Alpha-tocopherol metabolism is abnormal in scavenger receptor class B type I (SR-BI)-deficient mice

Despite the physiologic importance of vitamin E, in particular its alpha-tocopherol (alpha-T) isoform, the molecular mechanisms involved in the cellular uptake of this antioxidant from plasma lipoproteins have not been well-defined. Recent studies have suggested that selective lipid uptake, rather than endocytosis, is important for alpha-T delivery to cells. Here we show that the scavenger receptor class B type I (SR-BI), which mediates cellular selective cholesteryl ester uptake from lipoproteins, facilitates efficient transfer of alpha-T from HDL to cultured cells. In SR-BI-deficient mutant mice, relative to wild-type control animals, there was a significant increase in plasma alpha-T levels (1.1- to 1.4-fold higher) that was mostly due to the elevated alpha-T content of their abnormally large plasma HDL-like particles. This increase in plasma alpha-T in SR-BI knockout mice was accompanied by a significant decrease (65-80%) in the alpha-T concentrations in bile and several tissues including ovary, testis, lung and brain. SR-BI deficiency did not alter the alpha-T concentrations of the liver, spleen, kidney or white fat. These data show that SR-BI plays an important role in transferring alpha-T from plasma lipoproteins to specific tissues. Also, in the case of the liver as was previously shown for SR-BI-dependent hepatic cholesterol transport, SR-BI-mediated uptake of alpha-T was primarily coupled to biliary excretion rather than to tissue accumulation. Defective tissue uptake of lipoprotein alpha-T in SR-BI-deficient mice may contribute to the reproductive and cardiovascular pathologies exhibited by these animals.     

Improving the consistency in cervical esophageal target volume definition by special training

PURPOSE: Three-dimensional conformal radiation therapy requires the precise definition of the target volume. Its potential benefits could be offset by the inconsistency in target definition by radiation oncologists. In a previous survey of radiation oncologists, a large degree of variation in target volume definition of cervical esophageal cancer was noted for the boost phase of radiotherapy. The present study evaluated whether special training could improve the consistency in target volume definitions. METHODS AND MATERIALS: A pre-training survey was performed to establish baseline values. This was followed by a special one-on-one training session on treatment planning based on the RTOG 94-05 protocol to 12 radiation oncologists. Target volumes were redrawn immediately and at 1-2 months later. Post-training vs. pre-training target volumes were compared. RESULTS: There was less variability in the longitudinal positions of the target volumes post-training compared to pre-training (p < 0.05 in 5 of 6 comparisons). One case had more variability due to the lack of a visible gross tumor on CT scans. Transverse contours of target volumes did not show any significant difference pre- or post-training. CONCLUSION: For cervical esophageal cancer, this study suggests that special training on protocol guidelines may improve consistency in target volume definition. Explicit protocol directions are required for situations where the gross tumor is not easily visible on CT scans. This may be particularly important for multicenter clinical trials, to reduce the occurrences of protocol violations.     

Cardiovascular risk factors in vegetarians. Normalization of hyperhomocysteinemia with vitamin B(12) and reduction of platelet aggregation with n-3 fatty acids

Hyperhomocysteinemia in association with vitamin B(12) deficiency, and increased platelet aggregation, probably due to dietary lack of n-3 fatty acids, constitute cardiovascular risk factors frequently observed in vegetarians. We tested if administration of vitamin B(12) normalizes the concentration of total plasma homocysteine, and if intake of eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) fatty acids modulates platelet function in a population of lactoovovegetarians. One week after a single intramuscular injection of cyanocobalamin (10000 microg) in 18 individuals, serum vitamin B(12) increased from 149+/-63 pg/mL to 532+/-204 pg/mL (p<0.0001) and total tHcy dropped from 12.4+/-4.7 to 7.9+/-3.1 micromol/L (p<0. 0001). Ten of fourteen of these vegetarians completed an 8-week supplementation with 700 mg/day of each eicosapentaenoic and docosahexaenoic acids. Increased incorporation of these fatty acids into plasma lipids was observed in all of them, together with a significant reduction in maximum percentage or slope of platelet aggregation with all the agonists tested (ADP, epinephrin, collagen, arachidonic acid). No significant change in bleeding time was observed after n-3 fatty acid trial. Supplementation with vitamin B(12) and n-3 fatty acids corrects hyperhomocysteinemia and reduces platelet reactivity to agonists in vegetarians. Whether this supplementation improves the already reduced cardiovascular morbidity and mortality associated with vegetarian diet has yet to be demonstrated.     

Plasma amino acid and protein concentrations in infants fed human milk or a whey protein hydrolysate formula during the first month of life

The aim of the study was to compare growth parameters, biochemical indices of protein metabolism and plasma amino acid concentrations in infants fed either human milk ( n = 12) or a whey protein hydrolysate formula ( n = 13) during the first month of life. Growth and gain in skin fold thickness were similar in both groups whereas serum protein concentration was significantly decreased (57.4 ± 3.9 versus 61.2 ± 2.9 g/l) in the infants fed the whey hydrolysate formula. The discrepancies between the plasma amino acid pattern of the whey hydrolysate formula group and that of the human milk group lessened during the first month. Nevertheless, at a mean age of 33 days the plasma threonine concentration remained twice as high and the plasma tyrosine, phenylalanine and proline concentrations were Significantly lower in the whey hydrolysate formula group than in the human milk group. Thus, compared with breast-fed infants, growth and most of the biological indices of protein metabolism were satisfactory in infants fed during the first month of life on a whey protein hydrolysate formula. Nevertheless, the decrease in total plasma protein concentration needs to be confirmed in a larger cohort of infants. In addition, further research is necessary to investigate the possible ways of reducing the hyperthreoninemia and preventing other plasma amino acid disturbances since it would be desirable to obtain plasma amino acid levels similar to those of breast-fed infants.     

Mineral balance and whole body bone mineral content in very low-birth-weight infants

Fat and mineral metabolic balance studies were performed in 25 normal very low-birth-weight infants ( 1500 g at birth) fed either pooled pasteurized human milk supplemented with calcium, phosphorus and magnesium, or a preterm formula. Calcium, phosphorus and magnesium intake were similar in both groups and averaged 100mg/kg/day, 72 mg/kg/day and 8 mg/kg/day, respectively. Calcium and phosphorus retention was higher in the subjects fed fortified human milk than in those receiving a preterm formula (65±14 and 62±9mg/kg/day versus 55±12 and 47±7mg/kg/day respectively). The difference was only significant for phosphorus. Magnesium retention was similar in the two groups and averaged 3 mg/kg/day. Fat intake and absorption was significantly higher in the preterm formula fed group than in the one fed fortified human milk (5.5±0.4 g/kg/day and 88±4% versus 4.2±1 g/kg/day, 79±6% respectively). Assessment of the whole body bone mineral content by dual energy X-ray absorptiometry was performed at 3 and 6 months of age in another group of 25 low-birth-weight infants fed either fortified human milk or a preterm formula. Whole body bone mineral content (BMCt) was low (43.3±30.8 g of hydroxyapatite) at 3 months of age (theoretical term) compared to normal full-term newborns at birth. There was no significant influence of the diet. At 6 months of age, BMCt reached 168.6±36.6g, a value similar to that of full-term newborns, with no significant difference between the two regimen groups. The deficit in the 12 subjects who had a BMCt under 30 g at 3 months of age had been corrected at age 6 months. Premature babies fed a pooled pasteurized human milk enriched with calcium, phosphorus and magnesium favored a better retention of calcium and phosphorus. However, no significant influence of the two diets studied was observed on the gain in BMCt over the first 6 months of life.     

Red blood cell fatty acid composition in low-birth-weight infants fed either human milk or formula during the first months of life

The fatty acid composition of red blood cell (RBC) phospholipids in low-birth-weight infants was determined immediately after delivery and during the first 3 months of life. In the first study, infants were fed either human milk or two formulas with different fatty acid compositions but no long chain polyunsaturated fatty acids (LCPUFA). Both groups of formula-fed infants had significantly lower levels of docosahexaenoic acid (DHA) in RBC phospholipids compared with breast-fed infants. RBC phospholipid DHA was similar in the two formula groups at all ages. In the second study, infants received either a non-supplemented or a LCPUFA-supplemented formula. DHA remained stable in RBC phospholipids of infants supplemented with LCPUFA, whereas DHA decreased in RBC phospholipids of unsupplemented infants. These results confirm that adding DHA to formulas is more effective than increasing 18:3 n-3 content, in maintaining RBC phospholipid DHA levels.     

Diagnostic value of infantile stridor: a perceptual test

INTRODUCTION: stridor is the most common presenting symptom of pediatric airway obstruction, yet its value in clinical diagnosis is undetermined. The purpose of this study was to determine what diagnostic information was available to clinicians based entirely on listening to infantile stridor. METHOD: ten taped samples of stridor and corresponding clinical summaries were independently scored by Pediatric Otolaryngologists and their trainees. Respondents were asked to score the 'perceived' severity of the stridor based on their aural perception. Participants were recruited by an advertisement on the Internet Pediatric Otolaryngology forum. Thirty-eight consultants and 22 trainees responded. The responses were compared to known outcomes in the ten patients presented. RESULTS: listening to stridor in isolation resulted in respondents performing at the level of chance when their score of 'perceived' severity was compared to the known clinical outcome. When the clinical summaries (of the same patients) were scored, the level of performance significantly improved (P < 0.001). There was no difference in the level of performance when responses of trainees were compared with consultants, although there was a trend towards improved performance by the consultants. CONCLUSION: the importance of infantile stridor judged in isolation is of limited diagnostic value. Clinical information contributes significantly to the rating of stridor severity. The combination of both clinical and auditory information will likely improve diagnostic acumen.     

Single-stage laryngotracheal reconstruction: the Great Ormond Street experience and guidelines for patient selection

OBJECTIVES: To review all patients undergoing single-stage laryngotracheal reconstruction and to determine guidelines to predict successful outcomes and prevent the necessity of tracheotomy following laryngotracheal reconstruction. DESIGN: Chart review. SETTING: Tertiary care children's hospital. PATIENTS: A retrospective chart review was performed at our institution involving all patients who underwent single-stage laryngotracheal reconstruction from 1993 through 1996. A total of 28 patients were reviewed. RESULTS: Based on this chart review, a statistically higher incidence of extubation complications (P = .045), ie, bleeding, reintubation, or subcutaneous emphysema, occurred in children who weighed less than 4 kg. Although not statistically significant (P>.99), the relative risks of failure, defined as tracheotomy dependent or significant airway compromise following single-stage laryngotracheal reconstruction, were 3.43 if the child's weight was less than 4 kg at the time of surgery and 2.31 if the gestational age was less than 30 weeks at the time of surgery. Length of time for intubation did not appear to have any effect on outcome. CONCLUSIONS: Patients' gestational age and weight at the time of surgery appear to have the most impact on successful outcome. Children weighing more than 4 kg and those with gestational age of greater than 30 weeks appear to have a greater chance at successful extubation and eventual patent airway. Duration of intubation following single-stage laryngotracheal reconstruction does not appear to affect outcome.     

Detection of glutamate/glutamine resonances by 1H magnetic resonance spectroscopy at 0.5 tesla

Midfield proton magnetic resonance spectroscopy (MRS) provides a noninvasive method to monitor glutamate and glutamine (Glx) levels in vivo. Experiments to detect the γ and β resonances of Glx have been performed by using commercial 0.5 T and 1.5 T MR scanners on seven patients with elevated blood ammonia and eight normal volunteers. Compared with the spectral sensitivity obtained on an otherwise identical system operating at 1.5 T, the singlet resonance of N-acetyl aspartate (NAA) was decreased by a factor of 1.48, which is significantly less than expected using the ratio of Boltzman populations at the two field strengths. However, the resonances of Glx at 0.5 T increased in signal-to-noise ratio (SNR) by a factor of 2. The increased SNR of Glx is principally due to improved B ₀ main-field homogeneity and collapse of the strongly J -coupled Glx resonances. Our preliminary results suggest that midfield proton MRS will provide significant clinical utility in the detection of Glx levels in human brain.