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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The MCR and half-disappearance time of exogenously administered somatostatin have been measured during and after cessation of a constant infusion. Studies were performed on normal volunteers and patients with chronic liver disease and failure. Immunoreactive somatostatin was measured by a sensitive and specific RIA using an antiserum directed against the core of the molecule. Normal subjects had a mean MCR of 1949 +/- 250 ml/min (28.4 +/- 4.2 ml/min . kg BW) (mean +/- SEM), similar to values found in five patients with chronic liver disease. However, patients with chronic renal failure showed a highly significant (P less than 0.001) lowering of the MCR (501 +/- 32.7 ml/min or 7.8 +/- 0.6 ml/min . kg). The rate of disappearance of somatostatin after infusion was linear for 7-10 min, after which a much slower component was observed. In normal subjects, the t 1/2 of the first component varied from 1.1-3.0 min, in patients with liver disease it varied from 1.2-4.8 min, and in patients with chronic renal failure it varied from 2.6-4.9 min. Exogenously administered somatostatin is rapidly cleared in normal subjects and patients with chronic liver disease, but the MCR in end stage chronic renal failure is markedly lowered. The kidney may have a role in the metabolic clearance of exogenously administered somatostatin, or uremia may impair catabolism nonspecifically.
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PMID:Metabolic clearance and plasma half-disappearance time of exogenous somatostatin in man. 42 6

Electrochemical disturbances of skeletal muscle cells in untreated uremia are characterized by an increase in the intracellular sodium and chloride content, a decrease in intracellular potassium, and a low resting membrane potential. In this study, we have reexamined the foregoing and, in addition, have examined the effects of hemodialysis. Three groups of patients were studied. In the first group of 22 uncomplicated uremic patients, whose creatinine clearance (Ccr) ranged from 2 to 12 cm(3)/min per 1.73 m(2), resting transmembrane potential difference (Em) of skeletal muscle cells was measured. In each of the nine patients whose Ccr ranged between 6.3 and 12 cm(3)/min, the Em was normal (i.e., -90.8+/-0.9 mV, mean+/-SEM). However, as Ccr dropped below 6.3 cm/min, the Em became progressively reduced and assumed a linear relationship with the Ccr. In the second study, nine individuals with end-stage renal disease, whose mean Ccr was 4.3 cm(3)/min, underwent measurement of Em and intracellular electrolyte concentration before and after 7 wk of hemodialysis. Before dialysis, the Em was -78.5+/-2.1 mV, intracellular sodium and chloride were elevated, and the intracellular potassium was reduced. After 7 wk of hemodialysis the Em rose to -87.8+/-1.3 mV, and the intracellular sodium, chloride, and potassium became normal. In the third study, seven patients who were stable on 6-h thrice-weekly dialysis were studied before and after reduction of dialysis to 6 h twice weekly. In those individuals whose Em remained normal after 6 wk, dialysis time was reduced further. On thrice-weekly dialysis the Em was -91.2+/-1.0 mV. With reduced dialysis, the Em fell to -80.1+/-0.8 mV (P < 0.001). In each case, the Em became abnormal before significant signs or symptoms of uremia were noted. These findings demonstrate that end-stage renal disease is associated with serious electrochemical changes in the muscle cell which are reversed by hemodialysis and recur when dialysis time is reduced. Thus, serial observations of muscle Em may be a potentially powerful tool to assess adequacy of dialysis therapy.
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PMID:Resting skeletal muscle membrane potential as an index of uremic toxicity. A proposed new method to assess adequacy of hemodialysis. 42 69

Acute renal failure induced in Charles River rats by right nephrectomy and left renal artery clamping for 70 min, constantly produced high blood urea and serum creatinine levels 24 h following the experimental procedure. The intravascular administration of propranolol in different doses persistently alleviated the severity of uremia seen on the following day. The optimum dose in this experimental set-up was 1 mg/kg/h. The mean blood urea level was 237 +/- 15.5 (SEM) mg% in the saline-treated controls and 116 +/- 16 mg% in the group treated with propranolol 1 mg/kg/h. P113 alone and prostaglandin A1 alone were not effective in alleviating the ARF. The combination of P113 and propranolol produced the same amount of alleviation in uremia as propranolol alone. The PRA was low in the propranolol-treated rats and high in the group which received both P113 and propranolol, even though alleivation of ARF was produced in both of these groups. The mechanism by which the beta-adrenergic blockade produced by propranolol alleviates the anoxic type of acute renal failure is unknown. However, it does not seem to act through the suppression of renin release from the kidney.
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PMID:Alleviation of anoxic experimental acute renal failure in rats by beta-adrenergic blockade. 89 66

Bleeding times, von Willebrand activities, and platelet retentions were examined before and following d-DAVP in 13 uremic patients. Shortening of the bleeding time from 16.6 +/- 2.2 (SEM) to 6.8 +/- 0.7 min was seen in six patients. However, bleeding times remained greater than or equal to 20 min in the remaining seven individuals. The only baseline parameter that correlated with response to d-DAVP was the amount of blood loss (mg/min) during the bleeding time test. Responders had normal blood loss values averaging 6.2 +/- 1.5 mg/min. By contrast, these values were elevated in 6/7 of the non-responders and averaged 28.4 +/- 5.9 mg/min (P = 0.01). Von Willebrand activities increased following d-DAVP in the responders but not in the non-responders. Platelet retention was uniformly low in all patients and improved from 21.0 +/- 7.0% to 75.0 +/- 7.9% (P = less than 0.001) following d-DAVP in responders but not non-responders. To further define the retention abnormality in uremia, the two-stage platelet retention assay was performed prior to d-DAVP. Most of the patients (9/12) had both first- and second-phase abnormalities. Therefore, the retention defect in uremia appears to be more complex than that seen in von Willebrand's disease (2nd phase abnormality only). Nevertheless, d-DAVP seems to improve platelet rheology in uremic individuals whose von Willebrand activities increase with d-DAVP.
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PMID:Desmopressin (d-DAVP) effects on platelet rheology and von Willebrand factor activities in uremia. 155 Jan 12

To examine whether growth hormone (GH) secretion is adversely affected by chronic renal insufficiency (CRI), the GH secretory response of dispersed anterior pituitary cells perifused with GH-releasing hormone (GHRH) was investigated in 5/6 nephrectomized (CRI, N = 18) and sham-operated (N = 18) rats. Two weeks after nephrectomy, during a period of stable uremia, CRI rats had significantly higher serum concentrations (mean +/- SEM) of urea nitrogen and creatinine than sham rats, 16.8 +/- 1.4 mmol/liter (47 +/- 4 mg/dl) and 79.6 +/- 0.0 mumol/liter (0.9 +/- 0.0 mg/dl) versus 6.1 +/- 0.4 mmol/liter (17 +/- 1 mg/dl) and 35.4 +/- 0.0 mumol/liter (0.4 +/- 0.0 mg/dl), respectively (P less than 0.0001). Incremental gains in body weight and nose to tail-tip length of CRI rats over two weeks were also significantly depressed, 53.3 +/- 5.38 g (CRI) versus 87.0 +/- 3.78 g (sham; P less than 0.0001) and 3.2 +/- 0.2 cm (CRI) versus 3.6 +/- 0.1 cm (sham; P less than 0.05). The cumulative food intake as well as food efficiency (g food consumed/g weight gain) were also adversely influenced by the uremic state: food intake 304 +/- 1 g (CRI) versus 397 +/- 6 g (sham; P less than 0.0001) and food efficiency 0.173 +/- 0.013 g/g of weight gain (CRI) versus 0.219 +/- 0.008 g/g of weight gain (sham). No significant difference in GH secretory rate (ng/min/10(7) cells) was found between the uremic and sham animals under basal conditions, 65.2 +/- 2.1 (CRI) and 67.9 +/- 2.2 (sham) or in response to GH-releasing hormone, 282.8 +/- 42.4 (CRI) versus 306.2 +/- 42.6 (sham).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone secretion from pituitary cells in chronic renal insufficiency. 155 8

Acute, usually reversible, renal failure has been observed in patients with normal or minimally altered glomeruli on renal biopsy. This review aims to examine the clinical features of acute renal failure in these patients and to evaluate factors that may contribute to the reduction in glomerular filtration rate (GFR). In an analysis of 79 cases affecting 75 patients reported in the English literature since 1966, with acute renal failure associated with minimal change disease or mild histopathological changes in glomeruli, the average age was 58 +/- 2 years (mean +/- 5 SEM), urine protein excretion 11.6 +/- 0.6 g/d, and serum albumin level 19 +/- 1 g/L (1.9 +/- 0.1 g/dL). Acute renal failure was documented an average of 29 +/- 5 days after onset of nephrotic syndrome, and persisted for 7 weeks in 62 episodes in the 58 patients in whom recovery of renal function occurred. Fourteen patients died of uremia or required chronic dialysis, and 3 were lost to follow-up. Although plasma volume depletion was sometimes cited as the cause of renal failure, objective signs of hypovolemia were not documented and most patients did not improve after treatment designed to correct volume deficits. In contrast, histopathological changes consistent with acute tubular necrosis (ATN) were observed in at least 60% of cases. Since the pathogenesis of acute renal failure in minimal change nephrotic syndrome is unknown, we evaluated hemodynamic determinants of GFR in patients with minimal change disease with normal or near-normal renal function, and in relevant animal models, to obtain insights into the effect of nephrotic syndrome on GFR. Although acute renal failure is uncommon, GFR is reduced concurrently with nephrotic syndrome in approximately 30% of children and adults. Absolute and effective blood volume and renal plasma flow are relatively well preserved. However, clinical and experimental observations suggest that the glomerular ultrafiltration coefficient may be reduced by as much as 50%. These findings, together with renal biopsy changes in cases with acute renal failure, suggest that severe reductions in GFR in some patients with minimal change nephrotic syndrome may result from an interaction between acute ischemic tissue injury and preexisting intrinsic renal abnormalities.
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PMID:Reversible renal failure in the nephrotic syndrome. 155 65

To investigate the effects of growth hormone (GH) on the reversal of growth failure in uremia, recombinant human GH (rhGH) was administered to rats with chronic renal failure (CRF). The dosage of rhGH was 3 IU/day (i.p.) for 13 days after the induction of CRF by 5/6 nephrectomy. Animals were classified into four groups: untreated nephrectomized rats (NX, n = 40), GH-treated nephrectomized rats (NX+GH, n = 18), sham-operated rats fed ad libitum (SHAMAL, n = 27), and sham-operated rats pair-fed with 10 NX rats (SHAMPF, n = 10). NX and NX+GH rats developed a similar and moderate degree of CRF, serum urea nitrogen being (mean +/- SEM) 49 +/- 3 and 54 +/- 4 mg/dl, respectively, compared with 16 +/- 4 and 19 +/- 0 mg/dl in SHAMAL and SHAMPF groups. Weight (56.0 +/- 3.3 g) and length (3.5 +/- 0.1 cm) gains of NX rats were lower than those of SHAMAL rats (94.2 +/- 4.0 g, P less than or equal to 0.0001 and 4.1 +/- 0.2 cm, P less than or equal to 0.01). Growth of the SHAMPF group and the matched NX rats was not significantly different. Weight (56.2 +/- 5.0 g) and length (3.4 +/- 0.2 cm) gains of NX+GH and NX rats were similar, the beneficial effect of GH therapy on growth being observed in only those animals with more severe degrees of uremia. This growth-promoting action resulted from greater food efficiency and not from stimulated food intake. The hypercholesterolemia seen in NX rats, 81 +/- 2 mg/dl versus 55 +/- 3 mg/dl in SHAMAL (P less than or equal to 0.0001), was not increased in the NX+GH group, 87 +/- 3 mg/dl. There was a positive and significant correlation between serum cholesterol and serum urea nitrogen values in NX and NX+GH animals. This study suggests that growth impairment of mild CRF is mainly due to malnutrition and is refractory to GH administration. GH therapy improves the growth rate of animals with advanced CRF without aggravating their lipid abnormalities.
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PMID:The effect of growth hormone on the growth failure of chronic renal failure. 161 36

A role for histamine in the pathogenesis of uremic pruritus was investigated in maintenance hemodialysis patients. Venous plasma histamine levels, as determined by radioenzymatic assay, were significantly higher (p less than 0.05) in hemodialysis patients with pruritus (368 +/- 103 pg/ml [mean +/- SEM], n = 6) than in those without pruritus (146 +/- 22 pg/ml, n = 5) and in normal controls (142 +/- 16, n = 5). Arteriovenous fistula histamine levels (202 +/- 52 pg/ml, n = 6) were significantly lower (p less than 0.05) than simultaneously drawn venous samples. Markedly elevated histamine-degrading enzyme (histaminase) activities were found in both hemodialysis patients with (2.95 +/- 0.18 pg histamine degraded/minute) and without (2.44 +/- 0.28) pruritus, but was undetectable in normal controls. Histaminase activities did not significantly differ in simultaneously drawn venous and fistula samples. With hemodialysis, histaminase activities fell significantly (p less than 0.01), whereas plasma histamine did not change. We further examined the effects of ketotifen, a putative mast cell stabilizer, on severe uremic pruritus. Five of five patients had significant (p less than 0.01) reductions in pruritus, as judged on a six-point pruritus index, after 8 weeks of drug (x = 2.3), as compared to conventional therapy (x = 5.9). Despite these improvements, no significant differences were noted in pre- versus post-drug plasma histamine levels, histaminase activities, or the histamine content per gram of skin biopsy specimen. These data support prior hypotheses that mast cell activation contributes to the pruritus of uremia.
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PMID:Elevated plasma histamine in chronic uremia. Effects of ketotifen on pruritus. 181 35

Bleeding complications in uraemia are not uncommon. The pathogenesis of haemorrhage in uraemia is still a matter of controversy and the pattern of bleeding suggests a defect of primary haemostasis. Platelet aggregation and biochemistry, including calcium levels, have been studied; however, the results are controversial. We have examined platelet aggregation, platelet-free calcium and calmodulin in platelet-rich plasma because of the significant role of calcium and calmodulin in regulating platelet and other cells' functions. Platelet aggregation in uraemic subjects was similar to that of controls. Platelet basal free cytosolic calcium and platelet calcium in response to 10 microM Ca++ ionophore A23187 in eight subjects with uraemia were 117 +/- 33 nM and 2025 +/- 398 nM (mean +/- SEM) respectively. By contrast in seven matched healthy controls basal calcium and ionophore-stimulated calcium values were 47 +/- 14 nM and 1354 +/- 414 nM, significantly less than in the patients with uraemia (P less than 0.05). The sensitivity of uraemic platelets to A23187 was similar to that of controls. Calmodulin activity in platelet-rich plasma of 12 subjects with uraemia showed no significant difference from that of controls [1.86 +/- 0.29 micrograms/ml (mean +/- SEM) and 2.0 +/- 0.37 micrograms/ml (mean +/- SEM) respectively]. We conclude that despite elevation of platelet calcium in uraemia, which may be due to a plasma factor such as parathyroid hormone, platelet aggregation is normal and bleeding in uraemia is more likely to be due to other factors, including the effect of reduced haematocrit on platelet endothelial interaction. Disturbances in platelet calcium cannot explain the bleeding manifestations in uraemia but warrant further investigation in order to identify the pathogenic mechanisms responsible.
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PMID:Elevated platelet-free calcium in uraemia. 211 Apr 66

1. The effect of uraemia on the rates of protein synthesis and protein degradation in liver, heart and vastus lateralis muscle were examined in the rat. Uraemia was induced by a five-sixths nephrectomy and the rates of protein turnover were compared with pair-fed sham-operated littermate controls. 2. The procedure produced plasma concentrations (means +/- SEM) of urea of 7.3 +/- 0.4 mmol/l in control and 39 +/- 2 mmol/l in uraemic rats, and of creatinine of 41 +/- 1 mumol/l in control and 133 +/- 7 mumol/l in uraemic rats. 3. Uraemia reduced the rates of protein synthesis in liver, heart and muscle by 35 +/- 5, 4.0 +/- 1.2 and 4.0 +/- 0.6%/day, respectively, compared with control rats (P less than 0.01). Since the reductions in tissue growth rate were too small to be accounted for by the reduction seen in protein synthesis alone, this implied that protein degradation was also reduced. Uraemia also caused an 18% reduction in the rate of growth as measured by the increase in tail length (P less than 0.01). 4. Uraemia reduced both protein synthesis and protein degradation. Protein synthesis exceeded protein degradation in all tissues. This would cause a reduced rate of protein accumulation in the uraemic compared with the control rats, and hence a reduced rate of growth.
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PMID:Protein turnover in uraemia in the rat. 217 24


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