A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group Study.

PURPOSE: A randomized clinical trial was undertaken to compare the therapeutic effectiveness of idarubicin (IDR) to daunorubicin (DNR), and both were given in combination with cytarabine (CA) in acute myelogenous leukemic (AML) patients. PATIENTS AND METHODS: Newly diagnosed patients were given a daily infusion of CA (100 mg/m2) for 7 days and were assigned randomly to receive DNR (45 mg/m2) or IDR (12 mg/m2) daily for the first 3 days. Those patients who achieved a complete remission (CR) were given three consolidation courses that consisted of CA (100 mg/m2 intravenously [IV]) and thioguanine (TG; 100 mg/m2 orally) every 12 hours for 5 days and either DNR (50 mg/m2) or IDR (15 mg/m2) on the first day of each cycle. After consolidation, patients received late intensification, which consisted of the same drugs used for induction except that the CA was given for 5 days and the anthracycline for 2 days. Four courses were planned at 13-week intervals. RESULTS: The CR rates were 75 of 105 (71%) on the IDR arm and 65 of 113 (58%) on the DNR arm (P = .03). The median survival and median remission durations were 297 and 433 days, respectively, on the IDR arm. The median survival and median remission durations were 277 and 328 days, respectively, on the DNR arm. Six deaths occurred during late intensification, five on IDR and one on DNR; this approach was abandoned after 47 patients were entered. The median survival was significantly longer for patients who received late intensification. CONCLUSION: This trial demonstrated that IDR was more effective than DNR in remission induction in AML.

A randomized prospective assessment of recombinant leukocyte A human interferon with or without aspirin in advanced renal adenocarcinoma.

We performed a prospective, controlled trial of recombinant leukocyte A interferon (IFN-alpha 2A) with or without aspirin (ASA) in 176 patients with assessable advanced renal cell cancer in light of a 34% response rate (10 of 29 patients) from the two-agent regimen in an earlier nonrandomized trial. This encouraging result was substantially higher than the 15% response rate typically achieved with IFN therapy alone. Eighty-seven patients received IFN-alpha 2A 20 x 10(6) U/m2 intramuscularly three times a week, and 89 received the same IFN therapy with ASA 600 mg orally four times each day. Each group was balanced as to relevant prognostic discriminants. Response rates were 8% for the group receiving ASA in addition to IFN, and 13% for the group receiving IFN alone (P = .30). The median times to progression were 1.9 months for the group receiving IFN with ASA and 2.7 months for the group receiving IFN alone (log-rank P = .36). The median survival durations were 8.8 months for the IFN and ASA group and 8.0 months for the IFN-only group (log-rank P = .60). These figures are also inferior to those typically reported from other studies. Our findings reemphasize the crucial role of randomized trials, admittedly cumbersome and time-consuming, to determine accurately the value of apparently promising therapies. Although some patients may derive benefit from IFN therapy, our findings raise disturbing questions regarding the potential IFN-alpha 2A according to the dose and schedule used in this trial to have any substantive impact on the ultimate outcome of disseminated renal cell cancer.

Kaposi's sarcoma with a non-Hodgkin's lymphoma. Its association in a male homosexual with human T-cell lymphotropic virus type III infection.

Combined tumor syndromes, specifically reticuloendothelial malignancies and Kaposi's sarcoma, have long been recognized. With the recognition of the acquired immunodeficiency syndrome (AIDS), several patients with concurrent non-Hodgkin's lymphoma and Kaposi's sarcoma have been reported at high risk for developing AIDS. The present Centers for Disease Control definition of AIDS excludes these patients on the assumption that one tumor is affecting the cellular immunity, allowing for the development of the second malignancy. In evaluating such a patient who had serologic evidence of human T-cell lymphotropic virus type III infection, the probable cause of AIDS, we have reviewed reports of patients with similar concurrent malignancies before and since the onset of the AIDS epidemic. We conclude that patients in high-risk groups for AIDS who develop similar combined tumor syndromes should be classified as having AIDS.

Treatment of polyneuropathy in Waldenström's macroglobulinemia: role of paraproteinemia and immunologic studies.

A patient with polyneuropathy due to Waldenström's macroglobulinemia (WM) was treated successfully with chlorambucil and prednisone. Before therapy, 60% of peripheral lymphocytes were B cells, the nerve had IgM-bearing B-cell infiltrates, and the circulating IgM had antibody-binding activity to autologous and homologous nerves. Neurologic improvement, sustained for 4 years, began 3 months after therapy and coincided with the return to normal of bone marrow and circulating B cells. Binding of IgM to autologous and homologous nerves persisted after therapy, suggesting that not the IgM alone but other B-cell factors, possibly complexed to IgM, may have been responsible for the nerve damage.

Preoperative predictors of cost in Medicare-age patients undergoing coronary artery bypass grafting.

BACKGROUND: Identification of preoperative factors that contribute to the cost of coronary artery bypass grafting could aid in predicting the procedure's expense. In this study, 30 sociodemographic and clinical preoperative factors were examined with "survival analysis" techniques to determine characteristics related to total hospital cost. METHODS: Characteristics of all patients age 65 or older undergoing isolated coronary artery bypass grafting from July 1993 to April 1995 (n = 757) were recorded. Software was developed within the hospital's Transitions Systems, Inc, database to calculate the outcome variable of total cost. Nonparametric methods were used for the univariate analysis of the data, and the Cox proportional hazards model was used for the multivariable analysis, censoring 25 patients who died in the hospital. RESULTS: Median hospital cost from the day of the operation until discharge was $15,198. Median length of stay after the operation was 6 days. Multivariable analysis revealed that age, preoperative renal failure, history of cerebrovascular accident, low ejection fraction, and surgical urgency were independent predictors of total cost. CONCLUSIONS: This study, using an accurate representation of true hospital cost and a modeling technique that accounts for the confounding effect of in-hospital death on cost, provides a template for analysis of cost in other patient groups.

The Iowa prospective longitudinal study of recent-onset psychoses.

In this article, the methods of a prospective longitudinal study of recent-onset psychoses are described. Methodological issues that may be common to studies employing a similar design are discussed in the context of the rationale behind this study's strategies. Particular attention is paid to statistical strategies that maximally exploit longitudinal data.

The identification and functional significance of factor VIII components on normal platelets.

Factor VIII-related antigen (VIII R:Ag) has previously been identified on human platelets by fluorescein-labelled heterologous antibodies to factor VIII. However, it is not known whether these antibodies identify only VIII R:Ag or whether antigens associated with factor VIII coagulant activity (VIII:C Ag) are also present. The current studies utilize specific antibodies and their Fab' fragments to evaluate the presence of both VIII R:Ag and VIII:C Ag on human platelets and to study the functional role of the platelet-associated VIII R:Ag on ristocetin-induced platelet agglutination. Immunofluorescent studies demonstrate the presence of VIII R:Ag, but do not identify VIII:C Ag on platelets. The functional studies reveal that after incubation with either of the Fab' fragments, platelets retain their reactivity in the ristocetin cofactor assay. These results indicate that this population of VIII R:Ag is not essential for the ristocetin aggregation reaction and that no antigenic determinants for factor VIII coagulant activity (VIII:C) are detectable on human platelets by immunofluorescence.

Magnetic resonance imaging in familial versus sporadic cases of schizophrenia.

Magnetic resonance imaging findings were compared in 22 familial and 29 sporadic cases with DSM-III-R diagnoses of schizophrenia, schizoaffective, or schizophreniform disorders. Volumetric measurements were used to assess the size of brain structures, including the cranium, cerebrum, lateral ventricles, temporal horns, third ventricle, lenticular nuclei, amygdaloid-hippocampal complex, and cerebellum, as well as the asymmetry of the lateral ventricles. Increased volume of the lenticular nuclei and greater ventricular asymmetry (the left ventricle being larger) were found in familial cases compared with sporadic cases and normal control subjects. It is possible that increased lenticular nuclei volume and greater lateral ventricular asymmetry reflect the role of genetic factors in schizophrenia.

Spontaneous bacterial empyema in cirrhosis.

Spontaneous bacterial peritonitis in decompensated cirrhotic patients develops when bacteria invade preexising ascites. It is probable that other transudates such as pleural effusions can be afected in a similar manner. This paper describes a cirrhotic patient with long-standing pleural effusion in whom Escherichia coli caused a spontaneous bacterial empyema. The ascitic fluid was sterile.

Postsplenectomy infections.

Serious postsplenectomy infection is a significant threat to patients. Although the incidence of such infection is low, the resultant mortality is extremely high. This susceptibility to infection and ensuing mortality results from multiple immunologic changes that occur after splenectomy. These changes include alteration in immunoglobulin levels, loss of serum opsonizing proteins, and alterations in antigen clearance and cellular immunity.

Refractory aplastic anemia: concomitant therapy with antithymocyte globulin and high-dose corticosteroids.

Bone marrow transplantation is possible for only a minority of patients with severe aplastic anemia. There has been successful treatment in some patients with immunosuppressive agents: high-dose 6-methylprednisolone, antilymphocyte globulin, and antithymocyte globulin. We report the successful treatment of two patients with severe aplastic anemia with the simultaneous administration of antithymocyte globulin and high-dose 6-methylprednisolone after failure with antithymocyte globulin and low-dose corticosteroids.

A clinicopathologic correlation of the idiopathic hypereosinophilic syndrome. I. Hematologic manifestations.

A retrospective blind study of 32 patients with the hypereosinophilic syndrome was undertaken utilizing a hematologic scoring system that was based on peripheral blood and bone marrow findings, cytogenetics B12 levels, and leukocyte alkaline phosphatase determinations. In addition to the grading system, which allowed formulation of a hematologic score, the date could also be normalized for individuals who did not have all tests performed by use of the hematologic quotient. This study clearly defined two groups of patients within the idiopathic hypereosinophilic syndrome. One group were those individuals with low hematologic scores and quotients who did not require therapy or who responded to prednisone therapy, while the second group of patients required cytotoxic therapy. These patients had significantly higher hematologic scores and quotients and a significant number of abnormalities similar to those seen in myeloproliferative syndromes, such as myelofibrosis and cytogenetic abnormalities. This type of hematologic scoring seems useful in predicting therapy and/or evaluating individuals or groups of patients with the hypereosinophilic syndrome.

A clinicopathologic correlation of the idiopathic hypereosinophilic syndrome. II. Clinical manifestations.

The idiopathic hypereosinophilic syndrome, a disorder characterized by peripheral blood and bone marrow eosinophilia associated with single or multiple organ system dysfunction attributable to tissue invasion by eosinophils has, in the past, been associated with an extremely poor prognosis. Recently, we reported the favorable impact of a therapeutic protocol consisting of prednisone and/or hydroxyurea on the morbidity and mortality of this syndrome. We have reviewed the clinical and hematologic features upon admission and the subsequent clinical courses of 32 patients with this disease referred to the NIH between 1965 and 1979 in an effort to determine which features suggest a more rapidly progressive course. A grading system based on 22 clinical features involving the 8 organ systems commonly affected by the illness was devised. The disease followed a more aggressive course in patients with evidence of cardiac or neurologic dysfunction at the time of initial NIH evaluation. Although splenomegaly, in and of itself, caused little morbidity, splenic enlargement at presentation appeared to be a predictor of a more aggressive course. The clinical grading system accurately predicted which patients would require no specific antihypereosinophilic therapy, which patients would respond adequately to corticosteroids, and which patients would require therapy with cytotoxic agents. It is proposed that this clinical grading system, and the hematologic grading system outlined in the accompanying report be used as aids in the selection of initial therapy in this group of patients.

Epidemiological and clinical correlates of familial and sporadic schizophrenia.

We studied 68 schizophrenic cases with a schizophrenic first-degree relative (familial group) and 62 cases without such a family history (sporadic group). We compared them on: (i) clinical variables, including premorbid adjustment, age of onset and severity of symptoms; (ii) neural abnormalities, including abnormal involuntary movements, neural "soft" and "hard signs"; (iii) neuropsychological tests, including the Wechsler Adult Intelligence Scale and the Continuous Performance Test and (iv) environmental risk factors, including winter birth and obstetrical complications. Sporadic cases were more likely to be born in winter and had more severe psychotic symptoms, but most analyses yielded no difference between the groups. Our results offer some support that sporadic schizophrenia is a more environmental subtype, but they also suggest that the familial vs sporadic distinction of schizophrenia has limited power to identify distinct subgroups.

IgA inhibitor to factor VIII/von Willebrand factor.

A 60-year-old Black female presented with a haemorrhagic diathesis and an acquired factor VIII/von Willebrand factor (VIII/vWf) inhibitor. This inhibitor was classified as an IgA immunoglobulin and was active not only against factor VIII coagulant (VIII:C) activity but also against plasma von Willebrand factor (vWf). The purified IgA also interacted with normal platelets to inhibit ristocetin-induced platelet aggregation (RIPA). In contrast, studies with haemophilia A plasma and platelets revealed that the inhibitor did not react significantly with these plasmas or platelets. The significant differences in the inhibition of vWf assay both of the plasma and the platelets of the haemophilia A patients suggests that part of the haemorrhagic diathesis may be related not only to the inhibition of VIII:C but also to interference with platelet function. In addition, these studies suggest that there may be significant differences in the factor VIII-related antigen (VIII R:Ag) on platelets in haemophilia A patients compared to normal.

The antiemetic efficacy of secobarbital and chlorpromazine compared to metoclopramide, diphenhydramine, and dexamethasone. A randomized trial.

The efficacy of secobarbital sodium plus chlorpromazine (SC) in the prevention of cisplatin induced emesis was compared to the combination of metoclopramide, diphenhydramine, and dexamethasone (MDD). Twenty-three patients were entered onto protocol. Eighteen were evaluable. Good to excellent antiemetic prophylaxis was obtained in 72% with MDD versus 17% with SC (P less than 0.01). Sedation and anticholinergic side effects were more common with SC. Extrapyramidal reactions were more commonly seen with MDD. Significantly more patients preferred the combination of metoclopramide, diphenhydramine, and dexamethasone (P less than 0.05).

The hemostatic imbalance of plasma-exchange transfusion.

Plasma exchange has been proposed as a treatment for multiple disorders. Three patients with amyotropic lateral sclerosis, who were hemostatically normal, were studied through a total of 11 4-liter exchanges. Plasma was replaced by an equal volume of 5% albumin or 5% plasma protein fraction. Serial studies revealed that immediately after the exchange transfusion, there was significant prolongation of the prothrombin, partial thromboplastin, and thrombin times with reduction of the fibrinogen and antithrombin III levels. Factors V, VII-X, IX, and X were all significantly decreased, as were the factor VIII antigen, procoagulant, and the ristocetin cofactor activities. Platelet counts were obtained before and after exchanges and revealed significant decreases. Four hours after exchange, all parameters remained abnormal except the factor IX, ristocetin cofactor, and factor VIII procoagulant activities. By 24 hr, all hemostatic parameters had returned to normal. These studies indicate that plasma-exchange transfusion with material devoid of coagulation factors results in a coagulation defect that may be of clinical significance in a hemostatically compromised patient.