Gender influences upon the executive role.
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Biomedical subjects
Publications and source records attributed to J O'Malley.
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Primary nursing has been both a philosophy of care and a delivery model for many hospitals during the past decade. Although the authors still value the philosophy of primary nursing, they believe the model no longer is effective in their hospital. The authors describe the experience of changing the nursing care delivery system from primary nursing to case management in leveled practice.
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The interferon inducer poly ICLC has toxic side effects; the carboxymethylcellulose (CMC) component is a possible source of this toxicity. We have purified CMC by ethanol extraction, and found that poly ICLC made with purified CMC is not significantly different in its effectiveness as an interferon inducer in mice than poly ICLC made with unpurified CMC, but is less toxic.
Serial cerebrospinal fluid samples were obtained from 14 multiple sclerosis patients over a period of several months and were tested under code for Inoue-Melnick virus. In five of the positive patients, virus was present in 28 of 32 specimens collected over a period of 2 to 5 months. Four patients, from whom a total of 34 specimens were taken, yielded only a single isolate each. Five patients contributed 28 specimens, all of which were negative. In six patients (three virus positive and three virus negative), neutralizing antibody was detected in serum and in cerebrospinal fluid.
We have prepared soluble complexes of poly ICL-CM dextran that are as effective interferon IFN inducers, in mice and in rhesus monkeys, as poly ICLC. Toxicity testing was carried out in mice and, poly ICL-CM dextran is less toxic, in mice, than poly ICLC is.
Using a new spectrophotometric assay, we found that human serum digests predominately (rC)n of (rI)n X (rC)n, in agreement with results of Nordlund et al. (Proc. Soc. Exp. Biol. Med., 1970, 133, 439-444) and DeClercq (Eur. J. Biochem., 1979, 93, 165-172) while rhesus monkey, cat, and rabbit sera digest primarily (rI)n. The results of Nordlund et al. also show (in agreement with our results) that human serum digests more of the (rC)n strand of (rI)n X (rC)n than rabbit serum. However, their results differ from ours, since they found that rabbit serum digests nearly equal, but small amounts of (rI)n and (rC)n. Results are discussed in relation to interferon (IFN) induction and toxicity following administration of (rI)n X (rC)n.
Twenty-one patients with primary humoral immunodeficiency were treated for 1 year with a chemically intact immunoglobulin, 300 mg/kg body weight given intravenously every 3 weeks, to compare immunoglobulin levels and clinical status with results achieved after standard treatment with intramuscular immunoglobulin given previously for 1 year. A substantial reduction of specific acute illnesses and antibiotic use was found for 18 of the 21 patients, particularly during the second 6 months of treatment. Average IgG levels before intravenous infusion were increased 243 mg/dL over previous intramuscular pre-injection levels. Adverse effects were recorded for 2.5% of infusions.
Intravenous gammaglobulin (IVIgG) was used to treat autoimmune neutropenia of infancy in two males with repeated infections. The neutrophil count increased significantly in both patients with the initial IVIgG therapy; 1 patient went into remission. The neutrophil count in the other remained above baseline for 3 wk, and a subsequent booster infusion also caused the neutrophil count to increase. The patients have remained clinically well since their treatment began. Serial studies of antineutrophil antibody and serum lysozyme, performed to elucidate the mechanism of action, suggested decreased neutrophil destruction, perhaps by Fc receptor blockade, as well as decreased synthesis of antineutrophil antibody. Neutrophil function was not impaired after the neutrophil count increased. Many patients with immune neutropenia have a benign course, but those who have significant infections could be treated, acutely or prophylactically, with intravenous gammaglobulin.
High-dose intravenous gammaglobulin (IVIgG) was given to 12 children and adults with chronic idiopathic thrombocytopenic purpura (ITP) to avoid splenectomy or because they either failed to respond to or required maintenance with high doses of steroids and/or immunosuppressives. The average platelet count increase to initial therapy was 239,500/microliters (range 23,000-790,000). A concomitant IgG Fc receptor blockade, measured by IgG-sensitized 51Cr-labeled autologous erythrocytes, was seen in 11 of 11 patients tested, both splenectomized and not splenectomized, lasting 3-4 wk. Six or more months after treatment, 2 children are in remission, 2 children and 2 adults are stable requiring no therapy with platelet counts of approximately 50,000 and 30,000, respectively, 3 children require maintenance IVIgG therapy at 2-10-wk intervals, and 1 child and 2 adults have become refractory to further IVIgG. Splenectomy was not performed in 4 children. Two adults were able to discontinue daily prednisone. The 3 patients who became unresponsive to Swiss Red Cross gamma-globulin (IgSRK) therapy did so in conjunction with a markedly elevated platelet-associated IgG and IgM. Serum IgM increased an average of 103 mg/dl after the IVIgG infusions. No significant side effects were seen.
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A single rising dose tolerance trial of rDNA interferon-alpha 2 (IFN-alpha 2) was conducted in eight patients with the diagnoses of non-Hodgkin's lymphoma (NHL), multiple myeloma, and chronic lymphocytic leukemia (CLL). Patients received a total of six i.m. doses at weekly intervals as follows: 1, 3, 10, 30, 60, and 100 x 10(6) IU. Patients were monitored at each dose level for serum IFN activity, anti-IFN antibodies, immunomodulation, clinical toxicity, and response. All patients exhibited clinical toxicity, including fever, chills, fatigue, headache, anorexia, mild-to-moderate leukopenia, nausea, and vomiting. Toxicity was dose-related, with significant side effects occurring in all patients at levels of 10 x 10(6) IU and above and some evidence of tachyphylaxis at higher doses. All side effects, including leukopenia and thrombocytopenia, were of short duration and were resolved within 3-5 days. Fevers, rigors, myalgias, and fatigue were partially alleviated by premedication with acetaminophen or hydrocortisone. Pharmacokinetic data indicated mean peak serum IFN titers greater than 90 at a dose of 10 x 10(6) IU and greater than or equal to 200 at doses greater than or equal to 30 x 10(6) IU 8 h after injection. No anti-IFN antibodies were detected. However, the serum levels achieved at higher doses were not linear, possibly indicating in vivo degradation. Total T cells, B cells, monocytes, and T subsets monitored by flow cytometry with monoclonal antibodies remained essentially constant throughout the trial. Although some patients demonstrated minor augmentations of antibody-dependent cellular cytotoxicity (ADCC) and natural killing (NK) activity at the lowest IFN-alpha 2 doses, the majority of patients demonstrated decreases in NK activity after higher IFN doses. No correlation between immunomodulation and clinical response to IFN was observed. At higher dose levels, the predominant immunomodulatory effect of IFN-alpha 2 was suppression of NK, ADCC, and blastogenic responses to T-cell mitogens and recall antigens. B-cell functional deficits as well as radioresistant T-helper and radiosensitive T-suppressor function assessed in a pokeweed mitogen-driven immunoglobulin secretion assay appeared unaffected by IFN administration. One myeloma patient showed progression and was discontinued after 60 x 10(6) IU. There were four patients (3 NHL, 1 myeloma) who achieved partial remission (greater than or equal to 50% tumor reduction) and three (1 CLL, 2 NHL) who showed objective tumor responses of less than 50%. These data suggest that rDNA IFN-alpha 2 is well-tolerated and may have significant antitumor activity against lymphoproliferative malignancies. Clin