The effects of terminal illness on patients and their carers.

As part of a larger study, this paper describes the development and design of a project looking at the experiences of the relatives and carers of terminally ill patients in one health authority, as a replication of a similar study undertaken in another area. Following a description of the problems associated with studies into the problems of dying people and of the method used here, the results indicate that there are quite important effects on the household and carers, which include the problem of obtaining a diagnosis of terminal illness, and the actual process of dying. The study also highlights some of the effects of the terminal illness on the patients and their carers. In particular the results indicate that it was usually a spouse or the daughter who bore the brunt of the care, but that most preferred to retain their independence of the services as long as possible. Often, carers (and the patients) were not fully appraised that a terminal stage had been reached. Some doctors seemed reluctant (or found it difficult) to admit that such a stage had been reached. For many, the experience of dying was a very slow, distressing and often painful period, with serious limitations on their lifestyle imposed by the illness. A number of these limitations could have been reduced if earlier diagnosis had been made or if community nursing or social services had been called in sooner.

Effects of transforming growth factor beta on megakaryocytic cell fusion and endomitosis.

Transforming growth factor beta (TGF-beta) is a cytokine secreted by megakaryocytes and platelets which inhibits the proliferation of megakaryocyte progenitors in vitro. We have studied the effects of TGF-beta on more mature megakaryocytes, using cell lines CMK, DAMI, and CHRF as well as isolated human marrow megakaryocytes as models. Proliferation of these megakaryocytic cell lines was inhibited by TGF-beta 1 at concentrations of 10-100 ng/ml. Although these cell lines secreted small amounts of TGF-beta (up to 100 pg/ml), it was predominantly in an inactive form. Upon induction with 12-phorbol 13-myristate acetate (PMA), they secreted greater amounts of TGF-beta (500-1250 pg/ml), most of which was still inactive in a bioassay. Addition of exogenous active TGF-beta 1 had no effect on ploidy of unstimulated megakaryocytic cell lines or on [3H]thymidine incorporation of isolated human marrow megakaryocytes. Following PMA induction, exogenous TGF-beta 1 had a significant inhibitory effect on ploidy in DAMI cells but not CMK or CHRF cells, suggesting that the phenomenon is restricted to DAMI cells. Because certain cell lines may fuse in vitro, and phorbol esters can promote this phenomenon, we investigated the possibility that fusion was contributing to the increase in ploidy in megakaryocytic cells. Unstimulated megakaryocytic cells did not show spontaneous fusion; when PMA was added to the cultures, fusion was markedly increased, particularly in DAMI cells. These results demonstrate that in vitro fusion accounts for a proportion of the apparent increase in DNA content of megakaryocytic cell lines upon induction with PMA.(ABSTRACT TRUNCATED AT 250 WORDS)

Major histocompatibility complex class II antigen expression in nerves in leprosy; an immunoelectronmicroscopical study.

A technique for immunoelectronmicroscopy has been used to investigate major histocompatibility class II expression in leprosy nerves. In normal nerves, endothelial cells and occasional endoneural cells (not Schwann cells) were constitutively class II positive. In both paucibacillary and multibacillary leprosy nerve biopsies, infiltrating leukocytes were positive but class II-positive Schwann cells were not seen. These observations indicate that Schwann cells may not be involved in presenting Mycobacterium leprae antigens to T cells in leprosy. This conflicts with evidence from in vitro studies, but may be explained by the fact that in vivo Schwann cells are surrounded by basement membranes and are closely associated with axons.

Denatured muscle grafts for nerve repair. An experimental model of nerve damage in leprosy.

About 20% of patients with leprosy develop localised granulomatous lesions in peripheral nerves. We report experiments in guinea-pigs in which freeze-thawed autogenous muscle grafts were used for the treatment of such mycobacterial granulomas. Granulomas were induced in guinea-pig tibial nerves and the animals were left for 7 to 100 days in order to assess maximal damage. The local area of nerve damage was then excised and the gap filled with denatured muscle grafts. Clinical assessment after periods up to 150 days showed good sensory and motor recovery which correlated well with the histological findings. The muscle graft technique may be of value for the treatment of chronic nerve lesions in selected cases of leprosy.

An immunoelectronmicroscopical study of the expression of major histocompatibility complex (MHC) class II antigens in guinea pig sciatic nerves following induction of intraneural mycobacterial granulomas.

A guinea pig model of nerve damage in leprosy has been used to investigate the expression of major histocompatibility complex (MHC) class II antigens in granulomatous lesions in nerves. Using an immunoelectronmicroscopical technique, infiltrating mononuclear cells and endoneural fibroblast-like cells are shown to be class II-positive in the experimental neural lesions. Schwann cells are not class II-positive under these conditions, although at the light microscope level Schwann cell-like cells appear to be positively stained. This illustrates the value of immunoelectronmicroscopy in the investigation of cell surface proteins in situ as compared with conventional light immunohistochemistry.

Nerve damage induced by mycobacterial granulomas in guinea pig sciatic nerves.

A possible model for nerve damage in leprosy has been developed in the sciatic nerve of the guinea pig. Intraneural injection of 10(7) BCG organisms into an unsensitized animal induces an epithelioid cell granuloma in 2 weeks similar to that found in tuberculoid leprosy patients. In contrast, intraneural injection of 10(9) cobalt-irradiated Mycobacterium leprae organisms induces a macrophage granuloma in 5 weeks, similar to that found in lepromatous leprosy patients. Histological, immunohistochemical, electron microscopical and electrophysiological studies have demonstrated that the lesions induced in the experimental animals show many of the features documented in studies of nerve damage in leprosy patients.