A 31-year-old man with fever, sore throat, and difficulty swallowing.
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Adult↗
Biomedical subjects
S O'Brien
Publications and source records attributed to S O'Brien.
Intensive chemotherapy induction followed by interferon-alpha maintenance in patients with Philadelphia chromosome-positive chronic myelogenous leukemia.
In a pilot study, 32 patients with Philadelphia chromosome-positive chronic myelogenous leukemia were treated with intensive chemotherapy induction followed by interferon-alpha (IFN-A) maintenance. Intensive chemotherapy consisted of three cycles of daunorubicin 120 mg/m2 on day 1, cytarabine 80 mg/m2 daily for 10 days, vincristine 2 mg on day 1, and prednisone 100 mg daily for 5 days (DOAP). Maintenance therapy with IFN-A at a doses of 3 x 10(6) to 5 x 10(6) units/m2 daily was adjusted according to counts and toxicity. The outcome of patients was compared with a matched historic population of 64 patients treated with IFN-A alone. Overall, 60% of patients had a cytogenetic response (partial or complete) with induction chemotherapy, but only eight (25%) had a sustained cytogenetic response with IFN-A maintenance. After a median follow-up of 67 months, the 6-year survival rate of the 32 patients was 58%, compared with 36% for the matched historic group (P = 0.084). The incidence of lymphoid blastic transformation in the two groups was 25% and 48%, respectively (P = 0.10) and durable cytogenetic responses, 25% and 19%, respectively (P = 0.48). In summary, the addition of intensive chemotherapy induction to IFN-A maintenance does not improve the survival rate, incidence of lymphoid blastic transformation, or incidence of durable cytogenetic response compared with the results achieved with IFN-A therapy alone.
Adolescent↗
Use of polymerase chain reaction for rapid detection of gene insertions in whole yeast cells.
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Base Sequence↗
Mitoxantrone and high-dose etoposide for patients with relapsed or refractory acute leukemia.
Among 35 patients with relapsed or refractory acute myelogenous leukemia (AML) who received salvage chemotherapy, 28 were treated with mitoxantrone (7.5 mg/m2/d intravenously [IV] over 1 hour for 5 days) and etoposide (VP-16) (2 g/m2 over 4 days either as a daily infusion or as two daily doses). Seven patients received mitoxantrone (6 mg/m2/d for 5 days) and VP-16 (1500 mg/m2 over 3 days). The median duration of the initial complete remission (CR) was 6 months and 83% of the patients had initial CR that lasted 12 months or less. Forty-six percent of the patients were undergoing a second or subsequent salvage attempt. Eight patients (23%) achieved CR; seven of these CR were obtained after one course of therapy. Twelve patients (33%) died and 15 patients (42%) had disease that was resistant to treatment. Patients undergoing a first salvage attempt had a higher incidence rate of CR than those undergoing a second or subsequent salvage attempt (37% versus 6%; P = 0.03). CR rates were also higher in patients with a favorable (translocation 8;21 or 15;17) or diploid karyotype compared with other patients (32% versus 8%; P = 0.10). The median survival time was 2 months for all patients and 8 months for patients achieving CR. Mucositis occurred in 74% of the patients and was severe in 32%. Diarrhea and rash occurred in less than 33% of the patients. Fever was noticed in all but 1 of the patients and documented infections occurred in 65% of the patients. Six patients had pancytopenia or thrombocytopenia that lasted more than 42 days from the initiation of treatment. Although mitoxantrone and high-dose VP-16 is an effective antileukemic regimen, it is associated with a high incidence of mucositis. Strategies that are used to limit mucosal damage may improve the tolerance of this combination.
Adult↗
Extramedullary blast crisis in a patient with Philadelphia chromosome-positive chronic myelogenous leukemia in complete cytogenetic remission.
Treatment of Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) with recombinant interferon-alpha (IFN-A) results in complete disappearance of the Ph chromosome in about 10% to 15% of patients in early chronic phase. This group has a long survival and very low incidence of blast crisis. The first known case is reported of extramedullary blastic transformation in a patient with medullary complete cytogenetic response (0% Ph-positive metaphases) to IFN-A. Four episodes of extramedullary blast crisis have occurred in this patient. The first three episodes were lymphoid by morphology and cytochemical stains. Molecular analysis confirmed breakpoint cluster region rearrangement. The most recent transformation was myeloid in nature and involved bone and pulmonary parenchyma. The patient is currently undergoing a second autologous transplantation with stored bone marrow that is Ph negative. The patient has survived more than 18 months since the first episode of blast crisis, and the bone marrow is normal.
Adult↗
Phase I clinical investigation of benzisoquinolinedione (amonafide) in adults with refractory or relapsed acute leukemia.
After Phase I studies of benzisoquinolinedione (amonafide) in solid tumors identified myelosuppression as the dose-limiting toxicity, we conducted a Phase I study in patients with relapsed or refractory acute leukemia to define the optimal dose. Amonafide was given i.v. over 2-4 h daily for 5 days. The starting dose was 600 mg/m2/day with subsequent escalation to 750, 900, 1100, 1400, and 1800 mg/m2/day. Thirty-eight courses were administered to 24 patients, of whom 12 participated in concomitant pharmacological studies. Nausea and vomiting, transient orange discoloration of the skin, and tinnitus occurred at all dose levels. The latter symptom, along with lightheadedness and flushing, was related to infusion duration; this was increased to 4 h with doses greater than or equal to 900 mg/m2. The dose-limiting toxicities were mucositis and painful skin erythema which occurred in all 4 patients treated with 1800 mg/m2. No remissions occurred. Clearing of peripheral blood blasts occurred in 67% of patients treated with 1100 mg/m2 and in all patients treated with greater than or equal to 1100 mg/m2/day. A decrease in marrow leukemic infiltrate (% blasts x % cellularity) to less than 10% occurred in 15 and 50% of patients treated at these levels, respectively. There were 10 deaths (42%), which were unrelated to dosage. The harmonic mean terminal plasma half-life was 4.6 h (range, 2.5-35.5 h). Three patients had long drug half-lives of 9.7, 16.4, and 35.5 h and each had initial bilirubin levels greater than 1.0 mg/dl. The average urinary excretion of amonafide over 5 days was 3.5% of the total dose. This establishes 1100-1400 mg/m2/day for 5 days as the maximally tolerated dose of amonafide for studies in acute leukemia.
Acute Disease↗
Does tourniquet use during anterior cruciate ligament surgery interfere with postsurgical recovery of function? A review of the literature.
This article explores the issue of whether use of a tourniquet during arthroscopically assisted repair of the anterior cruciate ligament (ACL) slows the postoperative recovery of function. A tourniquet is customarily used to provide a bloodless field, thus enabling the surgeon to visualize the joint clearly. However, there is increasing evidence that tourniquets cause muscle and nerve damage that can have long-term consequences for the recovery of function following surgery. The two randomized trials that investigated tourniquet use during meniscectomy reached contradictory conclusions about the effects of the tourniquet. There have been no randomized trials of tourniquet use during the longer and more complex ACL surgery. This article reviews the pertinent literature and suggests some clinical implications of the available information.
Anterior Cruciate Ligament↗
Guinea-pig alveolar macrophage killing of Mycobacterium tuberculosis, in vitro, does not require hydrogen peroxide or hydroxyl radical.
Alveolar macrophages from the lungs of guinea-pigs that had been vaccinated, boosted and then intravenously challenged with Mycobacterium bovis BCG, killed both a hydrogen-peroxide-resistant and a hydrogen-peroxide-sensitive strain of M. tuberculosis, in vitro. Pretreatment of the alveolar macrophages, in vitro, with catalase or mannitol, agents which remove hydrogen peroxide and the hydroxyl radical, respectively, did not decrease the extent of killing of either strain. In contrast, pretreatment of alveolar macrophages with catalase, reversed the inhibition of growth of Listeria monocytogenes.
Animals↗
Guinea-pig alveolar macrophages kill Mycobacterium tuberculosis in vitro, but killing is independent of susceptibility to hydrogen peroxide or triggering of the respiratory burst.
Alveolar macrophages from the lungs of guinea-pigs that had been vaccinated, boosted and then intravenously challenged with Mycobacterium microti or Mycobacterium bovis BCG killed tubercle bacilli phagocytosed in vitro. The killing was modest, about 40% of phagocytosed bacilli were killed in a day, but alveolar macrophages from animals that had been vaccinated and boosted but had not received the intravenous challenge did not kill bacilli. Different strains of tubercle bacilli had different degrees of susceptibility to these activated macrophages but there was no correlation between killing by macrophages and mycobacterial susceptibility to killing by hydrogen peroxide. The different strains of tubercle bacilli triggered peroxide release from these macrophages but there was no correlation with susceptibility to killing by macrophages or with virulence in the guinea-pig. However, phagocytic uptake of these strains by the activated macrophages was inversely correlated with virulence, and uptake by activated macrophages was less than uptake by normal macrophages.
Animals↗
A comparative study of the electrocardiographic effects of tranylcypromine and amitriptyline when prescribed singly and in combination.
The authors treated 53 in-patients aged between 18 and 65 years who were suffering from major depression with either tranylcypromine, amitriptyline or a combination of tranylcypromine and amitriptyline. Electrocardiograms taken before and after treatment were compared. In clinically effective doses amitriptyline gave rise to a significant increase in heart rate when prescribed alone and in combination with tranylcypromine. Single tranylcypromine treatment had little effect on heart rate and gave rise to no change in cardiac conduction as measured by the electrocardiogram. Amitriptyline when prescribed in combination with tranylcypromine was associated with significant lengthening of the PR interval. None of the patients developed pathological changes in their electrocardiograms under the carefully monitored treatment conditions of the study.
Adolescent↗
Differential dose-related haematological effects of GM-CSF in pancytopenia: evidence supporting the advantage of low- over high-dose administration in selected patients.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifunctional haematopoietin which can promote production of several blood cell lineages, though the predominant target cells are neutrophils, monocytes, and their precursors. Occasional undesirable clinical effects include eosinophilia, an increase in blasts, or thrombocytopenia. Here, we describe four patients who were treated with GM-CSF, at subcutaneous doses significantly lower than are conventional, and experienced an unusual response pattern. Three patients had severe pancytopenia associated with chronic lymphocytic leukaemia (CLL) or myelodysplastic syndrome (MDS) and exhibited an unexpected switch in the responsive lineage on high- versus very low-dose therapy. The two CLL patients developed marked eosinophilia (up to 10.0 x 10(9) cells/l) without an increase in neutrophils on 125-300 micrograms/m2/d of GM-CSF. In contrast, when the dose was lowered to 10 micrograms/m2/d, the neutrophils rose to physiological levels, without significant eosinophilia. The MDS patient showed a rapid rise in peripheral blasts (baseline level = 0; post-therapy level = 5.0 x 10(9)/l), without a change in other cell types, when receiving 60 micrograms/m2/d of GM-CSF. After GM-CSF was held, blasts returned to baseline levels; reinstituting therapy at the very low dose of 6 micrograms/m2/d was followed by an increase in platelet counts from 50 to 185 x 10(9)/l with only a minor increase in blasts. The fourth patient, who suffered from severe aplastic anaemia complicated by recurrent gastrointestinal haemorrhage, was only treated with the low-dose regimen. He showed a predominant platelet effect with counts rising from 9 to 169 x 10(9)/l. Very low-dose GM-CSF therapy was devoid of constitutional side effects. The biological implications of these GM-CSF responses are discussed. Our results indicate that, in some patients, GM-CSF may stimulate different target cells depending on the dose. Therefore, in contrast to the results of administration of many classical drugs, there may not always be a direct relationship between the amount of GM-CSF given and the optimal effect.
Adult↗
Effects of low doses of recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with myelodysplastic syndromes.
There has been no previously published experience with granulocyte-macrophage colony stimulating factor (GM-CSF) doses less than 12 micrograms/m2 daily in patients with myelodysplastic syndromes, and most observations have been made at doses greater than or equal to 120 micrograms/m2 daily. We administered 5 micrograms/m2 daily by subcutaneous injection to 29 such patients increasing the dose in patients who did not show a haematologic response. Doses of 5 or 10 micrograms/m2 ('low-dose GM-CSF') produced an increase in neutrophils in 14/29 patients. Response was significantly (P = 0.03) more frequent in patients who had a higher pre-treatment neutrophil count (e.g. 11/16 in patients with greater than or equal to 0.5 x 10(9)/l). A rise in blasts followed administration of low-dose GM-CSF in five patients, all with either refractory anaemia with excess blasts (RAEB) or refractory anaemia with excess blasts in transformation (RAEBT). Platelets decreased in five patients, four of whom had no change in blasts, reverting to baseline when GM-CSF was discontinued. We and others have previously observed similar rises in blasts or decreases in platelets at doses of 120 micrograms/m2 daily. Low-dose GM-CSF produced no constitutional side effects. Our results suggest that low doses of GM-CSF might be initially employed in neutropenic patients with myelodysplastic syndromes who present with pretreatment neutrophil counts greater than 0.5 x 10(9)/l. Increasing the dose, and hence the risk of extramedullary toxicity, only in patients who do not respond to the low dose. Patients who present with lower pre-treatment neutrophil counts might begin treatment at doses above 10 micrograms/m2, but below the 120 micrograms/m2 commonly employed, which may be necessary in relatively few patients.
Aged↗
Pediatric feeding disorders.
Feeding problems occur in children who have normal development, who have failure to thrive, and who have developmental disabilities. This article focuses on the latter two groups. The characteristics and developmental concerns include family characteristics, parent-child interactions, cognitive development, and oral-motor development. The evaluation process for children with feeding problems should include an interdisciplinary approach with a medical, nutritional, occupational therapy, and behavioral evaluation. The behavioral treatments include the Premack principle, time-out plus reinforcement, and negative reinforcement. Future research should focus on the parent-child interaction process in both mealtime and nonmealtime situations, along with demonstrating parents' and teachers' ability to implement mealtime treatment protocols.
Behavior Therapy↗
Fludarabine: a new agent with marked cytoreductive activity in untreated chronic lymphocytic leukemia.
Thirty-three patients with chronic lymphocytic leukemia (CLL) with advanced Rai stage (III-IV) or progressive Rai stage (0-II) disease were treated with fludarabine as a single agent. Eleven patients (33%) obtained a complete remission (CR), 13 (39%) a clinical CR with residual nodules as the only evidence of disease (nodular partial remission [PR]), and two patients (6%) achieved a PR for a total response rate of 79%. Response was rapid, usually occurring after three to six courses of treatment. The major morbidity was infection. Febrile episodes occurred in 13% of the courses (pneumonia 6%, minor infection 4%, and transient fever of undocumented cause 3%). Fludarabine appears to be the most cytoreductive single agent so far studied in CLL.
Adult↗
Clozapine in the treatment of psychotic mood disorders, schizoaffective disorder, and schizophrenia.
BACKGROUND: Although growing research indicates that the atypical antipsychotic agent clozapine is effective in patients with schizophrenia, little is known about the efficacy of clozapine in patients with schizoaffective disorder or psychotic mood disorders. The purpose of this study was to assess whether or not clozapine is effective in some patients with schizoaffective disorder or psychotic mood disorders. METHOD: By surveying treating clinicians and chart data, we assessed treatment response in 85 consecutive patients, including 39 with schizophrenia, 25 with schizoaffective disorder, and 14 with bipolar disorder with psychotic features, who received clozapine for at least 6 weeks at our center. RESULTS: All patients were either inadequately responsive to or unable to tolerate standard somatic therapies. Compared to patients with schizophrenia, patients with schizoaffective disorder and bipolar disorder with psychotic features displayed significantly higher response rates to clozapine. CONCLUSION: Clozapine may be a useful drug in the treatment of patients with schizoaffective disorder or psychotic mood disorders who are treatment resistant or intolerant of side effects.
Adult↗
Erythropoietin treatment in patients with myelodysplastic syndrome and anemia.
Hematological disorders are commonly complicated by anemia, and the symptoms of red cell deficiency adversely affect the quality of life. Erythropoietin is a glycoprotein which controls red blood cell production. Recombinant human erythropoietin, 50 U/kg/day, was given subcutaneously to 16 patients with myelodysplastic syndrome and anemia. All but one patient was transfusion dependent. Diverse pretreatment endogenous serum erythropoietin levels were noted and ranged from 17 to 3616 IU/l. Two patients (12.5%) demonstrated an improvement in hemoglobin levels obviating the need for transfusions. Their responses lasted 5+ and 7 months with maintenance erythropoietin treatment. The responders had endogenous serum erythropoietin levels of 44 and 170, respectively. Treatment was generally tolerated without constitutional side-effects. However, three patients developed thrombocytopenia and one developed joint pain and leukocytosis on treatment. Overall, six patients showed changes in non-erythroid cells: two patients had an increase in platelet counts; three patients, a decrease in platelet counts; and one patient, an increase in white blood cell counts. Most of these changes reversed rapidly once erythropoietin was stopped. It is concluded that (a) serum erythropoietin levels are extremely variable in anemia patients with myelodysplastic syndrome, (b) only a minority of patients benefit from treatment with recombinant human erythropoietin, and (c) erythropoietin can affect cells of the myeloid and megakaryocytic lineage in a small proportion of patients.
Aged↗
Efficacy of fludarabine, a new adenine nucleoside analogue, in patients with prolymphocytic leukemia and the prolymphocytoid variant of chronic lymphocytic leukemia.
PURPOSE: To describe the results of fludarabine therapy in patients with prolymphocytic leukemia (PLL) and the prolymphocytoid variant of chronic lymphocytic leukemia (CLL-Pro). PATIENTS AND METHODS: Seventeen patients with a diagnosis of PLL or CLL-Pro received fludarabine 30 mg/m2 over 30 minutes daily for 5 days every 4 weeks alone (12 patients), or with prednisone (five patients). Previously defined criteria for response were used. Differences in response rates according to various characteristics were evaluated by chi-square test. RESULTS: Three patients (18%) achieved complete remission, and three (18%) had a partial remission, for an overall response rate of 35%. Responses were durable and occurred in all involved organ sites. Lower response rates were observed in patients with anemia, thrombocytopenia, advanced Rai stages, and primary resistance to prior therapy. Toxicities were minimal except for febrile episodes associated with therapy. CONCLUSION: Fludarabine has shown encouraging results in these patients and deserves further investigation in combination with other active agents, and in the setting of front-line therapy.
Aged↗
Panel recommends blood cholesterol health screening and education guidelines for children and adolescents.
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Adolescent↗