Diminished chemokine and cytokine-induced adhesion of CD4+ T cells to extracellular matrix ligands in patients with end-stage renal failure.

BACKGROUND: Cell-mediated immunity is impaired in uremia. Cell-matrix interactions of immune cells such as CD4+ T lymphocytes with extracellular matrix are an important requirement for an intact immune response. The adherence of CD4+ T cells of healthy subjects (normal T cells) to ECM components is inhibited in the presence of uremic serum. Such decreased adhesive capacity is also found in T cells of dialysis patients. Various chemokines and cytokines affect the attachment of CD4+ T cells to ECM. OBJECTIVE: To evaluate chemokine (MIP-1 beta and RANTES) and tumor necrosis factor-alpha-induced adhesion of CD4+ T cells to ECM in a uremic milieu. METHODS: We examined adhesion of normal CD4+ T cells (resting and activated) to intact ECM in response to soluble or bound chemokines (MIP-1 beta and RANTES) and to TNF-alpha following incubation in uremic versus normal serum. Thereafter, we evaluated the adhesion of resting CD4+ T cells from dialysis patients in a similar fashion and compared it to that obtained from a healthy control group. RESULTS: Addition of uremic serum diminished soluble and anchored chemokine-induced attachment of normal resting and activated CD4+ T cells to ECM compared to a normal milieu (a peak response of 10-11% vs. 24-29% for soluble chemokines, P < 0.001; 12-13% vs. 37-39% for bound chemokines on resting cells, P < 0.01; and 18-20% vs. 45-47% for bound chemokines on activated cells, P < 0.02). The same pattern of response was noted following stimulation with immobilized TNF-alpha (7 vs. 12% for resting cells, P < 0.05; 17 vs. 51% for activated cells, P < 0.01). Adherence of dialysis patients' cells to ECM following stimulation with both bound chemokines was reduced compared to control T cells (15-17% vs. 25-32%, P < 0.0000). In contrast, adherence following stimulation by TNF-alpha was of equal magnitude. CONCLUSIONS: Abnormal adhesive capacity of T lymphocytes to ECM in uremia may, in part, be related to a diminished response to MIP-1 beta, RANTES and TNF-alpha. However, whereas reduced adhesion to chemokines was present in both normal CD4+ T cells in a uremic environment and in dialysis patients' T cells, TNF-alpha-induced adhesion was found to be inhibited only in normal cells in a uremic milieu.

The efficiency and effectiveness of geriatric day hospitals.

One hundred patients who were referred consecutively to two geriatric day hospitals were followed for 3 months, to determine the efficiency and effectiveness of day hospital management. Transport was highly efficient; only one in every 40 attendances failed because of transport. Selection of patients may have been less efficient, in that only half completed planned treatment. In most cases this was because of progression of the illness. Time at the day hospital was on the whole efficiently used, in that three-quarters of the time was devoted to programmed activities. The effectiveness of the day hospital was limited. In only about one-third of referred patients were the objectives set by the doctor attained. Likewise only one-third of patients felt that they had improved, and one-third of carers experienced relief of strain.

Colonoscopy in patients aged 80 years or older and its contribution to the evaluation of rectal bleeding.

Colonoscopies performed in patients aged 80 years or older at the Sheba Medical Center were analysed according to the primary indication for the procedure: 101 colonoscopies were performed because of rectal bleeding of at least 2 months duration, and 335 for all other indications. Carcinoma of the large bowel was found in 29 (28.7%) bleeders, with the rectum being the most frequently involved site (12 patients). Among the non-bleeders, the prevalence of cancer was significantly lower (33 cases, 9.8%; P less than 0.001), and rectal carcinoma was less common (five patients, P = 0.04), but proximal tumours were more frequent. Of patients with cancer who had operations, the majority (72%) had a tumour confined to the bowel wall (Dukes A or B). The rate of adenomas was similar for both groups (34% vs 29%). The non-bleeders complained more frequently of abdominal pain or a change in bowel habits as compared to the bleeders, but both groups had similar rates for anaemia and weight loss. In all, 47% of these octogenarians with cancer, and 26% with adenomas were referred for colonoscopy because of rectal bleeding. This procedure was found to be safe in old age, as we recorded only four (0.9%) non-fatal complications among our series, a similar figure to the overall incidence of complications at our Institute. In conclusion, our data indicate that rectal bleeding in octogenarians warrants a complete colonic investigation, preferably by total colonoscopy.

Intensive home-care surveillance prevents hospitalization and improves morbidity rates among elderly patients with severe congestive heart failure.

The purpose of this study was to examine the impact of intensive home-care surveillance on morbidity rates of elderly patients with severe congestive heart failure. Forty-two patients aged 78 +/- 8 years who had severe congestive heart failure (New York Heart Association functional classes III through IV, mean ejection fraction 27% +/- 6%), were examined at least once a week at home by internists from the district hospital and by a trained paramedical team. The year before entry to the home-care program was compared to the first year of home surveillance. The mean total hospitalization (hosp) rate was reduced from 3.2 +/- 1.5 hosp/yr to 1.2 +/- 1.6 hosp/yr and duration from 26 +/- 14 days/yr to 6 +/- 7 days/yr (p < 0.001 for both). Cardiovascular admissions decreased from 2.9 +/- 1.5 hosp/yr to 0.8 +/- 1.1 hosp/yr and duration from 23 +/- 13 days/yr to 4 +/- 4 days/yr (p < 0.001). The vital status (ability to perform daily activities, expressed in a 1 to 4 scale) was improved from 1.4 +/- 0.9 to 2.3 +/- 0.7 (p < 0.001). In conclusion, an intensive home-care program was associated with a marked decrease in the need for hospitalization and improved the functional status of elderly patients with severe congestive heart failure. Such a service might also have a cost-effective advantage and a major impact on health expenditure.