Autologous bone marrow mononuclear cell transplant and surgical decompression in a dog with chronic spinal cord injury.

OBJECTIVES: In dogs with deep analgesia caused by acute spinal cord injury from thoracolumbar disk herniation, autologous bone marrow mononuclear cell transplant may improve recovery. The purpose of the present study was to evaluate autologous bone marrow mononuclear cell transplant in a dog that had paraplegia and deep analgesia caused by chronic spinal cord injury. MATERIALS AND METHODS: Autologous bone marrow mononuclear cell transplant was performed in a dog having paraplegia and analgesia for 3 years that was caused by a chronic spinal cord injury secondary to Hansen type I thoracolumbar disk herniation. Functional recovery was evaluated with electrophysiologic studies and the Texas Spinal Cord Injury Scale. RESULTS: Somatosensory evoked potentials were absent before transplant but were detected after transplant. Functional improvement was noted (Texas Spinal Cord Injury Scale: before transplant, 0; after transplant, 6). No adverse events were observed. CONCLUSIONS: Autologous bone marrow mononuclear cell transplant into the subarachnoid space may be a safe and beneficial treatment for chronic spinal cord injury in dogs.

Crise familiar e transplante de medula óssea: evidências para assistência de enfermagem / Family crisis and Bone Marrow Transplantation: evidences for nursing care

Trata-se de uma pesquisa que utilizou a revisão integrativa da literatura que objetivou as possíveis intervenções de enfermagem para os familiares de clientes transplantados de medula óssea. Realizou-se a busca de artigos e teses nas bases de dados eletrônicas Lilacs e Medline (período de 01/01/1990 a 05/05/2005), utilizando-se as palavras: "bmt" e "family" e "bone marrow transplantation" e "family" respectivamente. Foram identificadas duas publicações no Lilacs, sendo que apenas uma foi pertinente ao tema proposto e 807 publicações no Medline, das quais apenas 24 abordavam o tema proposto, a amostra foi constituída por 25 publicações. Para análise dos artigos utilizou-se um instrumento para identificação das características dos artigos, níveis de evidências, delineamento da pesquisa, características da crise familiar, fatores que influenciam a habilidade das famílias para enfrentar e se adaptar a uma crise e, por fim, intervenções de enfermagem propostas. Foi utilizado o modelo de crise proposto por Hill e Hansen que classifica a crise em quatro categorias: características do evento, ameaças percebidas, avaliação dos recursos da família e experiência passada em crises. Os resultados mostraram que 96% dos artigos foram obtidos do Medline, sendo que 12 (48%) artigos foram desenvolvidos por enfermeiros e os demais por outros profissionais. Em relação ao tipo de revista, 36% dos artigos foram publicados em periódicos específicos de enfermagem, sendo que 72% provém dos EUA, 16% da Grécia, Canadá, Polônia e Brasil (distribuídos igualmente) e 12% não foi possível identificar a procedência. ...

Clofazimine enteropathy in a pediatric bone marrow transplant recipient.

Clofazimine, previously used in the treatment of leprosy, is now used for treatment of Mycobacterium avium complex infection in patients with acquired immune deficiency syndrome, dermatologic disorders, and graft-versus-host disease. An 11-year-old boy developed a severe enteropathy 2 years after initiation of clofazimine treatment for graft-versus-host disease. Clofazimine enteropathy caused by crystal deposition can be life-threatening.

Thalidomide in children undergoing bone marrow transplantation: series at a single institution and review of the literature.

Thalidomide has one of the most notorious drug histories because of its teratogenicity. Its widespread use in the 1960s led to a worldwide epidemic of phocomelia in inborns; this in turn led to its complete ban in most of the world. However, it has now been licensed for selected indications including graft-versus-host-disease (GVHD) after bone marrow transplantation, wasting associated with tuberculosis and human immunodeficiency virus infection, and leprosy. Little is known, however, about its use in children in these settings. Therefore, we report our experience and review the literature on thalidomide in children for GVHD after bone marrow transplantation. We studied 6 patients, 2 with chronic GVHD, 2 with acute GVHD, and 2 with acute GVHD progressing into chronic disease. One patient with chronic GVHD had a complete response, whereas the other had a partial response. Side effects consisted primarily of sedation and constipation, which are reported previously and well known side effects. None had neuropathy. One patient had rash, eosinophilia, and early pancreatitis that began shortly after initiation of thalidomide, persisted, and resolved only after discontinuation of thalidomide. Eosinophilia and pancreatitis are both previously unreported side effects or associated findings of thalidomide treatment. Review of the literature reveals three major studies of thalidomide in GVHD; of these two included children and adults together, and one in which age range of patients was not mentioned. In addition, four series of children receiving only thalidomide are reported. These series contained 1 to 14 patients each. Results show efficacy in at least 50% of children with chronic GVHD and little or no efficacy in children with exclusively acute GVHD. Side effects are similar to those reported in adults and consisted mostly of sedation and constipation, both of which subsided over time and resolved after discontinuing the drug. We speculate on the reasons for which thalidomide is more effective in chronic, compared with acute, GVHD in children, and make recommendations for future study.

[Thalidomide once more in the spotlight]. / Thalidomide opnieuw in de belangstelling.

Thalidomide was withdrawn from the market in the early sixties because of major teratogenic effects such as reduction defects of the limbs. Since, however, it has been found to be an effective drug in erythema nodosum leprosum. In the United States it was decided in September 1997 to admit thalidomide to the market for this indication, and in South America it has been available for this indication all the time. Thalidomide is also efficacious in other major disorders (e.g. aphtae and ulcers in aids) or its efficacy is being investigated in clinical trials (e.g. autoimmune diseases, other complications in aids). The American Food and Drug Administration has imposed conditions for the use of thalidomide. Users have to sign an informed consent and to take adequate contraceptive measures. Physicians should inform the patients and monitor side effects. Pharmacists should record and control the use.

Protection against tuberculosis by bone marrow cells expressing mycobacterial hsp65.

Although mice acquire only a slight degree of protection against tuberculosis by immunization with Mycobacterium leprae (M. leprae) hsp65 in incomplete Freund's adjuvant, protection is substantial following immunization by injection with J774 macrophage-like tumour cells that express the protein from the mycobacterial gene via a retroviral vector. We here took the same vector, used it to transfect the gene into normal murine bone marrow cells in vitro, and then used the transfected cells to reconstitute haematopoiesis in lethally irradiated mice. Bone marrow-cell clonal expansion and production of the protein in vivo resulted in specific delayed-type hypersensitivity and protection against challenge with Mycobacterium tuberculosis (M. tuberculosis) in about half of recipients. Counts of live bacteria in liver at 3 weeks were fivefold lower in delayed-type hypersensitivity (DTH)-positive than in DTH-negative mice. Other mice acquired neither DTH nor protection despite the presence of the protein in peripheral blood.

Thalidomide: rationale for renewed use in immunological disorders.

Despite its inherent teratogenic risk, thalidomide has over the years proven to be of clinical use in a small number of mainly immunological diseases (e.g. erythema nodosum leprosum, Behçet's syndrome and rheumatoid arthritis). The mode of action of thalidomide is still poorly understood. Recent research has shown a decrease in tumour necrosis factor-alpha (TNF alpha) during thalidomide treatment in several settings. Others have found altered expression of adhesion molecules. Currently, the most interesting new fields of application are the prevention and treatment of graft-versus-host disease in allogeneic bone marrow transplantation and the treatment of aphthous ulceration in HIV-positive patients. Contraceptive measures must be instituted in women receiving thalidomide, and careful monitoring for neurological adverse effects is required in all patients.

[Biological properties and therapeutic use of interleukin 2 (IL-2)]. / Wlasciwosci biologiczne i zastosowanie lecznicze interleukiny 2 (IL-2).

A cytokine produced by the subpopulation of activated helper lymphocytes T has been called interleukin-2 (IL-2). The obtaining of recombinant cytokine has facilitated the study of its biological properties and its application in the treatment of certain neoplastic and infectious diseases. IL-2 affects the target cells by means of a receptor of great affinity consisting of three independent chains: alpha, beta, gamma. The cytokine is the most important growth factor of lymphocytes T, conditioning their clonal expansion. Antigen stimulation is the condition for the expression of IL-2 does not, however, affect resting lymphocytes T. The expression of the receptor for this cytokine on NK cells is, however, continuous in character but only a very small percentage of these cells has receptors of great affinity. IL-2 plays a great role in adoptive immunotherapy consisting in intravenous administration of cells with cytotoxic properties. Cells obtained from peripheral blood and grown in vitro are called LAK cells (lymphocyte activated killer cells), while cells obtained from neoplasms and grown in similar conditions are named TIL cells (tumor infiltrated lymphocytes). LAK and TIL cells reveal a similar antineoplastic activity in vivo. At present, however, recombinant IL-2 alone is used more often, either intravenously or subcutaneously. The cytokine is effective in the treatment of patients with disseminate cancer of the kidney and melanoma, and in adjuvant therapy of acute myeloid leukemia. Attempts have been made to apply it in the treatment of AIDS and leprosy. The toxic effect of IL-2 depends on the dose and the mode of administration. In the majority of patients parainfluenza symptoms appear. Most undesirable effects are connected with multisystemic syndrome of capillary vessels hyperpermeability leading to the increased fluid retention into extravascular spaces, oedema, hypotonia and oliguria.

Resistance to mycobacteria in mice treated with fractionated total lymphoid irradiation (TLI) and in mice reconstituted with allogenic bone marrow cells following radiotherapy.

The increased clinical use of total lymphoid irradiation (TLI) as an immunosuppressive adjunct in transplantation suggested the need for determining the effects of TLI on the in vivo susceptibility of animals to infections controlled by cell-mediated immunity. TLI-treated, TLI-treated and splenectomized, and chimeric mice prepared with TLI were inoculated in the hind foot pad with Mycobacterium marinum or Mycobacterium leprae. Although M. marinum organisms multiplied in greater numbers in the TLI mice, ultimately they were destroyed as effectively in TLI mice as in the non-irradiated control mice. M. leprae multiplied at the same rate and to the same maximum in TLI mice as in controls. Mice previously challenged with M. marinum in one hind foot pad, and challenged subsequently with the same organism in the opposite hind foot pad, showed a solid immunity against this reinfection. It appears that upon recovery from the immediate effects of radiotherapy TLI-treated mice are able to mount an effective immune response to experimental infection with M. marinum and M. leprae.