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Biomedical subjects

B Lindholm

Publications and source records attributed to B Lindholm.

At least 127 records · Page 7Linked to original sources

Amino acid solutions for CAPD: rationale and clinical experience.

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.

Amino Acids↗

Nutritional assessment of continuous ambulatory peritoneal dialysis patients: an international study.

We examined the nutritional status of 224 patients from six centers in Europe and North America to assess the incidence of protein-energy malnutrition. A "subjective nutritional assessment" was made, using 21 variables derived from history and clinical examination, or anthropometry and biochemistry. Eighteen patients (8%) were severely malnourished, 73 (32.6%) were mildly to moderately malnourished, and 133 (59.4%) did not show evidence for malnutrition. There was a higher incidence of mild to moderate malnutrition in diabetics than in nondiabetics. A statistical analysis identified 12 variables, seven objective and five subjective, that correlated with subjective nutritional assessment. Actual intercenter differences for the incidence of malnutrition were related to patient age, nutritional status at the commencement of continuous ambulatory peritoneal dialysis (CAPD), the length of time on CAPD, and residual renal function. Variables that were most frequently correlated with subjective nutritional assessment and with one another included plasma albumin, mid-arm muscle circumference (MAMC), weight loss, and the clinical judgement of muscle wasting and loss of subcutaneous fat. Loss of residual renal function correlated with muscle wasting and months on CAPD. Our data identified differences between the two sexes. In women there was a trend for more anorexia, greater weight loss from muscle wasting, and a larger decrease in albumin, whereas in men there was a more gradual decrease in nutritional status. Loss of residual renal function contributed to anorexia and symptoms of severe malnutrition.

Adolescent↗

Endotoxin shedding by enterobacteria: free and cell-bound endotoxin differ in Limulus activity.

The endotoxin activities of gram-negative bacteria and their lipopolysaccharides (LPS) have been quantitated by a chromogenic Limulus amocbocyte lysate (CLAL) assay. When bacterial cell exposing various cell surface structures were compared, the highest Limulus activities were found in R strains of Escherichia coli and Salmonella typhimurium mutants. E. coli with K antigens did not differ from K-negative strains. By measuring beta-hydroxymyristic acid (3-OH tetradecanoic acid, beta-OHC14:0), it was possible to compare the CLAL activities of LPS bound to bacterial cells, LPS shed into the culture medium, and purified LPS. After 16 h of growth, the cell-free culture supernatants of three E. coli O1K1 strains and S. typhimurium showed CLAL activities 14.3 to 20.3 times higher than did the corresponding bacterial cell suspensions in relation to their beta-OHC14:0 contents. Four other E. coli strains (O serotypes O14, O24, and O75) and the S. typhimurium 395 R mutants MR5 and MR6 showed CLAL values 2.8 to 7.9 times higher in their culture supernatants. LPS of E. coli O1K1 and S. typhimurium had lower CLAL activities than the culture supernatants (1/10 and 1/4, respectively). Although the beta-OHC14:0 concentrations of the culture supernatants were approximately half those of the corresponding bacterial cells, all had CLAL values that were 2 to 21 times higher. The bacterial cell suspension, culture supernatant, and purified LPS of S. typhimurium MS were compared by CLAL assay and a quantitative enzyme-linked immunosorbent assay based on monoclonal antibodies to the O5 antigen. Endotoxin shed into the culture medium was the most CLAL-active form of LPS, while purified LPS was the most antigen-active form. The results emphasize the importance of appropriate standards when quantifying endotoxin in various states. In conclusion, E. coli and S. typhimurium bacteria shed significant amounts of endotoxin into the surrounding medium during growth. This form of LPS is more CLAL active than the cell-bound or purified LPS.

Animals↗

Simple models for description of small-solute transport in peritoneal dialysis.

The convective component in the general description of transport of solutes across the peritoneal membrane can be expressed as SQuc, where S is the sieving coefficient, Qu is the ultrafiltration flow rate, and c is the average concentration in the membrane (c = (1-F)cB + FcD, where cB and cD are blood plasma and dialysate solute concentration, respectively). F is a weighing function dependent on Qu, S, and the diffusive mass transport coefficient KBD. In this study a class of simple models of solute transport was considered in which S = 1 (justified for small solutes) was chosen, and F was selected as follows: F = 0 (as in the S = 1 (justified for small solutes) was chosen, and F was selected as follows: F = 0 (as in the widely used model of Garred and coworkers), F = 0.5 (theoretically justified model), F = 0.33 (theoretically justified for a high ultrafiltration period), and F = 1 (for convective transport from dialysate to blood). For all these models the estimation of KBD from clinical data can be performed with the aid of linear regression. The simple models were compared with the Pyle-Popovich model which takes into account the general expression for convective solute transport, for both the accuracy of the KBD determination (using linear regression) and the accuracy of theoretically calculated dialysate to plasma concentration ratios (D/P) to experimental D/P. Clinical evaluation of the new models was carried out in 28 6-hour dwell studies in 21 nondiabetic patients using 2 liters of hypertonic (glucose 3.86%) dialysis fluid. The differences between the simple models were small from the clinical point of view for urea, creatinine, glucose, and potassium, whereas for sodium the predictions were not satisfactory for any of the models. For urea and creatinine the model with F = 0.5 yielded the best fit of theoretical predictions to experimental data. For glucose and potassium small but systematic deviations of theoretical D/P from experimental D/P were observed for all simple models. The protein transport could be satisfactorily described by a model in which F = 1, as shown for total protein.

Creatinine↗

Peritoneal transport in CAPD patients with permanent loss of ultrafiltration capacity.

During a 10 year period, 14 out of 227 patients (6.2%) undergoing continuous ambulatory peritoneal dialysis (CAPD) developed permanent loss of ultrafiltration capacity (UFC). The risk of UFC loss increased from 2.6% after one year to 30.9% after six years of treatment. A six hour, single dwell study with glucose 3.86% dialysis fluid was carried out in nine of the UFC loss patients and in 18 CAPD patients with normal UFC. Intraperitoneal dialysate volumes were calculated using 131I-tagged albumin (RISA) as volume marker with a correction applied for its elimination from the peritoneal cavity. The RISA elimination coefficient (KE), which can serve as an estimation of the upper limit of the lymphatic flow, was also calculated. Diffusive mass transport coefficients (KBD) for investigated solutes (glucose, creatinine, urea, potassium, total protein, albumin and beta 2-microglobulin) were calculated during a period of dialysate isovolemia. Two patterns of UFC loss were observed: (a) seven patients had high KBD values for small solutes resulting in rapid uptake of glucose, whereas KBD values for proteins were normal; (b) two patients had normal KBD values but a threefold increase both in the fluid reabsorption rate and KE. We conclude that loss of the osmotic driving force (due to increased diffusive mass transport for small solutes) and increased fluid reabsorption (possibly due to increased lymphatic reabsorption) are the two major causes of permanent loss of UFC in CAPD patients.

Biological Transport↗

Fluid transport in peritoneal dialysis.

Standard peritoneal ultrafiltration characteristics in 18 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) were investigated in a total of 21 single dwell studies of 6 h duration with 2 L of 3.86% glucose dialysis fluid. Intraperitoneal dialysate volumes were determined using radioiodinated serum albumin (RISA). Calculations were based on a novel mathematical method in which RISA elimination from the peritoneal cavity was taken into account. The RISA elimination rate, KE, was calculated as 2.1 +/- 0.5 ml/min. The true dialysate volume after 360 min (2957 +/- 196 ml) was on the average 28% lower than the volume (3737 +/- 260 ml) calculated without correction for the elimination of RISA. The mean maximum true volume plus sampling losses was 3255 ml at 240 min corresponding to a mean ultrafiltration of 762 ml between 3 min and 240 min. Our method of peritoneal volume determination proved to be useful for clinical investigations. The present study demonstrates that CAPD patients, without any major ultrafiltration problems, exhibit relatively small interpatient variations in their peritoneal volume over time curve.

Dialysis Solutions↗

Plasma and muscle free amino acids during continuous ambulatory peritoneal dialysis.

Free amino acids (AA) were determined in plasma and in muscle tissue of 29 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) for 2 to 38 months. Muscle biopsies were taken in the morning after an overnight dwell with 1.36% glucose dialysis fluid. Muscle intracellular water was calculated using the chloride method. The intracellular (ic) and extracellular (ec) concentration and the ic/ec gradient for each AA was calculated and compared with values in matched healthy controls. Most of the essential and several non-essential AA were low in plasma. By contrast, none of the essential AA were low in muscle, and methionine was increased as were ornithine, asparagine, and aspartic acid; however, muscle taurine was markedly reduced. The ic/ec gradient was increased for most essential and several non-essential AA. In plasma, taurine precursors, methionine and cysteine, were not reduced and the ratios taurine/cysteine and taurine/methionine were low. Muscle taurine/methionine was also low. Thus, during CAPD muscle free AA are, in general, well maintained, suggesting that marked reductions of plasma AA levels in CAPD patients may reflect an ec to ic shift rather than depletion. The finding of low muscle taurine, but normal or increased cysteine and methionine pools, suggests that taurine depletion during CAPD is caused by blocked synthesis or low intake of taurine.

Amino Acids↗

Sulphur amino acids in plasma and muscle in patients with chronic renal failure: evidence for taurine depletion.

The sulphur amino acids methionine, cysteine (1/2-cystine) and taurine were determined by ion-exchange chromatography in plasma and muscle biopsy material obtained from 46 patients with chronic renal failure. Twelve patients were untreated, eight patients were treated with a low protein diet supplemented with essential amino acids, 11 patients treated with maintenance haemodialysis and 15 patients with continuous ambulatory peritoneal dialysis (CAPD). Patient data were compared to data obtained from 18 healthy subjects. Plasma cysteine was elevated in the untreated patients, in the patients treated with low protein diet and in the maintenance haemodialysis patients. Muscle methionine was significantly elevated in the CAPD patients. Plasma taurine was decreased in the untreated patients and in the CAPD patients and muscle taurine was borderline low in the untreated patients and significantly decreased in the other patient groups. The results show that taurine depletion may occur in patients with chronic uraemia despite normal or elevated concentrations of precursor sulphur amino acids, suggesting inhibited synthesis or enhanced degradation of taurine in the uraemic state.

Adult↗

Peritonitis in continuous ambulatory peritoneal dialysis (CAPD): diagnostic findings, therapeutic outcome and complications.

The analysis of all episodes of peritonitis occurring in a uniformly treated continuous ambulatory peritoneal dialysis (CAPD) population (N = 128) at one centre during a six-year period showed the following major findings. The initial white cell count (WCC) of the dialysate was less than 100 x 10(6)/L in 10% of the episodes and showed a predominance of mononuclear cells in 15%. The Gram stain results were consistent with the findings of the culture in 28% of the episodes and influenced the initial therapy in only 7% of the cases. Between 9% and 31% of all episodes would not have been classified as peritonitis if positive culture, a WCC of greater than 100 x 10(6)/L in the dialysate, or clinical symptoms had been required for the diagnosis. The proportion of negative dialysate cultures was 2% after the introduction of pre-culture membrane filtration. Tunnel infection as a cause of peritonitis was more frequent in episodes due to Staphylococcus aureus than in episodes due to coagulase-negative staphylococci (p = 0.009). Peritonitis caused by coagulase negative staphylococci were followed by a milder course than other organisms (p = 0.02). Of all episodes initially treated with cephradine only 62% were cured with this antibiotic (or cloxacillin) and 35% were followed by recurrency, protracted course or catheter loss, despite intermediate or full in vitro susceptibility. In only 53% of all episodes no complication was observed. Complications were more frequent in women and diabetics than in men (p = 0.01) and non-diabetics (p = 0.03), and were more common in episodes with clinical symptoms (p = 0.02). Peritonitis resulted in drop-out from CAPD in 6% of all episodes. Hospital care was needed in 68% of all episodes. We conclude that turbidity can be used as the sole criterion for the initial diagnosis of peritonitis, and that a first generation cephalosporin should not be used as a first line antibiotic in the treatment of CAPD peritonitis.

Aminoglycosides↗

Peritoneal ultrafiltration and fluid reabsorption during peritoneal dialysis.

Peritoneal ultrafiltration and fluid reabsorption characteristics for 18 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) were investigated in single dwell studies of 6 h duration with 21 of 3.86% glucose dialysis fluid. Dialysate volumes were determined in situ using radioiodinated serum albumin (RISA) as volume marker with a correction applied for the total elimination of RISA from the peritoneal cavity. The RISA elimination rate was calculated as 2.1 +/- 0.5 ml/min. The true dialysate volume after 360 min was on average 28% less than the apparent volume calculated without correction for the elimination of RISA. The mean maximum true volume plus sampling losses was 3255 ml at 240 min, corresponding to a mean net ultrafiltration volume of 762 ml between 3 min and 240 min. The mean net fluid reabsorption rate between 240 min and 360 min was 1.2 +/- 0.7 ml/min. This study of standard dialysate volume/time curves in clinically stable CAPD patients using hypertonic dialysis fluid shows that about 90% of the total net ultrafiltration is achieved during the first 90 min of the dwell. After an extended period of dialysate isovolaemia, usually lasting as long as between 120 min and 240 min, fluid reabsorption is observed in all patients.

Aged↗

Protein and amino acid metabolism in patients undergoing continuous ambulatory peritoneal dialysis (CAPD).

Several factors contribute to impaired nutritional status in patients undergoing CAPD. The protein loss into the dialysate varies between 5-15 g per day; during peritonitis protein loss increases by 50-100%. The loss of free amino acids during CAPD is of the same magnitude as under hemodialysis. The observed plasma amino acid abnormalities in CAPD patients probably reflect metabolic derangements in uremia, rather than depletion due to dialysate amino acid loss. Sustained hyperinsulinemia in CAPD patients also may contribute to reduced plasma amino acid concentrations. A further factor contributing to nutritional problems in CAPD is a decreased protein intake. Dietary protein intake should exceed 1.2 g/kg/day during long-term CAPD treatment to maintain nitrogen equilibrium. Total energy intake may exceed 35 kcal/kg/day.

Amino Acids↗

Availability of reaction with antibodies of the pneumococcal C-polysaccharide on the surface of capsulated pneumococci.

Antigen detection for diagnosis of pneumococcal infections has earlier been based on the use of antibodies against capsular antigens. Methods based on the demonstration of C-polysaccharide (PnC) have the advantage of using antibodies against one single species-specific antigen instead of applying a polyvalent mixture of antisera against 83 different capsular antigens. Very little has been done earlier to evaluate the accessibility of the PnC on the surface of pneumococcal cells, particularly cells carrying capsules, and the release of PnC to the environment. We have used a monoclonal anti-PnC antibody in an ELISA inhibition test to demonstrate PnC during growth from four different Streptococcus pneumoniae strains (capsular types 1, 3 and 19F) and a C-mutant strain, reported to carry PnC as a small capsule. Heavily-capsulated types 3 and 19F exposed more PnC on their surface than the type 1 strain, and considerable amounts of PnC were released to the culture medium during growth. The C-mutant strain differed from the other strains in that it exposed less PnC on its surface. The type 1 strain and the C-mutant released approximately the same amount of PnC to the culture medium. Treatment with antibiotics during growth caused a decrease in surface-located PnC but did not significantly affect the amount released. The total accessible PnC in these cultures was quite significant and well above the limit of detection in an ELISA earlier described for the detection of PnC in clinical samples. The results presented here give support to the notion that the demonstration of PnC in clinical samples should provide a good basis for diagnosis of pneumococcal pneumonia.

Antibodies, Bacterial↗

Serum lipids and lipoproteins during continuous ambulatory peritoneal dialysis.

The effects of continuous ambulatory peritoneal dialysis (CAPD) on serum lipids and lipoproteins over the initial year of therapy were studied in 23 uremic patients. Lipoprotein abnormalities typical for the uremic dyslipoproteinemia were present at the start of CAPD. During the first months of CAPD these abnormalities were accentuated. The concentrations of very low density lipoprotein (VLDL)-cholesterol (CHOL), low density lipoprotein (LDL)-CHOL, serum CHOL and serum triglycerides (TG) increased significantly. However, after one year of CAPD only the VLDL-CHOL and serum CHOL levels remained significantly higher than the baseline values. VLDL-TG, VLDL-CHOL and serum TG, and the changes of these variables over the study period, correlated with the amount of glucose in the dialysates. We conclude that the continuous peritoneal absorption of glucose (100-200 g/24 h) during CAPD contributes to potentially atherogenic changes in serum lipids and lipoproteins. However, some of the changes are transitory, indicating an adaptation to the peritoneal glucose load.

Adult↗

Glucose tolerance in patients undergoing continuous ambulatory peritoneal dialysis.

The effects of continuous ambulatory peritoneal dialysis (CAPD) on glucose tolerance and serum immunoreactive insulin and glucagon responses to oral glucose over the first year of therapy were studied in 13 uremic patients. Oral glucose tolerance tests were performed before treatment started, and again after 3 and 12 months on CAPD. Before CAPD, the patients showed decreased glucose tolerance. However, neither fasting blood glucose and serum insulin and glucagon levels nor the insulin and glucagon levels during the tests were significantly different from results obtained in 13 healthy controls. During CAPD, the mean intraperitoneal supply of glucose from the dialysates varied between 121 and 245 g/day and did not change during the study period. Glucose tolerance and hormone responses to glucose did not change during the study period. No patient developed manifest diabetes mellitus. We conclude that glucose intolerance in uremia persists during CAPD, but despite the continuous peritoneal absorption of 100-200 g of glucose during CAPD, the treatment had no effect on glucose tolerance and insulin secretory response.

Adult↗