Showing papers by "Tilman B. Drüeke published in 1986"

Presence of preactivated T cells in hemodialyzed patients: their possible role in altered immunity

Abstract: Interleukin 2 (IL-2) and B-cell growth factors I and II (BCGF I and BCGF II) are lymphokines produced by T cells that play a major role in T- and B-cell cooperation. Peripheral blood lymphocytes from 12 uremic patients undergoing intermittent hemodialysis were tested for their capacity to produce IL-2 and BCGFs and to respond to these soluble mediators. IL-2 and BCGF activities were determined by means of two biological assays (proliferation of IL-2-dependent cytotoxic T-cell line CTLL-2 and of anti-human IgM (mu chain)-stimulated normal B cells, respectively) in the supernatants of phytohemagglutinin A-stimulated T-cell cultures. IL-2 activity was significantly decreased in patients as compared to normal controls (mean +/- SEM, 0.28 +/- 0.09 unit per ml) in hemodialyzed patients versus 1.02 +/- 0.16 units per ml in normal controls). This profound abnormality contrasted with the normal activity of the BCGFs that was invariably observed in the same supernatants. A similar dissociation was detected when analyzing the sensitivity of uremic B and T cells to exogenous purified lymphokines. Anti-IgM (mu chain)-stimulated uremic B cells exhibited a normal response to recombinant IL-2 and to chromatography-purified BCGF I and BCGF II. Resting B cells did not show any increased reactivity to these lymphokines. In contrast, whereas in normal controls recombinant IL-2 exclusively induced the proliferation of T cells that had been previously activated by a mitogen, resting T cells from uremic patients were highly responsive to exogenous IL-2. This abnormal response was paralleled by significantly increased proportions of peripheral T cells recognized by the anti-Tac monoclonal antibody that specifically binds to the IL-2 receptor. These data clearly show the existence in hemodialyzed patients of abnormally high proportions of T cells presenting phenotypic and functional signs of preactivation. This increased T-cell IL-2 receptor expression may offer an explanation to the deficient IL-2 activity observed in patients' supernatants (by inducing increased absorption of the lymphokine). The potential relevance of these preactivated T cells to the depressed cell-mediated immunity observed in hemodialyzed patients is outlined.

Abnormal vitamin D metabolism, intestinal calcium transport, and bone calcium status in the spontaneously hypertensive rat compared with its genetic control.

Abstract: Abnormalities of intestinal calcium absorption and the vitamin D axis in the spontaneously hypertensive rat (SHR) are controversial. The present report documents a reduction in circulating 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in the 12-14-wk-old male SHR with evidence of its functional significance. Both plasma 1,25(OH)2D3 and mucosa-to-serosa duodenal calcium flux (Jm-s), measured by the Ussing chamber, were significantly lower (approximately 60% of value in Wistar-Kyoto rats [WKY]) in SHR on both normal (1%) and low (0.1%) calcium diets than in corresponding control WKY. Low dietary calcium increased both 1,25(OH)2D3 and Jm-s by approximately 80% in SHR and WKY, with levels of both parameters rising in the SHR to levels found in the WKY under baseline conditions. The latter fact suggests the improbability of intestinal resistance to the action of 1,25(OH)2D3 in the SHR. Plasma 25-hydroxyvitamin D3 (25(OH)D3) was not significantly different between the strains. Intraperitoneal 1,25(OH)2D3 increased Jm-s in 12-14-wk-old SHR to levels observed in equivalent WKY. In 20-24-wk-old SHR, calcium deprivation was associated with significantly reduced Jm-s compared with equivalent WKY. Bone density and bone calcium content in 20-30-wk-old SHR were significantly reduced. In summary, we provide evidence that the SHR was unable to sustain appropriate circulating levels of 1,25(OH)2D3, an impairment which resulted in reduced duodenal calcium absorption.

Reoperation for secondary hyperparathyroidism in hemodialysis patients.

Abstract: Parathyroidectomy (PTx) in uremic patients is only performed in case of severe hyperparathyroidism. In some instances, PTx may be either insufficient or, on the contrary, lead to intolerable hypoparathyroidism. Recurrence is always possible because of persistent renal failure. Reoperations may, therefore, be necessary. We report here on 25 reoperations done in 21 patients who are part of a series of 248 patients operated on for secondary hyperparathyroidism. Nine patients had initial parathyroidectomy (PTx) at another institution. Six patients underwent reoperation after initial surgery, which was incomplete leaving 1–3 glands in place. In 7 patients reoperation was done after initially successful, subtotal PTx. In these we found hypertrophic remnants and a supernumerary gland in 1. Seven patients had total PTx, with immediate parathyroid reimplantation in 5 instances. Reoperation on the graft was judged necessary in 5 patients, but hypertrophy of grafted fragments was observed in only 3 of them. In 3 patients secondary autografting was performed with cryopreserved tissue. The analysis of our cases shows the difficulties of localizing unique or multiple sites of parathyroid hormone overproduction despite the availability of many diagnostic approaches. From a practical point of view, we try at present to resect all parathyroid tissue in case of reoperation for recurrent hyperparathyroidism. If hypoparathyroidism results by this procedure or in case of hypoparathyroidism obtained unexpectedly, we then proceed to delayed parathyroid autotransplantation with cryopreserved tissue.

Correction by insulin of disturbed TG-rich LP metabolism in rats with chronic renal failure.

Abstract: To define the role of insulin in lipid disturbances of chronic renal failure, chronically uremic rats (U+) were supplemented by continuous insulin infusion over a 35-day experimental period and compared with control ad libitum-fed rats (C) and uremic rats without insulin (U). Uremic rats were characterized by hypoinsulinemia, an increase in both circulating very low-density lipoprotein (VLDL) and their cholesterol concentration, a normal hepatic triglyceride secretion rate (TGSR) determined with Triton WR 1339, and a low adipose tissue lipoprotein lipase (LPL) activity. Chronic insulin infusion at low rate (0.5 IU/24 h) to U+ rats normalized serum insulin (from 17.0 +/- 0.6 mU/l in U rats to 23.4 +/- 1.7 mU/l in U+ rats), serum VLDL triglycerides (from 804 +/- 65 to 410 +/- 36 mg/l), and serum VLDL cholesterol (from 43 +/- 8 to 16 +/- 3 mg/l). Hepatic TGSR decreased significantly after insulin treatment (from 0.58 +/- 0.03 to 0.44 +/- 0.03 mumol/min). Moreover, adipose tissue LPL was restored to normal by insulin supplementation (from 460 +/- 60 to 860 +/- 150 mU per total epididymal fat in U and U+ rats, respectively). Correction of the disturbed VLDL metabolism was associated with multiple actions of insulin including 1) a decrease of peripheral lipolysis, 2) a decrease of hepatic TGSR, and 3) an increase of adipose tissue LPL activity. Because cholesterol-rich VLDL are potentially atherogenic, their normalization with insulin treatment in this animal model suggests a viable area of investigation for the prevention of accelerated atherogenesis in chronic renal failure.

Theoretical mechanisms of dietary calcium's antihypertensive action.

Abstract: Theoretical mechanisms underlying dietary calcium’s antihypertensive action are reviewed. Based upon known defects in the regulation of membrane Ca2+ transport and regulation of intracellular free Ca2+ concentration, we conclude that maneuvers that favorably modify calcium homeostasis such as dietary calcium supplementation or 1,25 (OH)2 vitamin D3 administration appear to favorably modify these defects. Consequent improvements in vascular smooth muscle function may mediate the reductions in blood pressure that follows chronic dietary calcium supplementation in experimental hypertension and in the clinical setting.

The Role of Parathyroid Function and Parathyroidectomy in the Outcome of Aluminium-Related Dialysis Encephalopathy

Abstract: Aluminium (Al) intoxication in patients with chronic renal failure may lead to osteomalacia, microcytic anaemia, and encephalopathy. It has been suggested that the expression of Al toxicity may be related to the function of the parathyroid glands. The purpose of this study was to determine whether the functional state of the parathyroids influenced the evolution of Al-related encephalopathy in Al-intoxicated haemodialysed patients. The patients were subdivided into two groups according to outcome: group I patients (n = 6) had died with the clinical feature of severe cerebral dysfunction; group II patients (n = 15) had a favourable outcome with partial or complete recovery. The degree of hyperparathyroidism, as evaluated by plasma biochemistry and bone histology, was comparable in both groups. Three patients of group I and five of group II underwent parathyroidectomy. Before the clinical onset of encephalopathy the duration of Al overload in group I was not different from group II, but after its onset patients of group I were intoxicated significantly longer (8 months +/- 6.6) than those of group II (1.5 months +/- 1.9). This study shows that, in uraemic patients with Al-related encephalopathy, parathyroid function and parathyroidectomy do not play an essential role in clinical outcome. The duration of Al intoxication following the first signs of encephalopathy appears to be the major prognostic element.

Impaired intestinal calcium transport in the spontaneously hypertensive rat.

Abstract: The spontaneously hypertensive rat (SHR) exhibits a variety of abnormalities in its handling of calcium (1–3) and phosphorus (4,5) and calcium supplementation has been shown to reduce its arterial blood pressure (3,6). The relationship between disturbed calcium and phosphorus metabolism and hypertension, however, remains unclear. Several investi­gators have studied intestinal calcium transport in the SHR and have reported increased (7,8), unchanged (9) or decreased (10) absorption compared with its genetic control, the Wistar­Kyoto rat (WKY). In these studies, Ca2+ absorption has been determined by means of intestinal perfusion (10) or in situ uptake (8) in vivo,everted gut sacs in vitro (7,9,10), or by balance studies (8). The variety of experimental systems employed may in part explain the diversity in these findings. We have recently addressed this issue utilising the modified Ussing apparatus (11) which permits continuous monitoring of tissue viability and the study of active intestinal calcium transport under electrically controlled conditions.