Biomedical subjects
Publications and source records attributed to J Abrahm.
This consensus paper describes the essential skills that clinicians need to help persons who are experiencing grief after the death of a loved one. Four aspects of the grieving process are reviewed: anticipatory grief, acute grief, normal grief reactions, and complicated grief. Techniques for assessment and recommendations about interventions and indications for referral are provided for each aspect.
Patients at the end of life need not have unrelieved pain. Thorough assessment and multidisciplinary treatment can provide comfort with a minimum of adverse effects. Patients and their families can be freed to accomplish their final goals, and the bereaved families can be spared the pain of memories of loved ones who suffered in their final days.
In the face of widespread housestaff disenchantment with serving on oncology wards, the author's oncology consultation service is one of the most popular rotations among housestaff at the hospital. She discusses the factors contributing to the service's success in this regard: 1) focus of teaching efforts on residents; 2) interdisciplinary patient care model; 3) integration of ambulatory care into the rotation; 4) the consultative nature of the service.
Cisplatin is one of the most active cancer treatment agents available. Unfortunately, however, cisplatin causes many untoward side effects. Nurses play a major role in administering cisplatin and in preventing and managing the adverse effects associated with this drug. In order to maximize the quality of life of patients undergoing cisplatin treatment, nurses need a thorough knowledge of its uses, administration, and side effects. This article is the second of a two-part series about cisplatin. Part I provided a review of the mechanism of action, current uses, and administration guidelines. Part II discusses the most common side effects of cisplatin and the appropriate nursing assessment and management of patients undergoing treatment with this agent. In addition, future directions for the use of cisplatin and the use of alternative agents will be discussed.
Cisplatin is one of the most active cancer treatment agents available. Unfortunately, however, cisplatin causes many untoward side effects. Nurses play a major role in administering cisplatin and in preventing and managing the adverse effects associated with this drug. In order to maximize the quality of life of patients undergoing cisplatin treatment, nurses need a thorough knowledge of its uses, administration, and side effects. This article is the first of a two-part series about cisplatin. Part I will provide a review of the mechanism of action, current uses, and administration guidelines. Part II will discuss the most common side effects of cisplatin and the appropriate nursing assessment and management of patients undergoing treatment with this agent. In addition, future directions for the use of cisplatin and the use of alternative agents will be discussed.
The role of the KIT protooncogene in human hematopoiesis is uncertain. Therefore, we examined KIT mRNA expression in normal human bone marrow mononuclear cells (MNC) and used antisense oligodeoxynucleotides (oligomers) to disrupt KIT function. KIT mRNA was detected with certainty only in growth factor-stimulated MNC. Expression was essentially abrogated by making MNC quiescent or by inhibiting myb gene function. Oligomers blocked KIT mRNA expression in a dose-response and sequence-specific manner, thereby allowing functional examination of the KIT receptor. In experiments with either partially purified or CD34(+)-enriched MNC, neither granulocyte nor megakaryocyte colony formation was inhibited by oligomer exposure. In contrast, KIT antisense oligomers inhibited interleukin 3/erythropoietin-driven erythroid colony formation approximately 70% and "stem cell factor"/erythropoietin-driven colony formation 100%. The presence of erythroid progenitor cell subsets with differential requirements for KIT function is therefore suggested. Growth of hematopoietic colonies from chronic myeloid leukemia and polycythemia vera patients was also inhibited, while acute leukemia colony growth appeared less sensitive to KIT deprivation. These results suggest that KIT plays a predominant role in normal erythropoiesis but may be important in regulating some types of malignant hematopoietic cell growth as well. They also suggest that KIT expression is linked to cell metabolic activity and that its expression may be regulated by or coregulated with MYB.
Peripheral cytopenias are common in patients with myelodysplastic syndromes. We previously successfully treated three such patients with improvement of some cytopenias with the impeded androgen danazol. To confirm this finding and elucidate the mechanism of response, we treated an additional 22 patients with myelodysplasia with oral danazol (600-800 mg daily) for 3-12 months. Eleven of 22 evaluable patients taking danazol met our criteria for improvement of peripheral counts, mainly thrombocytopenia. Chromosome analysis, marrow culture studies and serial bone marrow biopsies revealed no alteration of the abnormal clone or normal haematopoiesis in patients on danazol therapy. This suggested that improvement in blood counts was not related to modulation of ineffective haematopoiesis. Investigation of the thrombocytopenia in these patients revealed that most patients presented with markedly elevated platelet associated IgG (PAIgG), elevated plasma platelet-bindable IgG (PBIgG), and an elevated number of monocyte Fc gamma receptors. Treatment with danazol was associated with a decline in monocyte Fc gamma receptor number without significantly altering the elevated PAIgG or PBIgG levels. These results are similar to our observations in patients treated with danazol for chronic idiopathic thrombocytopenia purpura (ITP). Our data suggest that a component of the thrombocytopenia occurring in patients with myelodysplasia may be due to enhanced peripheral blood cell destruction by abnormal macrophages. Danazol may modulate cytopenia by decreasing the number of monocyte Fc gamma receptors. Danazol treatment was associated with minimal toxicity, but clinically meaningful responses were rare.
We describe 2 patients who presented with hemarthrosis and were found to have an underlying Factor VIII inhibitor. One case was associated with a renal cell carcinoma. Factor VIII inhibitor should be included in the differential diagnostic lists of causes of hemarthrosis.
Median survival is as little as 6 months for patients with refractory anemia with excess blasts who demonstrate an abnormal karyotype in the majority of marrow cells. We treated a patient who presented with 29% marrow blasts and 90% abnormal metaphases with 13-cis-retinoic acid. He achieved a complete clinical and cytogenetic remission during therapy. To determine the mechanism of the response, serial studies were done of the effects of 13-cis-retinoic acid and dexamethasone on in vitro growth of his marrow cells. During clinical remission, when the drug was not administered, marrow growth remained significantly depressed. During relapse, the remission growth pattern was replaced by overgrowth of the karyotypically abnormal monocytoid clone. Clonal growth occurred in cultures containing colony-stimulating activity or dexamethasone but was absent in cultures containing concentrations of 13-cis-retinoic acid achieved in vivo. After the drug was reinstituted, a second clinical stabilization developed. Since 13-cis-retinoic acid inhibits normal monocyte colony growth, we postulate that the patient's unusual clinical responses to the drug were due to in vivo growth inhibition of the malignant monocytoid clone.
This article deals with the management of the immunocompromised host. Mechanisms of immunocompromise include alterations in skin and mucosal barriers, normal oral and intestinal flora, splenic function, and number or function of T cells, B cells, granulocytes, and monocytes. Discussed in this article are ways for maintaining those defenses not altered by the primary disease, minimizing the environmental risks to the patient, anticipating potential infections in order to institute appropriate prophylactic measures, and diagnosing and aggressively treating infections as they occur.
Phorbol diesters with tumor-promoting activity, in particular, 12-0-tetradecanoyl-phorbol-13-acetate (TPA), can induce or inhibit terminal differentiation in a variety of cell systems, with specificity for particular cell lineages. The phorbols are excellent tools to investigate the expression and control of differentiation in some cells and the mechanism by which oncogenic agents interfere with the process of terminal differentiation. The mechanism of action of the phorbols on different target cells is not understood at the present time. It is felt that the status of the cell is of major importance as, in some cases, opposite effects can be achieved by the same concentration of the phorbol diester used. Changes in membranes, receptors, in secretion of prostaglandins and in the level of cyclic AMP have all been reported. However, the relationship of these changes with the alterations in the genetic program involved in the differentiation process is not clear, and the recent report of a possible cell receptor for phorbol diesters should elucidate their mechanism of action. The findings on the effect of phorbol diesters on differentiation have suggested the testable hypothesis that promotion could be mediated through inhibition of cellular differentiation. It has also been suggested that changes in differentiating systems could be of future use in screening for unknown tumor promoters, however, this possibility seems quite remote. Finally, phorbol diesters with tumor-promoting activity appear to exert a specific effect on differentiation of leukemic cells of both mouse and human origin, and therefore, the application of this particular phenomenon in experimental therapy should be the subject of future investigations.
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Leukemic cells from patients with acute myeloid leukemia underwent morphological, functional, and histochemical changes within 24-48 hr after treatment with 1.6 x 10-18 M 12-0-tetradecanoylphorbol-13-acetate (TPA). The changes included adhesion to the plastic substrate, a 4-6-fold increase in the number of phagocytic cells, and an increase in the number of alpha-naphthyl-acetate esterase (alpha-NAE) positive cells. In contrast, TPA treatment of cells from patients with acute lymphoblastic leukemia caused some aggregation of cells in suspension, but no changes in adhesion, phagocytosis, or alpha-NAE. Of the four cases of undifferentiated or unclassified leukemias studied, two failed to respond to TPA, one responded with a myeloid (adhesion) pattern, and one with a lymphoid (aggregation) pattern. These data suggest that leukemic myeloblasts retain the ability to express a variety of differentiated functions, and in some cases, it may be possible to use TPA as a tool to test the differentiative potential of undifferentiated human leukemias.
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This study describes the response to therapeutic plasma exchange in a 60-year-old man with Waldenström's macroglobulinemia who developed a clinically severe bleeding disorder with laboratory features characteristic of acquired von Willebrand's disease. The patient's plasma levels of factor VIII coagulant activity, von Willebrand's factor antigen, and ristocetin cofactor activity were all less than 15 percent of normal, and the bleeding time was more than 20 minutes. In vitro studies did not demonstrate an inhibitor to factor VIII/von Willebrand factor, nor was a precipitating antibody to von Willebrand's factor antigen found in the patient's plasma. Neither infusions of cryoprecipitate nor combination chemotherapy corrected the clinical or laboratory abnormalities. In contrast, plasma exchange corrected the in vitro coagulation abnormalities and was effective in preventing surgical hemorrhage and controlling severe mucosal bleeding on 11 separate occasions. The current case demonstrates that the clinical and laboratory abnormalities in a patient with acquired von Willebrand's disease can be corrected completely by plasma exchange; it is recommended therefore that plasma exchange be considered as a mode of therapy in symptomatic patients with this disorder.
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Cancer pain remains problematic for many patients. No standardized guidelines were available for the management of cancer pain until the early 1990s. In addition, many healthcare personnel have not been trained adequately in pain management, despite the abundance of literature. As a result, clinicians often manage patient's pain poorly. This article provides an overview of the process of development and implementation of a 5-year multidisciplinary cancer pain education program, begun in 1989 by the University of Pennsylvania School of Nursing, School of Medicine, and Cancer Center. The program was comprised of a multidisciplinary cancer pain consultation panel that sought to educate healthcare personnel in community hospitals and nursing homes in southeastern Pennsylvania about cancer pain. This was accomplished by providing consultations for agencies with patients experiencing uncontrolled and/or progressive cancer pain. The panel also provided education through lectures, newsletters, and symposia. A total of 1949 healthcare personnel attended 92 consultations, lectures, and symposia during the 5 years that the program has operated. With the linkage approach to innovation diffusion framework used in this consultation program, and the implementation of the guidelines now available, many healthcare personnel may be able to increase their skills and manage pain more effectively, thus reducing and/or eliminating needless suffering for patients. Developing role models in the area of pain management at community hospitals may be the most effective means of incorporating pain control guidelines and fostering innovation.