Severe aplastic anaemia - complete response to antilymphocyte globulin and cyclosporin

Severe aplastic anaemia is uniformly fatal unless treated with immunosuppressive therapy or bone marrow transplantation. The latter is curative in 65 percent of patients and is the treatment of choice in children and young adults. Antilymphocyte globulin (ALG) and cyclosporin may be used successfully in the absence of an HLA matched sibling donor. We report the case of a twelve year old boy with severe aplastic anaemia who received immunosuppressive with ALG and cyclosporin and is alive and well three years an six months post treatment.(AU)

Treatment of uveitis: past, future and present

This presentation will review the different treatments of uveitis. The use of corticosteroids, immunosuppressive medications and the upcoming newer modalities for treatment will be reviewed. The discoveries of the different types of immune reactions, the T helper subset functions (Th1 and Th2), the understanding of ACAID (anterior chamber associated immune deviation), the identification of the intraocular immune cell types, and the role of cytokines in the pathogenesis of inflammation, result in a better understanding of autoimmune diseases such as non-infectious uveitis. This improved understanding has allowed the development of new experimental uveitis treatments that may become the standard of care. For example, processing of specific antigens in the gut was demonstrated to induce tolerance by the release of suppressor cytokines like tumour growth factor-B, interleukin (IL)-4 and IL10. Therapeutic approaches like immune modulation with interferon, the use of soluble tumour necrosis factor receptor, anti-Tac, monoclonal antibodies against cell adhesion molecules, and antisense therapies are becoming useful in the treatment of severe uveitis. Intervitreal sustained release devices for the delivery of drugs like corticosteroids, cyclosporins and other immunosuppressive medications will soon become commercially availble. Gene somatic therapy appears another promising therapeutic approach. The use of viral and non viral vectors, and the host immune response against modifies adenoviruses, are solved.(AU)

Clostridium difficile infection in immunocompromised patients a three health-care facilities in Jamaica

A cross-sectional study was conducted (April 96 to July 97) to investigate the prevalence of Clostridium difficile infection in immunocompromised patients at 3 health care institutions. Standard bacteriological procedure, tissue culture and enzyme immunoassay were used to investigate faecal specimens from immunocompromised inpatients (N = 113) including 21 patients treated with immunosuppressive drugs, 39 patients had received radiotherapy and 53 patients who were not treated with immunosuppressive drugs. The overall prevalence of C. difficile infections was 14.2 percent (16/113). All the C. difficile isolates were identified as toxigenic strains. The prevalence of C. difficile infection in patients who had received immunosuppressive drugs (23.8 percent, 5/21) did not differ significantly from those who had not (20.7 percent, 11/53), but was significantly lower in patients who received radiotherapy (p<0.01). The occurrence of C. difficile was not significantly associated with antibiotics in patients who were on immunosuppressive drugs (2/13, 15.4 percent vs 3/8, 37.5 percent) or patients who were not (7/32, 21.8 percent vs 4/21, 19.0 percent). Eighty percent (4/5) of C. difficile isolates from patients on immunosuppressive drugs were from those whose regimens include cytotoxic drugs. Similarly, anti-tubercolosis drugs were the antibiotics most frequently associated with C. difficile infections (4/8, 50 percent). C. difficile infections are likely to occur in patients treated with cytotoxic drugs and certain antibiotics.(AU)

T cells and the skin

In addition to its role as a mechanical barrier, the skin plays an important role in temperature regulation, vitamin D synthesis and absorption of ultraviolet radiation. The importance of the skin as an immunological organ was not fully appreciated until the advent of immunosuppressive agents such as cyclosporin and tacrolimus, which have a predominant action against T lymphocytes and have been found to be effective in the management of common skin diseases such as atopic eczema and psoriasis. T lymphocytes are of fundamental importance to the immune system. Access from the vascular compartment into the skin is facilitated by adhesion molecules located on the endothelial of dermal blood vessels. Selective upregulation of adhesion molecules occurs in various inflammatory skin diseases and specific skin homing T lymphocytes preferentially enter the skin rather than other organs. T cell have recently been classified into Th1 and Th2 cells based on their cytokine profile. Th1 cells produce interleukin 2 (IL-2) and interferon gamma, important in macrophage activation and cytotoxity, and Th2 cells produce IL-4 and IL-5, important in B cell maturation and humoral immunity. Contact dermatitis and psoriasis are characterised by Th1 cells and atopic dermatitis by Th2 cells. The Th1/Th2 profile is also important in infectious diseases such as leprosy in which polarisation towards tuberculoid or lepromatous disease depends on a predominance of Th1 or Th2 cells, respectively. Future management of diseases affecting the skin is likely to depend on a greater understanding of the infiltrating T cell subsets and appropriate modulation of the Th1 and Th2 profile.(AU)

Systemic lupus erythematosus Barbados: the renal complications - abstract

Over the past 10 years, 75 patients with systemic lupus erythematosus (SLE) have been followed, and this paper reports the clinical findings with emphasis on renal complications and mortality. The diagnosis of SLE was based on the presence of 4 or more of the 1982 "revised criteria" of the American Rheumatism Association. The female: male ratio was 14:1 and the mean age of onset was 27.4 years (range 6-54 years). Six patients (5 girls and 1 boy) presented at < 12 years of age. Patients presented most frequently with polyarthalgia/ polyarthritis (59 per cent), skin rashes (57 per cent), fever (55 per cent), anorexia (39 per cent) and weight loss (33 per cent). Eight patients (11 per cent) presented with acute renal failure and 4 of these had associated nephrotic syndrome (NS). Of 8 patients presenting with NS, 4 had normal renal function. During follow-up, 69 per cent of patients developed significant renal involvement (sustained proteinuria >0.5 g/24 hr. and/or cellular urinary casts) and 14 patients had nephrotic range proteinuria (>3 g/24 hr.). All patients received prednisone at some time for vital organ involvement. Some degree of remission of proteinuria usually occurred over the course of several months. Twelve patients (16 per cent) died during the study, 5 from infection with immunosuppression being the major precipitating factor. Infection is of critical importance in this disease, and renal disease can be modified by the aggressive use of immunosuppressive agents which, however, are potentially hazardous (AU)

The psychophysiological mediators of stress as it relates to oncology in humans and animals

This study was designed to investigate the effect of stress on cancer development and treatment, and also to determine whether there is any cancer association personality profile. Human studies were supplemented by controlled animal studies. Twenty-nine male and female cancer subjects were studied along with twenty-nine controls. The animal study comprised ninety female Sprague-Dawley rats, which were divided into nine groups of ten. One group was treated with noise stress alone, while another group received no treatment at all. Three groups received the carcinogen 7,12-Dimethylbenz(a)anthracene together with either noise stress, cortisone acetate or 6-mercaptopurine and the rate of tumour growth in these animals was compared to a group that received only the carcinogen, and after tumour growth these animals were subjected to chemotherapy. In addition to the chemotherapy, one of these groups received noise stress and another cortisone acetate. The stress level of the humans and animals was determined by physiological and psychological tests where applicable. The results of the human study revealed that the level of stress among the cancer subjects was higher than among the controls. Even though in some cases cancer development occured after an event that may be considered stressful, it was not easy to conclude whether stress occurred before or after the cancer development. The controlled animal studies revealed, though, that stress alone could not induce tumour development in the observation period of 280 days. Stress, however, influenced tumour growth when the rats were treated with the carcinogen. The findings of this study also suggested that immunosuppression might play a vital role in cancer development. A cancer associated personality profile, depicting among other things a schizophrenic character, was also detected among the human cancer subjects. The treatment of the cancer subjects who had high stress levels was less successful, and this was substantiated by the results of the animal study, which showed that stressed decreased the life span of the animals receiving chemotherapy and stress. The findings of this study suggest that even though stress may not initiate tumour growth, stress influences the growth of potential tumour cells, and may interfere with the response to treatment (AU)

Lung transplant

What is the future of lung transplantation in so far as its clinical application is concerned ? The actual surgery is not difficult but, as with all transplantations, the major problems occur post operatively. Our understanding of the immunologic response is still too superficial for us to be too optimistic about overcoming the rejection problem. In none of the human transplants discussed was rejection reported at autopsy. This is not really as encouraging a sign as it might appear, since human transplant centres report rejection only after eighteen days post operatively and none of the patients discussed above lived that long. But, many experimental units and research teams are now hard at work on the rejection problem, and at moment there could be a breakthrough, opening the way for lung transplantation as a form of therapy in chronic pulmonary disease. (Summary)