Biomedical subjects

S O'Brien

Publications and source records attributed to S O'Brien.

At least 253 records · Page 14Linked to original sources

PubMed1994

Abnormalities in the long arm of chromosome 11 (11q) in patients with de novo and secondary acute myelogenous leukemias and myelodysplastic syndromes.

Leukemias with abnormalities in chromosome 11q23 occur frequently after exposure to topoisomerase II-reactive drugs. We investigated the characteristics and outcome of patients with de novo or secondary acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) with abnormalities in chromosome 11q. Sixty-one patients had 11q abnormalities. Alterations involved 11q23 in 38 patients and other 11q abnormalities in 23. Sixteen patients had secondary disease, 12 involving 11q23, and four with other 11q abnormalities; 26 patients with de novo disease had 11q23 abnormalities and 19 other 11q abnormalities. The most common 11q23 abnormality was t(9;11), significantly more common in secondary (9/12) than in de novo (6/26) leukemias (p = 0.003). There were no significant differences in clinical characteristics between de novo and secondary groups involving 11q23. Five of 12 patients (42%) with secondary and 20/26 (77%) with de novo disease achieved complete remission (p = 0.05). Median survival was 6 weeks in the secondary group and 71 weeks in the de novo group (p = 0.001). There were no long-term survivors in either group. Results are similar when other 11q abnormalities are included. Adults with AML or MDS with 11q abnormalities secondary to prior chemotherapy have a worse prognosis than patients presenting de novo. However, 11q abnormalities define a population with a poor prognosis even when presenting de novo.

Adolescent↗

PubMed1994

Near infrared spectroscopy used to observe changes in fetal cerebral haemodynamics during labour.

Near Infrared Spectroscopy (NIRS) has been used in the neonate to observe changes in the cerebral haemodynamics and concentration of oxygenated haemoglobin. Specific changes have been demonstrated in response to spontaneous bradycardias and alterations in the inspired oxygen concentration. We report here changes in fetal cerebral haemodynamics using NIRS in response to rapid spontaneous delivery and the "topping up" of a maternal epidural with bupivacaine. NIRS offers a new way of observing changes in cerebral haemodynamics in the fetus during labour.

Brain Chemistry↗

PubMed1994

Self-efficacy, perfectionism, and stress in Canadian nurses.

The current study examined the relationship between stress in nurses and their reported levels of job and life satisfaction, while also assessing the construct validity of theories of perfectionism and self-efficacy as these apply to the profession of nursing. One hundred and ninety-six nurses employed in Toronto and Windsor, Ontario completed measures of stress, perfectionism, self-efficacy, and job and life satisfaction as dependent variables. Generally, nurses who reported high levels of socially-prescribed and other-oriented perfectionism, and low levels of self-efficacy, also reported low levels of job satisfaction. Significant negative correlations were obtained between the number of reported nursing stressors and job satisfaction. The data also indicated that higher levels of socially-prescribed perfectionism and higher levels of self-efficacy were strongly related to both job and life stress. Some comments, interpretation, and implications of findings are presented.

Adult↗

PubMed1993

Granulocyte colony-stimulating factor supportive treatment following intensive chemotherapy in acute lymphocytic leukemia in first remission.

BACKGROUND: The efficacy of granulocyte colony-stimulating factor (G-CSF) in reducing neutropenia and its associated complications in adults with acute lymphocytic leukemia (ALL) undergoing intensive chemotherapy in first remission was evaluated. METHODS: Fourteen adult patients with ALL in first remission received intensive chemotherapy consisting of mitoxantrone 5 mg/m2 intravenously (IV) over 1 hour daily for 3 days, cytosine arabinoside (ara-C) 3 g/m2 IV over 2 hours every 12 hours x 4 on days 1 and 2, vincristine 2 mg IV on day 1, solumedrol 50 mg IV twice daily for 5 days, and G-CSF 5 micrograms/kg subcutaneously daily starting on day 4 until granulocyte recovery. Their outcome was compared with that of 14 consecutive patients who received the same intensification chemotherapy, but without G-CSF. The latter patients had been entered on the same ALL protocol from April 1990 through June 1991. RESULTS: G-CSF administration was associated with a significant shortening in the duration of neutropenia. The number of days to granulocyte recovery above 0.5 x 10(3)/microliters was 14 in the G-CSF group versus 18 days in the historical group (P < 0.001). Two episodes of documented infections were observed in the G-CSF group compared with four episodes in the historical group. Death during intensification therapy occurred in 2 of 14 patients in the historical group, but in none of the 14 patients receiving G-CSF. CONCLUSIONS: G-CSF as an adjunct to intensive chemotherapy in adults with ALL in first remission yielded positive results. Future studies incorporating growth factors supportive care during remission, induction, and consolidation may reduce treatment-related morbidity and mortality, increase the dose-intensity delivery of therapy, and potentially improve patient outcome.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

Fludarabine and cytosine arabinoside in the treatment of refractory or relapsed acute lymphocytic leukemia.

BACKGROUND: The objectives of the study were to evaluate the antileukemic efficacy and toxicity profiles of the combination of fludarabine and intermediate-dose cytosine arabinoside (ara-C) in refractory or relapsed adult acute lymphocytic leukemia (ALL). PATIENTS AND METHODS. Thirty adults with refractory or relapsed ALL were treated. Their median age was 45 years, 60% were in second or subsequent relapse, and 37% had Philadelphia chromosome-positive disease. Treatment consisted of ara-C 1 g/m2 during a period of 2 hours daily for 6 days, and fludarabine 30 mg/m2 during a period of 30 minutes daily for 5 days on days 2-6. Fludarabine was given 4 hours before ara-C to increase the rate of ara-C 5'-triphosphate (ara-CTP) accumulation in leukemic cells. Courses were repeated every 3 weeks or longer, depending on patient response and side effects. RESULTS: Nine (30%) patients achieved a complete remission (CR), 8 (27%) died during remission induction, and 13 (43%) had resistant disease. The median CR duration was 22 weeks, and the median survival was 12 weeks for all patients, and 34 weeks for those who had a response to treatment. Except for low platelet counts, which predicted shorter survival time, no other prognostic factors were demonstrated, considering the small number of patients treated. Myelosuppression-associated febrile episodes were the most common side effects, occurring in 28 (93%) patients. Neurotoxicity was noted in two (7%) patients. CONCLUSIONS: Fludarabine and ara-C are an active and relatively safe antileukemic combination in refractory or relapsed ALL. Future studies will incorporate other anti-ALL agents, such as topoisomerase II-reactive drugs, to improve the overall efficacy, and growth factors, to reduce myelosuppression-related complications.

Adult↗

PubMed1993

Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivariate analysis-derived prognostic model for response to treatment.

Two hundred sixty-four patients with chronic lymphocytic leukemia were treated with fludarabine 30 mg/m2 intravenously for 30 minutes each day for 5 days and with prednisone 30 mg/m2 orally each day for 5 days. Courses were repeated monthly. Of the 264 patients. 125 patients (47%) had Rai stage III-IV disease; 169 patients (64%) were previously treated with a median of 3 prior regimens; and 138 of them (82%) were refractory to therapy with alkylating agents. The overall response (OR) and complete response (CR) rates in the 169 previously-treated patients were 52% and 37%; these were 74% and 63%, respectively, in Rai stage O-II patients and declined to 64% and 46%, respectively, in Rai III-IV disease. Among the previously untreated patients, the OR and CR rates were 79% and 63%, these being 85% and 70%, respectively, in Rai O-II patients, and declining to 64% and 46%, respectively, in Rai III-IV disease. The incidence of minor infections or fever of unknown origin was similar in all patient groups and occurred in 22% of courses. The incidence of sepsis and/or pneumonia was significantly correlated with the extent of prior therapy and with Rai stage, and ranged from 3% of courses in the previously untreated Rai O-II patients, to 13% of courses in the previously treated Rai III-IV patients. Listeria sepsis or Pneumocystis carinii pneumonia was noted in 14 patients. With therapy, CD4 levels were uniformly depressed from a median 1,015/microL pretreatment to a median 159/microL after 3 months of fludarabine therapy. Median time to progression in previously treated patients was 22 months. In previously untreated patients, median time to progression was 30 months for patients who achieved a partial remission and has not been reached in patients who achieved a CR with a median follow-up of 2 years. The median survival was 18 months for previously treated patients and has not been reached for previously untreated patients. Response rates in previously treated and untreated patients, as well as infection rates, were identical to those seen in 110 patients treated with the same dose schedule of fludarabine alone. Logistic regression analysis selected 4 factors to be significantly associated with worse response: Rai III-IV stage disease, prior therapy, older age, and low albumin levels. The regression equation was used to derive a probability of response based on the 4 characteristics. When the model was applied to the same population, patients could be divided into 4 prognostic groups with different outcomes.

Antigens, CD↗

PubMed1993

Preliminary results of treatment with filgrastim for relapse of leukemia and myelodysplasia after allogeneic bone marrow transplantation.

BACKGROUND: Patients whose leukemia relapses after allogeneic bone marrow transplantation have a poor prognosis; few respond to further chemotherapy, and almost none survive over the long term. We present preliminary observations on the use of filgrastim (granulocyte colony-stimulating factor) for relapse after transplantation. METHODS: Seven female patients with leukemia (one with chronic myelogenous leukemia, five with acute myelogenous leukemia, and one with a myelodysplastic syndrome that transformed into acute myelogenous leukemia) whose disease relapsed within 360 days after allogeneic bone marrow transplantation received filgrastim (5 micrograms per kilogram of body weight per day by subcutaneous injection) to reinduce remission by stimulating residual donor marrow cells. Cytogenetic analysis of bone marrow, fluorescence in situ hybridization, and determination of restriction-fragment--length polymorphisms were used to assess response and chimerism. RESULTS: Three of the seven patients had a complete hematologic and cytogenetic remission, with reestablishment of hematopoiesis of donor origin. Mild chronic graft-versus-host disease developed in one patient, and acute graft-versus-host disease in none. One patient had a relapse 12 months after treatment, and two others remained in remission after 10 and 11 months. In two of the patients with a response, fluorescence in situ hybridization demonstrated stimulation of donor cells without differentiation of the leukemic clone. CONCLUSIONS: Filgrastim may be effective in selected cases of leukemic relapse after allogeneic bone marrow transplantation.

Adolescent↗

PubMed1993

Biological properties and growth in SCID mice of a new myelogenous leukemia cell line (KBM-5) derived from chronic myelogenous leukemia cells in the blastic phase.

The establishment and the biological properties of a new leukemic cell line (KBM-5) derived from a patient in the blastic phase of chronic myelogenous leukemia are described. The cells exhibited multiple copies of the Philadelphia chromosome, and a high level of p210Bcr-Abl kinase activity was detected with rabbit anti-Abl and anti-Bcr (exon 3) peptide antisera. Use of specific primers and polymerase chain reaction followed by Southern blotting revealed that KBM-5 cells carried a bcr3-ABLII splice junction. While a normal BCR message was detected, no normal ABL message was found. The cells were phenotypically myeloid with monocytic differentiation. The high cloning efficiency in semisolid media was independent of the presence of exogenous colony-stimulating factors. In vitro exposure to induces of differentiation, such as retinoic acid, dimethyl sulfoxide, or hemin, failed to influence the growth rate of the cells and their level of differentiation. KBM-5 cells are highly resistant to the antiproliferative action of recombinant alpha- and gamma-interferons. Although sensitive to recombinant tumor necrosis factor alpha, they were completely resistant to natural killer cell action. KBM-5 cells constitutively expressed mRNA for tumor necrosis factor alpha but not for gamma-interferon, other interleukins, or hematopoietic growth factors. The KBM-5 cells that were transplanted into SCID mice manifested metastatic potential and tissue invasiveness similar to the way leukemic cells in humans do. This new KBM-5 cell line represents a helpful model for examining in vitro and in vivo modulation of the growth and properties of leukemic cells by using biological and chemotherapeutic agents.

Aged↗

PubMed1993

Long-term follow-up of patients with chronic lymphocytic leukemia treated with fludarabine as a single agent.

The clinical response and survival of 113 patients with at least 3-year follow-up after treatment with fludarabine as a single agent for chronic lymphocytic leukemia has been evaluated. Seventy-eight patients were previously treated and 35 were untreated. The response to therapy and survival were strongly correlated with the degree of previous therapy, the stage of disease, and whether or not the patients were refractory to alkylating agents. Other characteristics associated with survival were the age of the patient and the serum albumin level at the start of therapy. The median time to progression of responders who had not received prior therapy was 33 months and was 21 months for previously treated patients. Survival after progression of disease was also strongly correlated with the degree of prior therapy. No successful salvage regimen after initial fludarabine therapy was shown for patients refractory to alkylating agents, although fludarabine achieved further remissions in patients who had received fludarabine as their initial treatment or were not refractory to alkylating agents. The morbidity of patients in unmaintained remission on discontinuation of fludarabine was low, with less than one episode of infection per patient-year at risk. The morbidity during this time was correlated with clinical response and whether the patients had received prior therapy. Although fludarabine is a very effective cytoreductive regimen, most patients, including those who achieved true complete remissions, will have recurrent disease. Longer follow-up and comparative trials are required before the effect of fludarabine on survival is shown.

Adult↗

PubMed1993

Utilization of transferrin-bound iron by Listeria monocytogenes.

It has been demonstrated that under iron-restricted conditions, Listeria monocytogenes can utilize iron-loaded transferrin (Tf) from a range of species as its sole source of iron for growth. Human transferrin conjugated to horseradish-peroxidase (HRP-Tf) bound directly to whole cells of L. monocytogenes. This binding was blocked by apotransferrin indicating that the receptor can bind transferrin in either the iron-bound or iron-free form. Transferrin-binding was not host specific because both bovine and equine transferrin inhibited the binding of HRP-conjugated human transferrin. SDS-PAGE and Western blotting of bacterial surface extracts revealed the presence of a transferrin-binding protein of approximately 126 kDa.

Animals↗

PubMed1993

Phase I study of Topotecan, a new topoisomerase I inhibitor, in patients with refractory or relapsed acute leukemia.

The purpose of this study was to define, in a phase I study in leukemia, the maximally tolerated dose (MTD), major toxicities, and possible antitumor activity of Topotecan, a new topoisomerase I (topo I) inhibitor. Topotecan was delivered by a 5-day continuous infusion every 3 to 4 weeks to patients with refractory or relapsed acute leukemia, at doses ranging from 3.5 mg/m2 to 18 mg/m2 per course. Twenty-seven patients were treated, including 17 patients with acute myelogenous or undifferentiated leukemia, 7 with acute lymphocytic leukemia, and 3 with chronic myelogenous leukemia in blastic phase. Severe mucositis was the dose-limiting toxicity occurring in two of five patients treated with Topotecan 11.8 mg/m2 per course; a third patient had prolonged myelosuppression. At the MTD of 10 mg/m2 per course, 1 of 12 patients had severe mucositis and 5 had mild-to-moderate mucositis. Nausea, vomiting, diarrhea, and prolonged myelosuppression were uncommon. Three patients (11%) achieved a complete response, two (7%) had a partial response, and one (4%) had a hematologic improvement. The overall complete plus partial response rate was 19%, and 24% in acute myelogenous or undifferentiated leukemia. A novel in vitro assay that quantifies Topotecan-stabilized topo I-DNA complexes in patient samples was used, which demonstrated heterogeneity in the ability of Topotecan to interact with topo I, the intracellular target of Topotecan. This phase I study defined the MTD of Topotecan to be 10 mg/m2 by continuous infusion over 5 days every 3 to 4 weeks in patients with refractory or relapsed acute leukemia. Severe mucositis was the dose-limiting toxicity. Future studies will define the precise activity of Topotecan in different leukemia subsets, its efficacy in combination with other antileukemic drugs, and correlations between Topotecan-induced topo I-DNA complex formation and individual patient response to Topotecan.

Acute Disease↗

PubMed1993

Treatment of Waldenstrom macroglobulinemia with 2-chlorodeoxyadenosine.

OBJECTIVE: To evaluate the activity of 2-chlorodeoxyadenosine (2CdA) in the treatment of patients with Waldenstrom macroglobulinemia. DESIGN: Uncontrolled phase II trial. SETTING: Tertiary, referral cancer center. PATIENTS: Twenty-nine consecutive, symptomatic patients with Waldenstrom macroglobulinemia, of whom 9 were previously untreated. INTERVENTION: 2-Chlorodeoxyadenosine was administered as a continuous intravenous infusion at a dose of 0.1 mg/kg body weight per day for 7 days. Only two courses of 2CdA were given and responding patients were then followed without further treatment. MEASUREMENTS AND MAIN RESULTS: A total of 17 (59%) patients responded, including all of those who were newly diagnosed and 40% of those who had failed previous therapies. Treatment was well tolerated except for one death in a patient who had presented with severe pancytopenia. With a median follow-up of 7 months, only one responding patient has relapsed. CONCLUSION: 2-Chlorodeoxyadenosine is a nucleoside analog that was effective in most patients with Waldenstrom macroglobulinemia and was associated with little toxicity.

Adult↗

PubMed1993

Fludarabine therapy in Waldenström's macroglobulinemia.

PURPOSE: To assess the response rate, remission duration, and survival of patients with Waldenström's macroglobulinemia treated with the adenine nucleoside analogue fludarabine. PATIENTS AND METHODS: Twenty-eight patients with Waldenström's macroglobulinemia, of whom only 2 were previously untreated, received fludarabine at a dose of 20 to 30 mg/m2 intravenously daily for 5 days (20 patients) or 30 mg/m2 intravenously daily for 3 days (8 patients). Treatment was continued until maximum response was achieved. Responding patients were followed with no further treatment until relapse. RESULTS: Ten patients responded (36%), including the 2 previously untreated patients and 8 of 26 patients (31%) who were resistant to prior therapies. Unmaintained remissions lasted for a median of 38 months. There were no fatalities associated with this treatment. Previously untreated patients and those with a primary resistant disease of relatively short duration were more likely to benefit from this treatment. CONCLUSION: Fludarabine is an effective salvage agent for the treatment of patients with resistant Waldenström's macroglobulinemia. Further investigations of fludarabine in untreated patients and in combination with other active agents are warranted.

Adult↗

PubMed1993

Health after childbirth: a comparison of normal and assisted vaginal delivery.

413 women were included in the study: 100 who had had a normal delivery and 313 who had participated in a randomised controlled comparison of forceps or ventouse delivery. The study comprised a questionnaire and assessment at 24-48 hours after delivery and a questionnaire in the second year after delivery. There was significantly more morbidity in the women in the instrumental delivery group compared to women in the normal delivery group at both the early assessment and long-term follow-up.

Adult↗

PubMed1993

Effectiveness of an oral triazole for opportunistic mold infections in patients with cancer: experience with SCH 39304.

Fungal infections are the most common infectious cause of death among patients with hematologic malignancies. Conventional antifungal agents have limited activity and a narrow therapeutic index. In an open-label study we assessed the activity of an oral triazole, SCH 39304, in the treatment of refractory life-threatening mold infections in 50 patients with cancer, most of whom had previously received amphotericin B and/or fluconazole. SCH 39304 was given at a daily dose of 200-400 mg for a median of 8 weeks. The overall rate of response was 79% among 34 evaluable patients, with a complete response in 22 instances and a partial response in 5. Some patients responded despite persistent, profound immunosuppression. Three patients developed relapses, and two developed fungal superinfections. SCH 39304 was well tolerated. We conclude that oral triazoles such as SCH 39304 may represent effective and safe treatment of mold infections in immunosuppressed patients, at least after standard antifungal chemotherapy. Unfortunately, the carcinogenic potential of SCH 39304 in animals has precluded its development. Our hope is that analogues with similar efficacy but without carcinogenic potential can be developed.

Administration, Oral↗

PubMed1993

An open trial of cefoperazone plus sulbactam for the treatment of fever in cancer patients.

Cancer patients received cefoperazone plus sulbactam for 673 febrile episodes presumed to be caused by infection. Overall, 415 (76%) of the 545 evaluable episodes responded. There were 213 responses (84%) amongst the 254 fevers of unknown origin and 202 responses (69%) amongst the 291 documented infections. Fifty-one (61%) of the 83 episodes pneumonia and 74 (64%) of the 115 episodes of bacteraemia responded. Only 39 (58%) of the 67 infections caused by Gram-positive bacteria responded compared with 55 (86%) of 64 Gram-negative infections which included seven of eight caused by Pseudomonas aeruginosa. Eighteen (67%) of 27 polymicrobial infections responded to the regimen. Response rates were significantly lower amongst the 125 patients whose neutrophil counts decreased during therapy than amongst the 158 patients whose neutrophil counts increased. Adverse events which were possibly or probably related to antibiotic therapy were observed during 73 of the episodes; the most commonly reported side-effects were diarrhoea and skin rash. Six patients developed a coagulopathy without haemorrhage and two experienced anaphylactic reactions. In this open trial cefoperazone plus sulbactam proved to be an effective regimen for initial therapy of fever in cancer patients. It should be combined with a glycopeptide in those institutions where infections caused by methicillin-resistant staphylococci are frequently encountered.

Adolescent↗

PubMed1993

Intestinal bile acid malabsorption in cystic fibrosis.

This study aimed at examining the mechanisms participating in excessive faecal bile acid loss in cystic fibrosis. The study was designed to define the relation between faecal fat and faecal bile acid loss in patients with and without cystic fibrosis related liver disease; to assess terminal ileal bile acid absorption by a seven day whole body retention of selenium labelled homotaurocholic acid (SeHCAT); and to determine if small intestinal bacterial overgrowth contributes to faecal bile acid loss. The study population comprised 40 patients (27 men; median age 18 years) with cystic fibrosis (n = 8) and without (n = 32) liver disease and eight control subjects. Faecal bile acid excretion was significantly higher in cystic fibrosis patients without liver disease compared with control subjects (mean (SEM) 21.5 (2.4) and 7.3 (1.2) micromoles/kg/24 hours respectively; p < 0.01) and patients with liver disease (7.9 (1.3) micromoles/kg/24 hours; p < 0.01). No correlation was found between faecal fat (g fat/24 hours) and faecal bile acid (micromoles 24 hours) excretion. Eight (33%) of cystic fibrosis patients had seven day SeHCAT retention < 10% (normal retention > 20%). SeHCAT retention in cystic fibrosis patients with liver disease was comparable with control subjects (30.0 (SEM) 8.3% v 36.8 (5.9)%; p = NS) while SeHCAT retention in cystic fibrosis patients who did not have liver disease was significantly reduced (19.9 (3.8); p < 0.05). Although evidence of small bowel bacterial overgrowth was present in 40% of patients no relation was found between breath hydrogen excretion, faecal fat, and faecal bile acid loss. The results are consistent with the presence of an abnormality in terminal ideal function in patients with cystic fibrosis who do not have liver disease and that a defect in the ileal absorption of bile acids may be a contributory factor to excessive faecal bile acid loss. Faecal bile acid loss in cystic fibrosis is unrelated to the presence of intraluminal fat or intestinal bacterial overgrowth.

Adolescent↗

PubMed1993

The efficacy and tolerability of combined antidepressant treatment in different depressive subgroups.

Eighty patients admitted to hospital with major depression were randomly allocated to six weeks of treatment with tranylcypromine, amitriptyline, or tranylcypromine and amitriptyline in combination, in a double-blind study. Scores on the HRSD improved significantly in all three groups, but there were no differences between the three groups. Patients on tranylcypromine and amitriptyline combined improved more according to their self-ratings after six weeks, and response was earlier as measured by a clinical global improvement scale. Those with endogenous depression improved more than those with neurotic depression, irrespective of treatment group. Combined treatment was less well tolerated than single treatments and gave rise to more side-effects, although there was no serious toxicity. Orthostatic hypotension was observed more frequently in patients on combined treatment. This group also experienced a significant increase in weight and prolongation of the P-R interval on ECG.

Adult↗