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S O'Brien

Publications and source records attributed to S O'Brien.

At least 325 records · Page 18Linked to original sources

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↗

Mitoxantrone and high-dose cytosine arabinoside for the treatment of refractory acute lymphocytic leukemia.

Twenty-five adult patients with refractory acute lymphocytic leukemia received salvage therapy with mitoxantrone 5 mg/m2 intravenously over 1 hour daily for 5 days and cytosine arabinoside 3 g/m2 intravenously over 2 hours every 12 hours for six doses. Overall, nine patients (36%) achieved complete remission, eight (32%) died during induction, and eight (32%) had resistant disease. No significant associations were found between pretreatment patient characteristics and remission. Remission durations toxic effects were related to myelosuppression. Febrile episodes requiring hospitalization occurred in 23 patients (92%), including five episodes of fever of unknown origin (20%) and 18 episodes of documented infections (72%). The authors conclude that the combination of mitoxantrone and high-dose cytosine arabinoside has significant activity in adults with refractory acute lymphocytic leukemia. The addition of colony-stimulating growth factors to the intensive chemotherapy, and the use of the combination regimen as part of front-line maintenance intensification therapy may further improve the prognosis in these patients.

Adolescent↗

Results of the vincristine, doxorubicin, and dexamethasone regimen in adults with standard- and high-risk acute lymphocytic leukemia.

One hundred five untreated adult patients with acute lymphocytic leukemia (ALL) were entered on the vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and Decadron (dexamethasone; Merck Sharp and Dohme, West Point, PA) (VAD) regimen. Induction therapy with VAD and VAD plus cyclophosphamide (CVAD) was followed by a 2-year rotating maintenance program with multiple antileukemic combinations, and included early intensifications with Adriamycin and high-dose cytarabine (ara-C) and a late intensification with cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) followed by autologous bone marrow transplantation (BMT). Duration of therapy was 24 to 30 months. Eight-eight patients (84%) achieved complete remission (CR) with VAD-CVAD, and 94 (90%) ultimately had CR with continuation of the maintenance as planned. Induction mortality was 3%; only half of the patients required prolonged hospitalization of 1 week or longer, or intravenous antibiotics. Maintenance therapy was given to 79 patients, while nine with histocompatibility locus antigen (HLA)-matched related donors underwent allogeneic BMT. The median remission duration was 22 months, and the median survival was 19 months. Factors associated with significantly worse CR rates were older age, the presence of hypoalbuminemia or hyperbilirubinemia, L2 or L3 morphology, and myeloid markers on leukemic cells. Those associated with significantly worse remission durations were the presence of elevated leukocyte or absolute peripheral blast counts, Philadelphia chromosome (Ph)-positive or B-cell ALL, L2 morphology, and more than one course to achieve CR. Patients could be divided into standard-risk ALL (28% of patients) and high-risk ALL (72% of patients) with long-term remission rates of 70% versus less than 30%. The 26 patients who underwent CBV autologous BMT had similar long-term outcome compared with 21 patients who did not (older age, medical contraindications, or socioeconomic problems). The presence or absence of myeloid markers on leukemic cells did not affect long-term prognosis. We conclude that VAD therapy is a well-tolerated effective induction regimen. High-risk ALL patients require alternative maintenance investigational approaches.

Adolescent↗

Cholesterol education at the worksite.

1. Risk factors for coronary heart disease include age, sex, family history, high cholesterol, blood pressure, smoking, and severe obesity. The last four risk factors can be modified with lifestyle changes. 2. Occupational health nurses who provide primary care to workers can assist employees in detecting and treating their elevated cholesterol. Cholesterol screening at the workplace is an effective means for employees to learn their cholesterol level or monitor their dietary progress in lowering their cholesterol. 3. Employees can modify their eating behaviors by developing the skills to make wise dietary choices. Simple dietary self assessment and self monitoring tools will aid employees in monitoring and evaluating their efforts. 4. To successfully implement a cholesterol education program and counsel employees, occupational health nurses need to increase their knowledge of nutrition, specifically the composition of a diet that will help reduce the risks associated with heart disease.

Decision Making↗

Recombinant interferon-alpha therapy of Philadelphia chromosome-negative myeloproliferative disorders with thrombocytosis.

PURPOSE: The clinical course of patients with myeloproliferative disorders and excessive thrombocytosis may be complicated by serious hemorrhagic or thrombotic events. We have previously reported that interferon-alpha can control severe refractory thrombocytosis in patients with advanced chronic myelogenous leukemia. Therefore, we treated a group of thrombocythemic patients with Ph-negative myeloproliferative disorders, including polycythemia vera and essential thrombocythemia, with recombinant interferon-alpha (rIFN-alpha 2a). PATIENTS AND METHODS: Eight patients with profound elevations in platelet counts received a median induction dose of 5.4 X 10(6) U/day (range, 5.0 to 10.0 X 10(6) U/day) of rIFN-alpha 2a administered intramuscularly or subcutaneously. RESULTS: We observed a significant decline in platelet counts from a median baseline value of 1,929 X 10(9)/L (range, 960 to 2,960 X 10(9)/L) to a median posttreatment value of 431 X 10(9)/L (range, 71 to 1,150 X 10(9)/L) (p less than 0.01). Concomitantly, white blood cell counts declined from a median baseline value of 20.8 X 10(9)/L (range, 10.5 to 40.8 X 10(9)/L) to a median posttreatment value of 6.1 X 10(9)/L (range, 2.9 to 29.0 X 10(9)/L) (p less than 0.02). Correction of thrombocytosis was rapid, with a median of only eight days from the start of therapy to the achievement of a platelet count less than 1,000 X 10(9)/L. Six of eight patients have shown an ongoing response with a median follow-up period of 11 months (range, one to 30 months). There have been no bleeding or thrombotic events during the study. Side effects of rIFN-alpha 2a therapy consisted of fever and flu-like symptoms, with tachyphylaxis developing after one to two weeks of therapy. CONCLUSION: Our observations suggest that alpha interferon may be a promising therapeutic agent for myeloproliferative disorders characterized by thrombocytosis.

Adult↗

A glutaminase (gis) gene maps to mouse chromosome 1, rat chromosome 9, and human chromosome 2.

A rat cDNA clone encoding a portion of phosphate-activated glutaminase was used to identify DNA restriction fragment length polymorphisms (RFLPs) in sets of somatic cell hybrids and between wild-derived and inbred strains of mice. Segregation of rat and mouse chromosomes among somatic cell hybrids indicated assignment to rat chromosome 9 and mouse chromosome 1. Analysis of chromosome 1 alleles for several genes in an interspecific cross between Mus spretus and C3H/HeJ-gld/gld mice indicates that glutaminase can be positioned within 5.5 +/- 2.0 cM proximal to Ctla-4. Similarly, human-hamster somatic cell hybrids were examined for RFLPs, and four human EcoRI restriction fragments were found to hybridize with the rat glutaminase probe. Two of these restriction fragments cosegregated and mapped to human chromosome 2 in a region that is syntenic with mouse chromosome 1 and rat chromosome 9.

Animals↗

Genetic characterization of FLA, the cat major histocompatibility complex.

The major histocompatibility complex (MHC) of the domestic cat (termed FLA) has been refractile to genetic and serological definition largely because of repeated failure to detect cytotoxic antibodies in multiparous cats or to elicit antibody following allogeneic lymphocyte immunization. We have developed a protocol for producing cytotoxic alloantisera in the cat following rejection of multiple surgical skin grafts. Of 59 cats subjected to grafting, 13 produced lymphocytotoxic antisera which had varying specificities among a panel of outbred cat cells. A population cluster analysis of the 13 alloantisera permitted the identification of six clusters of overlapping FLA specificities. Serological analysis of cells from 12 cat kindreds led to the definition of 24 allogeneic haplotypes, which segregate as a single Mendelian complex. Feline FLA antisera were characterized as class I or class II specific by immunoprecipitation of FLA gene products on lymphocyte cell surfaces. Abundant antigenic polymorphisms for both class I and class II MHC determinants were discovered, a result consistent with precedence in other species and the common expectation of the adaptive value of MHC variation. Development of feline MHC typing reagents and the definition of haplotypes for the cat hold promise for experimental analysis of valuable feline models for virus-induced immune deficiencies.

Animals↗

Association of granulocytosis with poor prognosis in patients with acute myelogenous leukemia and translocation of chromosomes 8 and 21.

Forty-three patients with acute myelogenous leukemia (AML) and a translocation 8;21 were reviewed. The patients' median age was 30 years, and 62% were men. Twenty-three patients (53%) had loss of a sex chromosome and ten (23%) had other chromosomal abnormalities in addition to the 8;21 translocation. Complete remission (CR) with induction chemotherapy was achieved in 40 patients (93%). The median CR duration was 18 months (range, 1 to 137+ months). Median survival time was 17 months (range, 0.5 to 138+ months) with a 3-year survival rate of 31%. Twenty-three patients (53%) relapsed between 1 and 58 months after entering remission with reinduction therapy resulting in 8 CRs (35%). Thirteen characteristics were examined for an effect on survival. The most striking finding was a significant association between elevated absolute granulocyte count and poor survival (P = .002). WBC count greater than 10,000/microL was also associated with shorter survival (P = .05). Patient age, albumin level, and platelet count showed trends for survival association. Although patients with AML and t(8;21) are regarded as a favorable group with respect to survival, we found a subset of patients who do very poorly. Intensive or more investigational approaches in first remission should be considered for these patients.

Adolescent↗

High dose chemotherapy with autologous hematopoietic stem cell support in the treatment of refractory stage IV breast carcinoma.

Fourteen patients with refractory metastatic breast cancer were treated with high dose chemotherapy and autologous hematopoietic stem cell rescue. All patients received cyclophosphamide (7.5 g/m2 over 3 days) and thiotepa (150-225 mg/m2 over 3 days), three patients in addition received melphalan (4.5 mg/kg), and seven patients received carmustine (150-562 mg/m2). Toxicities included pancytopenia, infection, hemorrhagic cystitis, skin rash, nausea, vomiting, diarrhea, and mucositis. There was one toxic death secondary to sepsis and ventricular tachycardia. The overall response rate was 77% including a 15% complete response rate. The overall median survival for all patients was 6.0 months (range 2-22 months). The median survival for nonresponders was 3.5 months. The median duration of response was 89 days (range 40-262). In our experience high dose chemotherapy with autologous stem cell reinfusion produces a high response rate in refractory breast cancer. However, because of the short duration of response and overall survival, we feel this type of therapy should be utilized earlier in the course of disease.

Adult↗

A special challenge.

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Dental Care for Persons with Disabilities↗

Fetal heart rate monitoring by telephone. II. Clinical experience in four centres with a commercially produced system.

A commercially produced domiciliary fetal monitoring (DFM) system was assessed in four centres in the UK (Bristol, Glasgow, London and Nottingham) chosen to allow for comprehensive assessment in various settings in many different women. Overall, 825 recordings were made from 368 women (2.24 per woman). There were 56 unsuccessful attempts at transmission (6.8%), most were due to problems with telephone equipment. The system worked most efficiently when a dedicated direct line was used. The data transmission time varied between 40 and 60 s. The median telephone time (including data transmission and conversation) with a dedicated direct line was 7 min. Mean acceptance times from the four centres were between 70 and 80%. All recordings with acceptance times of 40% or more were interpretable. Ten recordings were abnormal. The women and mid-wives were equally proficient at using the DFM system. The DFM system represents an important addition to current methods of fetal assessment. Specific guidelines are outlined.

England↗