Pauline B. Darling

Longitudinal trends in nutritional status and the relation between lung function and BMI in cystic fibrosis: a population-based cohort study

BACKGROUND A high-calorie diet has been a standard of care in cystic fibrosis (CF) for >3 decades. However, energy requirements may have changed with new treatments and milder genotypes. OBJECTIVES The objectives of this study were to describe longitudinal trends in nutritional status and to evaluate the relation between nutritional status and lung function. DESIGN This longitudinal cohort study included 909 individuals followed at the Adult CF Clinic in Toronto from 1985 to 2011. Nutritional status was classified on the basis of WHO BMI guidelines. Multivariable linear regression with the use of generalized estimating equations was applied to evaluate the relation between BMI and lung function. RESULTS The proportion of underweight individuals decreased from 20.6% before 1990 to 11.1% in the most recent decade, whereas the proportion of overweight and obese subjects increased from 7.0% to 18.4% (P < 0.001). Overweight and obese subjects were older, had better lung function, had milder genotypes, and were more often male and pancreatic sufficient. Multivariable regression analyses showed that within the underweight group, an increase in BMI resulted in improved lung function, whereas this effect was half of that in overweight individuals. The greatest advantage of improved nutrition on lung function was observed in the underweight group and in pancreatic- insufficient patients. CONCLUSIONS Modification to a high-fat diet may be required in some individuals with CF to optimize nutritional health. Higher BMI is associated with improvements in lung function, although the lung function benefit of increasing ones BMI (in kg/m(2)) to >25 is small and needs to be balanced against the known health risks of obesity.

Free amino acids in milks of human subjects, other primates and non-primates

Preterm and term transitional milks of human subjects and mature milks of human subjects, non-human primates and non-primates were analysed for free amino acids (AA) using precolumn phenylisothiocyanate derivatization and liquid chromatography. Differences in free AA between three types of human milk were small. Milks of pinnipeds (seals and sea lions) contained the highest levels of total free AA (8634-20,862 mumol/l), while the milks of cows and sheep had the lowest levels of total free AA (1061-1357 mumol/l). The milks of human subjects, chimpanzees (Pan troglodytes), gorillas (Gorilla gorilla), elephants (Elephas maximus), horses and pigs had intermediate levels of total free AA (3069-7381 mumol/l). Glutamic acid was the most abundant free AA in milks of human subjects (1339-2157 mumol/l), non-human primates (423-2528 mumol/l), elephants (1332 mumol/l), horses (1119 mumol/l), and cows (349 mumol/l). Taurine was the most abundant free AA in milks of pinnipeds (5776-13,643 mumol/l), pigs (1238 mumol/l), goats (1150 mumol/l) and sheep (341 mumol/l). Taurine was the second most abundant free AA in milks of human subjects and non-human primates, while histidine was the second most abundant free AA in milks of pinnipeds. Milks of each species had a distinctive free AA pattern which may reflect the relative importance of the free AA during early postnatal development.

B-Vitamin Deficiency in Hospitalized Patients with Heart Failure

The impact of heart failure and its treatment on specific nutrient requirements is unknown. Furthermore, depletion of water-soluble B vitamins that play key roles in the production of cellular energy in patients with heart failure can contribute to depletion of energy reserves observed in the failing heart. A cross-sectional study recently reported that approximately one third of hospitalized patients with heart failure had tissue levels suggestive of thiamin deficiency (vitamin B-1). Riboflavin (vitamin B-2) and pyridoxine (vitamin B-6) are similar to thiamin in that they are water-soluble, subject to renal excretion, have limited tissue storage, and are dependent on intake. Therefore, it was hypothesized that the status of these B vitamins may also be adversely affected by heart failure. As a result, the prevalence of patients at risk of vitamin B-2 (erythrocyte glutathione reductase activity coefficient > or = 1.2) and B-6 deficiency (plasma B-6 < or = 20 nmol/L) was determined in a cross-section of 100 patients hospitalized with heart failure between April 2001 and June 2002 as well as in a group of volunteers without heart failure. Twenty-seven percent of patients with heart failure had biochemical evidence of vitamin B-2 deficiency, while 38% had evidence of B-6 deficiency. These prevalence rates were significantly higher than those observed in the volunteers without heart failure (2% and 19%, respectively; P < or = 0.02). Use of common B-vitamin-containing supplements by patients with heart failure did not significantly reduce deficiency rates in comparison with those who did not use supplements (B-2 P=0.38 or B-6 P=0.18)). Finally, while 80% of patients with heart failure took diuretics, neither the dose nor the duration of furosemide use was related to the presence of either B-2 or B-6 deficiency. Given the physiologic importance of these vitamins, further investigations aimed at determining the effect of heart failure on specific nutrient requirements as well as the safety and efficacy of B-vitamin supplementation are warranted.

Measurement of homocysteine and related metabolites in human plasma and urine by liquid chromatography electrospray tandem mass spectrometry

The sulfur amino acids, methionine and cysteine play crucial roles in cells as a substrate for protein synthesis, as a methyl donor, and for the synthesis of sulfur-containing compounds, including the key intracellular tripeptide, glutathione. Homocysteine is an intermediary metabolite formed during the metabolism of methionine to cysteine. Dysregulation of homocysteine metabolism is implicated in adverse clinical outcomes such as increased risk of cardiovascular disease, stroke, Alzheimers disease dementia and osteoporosis. While hyperhomocysteinemia is commonly observed in those conditions, the impact on other related metabolites is condition-specific. Therefore, there exists a need to establish precise and sensitive analytical techniques that allow for the simultaneous measurement of homocysteine and related metabolites in biological samples. The current review outlines the development and use of liquid chromatography electrospray tandem mass spectrometry (LC-MS/MS) to simultaneously measure metabolites involved in sulfur amino acid metabolism. Additionally, extensions of the technique in relation to the measurement of sulfur amino acid and one-carbon kinetics in vivo are discussed. The LC-MS/MS technique has the capacity for unambiguous analyte identification and confirmation, due to its high specificity and sensitivity. It has the greatest potential of being accepted and utilized as a dedicated homocysteine and its related metabolite Standard reference method (SRM).

Dietary fiber effects in chronic kidney disease: a systematic review and meta-analysis of controlled feeding trials

Background/Objectives:Chronic kidney disease (CKD) is a major health concern associated with increased risk of cardiovascular disease, morbidity and mortality. Current CKD practice guidelines overlook dietary fiber, which is chronically low in the renal diet. However, increasing dietary fiber has been proposed to ameliorate the progress of CKD. We therefore conducted a systematic review and meta-analysis on the effect of dietary fiber intake on serum urea and creatinine as classical markers of renal health in individuals with CKD.Subjects/Methods:We searched MEDLINE, EMBASE, CINHAL and the Cochrane Library for relevant clinical trials with a follow-up ⩾7 days. Data were pooled by the generic inverse variance method using random-effects models and expressed as mean difference (MD) with 95% confidence intervals (95% CIs). Heterogeneity was assessed by the Cochran Q statistic and quantified by I2.Results:A total of 14 trials involving 143 participants met the eligibility criteria. Dietary fiber supplementation significantly reduced serum urea and creatinine levels in the primary pooled analyses (MD, −1.76 mmol/l (95% CI, −3.00, −0.51), P<0.01 and MD, −22.83 mmol/l (95% CI, −42.63, −3.02), P=0.02, respectively) with significant evidence of interstudy heterogeneity only in the analysis of serum urea.Conclusions:This is the first study to summarize the potential beneficial effects of dietary fiber in the CKD population demonstrating a reduction in serum urea and creatinine, as well as highlighting the lack of clinical trials on harder end points. Larger, longer, higher-quality clinical trials measuring a greater variety of uremic toxins in CKD are required (NCT01844882).

Use of an abridged scored Patient-Generated Subjective Global Assessment (abPG-SGA) as a nutritional screening tool for cancer patients in an outpatient setting.

The scored Patient-Generated Subjective Global Assessment tool (PG-SGA), regarded as the most appropriate means of identifying malnutrition in cancer patients, is often challenging to implement in a busy outpatient setting. We assessed the validity of an abridged version of the PG-SGA (abPG-SGA), which forgoes the physical examination, and compared its usefulness in discerning malnutrition to the full PG-SGA and Malnutrition Screening Tool (MST). The nutritional status of 90 oncology outpatients receiving chemotherapy was assessed according to SGA global rating, PG-SGA, and MST. Receiver operating characteristic (ROC) curves were generated to estimate the sensitivity and specificity of various cut-off scores for malnutrition. Thirty-six percent of patients were malnourished (SGA). The abPG-SGA yielded 94% sensitivity and 78% specificity and area under the curve (AUC) = 0.956, which was slightly lower than PG-SGA (97% sensitivity, 86% specificity, AUC = 0.967) and higher than MST (81% sensitivity, 72% specificity, AUC = 0.823). Patient reported symptoms included loss of appetite (30%), altered taste (31%), fatigue (30%), and decreased ability to perform activities of daily living (53%). In conclusion, the abPG-SGA is a practical, informative and valid tool for detecting malnutrition in the outpatient oncology setting.

Isotopic enrichment of amino acids in urine following oral infusions of L-[1-13C]phenylalanine and L-[1-13C]lysine in humans : Confounding effect of D-[13C]amino acids

Urine sampling of the free amino acid pool serves to reflect plasma enrichment and is used as a noninvasive means to determine isotope enrichment in studies of amino acid metabolism. We determined the effect of D-[13C]phenylalanine and D-[13C]lysine content of tracers on urinary amino acid enrichment following oral infusion of L-[13C]phenylalanine in 18 preterm infants and L-[1-(13)C]lysine in seven healthy adult females. Urinary [13C]phenylalanine enrichment was higher (P < .0001) for L-[13C]phenylalanine containing 0.4% D-[13C]phenylalanine (28.6 +/- 7.1) versus L-[1-(13)C]phenylalanine that contained undetectable D-[13C]phenylalanine (10.2 +/- 1.5). D-[13C]phenylalanine, measured by chiral column gas chromatography-mass spectrometry (GC-MS), accounted for 10% to 30% (20.5% +/- 7%) of total phenylalanine in the urine of infants who received 0.4% D-[13C]phenylalanine, and was absent from the urine of infants receiving tracer with undetectable [13C]phenylalanine. Urinary L-[13C]phenylalanine enrichment did not differ between tracer groups (9.8 +/- 1.5 and 9.8 +/- 2.5). In adult females, the use of L-[1-(13)C]lysine (1.6% D-lysine) resulted in a higher (P < .02) urine total L,D-[13C]lysine enrichment compared with plasma enrichment (40.8 +/- 4.1 v 11.1 +/- 0.7). This study demonstrates the significant presence of D-[13C]amino acids in urine that originate as contaminants from commercially manufactured tracers, as a result of renal tubular discrimination of D-amino acids. A tracer containing detectable amounts of D-[13C]isomer cannot be recommended for any study in which urine will be used to reflect enrichment in the arterial plasma pool.

Volume of foremilk, hindmilk, and total milk produced by mothers of very preterm infants born at less than 28 weeks of gestation.

The purpose of this study is to describe foremilk volume (milk produced in the first 3 minutes of pumping), hindmilk volume (remainder of milk produced), and total milk volume produced by mothers of very preterm infants at 3 weeks postpartum and associated factors. Mothers (n = 24) mechanically pump their breasts a median (minimum, maximum) of 7 times (5, 9 times) per 24 hours for a total of 15 minutes (9.4, 23.9 minutes) each time. Foremilk, hindmilk, and total milk volumes are 183 mL per 24 hours (80, 810), 318 mL per 24 hours (98, 1007), and 545 mL per 24 hours (224, 1817), respectively. Milk volumes are not associated with mothers age, race or ethnic background, education, parity, reported prepregnancy body mass index, previous breastfeeding experience, frequency of milk pumping, longest time between pumps, infant birth weight, or multiple births. The degree of pre-maturity (<26 weeks vs 260/7-276/7 weeks) is significantly related to the relative proportion of foremilk/hindmilk volumes (45:55 vs 36:65, respectively). J Hum Lact. 25(3):272-279.

Glutathione and riboflavin status in supplemented patients undergoing home nocturnal hemodialysis versus standard hemodialysis.

BACKGROUND Patients on conventional hemodialysis (HD) have elevated markers of oxidative stress and chronic inflammation, which may contribute to a high prevalence of cardiovascular disease. Glutathione (GSH), an important intracellular antioxidant, requires cysteine as a rate-limiting amino acid for its synthesis and riboflavin for its regeneration. OBJECTIVES We aimed to examine whether erythrocyte GSH (eGSH) concentrations and riboflavin status are influenced by the increased dialysis dose provided to vitamin-supplemented patients receiving home nocturnal hemodialysis (HNHD) (6-8 hours/session, 5-7 nights/week) compared with patients on standard hemodialysis (SHD) (4 hours/session, 3 days/week). METHOD This was a cross-sectional comparative study involving 30 patients undergoing SHD or HNHD regimens and a group of 15 healthy control subjects (HC). We measured eGSH concentration by liquid chromatography-tandem mass spectrometry, riboflavin status by eGSH reductase activity coefficient (EGRAC) as well as plasma total cysteine (Cys) and total homocysteine (Hcy), vitamin C by high-performance liquid chromatography, and C-reactive protein (CRP) by standard method. Estimated dietary protein and energy intakes were determined by 3-day food records, and nutritional status was assessed by subjective global assessment (SGA). RESULTS There were no significant differences among groups in eGSH concentration, EGRAC, dietary protein intake, and SGA score. SHD patients had significantly higher plasma Cys (P < .001) and Hcy compared with HNHD and HC groups (P = .048). Vitamin C was significantly lower (P = .01) and CRP significantly higher (P = .048) in both HD groups compared with HC. CONCLUSION eGSH concentration appears to be unaffected by dialysis dose in well-nourished HD patients.

Pre-Operative Modification of Dietary Glycemic Index Improves Pre but Not Post-Operative Indices of Insulin Resistance in Patients Undergoing Coronary Artery Bypass Graft Surgery

Background: Improving insulin sensitivity in coronary artery bypass grafting (CABG) patients may translate into improved glycemic control and postoperative outcomes. The implementation of a low glycemic index (LGI) diet in the pre-operative period may improve insulin sensitivity and subsequently impact on the development of post-operative insulin resistance. The aim of this study was to determine whether a short term LGI diet would reduce postoperative insulin resistance. Methods: Eleven non-diabetic patients referred for elective CABG surgery were randomized to consume either a high glycemic index (HGI)(5) or LGI (6) diet for three weeks prior to their surgery. Outcomes, including insulin sensitivity (SITT, HOMA), were measured at baseline, preoperatively and postoperatively. Results: Substitution of HGI or LGI foods resulted in an average 8.6 unit increase, or 11.0 unit decrease, respectively, in glycemic index. Insulin sensitivity (HOMA) improved significantly in the LGI group preoperatively compared to the HGI group (p = 0.018). Insulin sensitivity (SITT) was significantly reduced postoperatively in both groups, but no significant difference was found between groups. There was a trend in the LGI group towards improved glycemic control which warrants further investigation. Conclusion: A preoperative LGI diet presents a non-invasive cardio-protective opportunity warranting clinical trial.