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Biomedical subjects

M Walser

Publications and source records attributed to M Walser.

At least 19 recordsLinked to original sources
PubMed2005

Identification by genome scanning approach (GSA) of a microsatellite tightly associated with the apple scab resistance gene Vm.

For all known major apple scab resistance genes except Vr, molecular markers have been published. However, the precise position of some of these genes, in the apple genome, remains to be identified. Knowledge about the relative position of apple scab resistance genes is necessary to preliminarily evaluate the probability of success of their pyramidization. Pyramidization of different resistance genes into the same genotype is a reliable way to create cultivars with durable apple scab resistance. Applying the genome scanning approach (GSA), we identified the linkage group of the scab resistance gene Vm, derived from Malus micromalus, and we found a new molecular marker tightly associated with the gene. The simple sequence repeat Hi07h02, previously mapped on linkage group 17, cosegregates with the Vm gene (no recombinants in the 95 plants tested). The already published sequence-characterized amplified region Vm marker OPB12(687) was found to be linked at about 5 cM from the resistance gene and, therefore, this marker also maps on linkage group 17 of apple. This is the first report of the discovery of a major apple scab resistance gene on linkage group 17. The advantages of using GSA for the identification of molecular markers for qualitative traits are discussed.

Alleles↗
PubMed2000

Randomized double-blind trial of oral essential amino acids for dialysis-associated hypoalbuminemia.

BACKGROUND: Hypoalbuminemia is associated with substantial morbidity and mortality in dialysis patients. METHODS: Subjects with a mean three-month prestudy serum albumin of 3.8 g/dL or less and who demonstrated >/=90% compliance during a two-week run-in period were randomized to 3.6 g of essential amino acids (EAAs) or placebo three times daily with meals for three months. Randomization was stratified by dialysis modality and by severity of the hypoalbuminemia. The primary study outcome was change in the average of three monthly serum albumin measurements between baseline and follow-up. RESULTS: Fifty-two patients were randomized; 47 patients (29 hemodialysis and 18 peritoneal dialysis) met the predetermined primary analysis criteria. The mean compliance rates averaged 75, 70, and 50% at months 1, 2, and 3, respectively, and were similar for EAAs and placebo. Serum albumin in the hemodialysis patients, EAA versus placebo, improved [(mean +/- SE) 0.22 +/- 0.09 g/dL, P = 0.02]. Changes in peritoneal dialysis patients were not significant (0.01 +/- 0.15 g/dL), but approached significance for the total study group (0.14 +/- 0.08 g/dL, P = 0.08). Patients in the very low albumin strata (<3.5 g/dL) improved more than those in the low albumin strata (3.5 to 3.8 g/dL, P < 0.01). There was a significant correlation (r = 0.83, P = 0.001) within the hemodialysis EAA group between the baseline C-reactive protein level and improvement in serum albumin. Improvements were also seen in grip strength and SF-12 mental health score, but not in serum amino acid levels, SF-12 physical health score, or anthropometric measurements. CONCLUSIONS: Oral EAAs induce a significant improvement in the serum albumin concentration in hemodialysis but not peritoneal dialysis subjects. Further study of their long-term effects on morbidity and mortality is warranted.

Administration, Oral↗
PubMed1999

Enteral infusion of sodium 2-ketoisocaproate in endotoxic rats.

OBJECTIVE: In view of our previous finding that the intravenous infusion of 2-ketoisocaproate (KIC) improved survival in septic rats, we endeavored to determine whether the enteral infusion of KIC improves survival in endotoxic rats, and, if so, the mechanism of this effect. SUBJECTS: Eighty-five rats were given 15 mg/kg of Escherichia coli lipopolysaccharide (026:B6). INTERVENTIONS: KIC, sodium pyruvate (PYR), or sodium bicarbonate (HCO3) was infused continuously intragastrically at 18.75 mmol/kg/day. MEASUREMENTS AND MAIN RESULTS: KIC administration increased circulating concentrations of KIC and ketone bodies. Survival rates were: KIC 17/32; PYR 2/22; and HCO3 8/31. The significant improvement in survival with KIC, in contrast with HCO3 (p<.04) or PYR (p<.002), points to an effect specific to KIC rather than to ketoacids generally, and argues against an antioxidant mechanism to explain improved survival with enteral administration. To determine whether altered nitric oxide production was responsible, plasma nitrite plus nitrate concentrations were measured sequentially in rats given a lower dose of lipopolysaccharide plus continuous intragastric KIC, PYR, or HCO3. All rats exhibited pronounced increases in plasma nitrite plus nitrate concentrations, peaking at 8 hrs, but both KIC and PYR caused greater increases than HCO3. Thus, differences in nitric oxide production cannot account for the different effects of PYR and KIC on survival. However, KIC infusion for 8 hrs substantially increased ketone bodies in blood and liver, in comparison with the infusion of HCO3 or PYR. CONCLUSION: Continuous enteral infusion of KIC improves survival in endotoxemia, probably by its conversion to ketone bodies, which serve as an alternative energy substrate.

Animals↗
PubMed1999

Can renal replacement be deferred by a supplemented very low protein diet?

Patients with chronic renal failure are commonly started on renal replacement therapy (RRT) as soon as (or, in some centers, before) the usual criteria for severity are met, i.e., GFR <10 ml/min for nondiabetic patients and <15 ml/min for diabetic patients. To determine whether RRT can safely be deferred beyond this point, adults with all types of chronic renal failure who met these criteria on presentation (23 patients) or who reached these levels of severity during treatment (53 patients) were managed conservatively until RRT was judged necessary by their chosen dialysis or transplantation team, without input into this decision from the present authors. Patients were prescribed a very low protein diet (0.3 g/kg) plus supplemental essential amino acids and/or ketoacids and followed closely. The intervals between the time at which GFR became less than 10 ml/min (15 ml/min in diabetic patients) and the date at which renal replacement therapy was started were used as estimates of renal survival on nutritional therapy. Kaplan-Meier analysis showed median renal survival of 353 d. Acidosis and hypercholesterolemia were both predictive of shorter renal survival. Signs of malnutrition did not develop. Final GFR averaged 5.6 +/- 1.9 ml/min. Two patients died; thus, annual mortality was only 2.5%. Hospitalizations totaled 19 in 93 patient-years of treatment, or 0.2 per year. Thus, these well motivated patients with GFR <10 ml/min (<15 ml/min in diabetic patients) were safely managed by diet and close follow-up for a median of nearly 1 yr without dialysis. It is concluded that further study of this approach is indicated.

Adolescent↗
PubMed1998

Assessing renal function from creatinine measurements in adults with chronic renal failure.

Measurement of glomerular filtration rate (GFR) following the injection of one of several suitable marker substances remains the best method to determine the severity of renal insufficiency as well as its rate of progression. However, the expense of these procedures continues to restrict their use. A second alternative is the determination of creatinine clearance (CCr) after oral administration of cimetidine. This drug blocks tubular secretion of creatinine almost completely, and CCr measured under these conditions is reported to be nearly identical to GFR in mild or severe renal failure. The optimal dose and timing of cimetidine for this purpose is still uncertain, but a single 1,200-mg dose 2 hours before beginning urine collection is probably suitable. A third alternative is simply the measurement of serum or plasma creatinine (PCr) concentration. However, it is well established that substantial reductions in renal function may occur before PCr becomes abnormal. GFR in adults with chronic renal failure can be approximately estimated from PCr, provided it is greater than 2 mg/dL, with the aid of additional demographic and biochemical variables. Gender, height, weight, age, and race should be taken into account. Further study is needed to derive the best formula for predicting GFR from PCr and other variables. Finally, CCr (without cimetidine) is still in use. This is unfortunate because it has been established that rather than improving on the estimation of GFR from PCr, CCr (determined from urinary creatinine measurements as well as PCr) is a less reliable guide to GFR than PCr alone. The CCr/GFR ratio is almost always greater than unity and increases with decreasing GFR to a maximum of approximately 1.7 at a GFR of approximately 20 mL/min. Furthermore, the variability of CCr is greater than that of PCr. Measurement of CCr (without cimetidine) is an anachronism and should be abandoned.

Adult↗
PubMed1998

Effects of a supplemented very low protein diet in predialysis patients on the serum albumin level, proteinuria, and subsequent survival on dialysis.

A very low protein diet (0.3 g/kg ideal body weight) supplemented with essential amino acids (or ketoanalogues) is seldom employed at present in chronic renal failure for fear of inducing protein deficiency, especially in patients who also have the nephrotic syndrome. Nevertheless, we have used this dietary regimen in predialysis patients for a number of years. We have shown that when these patients reach the end stage, they rarely exhibit hypoalbuminemia, in contrast to the reported 25-50% hypoalbuminemia at the onset of dialysis nationwide. Furthermore, their survival for the first 2 years on dialysis is much improved, in comparison with the national experience, adjusted for age, sex, and cause of renal disease. When nephrotic patients are given this regimen, they exhibit some improvement in parameters of the nephrotic state, but nevertheless progress to dialysis, provided their initial glomerular filtration rate (GFR) is < 30 ml/min. However, if their initial GFR is > 30 ml/min, they may show gradual but complete remission of the nephrotic syndrome, even when the underlying disease is diabetic nephropathy or focal segmental glomerulosclerosis. We conclude that this dietary regimen is not only safe in patients with renal failure, with or without the nephrotic syndrome, but may be of substantial benefit. The mechanism remains to be explained.

Dietary Proteins↗
PubMed1998

Effect of a ketoacid-aminoacid-supplemented very low protein diet on the progression of advanced renal disease: a reanalysis of the MDRD feasibility study.

BACKGROUND: We reanalyzed the data of the Modification of Diet in Renal Disease (MDRD) feasibility study to ascertain the effects of ketoacid- and aminoacid-supplemented very low protein diets. METHODS: Sixty-six patients with advanced renal disease (Study B, baseline glomerular filtration rate (GFR) 7.5-24 ml/min/1.73 m2) were randomly assigned to a low protein diet (L, 0.575 g/kg/d), or a very low protein diet (0.28 g/kg/d) supplemented either with a ketoacid-aminoacid mixture (diet K) or with a mixture of essential aminoacids (diet J). Thirty patients with moderate renal disease (Study A, baseline GFR 25-80 ml/min/1.73 m2) were randomly assigned to a usual protein diet (M, 1.2 g/kg/d), diet L, or diet K. Mean follow-up was 14 months. RESULTS: In Study B, GFR decline differed among the three diets (p = 0.028). Pairwise comparisons showed that the mean +/- SE GFR decline in ml/min/mo in diet K [-0.250+/-0.072] was slower than in diet J [-0.533+/-0.074] (p = 0.008) despite similar achieved protein intakes. The mean GFR decline in diet L [-0.394+/-0.068] was intermediate between, and did not differ significantly from the rates of decline in the other two groups. In Study A, consistent with a hemodynamic effect, the mean GFR decline varied directly with the reduction in protein intake in diets M, L and K (p = 0.028) during the first four months of follow-up, but thereafter did not differ among the diet groups (p = 0.76). CONCLUSION: The study suggests that supplementation of a very low protein diet with the ketoacid-aminoacid mixture used in this feasibility study slowed the progression of advanced renal disease more than supplementation with an amino acid mixture.

Adult↗
PubMed1997

Effect of ketoconazole plus low-dose prednisone on progression of chronic renal failure.

Patients with any of four different types of chronic renal failure (CRF) (glomerular disease, interstitial nephritis, diabetic nephropathy, or polycystic disease) were observed using sequential determinations of glomerular filtration rate (GFR). Those whose GFR showed progression were either given ketoconazole 200 to 600 mg/d (to suppress cortisol production) plus prednisone 2.5 mg/d (to prevent anterior pituitary escape) and observed with the use of more GFRs, or were observed while four additional GFRs were determined before starting these drugs; some patients were subsequently withdrawn from these drugs and were observed using more GFRs. The effect of these drugs on rate of progression was estimated by a linear spline technique, using observations before, during, and (when available) after treatment. In 20 patients, sufficient data were obtained to estimate the magnitude of this effect. In seven patients with chronic glomerular disease, progressing at -0.62 +/- 0.12 mL/min/mo, progression slowed by 66% +/- 12% (P < 0.01). In five patients with interstitial nephritis of various etiologies, progressing at -1.19 +/- 0.34 mL/min/mo, progression slowed by 55% +/- 27% (P < 0.05). In five diabetic patients progressing at -1.22 +/- 0.14 mL/min/mo, progression slowed by an average of 77% +/- 14% (P < 0.01). In contrast, in four patients with polycystic kidney disease, progression accelerated by 99% +/- 63%. Mean urinary steroid excretion decreased significantly; plasma corticotropin did not increase. Neither proteinuria nor serum lipid levels changed. Urinary nitrate excretion decreased significantly, but serum nitrate did not change. Blood pressure decreased slightly (4.3 mm Hg). Three patients developed transiently elevated serum transaminase levels; two others withdrew because of side effects. We conclude that in chronic glomerular disease, diabetic nephropathy, and interstitial nephritis, this combination of drugs is as safe as ketoconazole in the absence of renal disease and shows promise of slowing progression. In polycystic kidney disease, it is apparently ineffective or harmful.

Adrenocorticotropic Hormone↗
PubMed1996

Treatment of nephrotic adults with a supplemented, very low-protein diet.

Optimal dietary protein intake for adults with the nephrotic syndrome has not been established; very low-protein diets are believed to be contraindicated. Sixteen patients with the nephrotic syndrome were nevertheless prescribed a very low protein diet (0.3 g/kg) supplemented by 10 to 20 g/d essential amino acids (or, in a few cases, ketoacids) for an average of 10 months (range, 1 to 36 months). In 11 patients with initial glomerular filtration rates (GFRs) < or = 30 mL/min/3 m2 of height (ht)2, significant but modest improvement was seen (on the average) in proteinuria, serum albumin, and serum cholesterol; all 11 eventually went on to dialysis. The other five patients, with initial GFRs of 32 to 69 ml/min/3 m2 of ht2, had either focal segmental glomerulosclerosis, diabetic nephropathy, or, in one patient, both. The nephrotic syndrome associated with these disorders rarely remits spontaneously. However, during the following 3 to 15 months mean proteinuria decreased from 9.3 to 1.9 g/d, mean serum albumin increased from 2.5 g/dL to 3.8 g/dL, and mean serum cholesterol decreased from 415 mg/dL to 255 mg/dL (all P < 0.001). The GFR either remained constant or increased. Four of these five patients have resumed normal or nearly normal diets and remain in remission or near-remission for 6 to 24 months. We conclude that severe protein restriction plus an essential amino acid supplement may induce prolonged remission in adults with the nephrotic syndrome provided that GFR is not severely reduced. The mechanism of this paradoxical response to protein restriction remains to be determined.

Adult↗
PubMed1995

Survival on dialysis among chronic renal failure patients treated with a supplemented low-protein diet before dialysis.

Concerns have been raised about the possibility of protein restriction resulting in malnutrition and poor subsequent survival on dialysis. However, no studies have examined patients treated with protein restriction to determine their subsequent survival on dialysis. This study prospectively monitored 67 patients with established chronic renal failure (mean initial serum creatinine of 4.3 mg/dL) who were treated with a very low-protein diet (0.3 g/kg per day) supplemented with either essential amino acids or a ketoacid-amino acid mixture and observed closely for clinical complications. Forty-four patients required dialysis. Once dialysis was started, dietary treatment was no longer prescribed. The cumulative mortality rate during the first 2 yr after starting dialysis was 7% (95% confidence interval, 0 to 16%). During this period, only two deaths occurred compared with 11.5 deaths expected on the basis of national mortality rates adjusted for age, sex, race, and cause of renal disease (P = 0.002). However, the protective effect was limited to the first 2 yr on dialysis. Thereafter, mortality rates increased, resulting in a total of 10 deaths during 96.4 person-years of follow-up, which was not significantly lower than the 14.9 deaths expected (P = 0.25). Extrapolation of sequential serum creatinine measurements made before dietary treatment suggests that the improved survival cannot be due to the early initiation of dialysis. Although the lack of an internal control group and data on dialysis lends uncertainty, the large difference in mortality rate between these patients and the nationwide experience indicates that protein restriction and close clinical monitoring predialysis does not worsen and may substantially improve survival during the first 2 yr on dialysis. These findings point out the importance of studying predialysis treatments as a means for lowering mortality on dialysis.

Adult↗
PubMed1994

Patterns of fasting plasma amino acid levels in chronic renal insufficiency: results from the feasibility phase of the Modification of Diet in Renal Disease Study.

Fasting plasma amino acid levels were measured in 78 patients with chronic renal insufficiency (glomerular filtration rate [GFR], 8.0 to 56.0 mL/min), who had been enrolled in phase II of the Modification of Diet in Renal Disease study, prior to their beginning the experimental portion of the protocol. Alterations in many plasma amino acid levels were observed in the patients with the mildest degrees of renal insufficiency, and the number and severity of abnormalities tended to be greater in the patients with more severe renal failure. In patients with GFRs greater than 24.5 mL/min, 15 to 24.5 mL/min, and less than 15 mL/min, statistically significant abnormalities were observed in the concentrations or ratios of 9, 14, and 18 amino acids, respectively. The following correlations of amino acid levels or ratios with GFR were observed (all P < 0.001): citrulline, r = -0.41; citrulline to arginine ratio, r = -0.42; glycine to serine ratio, r = -0.37; N-tau methylhistidine, r = -0.65; and cystine, r = -0.37. Other weaker correlations observed were valine, r = 0.26 (P < 0.025); valine to glycine ratio, r = 0.32 (P = 0.004); and sum of isoleucine, leucine, and valine, r = 0.21 (P = 0.061). N-tau methylhistidine and the essential to nonessential amino acid ratio became altered with declining GFR in a nonlinear fashion. Thus, many of the characteristic alterations in the plasma amino acid profile that are observed in chronic end-stage renal disease are already present in mild renal insufficiency. Progressive loss of renal function generally results in increasing abnormalities; these changes in plasma amino acid concentrations with reduction in GFR were usually linear.

Adult↗
PubMed1994

Nutritional therapy for progressive renal failure.

Results of the Diabetes Control and Complications Trial indicate that intensive insulin treatment of patients with type I diabetes would greatly reduce the incidence of diabetic nephropathy. Another multicenter trial indicates that modest protein restriction is of no value in children with chronic renal failure. The relationship between urea nitrogen excretion and total nitrogen excretion in children differs from that in adults. A repeated crossover study found that ketoacids slow progression of renal failure, in comparison with amino acid supplements to the same diet. Long-term protein restriction does not lead to protein deficiency at the onset of dialysis. When combined with essential amino acid supplements, a low-protein diet may gradually correct hypoalbuminemia in nephrotic subjects.

Amino Acids↗