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Biomedical subjects

S O'Brien

Publications and source records attributed to S O'Brien.

At least 271 records · Page 15Linked to original sources
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↗
PubMed1993

Richter's syndrome: a report on 39 patients.

PURPOSE: The incidence, clinical features, laboratory findings, and treatment results of 39 patients with Richter's syndrome (RS) are reported. PATIENTS AND METHODS: Thirty-nine of 1,374 patients with chronic lymphocytic leukemia (CLL) developed RS. RESULTS: Features associated with RS included systemic symptoms (59%), progressive lymphadenopathy (64%), extranodal involvement (41%), elevation of lactate dehydrogenase (LDH; 82%), and a monoclonal gammopathy (44%). Analysis of the CLL karyotype showed no specific chromosomal abnormality that conferred increased risk; however, multiple abnormalities were common. Patients at all Rai stages and in complete response (CR) were at risk, including three CR patients with no residual disease at the level of detection by dual-parameter flow cytometry or restriction analysis for immunoglobulin (Ig) gene rearrangements. The incidence was not higher in patients who had received prior fludarabine or chlorodeoxyadenosine. The median survival duration was only 5 months, despite multiagent therapy. Patients who responded had prolonged survival durations (P < .001). Three of eight patients who survived more than 1 year had a de novo presentation of both CLL and large-cell lymphoma (LCL). Comparison of surface light-chain analysis from both low- and high-grade components demonstrated isotypic light-chain expression in 12 of 15 patients. Ig heavy- and light-chain gene rearrangement analysis showed identical rearrangement patterns in five of five patients. CONCLUSION: The clinical, laboratory, and survival characteristics of our RS patients were similar to those reported in earlier studies. Ig gene rearrangement and light-chain isotype analysis support a common origin for CLL and LCL. Despite progress in the treatment of CLL, the development of LCL remains a serious complication and continued surveillance in all CLL patients is warranted.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Autoimmune hemolytic anemia in chronic lymphocytic leukemia patients treated with fludarabine.

Autoimmune hemolytic anemia (AHA) is a frequent complication of chronic lymphocytic leukemia (CLL). Although the pathogenesis of AHA is still unknown, an imbalance of normal residual T cells is believed to play a central role. Since fludarabine is reported to affect primarily T lymphocytes, we conducted a retrospective study to evaluate the incidence and outcome of AHA in 112 CLL patients treated with fludarabine alone. Eight patients had AHA before therapy; only one achieved remission of both CLL and AHA after fludarabine alone. In the other seven patients, we observed no effect or even a worsening of AHA, although the CLL was responding to fludarabine. Five patients developed AHA from 1 to 19 months after fludarabine therapy while the CLL was responding. One additional patient developed pure red cell aplasia (PRCA) 3 months after starting therapy. Most patients in both groups responded to steroids or other immunosuppressive therapy. The study showed that in these patients, AHA evolved independently of CLL and was not affected by fludarabine.

Aged↗
PubMed1993

Treatment of Waldenstrom's macroglobulinemia with nucleoside analogues.

Sixty-eight patients with Waldenstrom's macroglobulinemia were treated either with fludarabine (28 patients) or 2-chlorodeoxyadenosine (40 patients) and responding patients were followed without further treatment. Both programs were well tolerated and myelosuppression was moderate but reversible. Overall, 35 patients responded including 93% of previously untreated patients, 83% of those relapsing off therapy, 48% of patients with primary refractory disease and 15% of those treated during refractory relapse. With a median follow up of 18 months, only two of 15 previously untreated patients have relapsed whereas the median remission duration and survival of previously treated patients were 38 and 43 months respectively. Fludarabine and 2-chlorodeoxyadenosine are both highly active agents against Waldenstrom's macroglobulinemia, especially when administered early in the disease course.

Adult↗
PubMed1993

Chronic lymphocytic leukemia--correlation of response and survival.

Chronic lymphocytic leukemia (CLL) is considered to be an incurable hematologic malignancy using conventional therapy. Complete remissions (CR) were unusual with conventional approaches such as chlorambucil with or without prednisone or cyclophosphamide, vincristine, and prednisone (CVP). Pathologic complete remissions including negative bone marrow biopsies were seldom mentioned in the literature. Two parameter flow cytometry has demonstrated that CLL cells co-express CD5 and pan-B cell antigens such as CD19 and CD20. In addition, immunoglobulin gene rearrangement occurs predictably in B-cell CLL and can be used as a further marker of completeness of remission. The National Cancer Institute (NCI) has published criteria for complete remission which allow persistent lymphoid nodules to be present on the bone marrow biopsy and the patient can be considered in complete remission. Our group has considered these patients to have a nodular CR (Nod CR) to separate them from having a true remission on bone marrow biopsy (CR-bx). Thus bone marrow biopsy criteria, two parameter flow cytometry, and immunoglobulin gene rearrangement are now available for routine clinical application to re-define completeness of remission in CLL. With the use of fludarabine monophosphate (Fludara), complete and partial responses are obtained in 50-55% of previously treated patients with CLL and 75-80% of patients with previously untreated CLL. There was a strong correlation of probability of response with degree of previous therapy, stage of disease, age, hemoglobin level, platelet count, serum albumin and beta 2-microglobulin, and bone marrow infiltration with lymphocytes. Patients can be identified as being at high/low risk of achieving a complete or partial response.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1993

Phase II clinical trial of fludarabine in chronic lymphocytic leukemia on a weekly low-dose schedule.

The major complication during therapy of chronic lymphocytic leukemia (CLL) with the purine nucleotide analogue fludarabine is infection, which is also the main cause of morbidity and mortality in the disease. As the incidence of infectious episodes during therapy correlated with severity of neutropenia, stage of disease, and response to therapy, an effort was made to reduce therapy-related myelosuppression and improve response by altering the conventional therapy regimen. The protocol which yielded a response rate of 57% in previously treated patients with CLL consisted of five consecutive daily doses of 25-30 mg/m2 fludarabine given every three to four weeks. Based on observations from intracellular pharmacology studies it was hypothesized that repetitive single weekly doses of fludarabine would allow normal bone marrow cells to recover while maintaining cytotoxic levels in the leukemic cells. The cumulative four-week dose of the once-weekly regimen was approximately 80% of the original protocol. Eleven out of 46 evaluable patients (24%) responded to the therapy. Seven patients (15%) achieved a complete remission, and four (9%) a partial remission. While myelosuppression was reduced by about 30% compared with the original protocol, the incidence of febrile episodes was increased by 17%. Pretreatment serum IgG levels below the normal range correlated significantly with a high incidence of infectious episodes and with a short median survival time. These observations suggest that in addition to myelosuppressive therapy, disease related depressed immune function causes morbidity and mortality due to infections. The results further show that changes in the scheduling of the therapy regimen, associated with a slightly lower dose, resulted in reduced efficacy as measured by the response rate.

Adult↗
PubMed1993

Proliferating cell nuclear antigen (PCNA) expression in chronic lymphocytic leukemia (CLL).

Chronic Lymphocytic Leukemia (CLL) is usually an indolent disorder which in some patients assumes an aggressive clinical course. In order to assess at presentation the prognosis of a given patient, several staging systems and prognostic variables have been proposed including the expression of the Proliferating Cell Nuclear Antigen (PCNA). PCNA is a 36 kd nuclear protein, the regulation of which is cell cycle-dependent. In CLL, PCNA levels correlate with cell proliferation, clinical stage and the lymphocyte doubling time (LDT). Furthermore, preliminary data suggests that PCNA expression may also predict response to Fludarabine-based chemotherapy. Since PCNA is a cofactor for Delta DNA polymerase, PCNA overexpression in CLL may also reflect the intrinsic DNA repair activity of the leukemic cells and thus their resistance to chemotherapy. Further studies aiming at modulation of PCNA expression in CLL cells may clarify this issue and may offer a future new therapeutic strategy with which to treat this disorder.

Antigens, Neoplasm↗
PubMed1993

Nucleoside analogs in treatment of chronic lymphocytic leukemia.

The nucleoside analogs fludarabine monophosphate, 2-chlorodeoxyadenosine, and 2-deoxycoformycin (pentostatin) all have activity in chronic lymphocytic leukemia. The most widely studied drug is fludarabine which is able to obtain complete or partial responses in more than 50% of previously treated patients. The response rate is 44% for 2-CDA and approximately 25% for pentostatin. Fludarabine has also been used to treat patients as initial therapy, and has resulted in overall response rate of 79% with 75% of the patients achieving complete remission. The NCI and International Working Group for CLL criteria for complete remission allow for persistent nodules or lymphoid infiltrates in the bone marrow biopsy. Studies have now demonstrated persistent lymphoid aggregates are associated with a shorter time to progression for responders but no survival disadvantage. There is a strong association of documented refractoriness to alkylating agents with probability of response to fludarabine and also survival. The major morbidity associated with the use of these drugs are infections, which, in some circumstances, are associated with neutropenia but in other circumstances are probably related to the hypogammaglobulinemia and T-cell immunodeficiency which are part of the disease. The T-cell immunodeficiency is aggravated by the nucleoside analogs. Even after discontinuation of therapy the immunodeficiency as measured by CD4 cell number is sustained for 12 to 24 months. Opportunistic organisms such as herpes simplex, herpes zoster, Listeria monocytogenes, and pneumocystis carinii are being noted in patients treated with these agents. The potency of these drugs and low incidence of toxicities to other organs suggests that they will be effectively combined with other agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1993

New initiatives with fludarabine monophosphate in hematologic malignancies.

Fludarabine monophosphate (fludarabine) was initially discovered to have significant activity in indolent lymphoma and chronic lymphocytic leukemia (CLL). The major clinical experience with fludarabine is in previously treated patients with CLL. In such patients the complete and partial response rate (CR + PR) is over 50%. These results were obtained with 5-day schedules of fludarabine 25 to 30 mg/m2/d. Subsequent schedules have explored once-a-week fludarabine and a 3-day schedule every 4 weeks. These strategies, in particular the once-a-week schedule, have obtained inferior results. The addition of prednisone has not been associated with an improvement in response rate or survival. The application of fludarabine to previously untreated patients demonstrated a CR + PR rate of 75% to 80%. The addition of prednisone did not improve the response rate or survival in this group of patients. A significant concern in patients with CLL treated with fludarabine is a decrease in the CD4 and CD8 counts. Despite median posttreatment counts of approximately 200 CD4 lymphocytes/microL, the incidence of infections in patients in remission off therapy is low. Major clinical activity has been demonstrated with fludarabine in Waldenstrom's macroglobulinemia, in which more than one third of refractory patients achieve a CR or PR. Responding patients with anemia or thrombocytopenia have a marked improvement in blood counts. The duration of response has been long (> 30 months) in most responders. The early activity of fludarabine as a single agent in phase I/II studies in indolent lymphoma subsequently has been confirmed by a number of investigators. Fifty percent to 60% of patients with follicular lymphomas respond to fludarabine as a single agent. A number of these responses are complete despite the patients having received extensive prior treatment. A number of combination programs are being developed in CLL and indolent lymphoma. The combination of fludarabine with doxorubicin and prednisone has been developed and is being studied in phase I/II clinical trials. In addition, combinations of fludarabine and cytarabine with or without cisplatin based on elegant preclinical pharmacokinetic rationales have been applied to CLL with impressive cytoreductive activity but significant myelosuppression. A new combination of fludarabine, mitoxantrone, and dexamethasone has been developed for use in lymphoma. Phase I studies demonstrated a high response rate, especially in follicular lymphomas, with a number of patients achieving complete remission. Subsequent phase II studies demonstrate a response rate of 89% in patients with indolent lymphoma.(ABSTRACT TRUNCATED AT 400 WORDS)

Antimetabolites, Antineoplastic↗
PubMed1993

Chronic myelogenous leukemia in the lymphoid blastic phase: characteristics, treatment response, and prognosis.

PURPOSE: To determine the clinical and laboratory characteristics and outcomes of patients with chronic myelogenous leukemia (CML) in the lymphoid blastic phase. PATIENTS AND METHODS: Data from 296 patients with CML blastic-phase disease who were referred to our institution between 1967 and 1991 were analyzed. Sixty-eight patients had CML lymphoid blastic-phase disease. Pretreatment characteristics, responses to different therapies, and survival rates were evaluated. RESULTS: Compared with patients having myeloid or undifferentiated blastic-phase disease, those with lymphoid morphology were significantly younger, presented with significantly lesser degrees of anemia, lower white blood cell and peripheral blast counts, higher percentages of marrow blasts, lower lactic dehydrogenase levels, and higher albumin levels. Accelerated-phase CML preceded the blastic phase in 40% of patients with lymphoid disease, compared with 54% of those with other morphologic findings (p = 0.03). The common acute lymphocytic leukemia antigen (CALLA) was expressed on lymphoid blasts in 97% of patients. The incidence of chromosomal abnormalities was similar in the three morphologic categories, although patients with lymphoid disease tended to have a lower incidence of trisomy 8 (17% versus 27%; p = 0.10) and of isochromosome 17 abnormalities (10% versus 17%; p not significant). The incidence of lymphoid blastic phase disease has not increased over the past decade, and it is not higher in patients with the chronic phase of the disease treated with alpha interferon. Patients with lymphoid disease had a significantly higher response rate to chemotherapy during the first salvage (49% versus below 20% for other morphologies; p < 0.001), particularly with vincristine, Adriamycin, and dexamethasone therapy (complete response rate of 61%). Survival during the blastic phase of the disease was also significantly longer in patients with lymphoid morphology than in those with other morphologies (median survival of 9 months versus 3 months; p = 0.01). The benefit associated with lymphoid blastic-phase morphology is brief, and plans for allogeneic bone marrow transplantation or experimental maintenance or consolidation programs should be implemented rapidly. CONCLUSIONS: Patients with CML lymphoid blastic-phase disease have different clinical and laboratory features than patients with other blastic-phase morphologies. In patients developing CML blastic-phase disease, distinguishing those with lymphoid transformation is extremely important because of the different therapeutic requirements (acute lymphocytic leukemia-type therapy) and prognostic implications.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Dual-task interference and the cerebral hemispheres.

It has been argued that dual-task interference is reduced when the two cerebral hemispheres can carry out the two tasks independently. Evidence for this idea has arisen from studies involving manipulations such as lateralized stimulation or response, or requiring mental operations believed to depend primarily on a particular hemisphere. However, these studies have typically involved a very limited degree of response uncertainty, which appears critical in producing the most extreme dual-task interference (the psychological refractory effect). Pairs of tasks with independent response uncertainty were examined, and various manipulations were used to promote hemispheric task separation. Dual-task interference was not modulated by these manipulations. It seems likely that response selection represents a central bottleneck, in the sense that this process cannot operate simultaneously and independently in the two hemispheres.

Adult↗
PubMed1993

Deliberate self-harm and public holidays: is there a link?

It has previously been reported [Davenport & Birtle, 1990] that there is a positive association between nonfatal deliberate self-harm in adolescents and emotionally charged festivals, such as St Valentine's Day and Christmas Day. We studied all cases of nonfatal deliberate self-harm presenting to three Central London hospitals on St Valentine's Day and Christmas Day and on two control dates, between 1983 and 1989. No association was found between cases of deliberate self-harm and St Valentine's Day, but a negative association was found with Christmas Day.

Adolescent↗
PubMed1992

CI-973, a new platinum derivative with potential antileukemic activity.

We examined the effects of CI-973 (supplied by Parke-Davis) on several human leukemia cell lines and a Chinese hamster ovary (CHO) line and their drug-resistant counterparts. The cell lines used were HL-60, HL-60/mAMSA, HL-60/DOX, KBM3, KBM3/mAMSA 6, KBM3/mAMSA 6(85), CHO, and CHO/AC-7. DOX, mAMSA, and AC-7 indicate resistance to doxorubicin, amsacrine, or 1-beta-D-arabinofuranosylcytosine, respectively. Cells were incubated with CI-973, and the effect was evaluated by two methods: growth inhibition assay and inhibition of colony formation. All cell lines examined were inhibited by CI-973; two of three amsacrine-resistant lines and the one cytarabine-resistant line demonstrated collateral sensitivity. At equivalent dosages, a 4-day exposure provided much greater cell kill than a 1-h exposure. Clonogenic assay showed exponential killing over 3 log units. Maximum CI-973 levels required to kill 50% of cells were 10-fold lower than the peak plasma levels achieved in a phase I solid tumor study. A continuous infusion phase I study in acute leukemia has been initiated.

Animals↗