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Biomedical subjects

A P Kraus

Publications and source records attributed to A P Kraus.

At least 19 recordsLinked to original sources
PubMed1998

The search for the uremic toxin: the case for carbamoylation of amino acids and proteins.

Urea and cyanate, spontaneously transformed from urea, are increased with decreased renal function becoming potential toxins. Isocyanic acid, the active form of cyanate, carbamoylates proteins, amino acids and other molecules, changing molecular structure and function in vivo. Carbamoylation can occur at multiple sites with a cumulative effect over the the life-span of the molecule. Carbamoylation converts free amino acids to carbamoyl-amino acids (C-AA). C-AA interfere with protein synthesis and transamination reactions and contribute, in part, to protein-malnutrition. Insulin-sensitive glucose uptake is decreased by carbamoyl-asparagine. Cyanate inhibits superoxide release from neutrophils to an extent that interferes with microbiocidal activity. Antihomocitrulline antibodies identified homocitrulline (epsilon-amino-carbamoyl lysine) in situ in proteins in neutrophils in end stage renal disease. Also in uremic patients, homocitrulline was located in proteins in renal tissue but was not found in normal transplanted kidneys. Carbamoylated human low density lipoprotein interferes with human receptor binding, has decreased clearance, and is auto-immunogenic in animals. Carbamoylated insulin has decreased biological activity and changed immunological reactivity. Carbamoylation at a site of molecular activity can affect molecular function of enzymes, co-enzymes, antibodies, hormones and receptors. Carbamoyl-molecules can block, enhance, or be excluded from metabolic pathways, and can affect binding and trafficking, thereby influencing the fate of non-carbamoylated molecules. Normal renal function removes C-AA. In uremia, C-AA are removed by residual renal function or dialysis. Toxicity of cyanate is not an "all or none" phenomenon, but the actions of cyanate are a contributing factor in uremia. Removal of urea, cyanate and carbamoyl-molecules partially alleviates the morbidity and mortality of renal disease.

Amino Acids↗
PubMed1998

Essential carbamoyl-amino acids formed in vivo in patients with end-stage renal disease managed by continuous ambulatory peritoneal dialysis: isolation, identification, and quantitation.

Carbamoyl-amino acids (C-AA) are formed by reaction of amino acids with cyanate, which is spontaneously formed from urea at body temperature and pH. In vivo derivatized C-AA are not measured by the usual amino acid analysis methods, which require a free amino group for derivatization. Free-amino acids (F-AA) but no C-AA were found in the postabsorptive plasma of eight normal persons with blood urea nitrogen (BUN) levels ranging from 9 to 16 mg/dl. In a longitudinal study of postprandial plasma (n=43), essential amino acids, both C-AA and F-AA, were isolated and quantified by reverse-phase high-pressure liquid chromatography in six patients with end-stage renal disease who were managed by continuous ambulatory peritoneal dialysis. The mean BUN was 61 mg/dl (range, 36 to 79 mg/dl). In uremia, removal of F-AA from the essential amino acid pool to form C-AA is measured by the ratio of C-AA to F-AA (carbamoylation index (CI)). Using the mean value for each essential amino acid, the CIs were as follows: leucine, 4; valine, 3.3; isoleucine, 11.4; threonine, 9; lysine, 2; methionine, 3.5; histidine, 3.5; phenylalanine, 0.5; and tyrosine, 1.3. Carbamoylation of F-AA may account, in part, for the lower than normal levels of F-AA in patients with uremia. The derivatized amino group of C-AA interferes with formation of a peptide bond in protein synthesis, which requires an underivatized amino acid. A decrease in the F-AA pool available for protein synthesis and anabolism in the presence of C-AA may provide additional contributing factors for the development of malnutrition in uremia.

Adult↗
PubMed1994

Urea-derived cyanate forms epsilon-amino-carbamoyl-lysine (homocitrulline) in leukocyte proteins in patients with end-stage renal disease on peritoneal dialysis.

Carbamoylated proteins have been located by using a site-specific polyclonal antihomocitrulline antibody and a fluorescent secondary antibody in leukocytes from patients with end-stage renal disease who were undergoing maintenance continuous ambulatory peritoneal dialysis. A covalent reaction with urea-derived cyanate and the epsilon-amino group of lysine forms homocitrulline residues in carbamoylated proteins. Isocyanic acid, the reactive form of cyanate, is spontaneously formed from urea in aqueous solution at physiologic pH and temperature. In washed, fixed monolayers of cells, an intracellular fluorescent antigen-antibody complex was located throughout the cytoplasm of polymorphonuclear neutrophils (PMNs) and monocytes from 11 patients with blood urea nitrogen (BUN) levels ranging from 32 to 102 mg/dl who were undergoing dialysis for 2 to 135 months. A punctate fluorescence present in the cell surface proteins of living cells demonstrated that lysine residues in the external domain of proteins were carbamoylated, forming homocitrulline. In contrast, we found a perinuclear fluorescence in PMNs in normal subjects with no history of renal insufficiency and BUN levels of 6 to 19 mg/dl. This suggests that homocitrulline is located in carbamoylated proteins within the perinuclear membrane, a structural organelle continuous with the endoplasmic reticulum. It appears that continuous exposure to urea-derived cyanate in low levels results in increasing carbamoylation of stable proteins over the PMN's lifetime. When normal PMNs were exposed to 120 mmol/L cyanate ion in vitro for 10 to 30 minutes, the ability of PMNs to release microbicidal superoxide was strongly inhibited. Thus protein carbamoylation may provide a regulatory mechanism. The altered function of PMNs in renal disease may be due in part to the posttranslational modification of proteins by urea-derived cyanate.

Adult↗
PubMed1993

Osteonecrosis of the humeral head in sickle cell disease.

The prevalence and incidence of osteonecrosis (ON) of the humeral head in sickle cell disease was determined by a study of 2524 patients who were entered into a prospective study and followed for an average of 5.6 years. At entry, 5.6% had roentgenographic evidence of ON in one or both shoulders. There was little difference in age-adjusted prevalence among genotypes, but there were striking differences in age-specific rates. Observed at ages ranging from five to 24 years, 3.25% of sickle cell anemia (S/S) patients, but only 1.1% of sickle cell disease (S/C) patients, had ON. No S/beta+ thalassemia patients younger than 25 years of age had ON on entry. The highest age-adjusted incidence rate was found in S/S patients with concomitant alpha-thalassemia (4.85 per hundred patient-years), followed by S/beta zero-thalassemia (4.84 per hundred patient-years), S/beta+ thalassemia (2.61 per hundred patient-years), S/S without alpha-thalassemia (2.54 per hundred patient-years), and S/C (1.66 per hundred patient-years). Only 20.9% of patients reported pain or had limited range of movement at the time of diagnosis. Sickle cell disease is a frequent cause of ON of the humeral head, especially in children and young adults.

Adolescent↗
PubMed1992

Urea kinetics evaluation of hemodialysis and CAPD patients.

Urea kinetics have been used to measure adequacy of hemodialysis. The role of urea kinetics in CAPD has not been clearly established. Using urea kinetics, we studied 71 hemodialysis and 71 CAPD patients. Age was 53 +/- 12 and 45.8 +/- 12 respectively. Urea kinetics in hemodialysis were studied in the standard manner. CAPD patients collected 24 hr, dialysate fluid to measure urea, creatinine, glucose and protein. Urine was collected for 24 hr. to measure urea and creatinine. Protein catabolic rate (pcr) was calculated from the total amount of urea cleared in 24 h. Both groups of patients had similar body weight. Kt/V in CAPD (0.65 +/- 0.1) was at a level considered underdialysis for hemodialysis. In both groups, pcr increased as Kt/V increased. However, CAPD patients had levels of pcr higher than hemodialysis patients at the same level of Kt/V. BUN, serum albumin and serum potassium were significantly lower in CAPD patients. Patients who dialyze more, eat more. Differences in protein intake may be due to a more liberal diet in CAPD, patient selection, removal of middle molecules, or better control of the acidosis.

Adult↗
PubMed1991

Sickle cell disease as a cause of osteonecrosis of the femoral head.

BACKGROUND AND METHODS: Osteonecrosis of the femoral head is an important complication of sickle cell disease. We studied 2590 patients who were over 5 years of age at entry and followed them for an average of 5.6 years. Patients were examined twice a year, and radiographs of the hips were taken at least twice: at study entry and approximately three years later. RESULTS: At study entry, 9.8 percent of patients were found to have osteonecrosis of one or both femoral heads. On follow-up, patients with the hemoglobin SS genotype and alpha-thalassemia were at the greatest risk for osteonecrosis (age-adjusted incidence rate, 4.5 cases per 100 patient-years, as compared with 2.4 in patients with the hemoglobin SS genotype without alpha-thalassemia and 1.9 in those with the hemoglobin SC genotype). Although the rate of osteonecrosis in patients with the hemoglobin SC genotype did not differ significantly from that in patients with the hemoglobin SS genotype without alpha-thalassemia, osteonecrosis tended to develop in these patients later in life. Intermediate rates of osteonecrosis were observed among patients with the hemoglobin S-beta zero-thalassemia and the hemoglobin S-beta(+)-thalassemia genotypes (3.6 and 3.3 cases per 100 patient-years, respectively). Osteonecrosis was found in patients as young as five years old (1.8 cases per 100 patient-years for all genotypes). The frequency of painful crises and the hematocrit were positively associated with osteonecrosis. The mean corpuscular volume and serum aspartate aminotransferase level were negatively associated. Twenty-seven patients had hip arthroplasty during the study; 10 were under 25 years of age. Five of the 27 required reoperation 11 to 53 months after the initial operation. CONCLUSIONS: Osteonecrosis of the femoral head is common in patients with sickle cell disease, with an incidence ranging from about 2 to 4.5 cases per 100 patient-years. Patients with the hemoglobin SS genotype and alpha-thalassemia and those with frequent painful crises are at highest risk. The overall prevalence is about 10 percent. The results of hip arthroplasty are poor.

Adolescent↗
PubMed1991

Evaluation of CAPD prescription.

Adequacy of CAPD has not been established. The recommendation is a Kt/V (K, total urea clearance in ml/min; t. time in minutes on dialysis; and V, total body water which is the volume of distribution of urea) greater than 1.5/week and/or a creatinine clearance (residual + dialysis) greater than 40 l/week/1.73 m2. We followed 20 CAPD patients for 38.6 +/- 28 mo. We measured blood urea nitrogen, serum creatinine, body weight, residual renal function (Kr), normalized protein catabolic rate (NPCR), Kt/V/week and creatinine clearance (CC) l/w/1.73 m2. We obtained the following values: B Wt 72 +/- 16 kg, BUN 56 +/- 13 mg/dl, s. Cr. 12.6 +/- 5 mg/dl, Kr 0.6 +/- 1 ml/min, NPCR 0.84 +/- 0.3 g/kg/day, Kt/V/week 1.8 +/- 0.3 and CC 50.4 +/- 10 l/w/1.73 m2. Patients dialyzed with a wide range of prescription. There was a good correlation between Kt/V and CC. There was no correlation between the dialysis prescription changes in weight and biochemical determinations. There was a direct correlation between Kt/V and NPCR: patients who were dialyzed more eat more. Of the 20 patients, 10 had 24 hospitalizations, and of these were 12 due to peritonitis. Dialysis prescription and biochemical findings of these patients did not differ significantly from nonhospitalized patients. Larger prospective studies are necessary to determine the adequate range of CAPD prescription and its relationship to morbidity and mortality.

Adult↗
PubMed1991

Tyrosine and N-carbamoyl-tyrosine in end-stage renal disease during continuous ambulatory peritoneal dialysis.

Lower-than-normal tyrosine concentrations of unexplained pathogenesis in plasma and intracellular body water have been reported in patients with chronic renal failure. We found a derivative of tyrosine that is not measured by the usual methods of amino-acid analysis because its alpha-amino group is blocked and cannot react to form other derivatives. An in vivo covalent reaction with urea-derived cyanate forms alpha-amino-carbamoyl-tyrosine (N-C-Tyr) in patients with end-stage renal disease. A longitudinal study of patients with end-stage renal disease who were treated with continuous ambulatory peritoneal dialysis shows that plasma that is obtained within 4 hours of the morning meal contains 70.1 +/- 6 mumol/L of tyrosine (mean +/- SEM) and 77.2 +/- 12 mumol/L of N-C-Tyr (mean +/- SEM). Thus there is a molecule of N-C-Tyr for each molecule of tyrosine present. The carbamoylation index or ratio of N-C-Tyr to tyrosine, blood urea nitrogen, episodes of peritonitis, and changes in dialysis protocol were compared. A reduction in the number of peritoneal dialysis exchanges resulted in parallel increases in carbamoylation index and blood urea nitrogen. Altering dialysis by increasing the number of exchanges or adding supplemental hemodialysis resulted in a decrease in the carbamoylation index with a delayed decrease in blood urea nitrogen. We found a significant increase of N-C-Tyr (p = 0.005) and of the carbamoylation index (p = 0.004) during six episodes of peritonitis compared with 10 periods of no peritonitis in two patients who had multiple episodes of peritonitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Beta 2-microglobulin levels in patients with renal insufficiency.

beta 2-microglobulin (beta 2M) has been implicated in the pathogenesis of amyloidosis in long-term dialysis patients. beta 2M levels were measured in patients with chronic renal failure: before and after conventional hemodialysis in 30, before and after high-flux (HF) hemodialysis in 35, and during the first hemodialysis treatment in five patients, as well as in the serum and peritoneal fluid of 13 patients who were receiving continuous ambulatory peritoneal dialysis (CAPD) and in the serum and urine of three patients who had received kidney transplants. Dialysis patients had markedly elevated beta 2M levels; prehemodialysis values were not significantly different for patients receiving conventional v HF hemodialysis. Most of these patients were functionally anephric, and the beta 2M levels did not correlate with age, sex, or time on dialysis. In patients receiving conventional hemodialysis using cellulose acetate membrane, beta 2M levels increased 25.4% after hemodialysis, whereas in patients receiving HF hemodialysis using polysulfone membrane, beta 2M levels decreased significantly (43.0%) after hemodialysis. End-stage renal disease patients dialyzed for the first time had beta 2M values significantly lower than the other two groups because of residual glomerular filtration rate (GFR). CAPD patients also had lower values because they had an estimated loss of 80.4 mg/d of beta 2M in the dialysate fluid. In patients with chronic renal failure, beta 2M levels paralleled the increase in serum creatinine. Patients who received kidney transplants had a dramatic decrease in beta 2M levels that correlated with improvement in GFR. beta 2M correlated with the residual GFR, and its removal was membrane-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Leg ulcers in patients with sickle cell disease.

During the entry examination, leg ulcers were present in 2.5% of 2,075 patients 10 years of age and older with sickle cell disease who entered into the Cooperative Study of Sickle Cell Disease (CSSCD) between 1979 and 1986. Prevalence rates were highest among patients with sickle cell anemia and sickle cell anemia with thalassemia genotypes. Among sickle cell anemia patients free of ulcers at entry, the overall incidence was 5.73 per 100 person years in those having associated alpha-thalassemia and 9.97 for those without. Among sickle cell anemia patients with two alpha genes, the estimated incidence of leg ulcers is 2.38 per 100 person years and 6.12 per 100 person years among sickle cell anemia patients with three alpha genes (P less than .05). In both groups, the incidence was highest among those patients over 20 years of age and considerably higher among males than females (P less than .001). Leg ulcers were nonexistent in patients with sickle beta plus thalassemia and sickle hemoglobin C disease. Low steady-state hemoglobin is associated with a higher incidence of ulcer formation (P less than .0001) in sickle cell anemia patients. The protective effect of hemoglobin F is apparent at all levels of total hemoglobin among sickle cell anemia patients and those with associated alpha-thalassemia.

Adolescent↗
PubMed1987

Nutritional effects of peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients.

Peritonitis, a major complication of end-stage renal disease patients treated with continuous ambulatory peritoneal dialysis (CAPD), enhances peritoneal protein losses by increasing protein and energy requirements while simultaneously decreasing appetite, usually causing a negative nitrogen balance. The influence of peritonitis on the nutritional status of CAPD patients was evaluated. Fourteen end-stage renal disease patients being treated with CAPD and presenting with peritonitis were randomized to one group with and one without a nutritional supplement. Four CAPD patients without peritonitis served as controls. Anthropometric measurements, laboratory determinations, dietary protein intake, and protein catabolic rate were obtained. The control group lost an average of 9.6 gm protein per 24 hours in the peritoneal fluid vs. an average of 15.1 gm protein per 24 hours lost by patients with peritonitis (p less than .01). Serum albumin did not decrease except in two diabetic patients in whom it dropped an average of 42% and remained low. Nitrogen balance remained positive in all patients except one with diabetes who had very low daily protein intake and caloric intake. The catabolism produced by short uncomplicated peritonitis did not create a negative nitrogen balance in patients eating at least 1 gm protein per kilogram ideal body weight (IBW) and 25 kcal/kg IBW.

Adult↗
PubMed1986

Comparison of microbiologic characteristics of pathogenic and saprophytic coagulase-negative staphylococci from patients on continuous ambulatory peritoneal dialysis.

Twenty-one microbiologically documented episodes of coagulase-negative staphylococcal peritonitis occurred in 21 continuous ambulatory peritoneal dialysis patients. All strains involved in these infections were tested for antimicrobial susceptibility and in vitro adherence assays. Twenty of the strains were species identified using two commercially available systems. For comparison, 20 saprophytic strains of coagulase-negative staphylococci obtained from the nares and axillae of 10 uninfected, peritoneal dialysis patients were included for in vitro characterization. Staphylococcus epidermidis was the species most often identified for both clinical and saprophytic strains. Eighteen of the 21 (86%) clinical strains were resistant to penicillin G. Methicillin resistance, which was present in five clinical strains, was not found in saprophytic strains. Adherence assay determinations showed marked differences between clinical versus colonization strains, with the clinical isolates significantly more adherent (p less than 0.025) than colonization strains. Electron microscopic examination of silastic catheter segments incubated with a strain of S. epidermidis in used and unused dialysis fluids demonstrated marked differences in attachment of bacteria to catheter material.

Bacterial Adhesion↗
PubMed1984

Pelvic extramedullary hematopoiesis.

Extramedullary hematopoiesis is an infrequent cause of thoracic masses. Extrathoracic locations are even less common. We have studied two patients, one with suspected pelvic neoplasm, with technetium-99m sulfur colloid marrow image and transmission computerized tomography. This noninvasive evaluation established the diagnosis of pelvic extramedullary hematopoiesis in both. We recommend a similar diagnostic approach in patients with chronic anemia or other predisposing disease, presenting with a pelvic or abdominal mass.

Adult↗
PubMed1983

Avascular necrosis of the hip in the sickle cell hemoglobinopathies.

Two hundred and eighty-one patients with sickle cell disease were studied clinically and radiographically with emphasis on diagnosis of epiphyseal abnormalities and potential complications of hip replacement. Nineteen percent of patients with hemoglobin SS disease had avascular necrosis of the femoral head (ANF) while a 9% incidence was found in hemoglobin SC disease. Twenty of 47 patients with ANF had no hip pain. The degree of anemia did not correlate well with symptoms. Thirteen patients with avascular necrosis of the hip underwent hip replacement and four developed prosthesis-related complications.

Adult↗
PubMed1979

Zinc metabolism in sickle cell anemia.

Zinc metabolism was studied in 34 patients with sickle cell anemia in a steady state and in six patients during sickle cell crisis. The patients in steady state were found to have significantly lower plasma levels and higher urinary levels of zinc than the 50 healthy adults in the control group. During sickle cell crisis the plasma zinc levels dropped to a mean value of 0.54 microgram/microL. These results support the concept that zinc deficiency occurs in sickle cell anemia and that further drops occur in the serum zinc levels during sickle cell crisis.

Anemia, Sickle Cell↗