From aphorisms to APACHE: medicine's brave new world.
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Information Systems↗
Biomedical subjects
R B Davis
Publications and source records attributed to R B Davis.
Drug and alcohol use in the former Soviet Union: selected factors and future considerations.
As new nations form out of the wreckage of the Soviet Empire, they will be encumbered by the persistent political, economic, and social problems that have plagued this region for centuries. Today, the leaders of the emerging central Eurasian area are focused solely on political and economic concerns. They are paying little attention to the drug use that, like the more traditional heavy alcohol use, is a means by which many people of this region escape the reality and manifold uncertainties of today's world. If and when the political and economic climate of the central Eurasian area stabilizes, regional leaders will face an addiction problem that will have, by then, become the region's greatest obstacle to social progress and sound public health.
Adolescent↗
Bringing medical informatics into mainstream clinical medicine.
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Education, Medical, Undergraduate↗
Intervening with high risk youth: a program model.
This paper describes a program model being implemented for older, high-risk adolescents who are beginning to exhibit significant substance use problems. The program provides an initial assessment and refers clients to appropriate services. Only a small percentage are being referred to inpatient treatment; most clients enter outpatient intervention groups, which are conducted by the program. These groups have three purposes: to allow staff to monitor and evaluate clients so that those who are in imminent danger can be placed in protective treatment settings; to help clients see themselves as candidates for recovery and to introduce them to treatment resources by accompanying them to AA and NA meetings; and to change behavior, a goal that seems more immediately achievable for youth with stable community ties who have more to lose if they get into further trouble. Besides describing the program model, this paper examines some of the difficulties of getting referrals from a variety of community agencies.
Adolescent↗
Effects of treatment with 5-azacytidine on the in vivo and in vitro hematopoiesis in patients with myelodysplastic syndromes.
The myelodysplastic syndrome (MDS) comprises a group of clonal hematopoietic disorders derived from an abnormality affecting a multipotent hematopoietic stem cell. Despite trials testing numerous agents in patients with MDS, no single drug has yet emerged as the accepted standard of treatment. Observation and supportive care with blood products and antibiotics, when necessary, continue to be the mainstays of therapy. We administered 5-azacytidine, a cell-cycle specific ring analog of the pyrimidine nucleoside cytosine, as a continuous intravenous infusion, 75 mg/m2 per day for 7 days every 4 weeks. Patients had refractory anemia with excess blasts (RAEB) or refractory anemia with excess blasts in transformation (RAEB-T). Responses were seen in 21 (49%) of 43 evaluable patients: five (12%) in complete remission (CR, complete normalization of bone marrow and peripheral blood counts); 11 (25%) in partial remission (PR, > or = 50% restoration of the deficit from normal of all three peripheral blood cell lines, elimination of transfusion requirements, and a decrease in percentage bone marrow blasts by > or = 50% from prestudy values); five (12%) improved (> or = 50% restoration in the deficit from normal of one or more peripheral blood cell lines and/or a > or = 50% decrease in transfusion requirements). A trilineage improvement (CR and PR) occurred in 37% of the patients. The median survival for all patients was 13.3 months and the median duration of remission for those with CR and PR was 14.7 months. Mild to moderate nausea and/or vomiting was the most common side effect (63%). Myelosuppression, either bone marrow hypoplasia or drug related cytopenias requiring a reduction in the dose of azacitidine, occurred in only 33% of the patients. Prior to treatment, bone marrow erythroid progenitor cells were assayed in vitro. Colonies derived from erythroid burst-forming units (BFU-e) were undetectable in one patient and reduced in two. The number of colonies derived from erythroid colony-forming units (CFU-e)) were also reduced in two of the three patients. In the two patients with detectable colony growth prior to treatment, colony number decreased by day 8 of the first cycle, followed by a subsequent increase. Continued treatment with azacitidine led to normalization of the number of CFU-e derived colonies as well as an increase in the number of BFU-e derived colonies. This improvement in erythroid colony number correlated with the spontaneous rise in hemoglobin levels and red cell transfusion independence.(ABSTRACT TRUNCATED AT 400 WORDS)
Aged↗
An abnormal gallbladder presenting as a huge, rounded photon-deficient area in radionuclide hepatobiliary imaging.
Tc-99m DISIDA hepatobiliary imaging was used to evaluate a hemophiliac patient presenting with symptoms of acute cholecystitis and gastrointestinal bleeding. There was nonvisualization of this abnormal gallbladder even on 6 1/2-hour delayed DISIDA images. Instead, a huge photon-deficient area was seen in the gallbladder fossa. Ultrasound and computed tomography findings were consistent with an enlarged gallbladder filled with blood.
Adult↗
Effect of foscarnet therapy on human immunodeficiency virus p24 antigen levels in AIDS patients with cytomegalovirus retinitis.
Circulating human immunodeficiency virus (HIV) p24 antigen levels were measured in 22 AIDS patients who had detectable serum antigen at baseline after induction and maintenance therapy of foscarnet for cytomegalovirus retinitis in phase I/II multicenter trials. The HIV p24 antigen levels decreased from a baseline value of 199 +/- 236 (mean +/- SD) and 140 pg/mL (median) to 106 +/- 218 and 28 pg/mL after 14 days of foscarnet induction therapy (60 mg/kg every 8 h). During chronic foscarnet maintenance, there was a sustained decrease in mean HIV p24 antigen levels below pre-foscarnet therapy baseline concentrations for a median of 16 weeks after foscarnet induction. These results provide evidence for a sustained clinical antiretroviral effect of chronic foscarnet maintenance therapy, consistent with a recent report that foscarnet-treated AIDS patients live longer than ganciclovir-treated patients.
Acquired Immunodeficiency Syndrome↗
Intensive post-remission therapy with Ara-C in adults with acute myeloid leukemia: initial results of a CALGB phase III trial. The Cancer and Leukemia Group B.
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Acute Disease↗
A comparative study of two different doses of cytarabine for acute myeloid leukemia: a phase III trial of Cancer and Leukemia Group B.
Between 1982 and 1986, 326 evaluable patients with acute myeloid leukemia (AML) were randomized to receive cytarabine (Ara-C) at 200 mg/m2 (A200) or 100 mg/m2 (A100) for induction and maintenance therapy. Cycle 1 of induction therapy consisted of 7 days of continuous intravenous (IV) Ara-C and 3 days of i.v. daunorubicin (DNR); cycle 2, if needed, consisted of 5 days of Ara-C and 2 days of DNR. Complete responders (CR) then received monthly subcutaneous (SC) Ara-C at the respective doses (A100 or A200) with 6-thioquanine (6TG) at months 1 and 5, with vincristine (VCR) and prednisone at months 2, 4, 6, and 8, and with DNR at months 3 and 7. Complete response rates were 58% (A100) and 64% (A200) (P = .29). Median survival was 46 weeks (A100) and 38 weeks (A200) (P = .64); 5-year survival was 10% (A200) and 8% (A100). Median time to remission was 6.7 weeks (A200) and 8.1 weeks (A100) (P = .18). Median disease-free survival was 41 weeks (A200) and 44 weeks (A100) (P = .86). Deaths were attributed to therapy-related toxicities in 21% (A200) and 13% (A100) (P = .05). The 5-year survival was 15% for patients with performance status (PS) 0, 8% for PS 1 to 2, and 2% for PS 3 to 4, 18% for patients less than 40 years, 8% for ages 40 to 59, and 3% for age 60 or greater. Stratification of data by age and PS suggested that A200 may improve survival in patients less than 60 years with a good PS 0 (P = .05). This trial does not support the superiority of A200 over A100 in the treatment of AML.
Acute Disease↗
Prognostic value of lymphocyte surface markers in acute myeloid leukemia.
We studied the expression of cell surface antigens associated with myeloid and lymphoid leukemias on bone marrow-derived blast cells from 339 patients with newly diagnosed de novo acute myeloid leukemia (AML) enrolled on Cancer and Leukemia Group B (CALGB) chemotherapy protocols. Surprisingly, of 211 cases studied for the expression of CD2 (T-cell marker, sheep erythrocyte binding receptor for T lymphocytes) 45 were positive (21%). In addition, of 298 patients studied for CD19 (B-lymphocyte marker), 41 were positive (14%). Overall, of 170 patients studied for both CD2 and CD19, 56 (33%) were positive. Interestingly, central review of the French-American-British (FAB) morphology of the CD2- and CD19-positive cases showed that FAB M3 was twice as frequent, and M4E eight times as frequent compared with the CD2- and CD19-negative cases. Of 22 lymphocyte antigen-positive cases in which cells were available for studies of Ig or T-cell antigen receptor (TCR) gene rearrangement, 20 were germline, one had a rearranged Ig heavy chain gene, and one had rearranged TCR beta and Ig heavy chain genes. The presence of messenger RNA for CD2 was demonstrated in four CD2 surface antigen-positive cases, thus validating the cell surface data. Lymphocyte antigen-positive cases had karyotypes commonly seen in AML; 71% of cases with an abnormal clone had t(8;21)(q22;q22), inversion 16(p13q22), t(15;17)(q22;q12), or t(9;11)(p22;q23). The patients with lymphocyte markers had a significantly higher incidence of these karyotypic abnormalities compared with patients with lymphocyte antigen-negative AML (34% v 15%, P less than .02). When the outcome to therapy of the lymphocyte antigen-positive cases was compared with that for the CD2, CD19-negative cases, we found that the CD2, CD19-positive cases actually had higher complete remission rates (75% v 59%, P = .04), and significantly longer time to failure (P = .02; 32.4% +/- 6.0% v 18.0% +/- 4.1% at 2 years) and overall survival (P = .02; 43.5% +/- 6.3% v 26.0% +/- 4.5% at 2 years). CD2 antigen-positive cases also had a significantly superior survival (P = .02; 43.8% +/- 7.9% v 29.8% +/- 3.8% at 2 years). There were no significant differences (P less than or equal to .05) between the two groups in age, leukocyte count at diagnosis, incidence of extramedullary disease, or FAB classification.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Treatment of relapsed and refractory acute myeloid leukemia with diaziquone and mitoxantrone: a CALGB phase I study.
Twenty-one patients with relapsed or refractory acute myeloid leukemia (AML) were treated with mitoxantrone (12 mg/m2/day, days 1-3) and diaziquone (continuous infusion days 1-5). The dosage of diaziquone was increased for sequential cohorts of seven patients from 20 mg/m2/day to 24 mg/m2/day, and finally to 28 mg/m2/day to determine the maximum tolerated dose for this chemotherapy combination. Myelosuppression was the dose-limiting toxicity. The median time to recovery of blood counts was greater at the highest dose of diaziquone (48 days) than at the lower two doses (31 and 28 days). Other toxic effects were minimal. Overall, 9/21 (43%, 95% confidence interval, 0.22 to 0.66) patients achieved complete remission. We conclude that this combination of drugs shows sufficient antileukemic activity with acceptable toxicity to warrant further trials.
Adult↗
Mitoxantrone and constant infusion etoposide for relapsed and refractory acute myelocytic leukemia.
In an effort to search for new, synergistic and non-cross-resistant antileukemic regimens, the Cancer and Leukemia Group B (CALGB) investigated the activity and toxicity of mitoxantrone in combination with etoposide for the reinduction of patients with relapsed or refractory acute myelocytic leukemia (AML). Mitoxantrone, 12 mg/m2 daily for 3 days, was combined with three dose levels of etoposide, 100, 150 and 200 mg/m2 daily by constant infusion for 5 days. There were 19 male and 13 female patients, with a median age of 46 (range, 21-74). Of these, nine were primarily refractory to daunorubicin and ara-C; 17 had one prior complete remission (CR), five had two prior CR, and one had three prior CR. Thirteen patients were entered at the first dose level, 11 were entered at the second, and eight at the third. All but one patient, whose death occurred within the first 2 days of treatment, are evaluable for toxicity. There were five CR (four at the first and one at the second dose level) and six partial remissions (PR) (three at the first dose level and three at the second). Unmaintained responses lasted 6-33 weeks. Median survival for all patients was 12.6 weeks. Anti-leukemic effects with severe marrow hypoplasia were observed in all patients; severe nausea and vomiting were seen in four. Severe mucositis, often indistinguishable from superimposed candidiasis, occurred in 40% of all patients; it was associated with dose-limiting esophagitis (three of seven evaluable patients) at the highest etoposide dose. Hepatic and renal dysfunction was severe in three patients; no treatment-related severe pulmonary or cardiac toxicity was observed. Posttreatment infectious complications were severe in 11 patients. In three cases, they were fatal--an incidence not dissimilar from that of other reinduction regimens in heavily pretreated patients. The regimen appears to be active; the combination of mitoxantrone, 12 mg/m2 daily for 3 days, with etoposide, 150 mg/m2/day for 5 days, by constant intravenous infusion is now being explored by the CALGB in a randomized phase II study against mitoxantrone plus diazoquinone and diazoquinone plus etoposide.
Adult↗
Effects of exercise and exercise conditioning on blood platelet function.
The effects of exercise and exercise conditioning on blood platelet function were investigated in six healthy individuals who had not engaged in regular exercise for at least 1 yr prior to the study. The subjects (three men and three women) had a mean age of 28 (range 23-32) and participated in a supervised program of treadmill exercise. Subjects exercised for 20 min, three times weekly, for 12 wk at 70-80% of estimated maximum heart rate. Samples for platelet counts, platelet aggregation, and plasma beta-thromboglobulin (beta-TG) were obtained prior to training and after 6 and 12 wk of training. All subjects responded with an increase in aerobic capacity during training. Resting mean systolic and diastolic blood pressures decreased after training (P less than 0.05). Platelet counts increased after exercise, and the increment in week 12 exceeded that in the 1st wk by 57%. Platelet aggregation studies in platelet rich plasma (PRP) showed an increase in slope after exercise (week 1, P less than 0.05) which decreased with training (week 1 vs week 12, P less than 0.01). Aggregation studies utilizing impedance aggregometry in diluted native whole blood showed an acceleration of both spontaneous aggregation (P less than 0.01 weeks 6 and 12) and aggregation using epinephrine as an agonist (P less than 0.05) following exercise. Plasma beta-TG levels did not increase significantly after exercise; however, resting concentrations of beta-TG decreased with training (P less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Early contributions to hematology in Nebraska.
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Hematology↗
Morphologic and cytochemical characteristics of acute promyelocytic leukemia.
The existence of two distinct subtypes of acute promyelocytic leukemia was confirmed and characterized based on morphologic features of leukemic cells in a series of 63 patients studied by the Cancer and Leukemia Group B (CALGB). Seventeen patients (27%) had microgranular leukemic cells (M3V), and 46 patients (73%) had hypergranular leukemic cells (M3). These patient cohorts were studied for other laboratory and clinical features. Leukemic cells from M3V patients stained less frequently than leukemic cells from M3 patients for myeloperoxidase (median, 93% vs. 99%; P = .006), periodic acid-Schiff (median, 57% vs. 92%; P = .0001), ASD-chloroacetate esterase (median, 45% vs. 87%; P less than .0001), and alpha-naphthyl acetate esterase (0% vs. 37%; P = .0003). Patients with M3V had a higher platelet count (median, 50 vs. 30 x 10(9)/L; P = .01) and tended to have a higher leukocyte count (median, 7.4 vs. 2.2 x 10(9)/L; P = .06) than M3 patients. The patients with M3V morphology were more likely to be nonwhite (29% vs. 7%; P = .03), female (71% vs. 37%; P = .02), and to be infected at the time of presentation (71% vs. 35%; P = .02). No differences in the frequency of the t(15;17) karyotype or the immunophenotypic expression of the leukemic cells were noted in the two morphologic subtypes of acute promyelocytic leukemia. Fewer patients with M3V tended to enter complete remission (65% vs. 80%; P = .20), but no significant differences were found in the duration of complete remission (P = .81; 1 year rate, 50% vs. 85%), or probability of survival (P = .67; 1 year rate, 49% vs. 68%).
Adolescent↗
Exponential survival trees.
This paper concerns a recursive partitioning algorithm for incomplete survival data. The splitting criterion employed is exponential log-likelihood loss. The method has been integrated into a computer program similar in structure to the commercial package CART. Special features incorporated into the program include a modification to prevent zero hazard estimates during the the cross-validation procedure and a method based on the chi-square distribution for final tree selection. Simulation results demonstrate the program's capability to identify the underlying hazard structure in survival data. An example utilizing data from patients with diffuse large cell lymphoma is presented.
Algorithms↗
Observations on human platelet aggregation in native whole blood: synergism and sensitivity to aggregating agents in vitro.
Threshold sensitivity levels, as well as the synergistic effects of agonists for blood platelets have been evaluated by impedance aggregometry using whole blood without anticoagulation. Platelet aggregation was studied using adenosine diphosphate (ADP), epinephrine, and thrombin. Threshold responses to ADP, epinephrine, and thrombin were observed at lower concentrations in diluted native whole blood (NWB) than reported values for citrated whole blood, and appear to be similar to those of citrated platelet rich plasma (PRP). Potentiation of aggregation occurred when both ADP and epinephrine, or epinephrine and thrombin but not ADP and thrombin were present in combination. Synergism between agonists thus is similar but not identical to that of PRP, and NWB appears to provide a sensitive system with a more physiologic milieu than other in vitro aggregation systems.
Adenosine Diphosphate↗