Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression

Fifty-two of 175 (30%) survivors of allogeneic marrow transplantation developed chronic graft-versus-hose diseases (GVHD). Five with limited chronic GVHD had an indolent clinical course with involvement of only the skin and liver. Forty-seven with extensive chronic GVHD had an unfavorable multiorgan disorder that resembled several autoimmune diseases. Thirteen patients with extensive disease (group I) were not treated and only 2 survive with Karnofsky scores >- 70%. Mortality resulted from infections and morbidity from sica syndrome, pulmonary and hepatic insufficiency, scleroderma-like skin disease, and contractures. Another 13 (group II) received a median of 8 mo prednisone and/or a brief course of antithymocyte globulin, and 3 survive without disability. The other 21 (group III) were treated with a combination of prednisone (1.0 mg/kg/q.o.d.) and either cyclophosphamide, procarbazine, or azathioprine (all 1.5 mg/kg/day) for a median of 13 mo. Combination therapy was well tolerated with only modest myelotoxicity. Fifteen in group III had a good and 4 a fair response to treatment while 2 with no response died. Azathioprine and prednisone was the most effective regimen. All therapy has been discontinued in 12 group III patients: GVHD returned in 5 (including 2 who died in spite of retreatment) while 7 remain free of GVHD for a median of 11 (range 6-30) mo observation. Only I group III survivor is disabled and 16 of the original 21 are alive 2-4 yr after transplant with Karnofsky scores of 70%-100%. Thus, combination immmunosuppression appears to favorably affect and, in some cases, premanently arrest the adverse natural course of extensive chronic GVHD.     

Use of E mu-PIM-1 transgenic mice short-term in vivo carcinogenicity testing: lymphoma induction by benzo[a]pyrene, but not by TPA

E mu-pim-1 transgenic mice are predisposed to develop lymphomas. Due to their low spontaneous tumour incidence and their increased sensitivity towards the lymphomagen ethylnitrosourea these mice may present an interesting model for short-term carcinogenicity testing. Here, we report on the further exploration of this transgenic mouse model with two additional carcinogens known to have, among others, the lymphohaematopoietic system as target, i.e. benzo[a]pyrene (B[a]P) and 12-O-tetradecanoylphorbol-13-acetate (TPA). B[a]P, given three times a week (by gavage) for 13 weeks at 4.3, 13 or 39 mg/kg body weight, resulted in a dose-related increase in lymphomas up to a 90% incidence in E(mu)-pim-1 mice during the observation period of 40 weeks. B[a]P also induced tumours of the forestomach within this observation period, though at a lower incidence and apparently equally effective in wildtype and transgenic mice. TPA, on the other hand, was unable to induce lymphomas (or tumours in any other organ) in either transgenic or wildtype animals within the observation period of 44 weeks, when applied dermally at the maximum tolerated dose of 3 microg/mouse, twice a week for 35 weeks. Molecular analysis showed that B[a]P-induced lymphomas in transgenic mice were of T-cell origin, 80% of which had elevated levels of c-myc expression. None of the lymphomas had increased N-myc expression and mutation analysis of the ras-gene family revealed a K-ras mutation in only one out of eight tumours investigated. Also, none of the lymphomas showed aberrant expression of p53 as determined by immunohistochemistry. It is concluded that the E mu-pim-1 mouse model will not be very suitable for short-term carcinogenicity testing in general: only genotoxic chemicals that have the lymphohaematopoietic system as target for carcinogenesis in wild- type mice, appear to be efficiently identified.      

Thoracic empyema: a study of 56 patients

Fifty seven children with thoracic empyema (37 boys and 20 girls) aged less than 12 years were seen at the University of Port Harcourt Teaching Hospital between January 1989 and December 1991. Staphylococcus aureus was the most common organism isolated from the pus of these patients (36 (63%) patients). Pseudomonas aeruginosa, the next most common organism, was isolated in 10 (18%) patients. The most common symptoms at presentation were acute illness with fever and cough (51 (89%) patients). All the patients were treated with closed intercostal tube drainage and appropriate antibiotics. Decortication was resorted to in only one patient. There were two deaths and the overall survival rate was 97%.     

Is caring the ethical ideal?

This paper will examine the claim that caring is an appropriate ethical ideal for nursing. Initially it will examine nursing's philosophy of care and caring, highlighting some areas of difficulty and dissatisfaction articulated by many of its contemporary theorists Evaluation of the notion of caring as an appropriate ethical ideal for nursing will be balanced against those in opposition, and in this process their critique will be discussed This discussion will focus on areas such as virtue, virtue ethics, moral responsibility, feminine values, mothering and the debate between male and female caring Different forms of caring will be evaluated and balanced against different forms of nursing The paper will then suggest that current views which hold aloft nursing as a bedmate of caring may be detrimental to both the cared-for and the carer, advocating in the process a move toward change     

Establishing good practices in continuing care: a descriptive study of community nursing services for people with HIV infection

This paper presents findings from a 2-year study of community nursing services for people affected by HIV infection in six health authorities in England The research, commissioned by the Department of Health, England, aimed to identify the main bridges and barriers to effective home nursing care, focusing on discharge co-ordination, district nursing and multi-agency collaboration Using a triangulated, case study approach, the main methods of data collection included non-participant observation, case note analysis, semi-structured staff interviews, a postal questionnaire of district nurses and a series of focus groups with service users Study sites included three cities and surrounding districts in the north west, north and south east of England Findings suggest there is considerable room for improvement in discharge planning and that good practice is not the preserve of specialist units District nurses are shown to be willing providers of the majority of home nursing care to this client group, but there is a need for more focused training, greater use of care co-ordinators and more emotional and managerial support     

A preliminary study of users' and nursing students' views of the role of the mental health nurse

This paper is a preliminary study, part of a larger project which is endeavouring to ascertain the views of both users of mental health services and those of mental health branch students as to their perceived and desired role of the mental health nurse Four groups of users (n = 28) and four groups of students (n=44) were contacted, and recorded group discussions took place in gaining qualitative data that would feed into the main body of research The views expressed by both users and students are interestingly convergent, but much concern was expressed as to the needed changes in the provision of the service and the danger for students on qualifying to become quickly incorporated into the prevailing dominant culture     

Autologous bone marrow transplantation in acute myelogenous leukemia: in vitro treatment with myeloid cell-specific monoclonal antibodies

Second or third chemotherapy-induced remissions in acute myelogenous leukemia (AML) are limited by early relapse of the leukemia. We developed monoclonal antibodies (MoAbs) that are cytotoxic to myeloid leukemia cells to treat bone marrow from these patients ex vivo for autologous transplantation. In this pilot study, bone marrow was harvested from ten patients with AML in remission, treated with one or two complement-fixing MoAbs, PM-81 and AML-2-23, which react with myeloid differentiation antigens, incubated with rabbit complement, and cryopreserved. These MoAbs were chosen because they have broad reactivity with AML cells but not with pluripotent progenitor cells. At the time of transplant, 6 patients were in second complete remission, 1 each was in third complete or partial remission, and 2 were in early first relapse. The patients were treated with cyclophosphamide (60 mg/kg a day for 2 days) and total body irradiation (200 cGy twice a day for 3 days) and given infusions of MoAb-treated bone marrow. Full bone marrow reconstitution was observed in eight patients; two patients did not recover platelets. Seven of the ten patients are surviving and disease-free at 21.0, 15.0, 13.0, 10.0, 6.0, 3.0, and 2.0 months posttransplant. Treating bone marrow with MoAbs to myeloid differentiation antigens does not interfere with pluripotential stem cell engraftment. Longer follow-up and a controlled study are necessary to prove that the apparent efficacy of this therapeutic approach in some patients is attributable to MoAb-mediated killing of leukemia cells.     

Fanconi's anemia treated by allogeneic marrow transplantation

Eight patients with Fanconi's anemia were given cyclophosphamide alone (seven patients) or combined with procarbazine and antithymocyte globulin (one patient) followed by marrow grafts from HLA-identical siblings. All patients had engraftment. Seven developed acute and three chronic graft-versus-host disease (GVHD). Three patients died with GVHD and infectious complications (days 19, 56, and 82) and one with an intracerebral hemorrhage (day 540). Four patients are surviving 647- 3435 days after grafting, two are well, and two have chronic GVHD that is improving. These results show that Fanconi's anemia can be treated successfully by allogeneic marrow transplantation.