Are lipid values and BMI related to hospitalizations in the hemodialysis population?

OBJECTIVE: To examine the relationship between lipid values and BMI (body mass index) on hospitalizations in hemodialysis (HD) patients. DESIGN: Retrospective (2-year) study. SETTING: Outpatient dialysis center in a large metropolitan city. PATIENTS: This study used 158 HD patients stratified on the basis of ethnicity (non-Black and Black) and diabetic status (nondiabetic and diabetic). INTERVENTION: Subjects were observed for 2 years. Body weight, BMI, lipid parameters, and hospitalization duration were determined 8 times (3-month intervals). MAIN OUTCOME MEASURES: Body weight, BMI, lipid parameters (serum triglyceride concentration, serum total cholesterol, high-density lipoprotein [HDL]-, low-density lipoprotein [LDL]-, very low-density lipoprotein [VLDL]- cholesterol concentrations, serum Apo-protein A1 [Apo-A1] concentration, and serum Apo-protein B [Apo-B] concentration), and morbidity data were recorded. RESULTS: Hemodialysis subjects were hospitalized 2.3 +/- 1.6 times over the 2-year experimental period. Length of hospital stay averaged 6.6 +/- 0.5 days/hospitalization. Length of hospital stay was inversely related to HDL concentration (r = -0.21, P <.05, n = 89), but not significantly related to BMI in HD subjects. BMI was positively associated with LDL concentration (r = +0.28, P <.01, n = 97). Cholesterol concentration was directly associated with LDL concentration (r = +0.52, P <.01, n = 138), VLDL concentration (r = +0.47, P <.01, n = 139), and triglyceride concentration (r = +0.54, P <.01, n = 155). Mean concentration of HDL-cholesterol was inversely related serum triglyceride concentration (r = -0.43, P <.01, n = 140). Although Apo-A1 concentration was directly associated with HDL level (r = +0.39, P <.01, n = 139), Apo-B was inversely related to HDL level (r = -0.37, P <.01, n = 138) and directly related to cholesterol concentration (r = +0.71, P <.01, n = 138), VLDL concentration (r = +0.87, P <.01, n = 138), and triglyceride concentration (r = +0.81, P <.01, n = 138). CONCLUSION: Cardiac disease remains the primary cause of morbidity and mortality in HD patients, and results of the present study suggest that dyslipidemias present in the HD population negatively impact cardiovascular profiles which, in turn, influence the frequency/duration of hospitalizations. Among all lipid parameters analyzed in the present study, increased LDL and decreased HDL concentrations were more strongly related to length of hospital stay than was BMI.

The effects of zinc supplementation on serum zinc concentration and protein catabolic rate in hemodialysis patients.

OBJECTIVE: To examine the effect of zinc sulfate supplementation on serum zinc concentrations and protein catabolic rate (PCR) in hemodialysis (HD) patients. DESIGN: Randomized, double-blind, before-after trial. SETTING: Outpatient dialysis center in a large metropolitan city. PATIENTS: Twenty-eight maintenance HD patients were selected. Twenty (15 women, 5 men) subjects completed the study. Subjects were identified for inclusion in the study by the following criteria: a history of low PCR (<0.09 g/kg body weight), HD treatment for a minimum of 6 months, no signs of gastrointestinal disorders, and no record of hospitalizations for reasons other than access complication within the last 3 months. INTERVENTIONS: Patients consumed 7.7 pmol zinc sulfate (2,200 microg) or a cornstarch placebo capsule daily for 90 days. In addition, patients completed a 2-day food record representative of 1 dialysis day and 1 nondialysis day. MAIN OUTCOME MEASURE: Fasting, predialysis serum samples were collected on days 0, 40, and 90 to determine serum zinc concentration and PCR. Dietary parameters including intake of zinc, protein, and energy were analyzed on Days 0 and 90. RESULTS: Initial analysis at Day 0 of serum zinc concentration indicated subjects were below the normal range for serum zinc standards (12.2 micromol/L [80 microg/dL]). After supplementation, subjects in the zinc-supplemented group showed significant increases in serum zinc concentrations from 12.2 micromol/L (80 microg/dL) at Day 0 to 15.3 pmol/L (100 microg/dL) at Day 90. A significant positive correlation (r = +0.61) was shown between PCR and serum zinc concentrations at the end of the study. Reported dietary protein intake did not change with zinc supplementation. CONCLUSION: Low serum zinc concentrations are reversible with zinc supplementation. Improvement in serum zinc concentration increases the PCR of HD patients.

Substitution of Asp-210 in HAP1 (APE/Ref-1) eliminates endonuclease activity but stabilises substrate binding.

HAP1, also known as APE/Ref-1, is the major apurinic/apyrimidinic (AP) endonuclease in human cells. Previous structural studies have suggested a possible role for the Asp-210 residue of HAP1 in the enzymatic function of this enzyme. Here, we demonstrate that substitution of Asp-210 by Asn or Ala eliminates the AP endonuclease activity of HAP1, while substitution by Glu reduces specific activity approximately 500-fold. Nevertheless, these mutant proteins still bind efficiently to oligonucleotides containing either AP sites or the chemically unrelated bulky p-benzoquinone (pBQ) derivatives of dC, dA and dG, all of which are substrates for HAP1. These results indicate that Asp-210 is required for catalysis, but not substrate recognition, consistent with enzyme kinetic data indicating that the HAP1-D210E protein has a 3000-fold reduced K(cat )for AP site cleavage, but an unchanged K(m). Through analysis of the binding of Asp-210 substitution mutants to oligonucleotides containing either an AP site or a pBQ adduct, we conclude that the absence of Asp-210 allows the formation of a stable HAP1-substrate complex that exists only transiently during the catalytic cycle of wild-type HAP1 protein. We interpret these data in the context of the structure of the HAP1 active site and the recently determined co-crystal structure of HAP1 bound to DNA substrates.

Structure of the AAA ATPase p97.

p97, an abundant hexameric ATPase of the AAA family, is involved in homotypic membrane fusion. It is thought to disassemble SNARE complexes formed during the process of membrane fusion. Here, we report two structures: a crystal structure of the N-terminal and D1 ATPase domains of murine p97 at 2.9 A resolution, and a cryoelectron microscopy structure of full-length rat p97 at 18 A resolution. Together, these structures show that the D1 and D2 hexamers pack in a tail-to-tail arrangement, and that the N domain is flexible. A comparison with NSF D2 (ATP complex) reveals possible conformational changes induced by ATP hydrolysis. Given the D1 and D2 packing arrangement, we propose a ratchet mechanism for p97 during its ATP hydrolysis cycle.

The crystal structure of the human DNA repair endonuclease HAP1 suggests the recognition of extra-helical deoxyribose at DNA abasic sites.

The structure of the major human apurinic/ apyrimidinic endonuclease (HAP1) has been solved at 2.2 A resolution. The enzyme consists of two symmetrically related domains of similar topology and has significant structural similarity to both bovine DNase I and its Escherichia coli homologue exonuclease III (EXOIII). A structural comparison of these enzymes reveals three loop regions specific to HAP1 and EXOIII. These loop regions apparently act in DNA abasic site (AP) recognition and cleavage since DNase I, which lacks these loops, correspondingly lacks AP site specificity. The HAP1 structure furthermore suggests a mechanism for AP site binding which involves the recognition of the deoxyribose moiety in an extrahelical conformation, rather than a 'flipped-out' base opposite the AP site.

Proximal renal tubular acidosis secondary to FK506 in pediatric liver transplant patients.

We hereby report our experience with an index case of a pediatric liver transplant patient in whom FK506 administration was associated with the development of proximal renal tubular acidosis (RTA), as well the prevalence of acidosis and renal dysfunction in all pediatric liver transplant patients in our institution followed long term during a 6-year period. Data were grouped according to immunosuppressant regime: cyclosporine (CsA) only, FK506 only, or CsA with conversion to FK506. A 23-month-old female treated with FK506 after orthotopic liver transplantation (OLT) performed 15 months earlier presented with a 1-wk history of fever, watery diarrhea and metabolic acidosis. Although the acidosis did not improve following correction of her hydration status, administration of oral bicarbonate was effective. Discontinuation of this therapy resulted in acidosis. Since other indirect measurements of renal tubular function were normal, the patient was judged to have an isolated proximal RTA. In our group of pediatric liver transplant patients converted from CsA to FK506, FK506 administration was associated with a decline in serum bicarbonate (19 +/- 1 vs. 16 +/- 1 mEq/l, p < 0.02); neither blood urea nitrogen nor serum creatinine differed between the two groups. The number of rejection episodes/patient/month was comparable, allowing clinically relevant comparison of relative drug nephrotoxicities. We conclude that proximal RTA may be a relatively common treatable complication of FK506 administration in children.

Effect of major dietary modifications on immune system in patients with breast cancer: a pilot study.

A pilot study was conducted to evaluate the effect of diet on immune function in nine premenopausal, post-therapy patients with breast cancer. The patients were instructed on following the American Cancer Society dietary guidelines and were told to do so from day 0 to day 28. These guidelines recommend a high-fiber, low-fat diet. On day 29, the patients continued the diet but included fish high in omega-3 fatty acids until day 56. Twenty-four-hour urine and blood samples, and 3-day diet records were obtained on days 0, 28, and 56. The following parameters were monitored: lymphocyte subsets, T-cell function (proliferation and cytolytic response), and urinary prostaglandin E2 (PGE2). Results throughout the study suggested a benefit from decreasing dietary fat intake, and increasing fish intake. Helper T-cell (CD4) percentage increased from day 0 to days 28 and 56 (P = 0.048). Cytotoxic/suppressor T-cell (CD8) percentage decreased from day 0 to days 28 and 56 (P = 0.002). The CD4/CD8 cell ratio increased by days 28 and 56 (P = 0.0004). The proliferation of CD4 cells increased from day 0 to days 28 and 56 (P = 0.005). Significant changes were not found in the cytolytic activity of T cells, natural killer cells, total T and B cells, or urinary prostaglandin E2. Results suggest that patients with breast cancer may benefit from following American Cancer Society dietary guidelines and consuming cold-water ocean fish.

Effects of omega-3 and omega-6 fatty acid-rich oils on the cardiovascular system of thermally injured rabbits: changes in plasma triglycerides, plasma cholesterol, relative blood viscosity, platelet count, and bleeding time.

New Zealand white male rabbits were studied to determine how supplements of soybean oil, soybean + MaxEPA oil, or MaxEPA oil affected their cardiovascular status when they were burned. Plasma triglyceride concentrations increased at 2 hours after burn injury (28 days after supplement administration) and declined by the end of the study in all three experimental groups of rabbits. These same animals showed no noticeable differences in the plasma concentrations of total cholesterol or in the high-density lipoprotein cholesterol subfractions. Plasma low-density/very-low-density lipoprotein cholesterol levels remained unchanged at 2 hours after burn injury/sham treatment but increased by the end of the study in all three experimental groups of rabbits. The mean platelet number was significantly higher in burned/sham treated rabbits given soybean oil supplement as compared with numbers in those given either soybean oil + MaxEPA oil or MaxEPA oil supplement. Plasma relative viscosity was highest in the soybean oil-supplemented rabbits, decreased in animals fed soybean oil + MaxEPA, and lowest in MaxEPA oil-supplemented rabbits. Mean bleeding time was lowest in soybean oil-fed rabbits. The bleeding time was higher in rabbits fed soybean oil+MaxEPA oil and highest in MaxEPA oil-supplemented animals. Platelet number and plasma viscosity were highest in the soybean oil-supplemented rabbits and lowest in the MaxEPA oil-supplemented group. The reverse pattern occurred when bleeding time was established. Overall results obtained suggest that supplementation with oils rich in omega-3 and omega-6 fatty acids may have significant effects on the cardiovascular health of burned male New Zealand white rabbits.

Effects of supplemented omega-3 and omega-6 fatty acid rich oils on the cardiovascular system of thermally injured rabbits: changes in plasma and platelet fatty acids.

The effects of omega-3 fatty acid rich oil (MaxEPA oil), omega-6 fatty acid rich oil (soybean oil), and a combination of omega-3 and omega-6 oils (MaxEPA oil + soybean oil) on cardiovascular health-related parameters of thermally injured and control (sham) rabbits were determined. Plasma and platelet analyses of burned rabbits fed with MaxEPA oil revealed significantly higher concentrations of eicosapentaenoic acid and docosahexaenoic acid + myristic acid. Linolenic acid concentrations declined in animals supplemented with soybean oil + MaxEPA oil. At the end of this study the lowest concentrations of linoleic acid and arachidonic acid were found in the sham and burned groups supplemented with soybean oil + MaxEPA oil. Overall, favorable significant differences in plasma and platelet fatty acids concentrations were found in burned or sham groups supplemented with MaxEPA when compared with those of groups supplemented with soybean oil. These favorable changes in plasma and platelet lipids may have an impact on the risk of cardiovascular disease in thermally injured patients.

Resting energy expenditures measured by indirect calorimetry are higher in preadolescent children with cystic fibrosis than expenditures calculated from prediction equations.

OBJECTIVE: This study compared measured resting energy expenditures to resting energy expenditures calculated using Harris-Benedict equations (HBEs) and the Cystic Fibrosis Consensus Committee equations (CFCCEs). DESIGN: We studied 31 preadolescent boys and girls with cystic fibrosis who ranged in age from 3.25 to 12.75 years old. The patients were afebrile and not in pulmonary distress. Measured resting energy expenditures were determined using a portable metabolic measurement cart with fully automated calibration and data management. The measured resting energy expenditures obtained were compared with values obtained using HBEs and CFCCEs. RESULTS: For each patient, the measured resting energy expenditure value was above the predicted resting energy expenditure values derived from HBEs (P < or = .0001) and CFCCEs (P < or = .01). APPLICATIONS: The HBEs and the CFCCEs underestimated the energy expenditures of the study population by 13% and 8%, respectively. These findings support the usefulness of the measurement of energy expenditures in determining the energy needs of preadolescent patients with cystic fibrosis. In clinical practice, the resting energy expenditures would be multiplied by activity coefficients to determine the total daily energy expenditures of this population.

Crystal structure of a disulfide-linked "trefoil" motif found in a large family of putative growth factors.

Porcine pancreatic spasmolytic polypeptide (PSP) belongs to a large family of homologous growth factor-like polypeptides characterized by a disulfide-linked "trefoil motif," duplicated and conserved in various family members. PSP contains two trefoil motifs, has several pharmacological actions on the gut, and has growth factor properties on epithelial cells in vitro. The human PSP analogue, human spasmolytic polypeptide, appears to be involved in many regenerative situations and, especially, in healing gastrointestinal ulcers. One member of the trefoil family, pS2, is secreted in approximately 50% of estrogen-dependent human breast carcinomas, which has led to its use as a tumor prognostic marker. Both pS2 and human spasmolytic polypeptide are also widely expressed in chronic gastrointestinal ulcerative conditions such as Crohn disease. Here we report the three-dimensional structure at 2.6-A resolution of a trefoil-containing protein, namely PSP, purified from porcine pancreas. The structure shows two homologous domains that share a supersecondary structure and disulfide bond pattern. The two domains pack asymmetrically giving rise to a number of protruding loops, exposed clefts, and an unusual electrostatic surface potential. Knowledge of the structure of PSP should allow the design of mutants to investigate further the function of PSP and other trefoil-containing peptides.

Subjective global assessment: alternative nutrition-assessment technique for liver-transplant candidates.

The interpretation of most objective nutrition assessment parameters is affected by liver disease. A subjective global assessment (SGA) tool adapted for assessment of adult liver-transplant candidates was evaluated for interobserver reproducibility. Two dietitians assessed 20 liver-transplant candidates in regard to 25 SGA parameters based on patient history, physical appearance, and existing clinical conditions. Fifteen percent of the patients were found to be well nourished, 70% moderately malnourished, and 15% severely malnourished. Raters agreed on the nutrition status of the patients 80% of the time. Twelve individual parameters showed fair to good interrater reliability (kappa > or = 0.500). Muscle wasting and fat depletion were determined to be the strongest predictors of the final SGA rating (kappa = 0.737, p < 0.0001, kappa = 0.632, p < 0.0001, respectively). The assessment tool itself was determined to be reliable by the Cronbach coefficient alpha-test (0.707). Although this assessment method has limitations, the findings of this study suggest that SGA as an alternative test for assessing the nutrition status of adult liver-transplant candidates has an overall fair to good interobserver reproducibility rate.

Prevalence and characteristics of Blastocystis hominis infection in children.

Blastocystis hominis, a protozoan whose pathogenicity has been questioned, is sometimes found in the human gastrointestinal tract. We sought to determine the prevalence of Blastocystis in stool and to characterize clinical features of infection with Blastocystis in children. Forty-six (3%) of 1,736 patients undergoing fecal microscopy at Children's Hospital of Pittsburgh between January 1, 1985, and December 31, 1988, harbored Blastocystis. Of these 46 children, 75% had exposure to well water or had been in developing countries. Thirty-nine of the 46 (85%) experienced gastrointestinal symptoms, such as abdominal pain, diarrhea, vomiting, and weight loss. Blastocystis was the only parasite found in 35 of those 39 symptomatic children. Symptoms resolved within one month in 90% of patients receiving antiparasitic pharmacotherapy, but in only 58% (P < .04) of those receiving no therapy. We conclude that children infected with Blastocystis often experience gastrointestinal symptoms and that treatment increases the rate of symptomatic improvement. We speculate that Blastocystis is a human pathogen.

Crystallization and preliminary X-ray diffraction studies of pancreatic spasmolytic polypeptide.

Pancreatic spasmolytic polypeptide (PSP) isolated from porcine pancreas has been crystallized by the hanging drop vapour diffusion method. The crystals belong to the space group I222 or I2(1)2(1)2(1) with cell dimensions a = 181.9 A, b = 54.5 A, c = 72.9 A. The crystals diffract to at least 2.5 A resolution and the asymmetric unit contains two molecules (Vm = 3.9 A3/Da) with a solvent content of 68% as determined by density measurements of the crystals. The self-rotation function suggests that the two molecules within the asymmetric unit are related by a 2-fold axis at either 30 degrees or 60 degrees from a in a plane perpendicular to the b axis.

Lack of effect of vitamin B-6 supplementation on the lipoprotein profile of post-menopausal chronic hemodialysis patients.

This study was designed to analyze the effect of vitamin B-6 supplementation on the lipoprotein profile of chronic hemodialysis patients. Individuals on chronic hemodialysis experience an acceleration of atherosclerosis, which is often accompanied by abnormal lipid metabolism. Although total plasma cholesterol is usually normal, high-density-lipoprotein (HDL) cholesterol is often low. Recently, it has been suggested that the development of atherosclerotic lesions in chronic hemodialysis patients may be the result of a decreased plasma concentration of pyridoxal 5'-phosphate (PLP) and concomitant alterations in plasma amino acid and/or lipoprotein profiles. All subjects in this study were supplemented with 0.97 mmol (200 mg) pyridoxine hydrochloride per day for 28 days; then, concentrations of PLP, total cholesterol, and lipoprotein cholesterol fractions were determined in the plasma. No significant difference was noted in PLP concentration between Group 1 (five post-menopausal women with a history of atherosclerosis who were undergoing maintenance hemodialysis therapy) and Group 2 (six subjects who were non-symptomatic). However, both groups had significant increases in PLP concentrations between the pre- and post-supplementation periods (p less than .01). In contrast, there was a statistically significant difference in total plasma cholesterol and very-low-density- and low-density-lipoprotein (VLDL and LDL) cholesterol concentrations between groups, but no significant changes in total cholesterol or VLDL and LDL cholesterol content were found during vitamin B-6 supplementation. No statistically significant differences in HDL, HDL2, and HDL3 cholesterol concentrations were observed between Group 1 and Group 2 subjects or within either group during vitamin B-6 supplementation.

Effect of aspartame on plasma amino acid profiles of diabetic patients with chronic renal failure.

A randomized, double-blind study was conducted to determine the possible effects of aspartame on the plasma amino acid profiles of 23 diabetic patients with renal failure who were undergoing maintenance hemodialysis. Subjects were given a single dose of 10 mg aspartame/kg (approximately equivalent to 25 packets of Equal [NutraSweet Consumer Products, Inc, Chicago, IL] or the amount of phenylalanine in a 300-mL glass of milk) or a placebo in a crossover study design. Three postdialysis blood samples were drawn just before and 1 and 2 h after aspartame or placebo consumption. After aspartame consumption statistically significant increases in only two amino acids, phenylalanine and tyrosine, were noted at 1 and 2 h when compared with placebo values. The increases in phenylalanine were within the normal postprandial range for healthy subjects; no other increases in essential or nonessential amino acids, except for tyrosine, were detected. This study supports the view that aspartame is safe for diabetic subjects with chronic renal failure.

Attributes and qualifications that employers seek when hiring dietitians in business and industry.

A study was conducted to assess the employment trends of dietitians in business and industry and to identify attributes and qualifications essential to succeed in this segment of the industry. Results of the delphi process were utilized in the design of a questionnaire which would identify attributes and qualifications essential for success. The questionnaire was administered to a random sample of 300 members of the Dietitians in Business and Industry Practice Group and 300 prospective and current employers of dietitians. Response rates of 45.7% (no. = 137) and 29.0% (no. = 87) were attained for the dietitians and employers, respectively. The majority of current employers (72%) and prospective employers (62%) and dietitians (73%) responded that the trend of hiring dietitians in business and industry was increasing. Both dietitians (53%) and employers (41%) reported that new positions were being created for dietitians in their organizations. Operational experience was more important for positions in sales, whereas clinical experience was more important for positions in manufacturing organizations. Employers ranked a master's degree in business administration (MBA) as the second most important qualification; dietitians rated the MBA as fifteenth in importance. Dietitians ranked registration status (RD) as, fourth in importance; however, employers rated registration status as least important of the qualifications. Both employers and dietitians ranked communication skills as essential to succeed in business and industry positions.