Five-year follow-up of graft function and urinary protein excretion in kidney transplant patients immunosuppressed with cyclosporine or azathioprine.
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Biomedical subjects
Publications and source records attributed to J Bergström.
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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.
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Site-directed mutagenesis of the structural gene for azurin from Pseudomonas aeruginosa has been used to prepare azurins in which amino acid residues in two separate electron-transfer sites have been changed: His-35-Lys and Glu-91-Gln at one site and Phe-114-Ala at the other. The charge-transfer band and the EPR spectrum are the same as in the wild-type protein in the first two mutants, whereas in the Phe-114-Ala azurin, the optical band is shifted downwards by 7 nm and the copper hyperfine splitting is decreased by 4.10(-4)/cm. This protein also shows an increase of 20-40 mV in the reduction potential compared to the other azurins. The potentials of all four azurins decrease with increasing pH in phosphate but not in zwitterionic buffers with high ionic strength. The rate constant for electron exchange with cytochrome c551 is unchanged compared to the wild-type protein in the Phe-114-Ala azurin, but is increased in the other two mutant proteins. The results suggest that Glu-91 is not important for the interaction with cytochrome c551 and that His-35 plays no critical role in the electron transfer to the copper site.
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Muscle and plasma concentrations of free and acylated carnitine (short-chain acylcarnitine and long-chain acylcarnitine) were determined by employing an optimized radiochemical-enzymatic assay in 14 healthy volunteers and in 10 patients with oesophageal carcinoma prior to elective operation. No significant correlations between total carnitine and its subfractions in muscle and plasma were observed and no sex differences were apparent. The estimated total carnitine pool in the patients (75.0 +/- 27 mmol) was significantly reduced compared to controls (130 +/- 24.3 mmol). The reduction was still present when expressed per kg muscle tissue (3.5 +/- 1.0 mmol versus 4.5 +/- 0.7 mmol) in order to consider age related decreased muscle mass in the patients. The muscular ratio of acylcarnitines to free carnitine was higher in the patients (0.23 +/- 0.10) than in healthy subjects (0.15 +/- 0.07), whereas the corresponding plasma quotient in the patients (0.22 +/- 0.09) was lowered compared to controls (0.30 +/- 0.10), indicating that instead of glucose, oxidation of fatty acids can be maintained, resulting in a preservation of the glycogen stores and thus an energy-conserving metabolic adaptation as a response to prolonged energy deficit.
The muscle contents of water, electrolytes, creatine, alkali-soluble protein (ASP) and carnitine were determined using percutaneous muscle biopsy technique. Seven patients with prolonged catabolic states and subsequent respiratory failure were studied. Twelve age- and sex-matched healthy subjects were used for comparison. The muscle content of alkali-soluble protein in relation to the content of DNA was less than half of control values, indicating a loss of more than 50% of muscle protein content. The muscle carnitine content was 25.9 +/- 6.5 mumol/g alkali-soluble protein, suggesting a preserved muscle carnitine concentration. Total muscle water was increased by over 20%, mainly due to an increase in extracellular water. Muscle sodium and chloride contents were doubled. The content of magnesium was slightly reduced but muscle potassium was normal. The marked depletion of muscle protein may have contributed to the requirements for artificial ventilation and the difficulties in weaning off the ventilator. The increase in muscle water masks the loss of metabolically active muscle tissue yielding low values for energy expenditure when relating to body weight. The benefit of the use of the ASP/DNA ratio in nutritional assessment is emphasised.
An automatic on-line high-performance liquid chromatographic (HPLC) method is developed to quantitate free amino acids in the biological samples. The method is based on pre-column derivatization of amino acids with orthophthalaldehyde (OPA) in presence of 2-mercaptoethanol (2-ME). The derivatized amino acids were separated on a 5 micron C18 column using a multi-step gradient with two solvents and the detection was made at Eex = 340 nm and Eem = 450 nm. The results were highly reproducible with a relative standard deviation (RSD) between 0.5-2% for all amino acids. Each chromatographic run was completed within 40 min to separate 24 amino acids. The optimized method was applied to evaluate the levels of free amino acids in plasma and muscle samples of eight healthy subjects and 13 uremic patients under fasting conditions.
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.
To identify factors influencing the progression rate of chronic renal failure (CRF) in non-diabetics, the medical records of 124 patients with established CRF were reviewed retrospectively (serum creatinine between 200-350 mumols l-1 at the start of follow-up) for the period 1980-86. Sixteen patients were excluded because they did not fulfil the inclusion criteria. The remaining 108 patients were divided, using their original diagnosis, into four groups and were also assigned into one of three groups expressing their rate of progression. The definitions of these rates of progression were chosen arbitrarily. Comparisons with respect to mean arterial pressure (MAP), urinary protein excretion (UPE) and the progression rate of CRF were then made between the groups. In the group showing no progression of CRF (n = 17) there was a significantly lower MAP and UPE than in the two groups showing progression. Over all the patients and in the various diagnosis groups there was a strong correlation between UPE and the progression rate of CRF. There was no significant correlation between MAP and the progression rate of CRF in the diagnosis groups. These results indicate that an increasing magnitude of proteinuria is an adverse prognostic factor in CRF, irrespective of aetiology, and support the view that excessive glomerular protein filtration leads to glomerulosclerosis.
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.
The prevalence of chronic periodontal disease was investigated using the occurrence of diseased pocket sites as the diagnostic criterion. The study group comprised 250 dentally aware subjects aged 21-60 years, with a high number of teeth remaining in all age groups. The % of sites with a probing depth of greater than or equal to 4 mm was 16% for the total sample. Most diseased sites (69%) were in the 4-mm class, with only 4% at depths greater than or equal to 7 mm. 82% on the subjects had 1 or more sites greater than or equal to 4 mm. With probing depth as the sole criterion for diagnosis of chronic periodontal disease, prevalence in a sample is heavily dependent on the critical levels selected for probing depth and cut-off point. With critical levels of 4 mm for probing depth and 1 diseased site for the cutoff point, prevalence was 49% in the 21-30 year age group and 95% in the 51-60 year age group. A shift in cutoff point to 40 diseased sites gave a prevalence of 2% and 41%, respectively, in the 2 age groups. For a critical depth of 7 mm and a cutoff point of 1 diseased site, the prevalence was 2% and 43% for the 2 age groups, respectively. Aspects of importance for the decision-making process on disease are discussed.
Patients admitted to the School of Dentistry, Stockholm, for treatment of chronic periodontal disease during the years 1980-82 were retrospectively investigated with respect to their smoking habits. The investigation was designed as a case control study and covered all patients 30, 40, or 50 yr of age upon admission, in all 155. As control served a random sample of the Stockholm population. The periodontal variables under scrutiny were frequency of periodontally diseased teeth, frequency of periodontally diseased sites (probing depth greater than 4 mm), gingival index, and plaque index. The overall occurrence rate of smokers in the sample of cases was 56%, which is significantly greater than the population at large. This held true for all three age cohorts and for men as well as women. The risk ratio was 2.5, indicating more prevalent disease among smokers. Further, significantly greater frequencies of periodontally involved teeth and diseased sites were found in smokers, indicating more severe disease among smokers. Gingival index and plaque index did not notably differ between smoking groups. The results suggest increased prevalence as well as severity in smokers. Smoking, therefore, should be considered a risk factor for chronic periodontal disease.
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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.
Fifty-seven patients with chronic renal failure (CRF) of diverse etiology entered a prospective, randomized study to evaluate the effect of a low protein diet on the progression rate of CRF. All patients were followed for a control period of 12 or 24 months before randomization into two groups, one permitted unrestricted protein intake and the other prescribed a diet containing 0.4 g/kg body wt/day of protein and 0.1 g/kg body wt/day of essential amino acids, (LPD + EAA). During both the control and study periods, patients were clinically evaluated and had serum biochemistry and 24-hour clearance of creatinine, urea and protein excretion checked monthly. The 51Cr-EDTA clearance (plasma slope and urinary clearance) was determined every third month. The progression of renal failure was evaluated from the regressions of the reciprocal of serum creatinine (SCr-1), creatinine clearance and urinary 51Cr-EDTA clearance against time. Having defined criteria for progression, only patients in whom renal failure had progressed over 12 or 24 months were randomized. In 28 patients, data were available, permitting a comparison of the progression of renal failure (estimated from regression of SCr-1 and of creatinine clearance against time) during the retrospective and prospective periods. There was a significant correlation between the change in progression rate and the change in mean arterial pressure, a relationship which was also present in patients with mild hypertension or those with blood pressure within the "normal" range. The urinary protein excretion also correlated with the change in mean arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)