the disease-free survival of nonrandomized patients was inferior to that of randomized patients (P = .15). Thus, patients at high risk appeared to avoid randomization and adjuvant doxorubicin in this trial, resulting in an inferior disease-free survival for the nonrandomized control group. Important questions generally require randomized trials that reliably determine relative treatment differences. If, however, the patients in a clinical trial are not representative of the entire patient population because of patient and physician selection biases, the generalizability of the results to the entire patient population may be compromised. For example, the prognosis of the general population cannot necessarily be inferred from the selected group in the study. In this study, the randomized and nonrandomized series yielded differing conclusions regarding treatment efficacy, even when an adjustment was made for known prognostic facts.

Clinical Trials as Topic↗
PubMed1985

Combination chemotherapy followed by radiation therapy in patients with regional stage III unresectable non-small cell lung cancer.

A chemotherapy combination of cyclophosphamide, doxorubicin, and cisplatin (CAP) was administered to 30 patients with stage III M0 or M1 (supraclavicular nodes) unresectable non-small cell lung cancer before and after radiotherapy. All patients had mediastinal metastases and most had T2 or T3 primary lesions. The response rate (complete plus partial) after two cycles of CAP was 47%, which increased to 66% (24% complete response rate) following radiotherapy. The overall median survival from initiation of chemotherapy was 9 months. CNS relapse occurred in five (26%) of 19 responding patients who did not receive prophylactic cranial irradiation in the early part of the study.

Adenocarcinoma↗
PubMed1985

Heterogeneity of buoyant density and proliferative state of circulating erythropoietic progenitor cells (BFU-E) in man.

Normal human blood BFU-E are believed to be in a quiescent state with respect to DNA synthesis, since few or none of these progenitors can be killed by cycle-active agents. Using Percoll discontinuous density gradient centrifugation of normal human blood mononuclear cells, we have separated two subpopulations of BFU-E with different proportions in DNA synthesis. Mononuclear cells were obtained with Ficoll-Isopaque from 24 samples of normal blood. BFU-E were assayed with the methylcellulose technique, and their proliferative state was studied with the hydroxyurea (HU) suicide method. The results obtained with a five-step gradient of density range 1.060-1.068 g/ml showed that the vast majority of BFU-E were distributed approximately equally between pooled fractions with rho = 1.060 + 1.062 g/ml and those with rho = 1.064 + 1.066 g/ml. Among nonseparated cells or cells in the fraction of rho = 1.060 + 1.062 g/ml, we failed to detect a significant proportion of DNA-synthesizing BFU-E in the great majority of samples. In contrast, in the pooled fractions with rho = 1.064 + 1.066 g/ml, 14 of 24 samples showed significant kill, and among these 14, a highly significant proportion of BFU-E were killed by HU (39.3% +/- 3.4%). Therefore, the separation of mononuclear cells on the basis of their different buoyant densities revealed the presence of DNA-synthesizing BFU-E in normal human blood. Either DNA-synthesizing BFU-E have a higher buoyant density than non-DNA-synthesizing BFU-E, or else cells of lower buoyant density normally inhibit DNA synthesis in BFU-E.

Cell Division↗
PubMed1984

Adult T-cell leukemia-lymphoma with mediastinal involvement and an asymptomatic chronic phase.

A black, West Indian woman with adult T-cell leukemia-lymphoma (ATLL), hypercalcemia, peripheral and retroperitoneal lymphadenopathy, and serum antibodies to human T-lymphotropic virus (HTLV) was found to have massive mediastinal adenopathy, a feature not previously reported in patients with ATLL. In addition, she had had asymptomatic leukocytosis with marked lymphocytosis for at least 6 years before presenting with full-blown ATLL. These findings broaden the clinical picture of ATLL. Cell surface-marker studies and close follow-up are recommended for patients with apparent chronic lymphocytic leukemia, especially if they have pleomorphic lymphocytosis, are younger than usual or are from the Caribbean or Japan.

Adult↗
PubMed1984

Preliminary results of a randomized trial of adjuvant doxorubicin for sarcomas: lack of apparent difference between treatment groups.

Forty-two patients with localized intermediate and high-grade sarcoma were randomized after optimal primary treatment to receive five cycles of adjuvant doxorubicin 90 mg/m2 every three weeks (20 patients) or observation (22 patients). Patients were stratified for grade, size, extent of surgical margin, and soft tissue versus other sarcomas. Groups appeared balanced for histology and superficial versus deep lesions. Eight patients (19%) have died. Follow-up times range from two to 69 months (median, 16 months). Two patients receiving doxorubicin (10%) developed cardiotoxicity presenting as pulmonary edema. One patient returned to normal activity on digoxin and diuretics; the other (age, 28 years) died of intractable failure and arrhythmias after four weeks. While a nonsignificant difference in local control, metastasis-free survival, disease-free survival, and survival was observed for extremity lesions, the advantage may be outweighed by the risk of cardiotoxicity. Seventy-six percent of the control patients with extremity lesions remain disease free. Because control patients do well, a very large study is required to define the role of adjuvant doxorubicin.

Adult↗
PubMed1984

Adult T-cell lymphoma. A case report with lymph node studies by monoclonal antibodies and ultrastructure.

A case of retrovirus-associated adult T-cell lymphoma studied by monoclonal markers and ultrastructure is reported. The patient, who was born in Jamaica and emigrated to Canada 9 years previously, had a 5-year history of asymptomatic lymphocytosis preceding the onset of rapidly progressive disease. The peripheral blood lymphocytes were predominantly pleomorphic small lymphocytes with a smaller population of transformed lymphocytes. The peripheral blood lymphocytes were typed immunologically as T-cells of helper/inducer phenotype. Immunological typing of the lymph node lymphocytes, performed on tissue sections, demonstrated a similar phenotype. Morphological study of the lymph node showed a diffuse lymphoma, encompassing a wide range of cell sizes, including giant cells. In view of the morphological heterogeneity of this condition, immunological and viral studies are recommended to confirm the diagnosis.

Adult↗
PubMed1984

The proliferative state of early erythropoietic progenitor cells (BFU-E) in human umbilical cord blood: low probability of finding BFU-E in DNA synthesis.

We have investigated the proliferative behavior of early erythropoietic progenitor cells (BFU-E) in human umbilical cord blood with hydroxyurea and tritiated-thymidine suicide experiments. Our results indicate that the great majority of these progenitors are normally either in a quiescent state with respect to DNA synthesis or in a prolonged cell cycle experimentally indistinguishable from this state. In this regard, neonatal BFU-E resemble adult circulating BFU-E.

Cell Division↗
PubMed1983

Erythroid burst formation in cultures of bone marrow and peripheral blood from patients with refractory anemia.

We have studied the growth of erythroid bursts in methylcellulose cultures from bone marrow (7 cases) and peripheral blood cells (17 cases) of patients with primary acquired refractory anemias. In most cases, erythroid burst-forming units (BFU-E) were either absent or present in lower than normal numbers, and these levels remained low to absent in sequential studies. In 2 patients, circulating BFU-E were initially higher than normal, but subsequently declined to normal levels. 1 patient had low-normal numbers of circulating BFU-E initially, but these declined to zero in a later study. No clinical or routine hematological features permitted distinction between patients with initially high BFU-E and those with initially low or absent BFU-E. These findings parallel those reported for granulocyte-macrophage progenitors in refractory anemias, and support the concept that erythroid progenitor cells in these disorders are influenced by the disordered hematopoiesis.

Adult↗
PubMed1983

The clotting and staining of methylcellulose cultures of human hemopoietic cells.

We describe a technique for clotting, fixing and staining methylcellulose cultures of human hemopoietic progenitor cells. The entire cellular population of a 1-ml culture in a 35-mm plastic petri dish can be recovered and preserved permanently with this method. The technique also provides the opportunity for distinguishing between pure erythroid and mixed colonies, for examining cellular morphology without tediously picking individual colonies, and for terminating cultures on the appropriate day without the necessity of scoring on that same day.

Adult↗
PubMed1983

Differences among myeloproliferative disorders in the behavior of their restricted progenitor cells in culture.

We have studied the behavior in culture of circulating restricted hemopoietic progenitor cells from patients with idiopathic myelofibrosis (IMF), polycythemia vera (PV), and essential thrombocytopenia (ET). We have found differences in circulating granulocyte-macrophage, erythroid, and megakaryocytic progenitors that appear to be specific for these chronic myeloproliferative disorders. In IMF, most affected were granulocyte-macrophage progenitor cells (CFU-C), which circulated in increased numbers and were heterogeneous in their sensitivity to the regulatory factor(s) present in phytohemagglutinin (PHA) stimulated T-lymphocyte conditioned medium (CM). Most CFU-C were either highly sensitive to, or independent from, stimulatory factors, while others showed normal sensitivity. In some IMF patients, circulating megakaryocytic progenitors (CFU-M) were present that were capable of giving rise to colonies in the absence of added CM or erythropoietin (EPO). In PV, we confirmed the presence of circulating erythroid progenitor cells that give rise to colonies in culture without the addition of EPO. The number of circulating CFU-C was normal and they responded normally to CM. In ET, failure to detect 7-day circulating restricted progenitor cells was a common observation; the level of other circulating restricted progenitors was in the low normal range. Thus, despite certain common features, including a primary lesion at the level of the pluripotential hemopoietic stem cell, the myeloproliferative disorders differ with respect to the behavior in culture of their circulating restricted progenitor cells. These results have led us to postulate a second regulatory lesion in the pluripotential stem cell that differs in these disorders and is expressed at the level of the respective restricted progenitor cells.

Aged↗
PubMed1978

Leukaemia in Papua New Guinea.

All cases of leukaemia diagnosed between 1968 and 1976 in the Melanesian population of Papua New Guinea have been analysed, and comparisons made with an earlier series from this country and with findings reported from elsewhere. The major findings were: a low overall incidence (0.79/100,000), absence of a childhood or old age peak in incidence, a relatively lower proportion of acute lymphoblastic leukaemia in childhood, more than the expected proportion of cases of chronic granulocytic leukaemia under 20 years of age, and the rarity of chronic lymphocytic leukaemia.

Adolescent↗
PubMed1977

Malaria and hereditary ovalocytosis.

Hereditary ovalocytosis in Papua New Guinea is restricted to areas of endemic malaria and may confer increased resistance to the disease. The incidence of malaria was investigated in 1616 Melanesiams of known red cell morphology and severity of infection determined in a smaller subsample. Ovalocytics tended to be more resistant to severe malarial infections than normocytics. The ratio of parasitaemia in 112 ovalocytics compared with 741 normocytic children was 1.05 for P. falciparum; 0.90 for P. vivax; 0.54 for P. malariae, and 0.91 for infection with any species. The difficulties in conclusively demonstrating any selective advantage of the condition are discussed.

Adolescent↗
PubMed1977

Selective depression of blood group antigens associated with hereditary ovalocytosis among melanesians.

Recessively inherited ovalocytosis in coastal Melanesians is associated with widespread, but selective, depression of blood group antigens in homozygotes, who comprise about 15% of these populations. It is suggested that a membrane anomaly exists, and that the series of depressed determinants all depend, for their full expression, upon the same membrane component(s), the proper synthesis of which is being genetically affected. Affected antigens would thus be associated by position and/or structure. Antigens subject to depression include IT, IF, LW,D,C,e,S,s,U,Kpb,JKa,JKb,Xga,Wrb,Scl and Ena, which are simultaneously affected when present on oval cells. Reactivity of A1,ID,i,P1,M,N,Lub,k,Fya,Coa, Vel and Gea appears to be within the normal range on depressed cells, as does sialic acid content. Indirect evidence suggests that Z (associated with S and s) is among the depressed series, while NA and Leb are not. High H variants, common among Melanesians, seem absent among depressed bloods, and when such variants were excluded, H, A and B did not appear subject to depression. The distribution pattern of ovalocytosis suggests that it may confer some selective advantage in the tropical coastal environment. The findings also have implications concerning population genetic work in New Guinea.

ABO Blood-Group System↗