New aspects of erythropoietin treatment.
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Biomedical subjects
Publications and source records attributed to J Bergström.
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Peritoneal dialysis is associated with several metabolic and nutritional abnormalities, some of which are related to the use of glucose-based solutions. Furthermore, the catabolic effects of uremia per se, protein and amino acid losses into the dialysate, peritonitis and poor appetite contribute to amino acid abnormalities, negative nitrogen balance and a high prevalence of malnutrition in peritoneal dialysis patients. To overcome these problems the use of amino acid instead of glucose as an osmotic agent has been proposed. Short-term studies have shown that amino acid-based solutions in peritoneal dialysis may supplement in excess the daily losses of amino acids during dialysis with glucose-based solutions. The amino acid solutions produce similar ultrafiltration and solute transport as the standard glucose solutions although the period of effective ultrafiltration is rather short. However, it should be noted that some studies have reported that the transport of small and large solutes may increase in patients using amino acid solutions. During the early 1980s several investigators have developed and tested different amino acid solutions for peritoneal dialysis. The initial clinical experience from Toronto with amino acid solutions containing large amounts of non-essential amino acids and inadequate amount of buffer were in general discouraging. The patients, who were not always malnourished and tended to have a low energy intake, developed increased BUN levels, acidosis, no improvement in nutritional status or amino acid abnormalities and, in some cases, anorexia. In 1985 a new 1% amino acid solution, containing an increased buffer amount and amino acids (mainly essential) in proportions which take the amino acid abnormalities in uremic patients into account, became available. The use of this solution resulted in some improvement in amino acid pattern and nutritional parameters, but acidosis and increased BUN levels remained problems. The experiences from these and previous studies showed that: (1) the improvement of the composition of amino acid solutions was beneficial; (2) a further increase of the buffer amount was needed; (3) patients included should have signs of protein malnutrition combined with low dietary protein intake to benefit from intraperitoneal amino acid supply, and (4) energy intake should be sufficient to prevent amino acids to end up as energy source. For this purpose a new improved 1.1% amino acid solution has been developed containing a further increase of some essential amino acids and an increased amount of lactate (40 mmol/l). This solution has been tested in malnourished patients eating 0.8 g protein/kg/day and 25-30 kcal/kg/day.(ABSTRACT TRUNCATED AT 400 WORDS)
OBJECTIVE: To evaluate the potential clinical role of amino acids as an osmotic agent. DESIGN: The peritoneal transport of fluid, amino acids, and other solutes was investigated during a 6-hour single-cycle peritoneal dialysis with PDA 1% versus 1.36% glucose (n = 6) or PDA 2.7% versus 3.86% glucose solution (n = 9). PATIENTS: Fifteen stable nondiabetic continuous ambulatory peritoneal dialysis (CAPD) patients. RESULTS: The fractional absorption of the osmotic agents at 6 hours was higher with PDA 2.7% versus glucose 3.86% (p < 0.005). The diffusive mass transport coefficient, KBD, calculated for a period of dialysate isovolemia was higher with PDA 2.7% versus PDA 1% for essential, nonessential (p < 0.005), and total (p < 0.05) amino acids. The intraperitoneal volume-over-time curves and KBD values for urea, creatinine, glucose, albumin, beta 2-microglobulin, and total protein did not differ between the amino acid solutions and the corresponding glucose solutions. KBD for urea was significantly higher during the dwell with PDA 2.7% versus PDA 1% (p < 0.05). Plasma amino acid concentrations increased substantially during the first 1-2 hours and then decreased gradually. Valine and methionine rose to 792% and 1119% of baseline values, respectively. CONCLUSIONS: We conclude that the peritoneal transport of fluid and investigated solutes, except amino acids, was not different with the amino acid solutions compared with the corresponding equimolar glucose solutions. However, ultrafiltration tended to be lower with amino acid solutions. Furthermore, the fractional absorption of amino acids and KBD values for amino acids was higher with PDA 2.7% versus PDA 1%, suggesting an effect of the hypertonic amino acid solution on the peritoneal membrane transport properties. Also, the hypertonic PDA 2.7% solution yielded nonphysiologically high plasma levels of several amino acids. We therefore consider this solution not to be safe enough for long-term clinical use.
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Nutritional status, assessed by anthropometric and biochemical methods, and muscle water, protein and amino acid composition, were evaluated in a control group of 10 children with normal renal function who were undergoing elective surgery, and in 15 children with end-stage chronic renal failure. Samples of the rectus abdominis muscle were taken when surgery was performed in the control children and when a peritoneal catheter was implanted in the uremic children. Height and body weight were reduced in the uremic children compared to the controls but skinfold thickness, arm muscle circumference and serum proteins (total protein, albumin, transferrin, pseudocholinesterase) were essentially normal. The muscle contents of total, extracellular and intracellular water, and of alkali-soluble protein (ASP), DNA and the ASP-DNA ratio were not significantly different in uremic children from those in the controls. Plasma leucine, isoleucine, tyrosine, valine, and serine levels were significantly decreased, whereas plasma citrulline, 1-methylhistidine and 3-methylhistidine levels were increased. Muscle isoleucine and valine levels and the valine/glycine ratio were low in the uremic children. Our results demonstrate that children with chronic renal failure and growth retardation may maintain a satisfactory nutritional status but exhibit amino acid abnormalities typical of uremia.
Urinary excretion of 3-methylhistidine has been proposed as an index of internal protein breakdown provided that the intake of exogenous 3-methylhistidine (meat) is excluded. To evaluate the potential use of 3-methylhistidine in the metabolic assessment of patients with advanced renal failure, we studied a group of 11 patients with markedly reduced renal function who were put on a meat-free diet (the protein intake was kept constant). Steady-state plasma concentration and urinary excretion of 3-methylhistidine were not achieved until 14 d after exclusion of meat from the diet. At that time the plasma concentration and urinary excretion of 3-methylhistidine had decreased by 43% and 60%, respectively. We conclude that the delay in reaching steady state makes the clinical use of urinary excretion of 3-methylhistidine in patients with advanced renal failure unpracticable as an index of protein breakdown. The exclusion of meat also resulted in a continuous decrease in the plasma level and urinary excretion of creatinine, with the result that plasma creatinine or its reciprocal become misleading for evaluation of changes in renal function until a new steady state has been reached.
The aim of the present study was to elucidate the interrelationship between cigarette smoking and the occurrence of periopathogens, i.e., Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Bacteroides intermedius. The study was based on 145 patients with clinically severe periodontitis, 52 men (age range 32-73 years) and 93 women (age range 32-74 years). 83 patients were smokers (> or = 15 cigarettes/day) and 62 non-smokers. Bacterial samples were collected from one site with a probing depth > or = 6 mm for each individual. There were no statistically significant differences in bacterial counts between smokers and non-smokers (p > 0.05). The relative frequencies of smokers and non-smokers positive for A. actinomycetemcomitans were 31% and 31%, for B. gingivalis 42% and 44%, and for B. intermedius 65% and 53%, respectively. The differences between smoking groups were not statistically significant (p > 0.05). The occurrence in different combinations of these bacteria was also determined. There were no statistically significant differences between smoking and combinations of periopathogens (p > 0.05). The results suggest that smoker and non-smoker patients do not differ with regard to occurrence, relative frequency or different combinations of A. actinomycetemcomitans, B. gingivalis and B. intermedius.
The aim of this study was to determine the plaque extension rate following both a sucrose restricted and a sucrose supplemented diet. Eighteen female students, 19-32 yr of age, volunteered to participate in the study. The experiment comprised two periods, with each consisting of five consecutive days of no oral hygiene. The diet during one experimental period was composed of typical Swedish food with no addition of sucrose. The diet during the other experimental period was identical except for the daily addition of 100 g sucrose. Plaque was assessed after 24 h, 72 h, and 120 h with the aid of photographs which were evaluated photogrammetrically. The results showed a mean plaque extension rate of 0.32% per hour during the period with no additional sucrose and 0.36% per hour with sucrose addition. The difference was not statistically significant. The results suggest that moderate amounts of sucrose added to normal diet do not influence the plaque extension rate.
The clinical diagnostic features of gingivitis such as redness, swelling and bleeding are based on vascular changes. It would be desirable to directly make use of the vascular changes in the clinical evaluation of gingival inflammation. In the present study, capillary microscopy was used for quantitative evaluation of the vascular reaction of the marginal gingiva in response to experimental plaque formation in 6 healthy students. Low power stereomicroscopy was used and the number of vessel endings was evaluated from stereophotographs. A gradual increase in the number of visible vessel endings was observed over time of plaque accumulation. The mean +/- SEM at baseline was 24.0 +/- 6.30 as compared to 77.0 +/- 10.02 at day 28. After removal of plaque and re-institution of oral hygiene measures, a return toward pre-experimental numbers was observed. Throughout the test the number of vessel endings within the proximal-papillary part of the marginal gingiva was less than that within the basal-labial part. The results indicate that low power stereophotomicroscopy is a useful tool for the clinical study of inflammatory changes in the gingival vasculature.
Malnutrition, which is common in maintenance hemodialysis (HD) patients, is strongly associated with increased morbidity and mortality. Protein requirements in HD patients are increased twice or more compared to those of healthy subjects. Underdialysis leads to anorexia with low protein and energy intake in relation to the requirements, resulting in protein and energy malnutrition, generally accepted recommendations for dialysis prescription regarding dose of dialysis and protein intake are probably inadequately low in relation to the requirements.
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Microbes have selected primarily carbohydrates for attachment to host animal cells. Recent studies have revealed essential characteristics in the recognition of receptor carbohydrates. Of importance is the property of recognizing also sequences placed inside an oligosaccharide chain, which differs from most animal antibodies. This is the basis for series of isoreceptors with the minimum receptor sequence in common but with separate neighbouring groups. There are families of microbial ligands that show different preferences for members within one series of isoreceptors, indicating only slight differences in the complementary binding sites of the proteins. Such differences may explain shifts in the selectivity of separate host tissues for infection. A second characteristic is the low affinity interaction often found where simple receptor-containing saccharides are unable to inhibit attachment. Technical possibilities are rapidly developing for the design of synthetic receptor analogues to be used in the therapy of clinical infections. This is urgently needed in cases where no rational therapy exists today.
Peritoneal dialysis is associated with metabolic and nutritional abnormalities due to the combined effects of uremia per se, glucose absorption from the dialysate and a variety of catabolic factors, such as protein and amino acid losses into the dialysate, poor appetite possibly reflecting insufficient removal of small solutes, and recurrent episodes of peritonitis. Signs of protein-energy malnutrition are common, especially in patients with minimal or no residual renal function. Variables that best correlate with the degree of malnutrition include serum albumin, midarm muscle circumference, clinical signs of muscle wasting and loss of subcutaneous fat, and a history of anorexia. The incidence of malnutrition is higher in females than in males and in diabetics than in non-diabetics. CAPD patients generally have a lower protein intake than HD patients, but may have a lower average protein requirement than HD patients. Progression of malnutrition may occur in CAPD patients due to the synergistic effects of loss of residual renal function, underdialysis, anorexia and inadequate dietary intake. In underdialyzed CAPD patients, the amount of dialysis should be increased and measures should be taken to increase the supply of energy and protein. The use of amino acid-based dialysis fluid may provide new opportunities for compensation of dialytic losses of protein and amino acids, normalization of essential amino acids, supplementation of inadequate dietary protein intake, and improvement of the nutritional status in CAPD patients.
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Malnutrition is common in maintenance hemodialysis (HD) patients who are frequently anorectic. The protein requirements in HD patients are increased compared with nonuremics. Factors which tend to increase the protein requirements are: low energy intake, metabolic acidosis, leading to enhanced catabolism of branched-chain amino acids in muscle, and dialytic losses of amino acids and glucose. In addition, the HD procedure results in inhibition of muscle and whole body protein synthesis, and induces an inflammatory response (blood membrane interaction, endotoxins) leading to enhanced muscle protein breakdown. The relative importance of the various factors leading to enhanced net protein catabolism in HD patients remains to be elucidated.
Protein-calorie malnutrition is present in a sizable proportion of dialysis patients. In CAPD patients, constant glucose absorption from dialysate may displace other calorie sources, such as protein, and may suppress the appetite, thus contributing to malnutrition. Use of amino acids in place of glucose as the osmotic agent has been studied extensively. Ultrafiltration and small-molecule clearance similar to that with glucose can be achieved with amino acid solutions, but nitrogenous waste produced by amino acids limits the extent to which they can replace hypertonic glucose. Side effects of CAPD with amino acids appear to be minor and easily manageable. Most studies have found at least some nutritional benefit of amino acid solutions in addition to that of lowering the glucose load. Short-term studies of amino acid solutions for dialysis indicate that they may improve protein nutrition in malnourished CAPD patients.
To study whether the contact between dialysis membrane of various materials and blood may trigger protein catabolism in muscle and thus contribute to protein depletion in hemodialysis patients we measured the exchange of free amino acids across the leg in healthy subjects undergoing sham-hemodialysis (i.e. in vivo passage of blood through a dialyzer without circulating dialysate). The effect of dialyzers with regenerated cellulose (group CU, n = 16), cellulose acetate (group CA, N = 8) and polysulfone membranes (group PS, n = 8), respectively was studied. Plasma amino acid concentrations were measured in arterial and femoral venous blood and leg blood flow was determined by venous occlusion plethysmography. In group CU the total efflux of all measured amino acids from leg tissues (muscle) increased from 167 +/- 21 nmol/min/100 g tissue in the basal state to 308 +/- 41 nmol/min/100 g tissue at 345 minutes after the start of sham-hemodialysis procedure (p less than 0.01) indicating a protein catabolic effect of contact between blood and regenerated cellulose membranes. In contrast sham-hemodialysis in group CA and group PS, respectively, did not result in significant increases in amino acid efflux from the leg implying that the protein catabolic effect of blood membrane contact depends on the chemical properties of dialysis membranes. In group CU sham-hemodialysis resulted in enhanced net protein breakdown. Increases in arterial concentrations and leg release of 3-methylhistidine suggest that this may be due primarily to increased protein breakdown.