Progression of diabetic retinopathy after bariatric surgery.

AIM: To assess the impact of bariatric surgery on the progression of diabetic retinopathy in patients with Type 2 diabetes. METHOD: We conducted a retrospective, observational study of patients with Type 2 diabetes who underwent bariatric surgery between 1 January 2001 and 31 December 2012 and had hospital-based retinal screening records. Data were collected from four surgical centres. Those who had pre-operative retinal screening and at least one post-operative retinal screen were eligible for analysis. A generalized linear mixed model was used to explore significant clinical predictors on the post-operative grade severity over time, controlling for important baseline characteristics. RESULTS: Three hundred and eighteen patients were eligible for analysis. Of these, 68.6% had no diabetic retinopathy pre-operatively compared with 18.9%, 8.5% and 4% with a diabetic retinopathy grade of minimal, mild or moderate and higher, respectively. First post-operative retinal screening results showed that after surgery 73% had no change in their diabetic retinopathy grade, 11% regressed and 16% progressed. The probability of having a diabetic retinopathy grade of moderate or higher over time post surgery was significantly associated with the magnitude of HbA1c reduction from pre-surgery HbA1c levels, a shorter post-operative retinal screening duration, more severe pre-operative retinal screening grade, male gender and non-Maori/Pacific ethnicity. CONCLUSIONS: A higher pre-operative diabetic retinopathy grade, and a large decrease in HbA1c post surgery warrant closer monitoring of diabetic retinopathy after bariatric surgery. Further prospective, randomized studies are required to investigate the gender and ethnic differences found.

Outcomes in verteporfin photodynamic therapy for choroidal neovascularisation--'beyond the TAP study'.

AIMS: To report on the clinical efficacy of verteporfin photodynamic therapy (PDT) in the treatment of choroidal neovascularisation (CNV) in an NHS setting and to compare treatment rates and outcomes with those in the published literature. PATIENTS AND METHODS: Patients with a visual acuity of 6/60 or better Snellen equivalent and predominantly classic or classic/no occult CNV within 200 microm of the centre of the fovea were enrolled and followed for a minimum of 12 months. Assessment at baseline and all follow-up visits comprised refraction protocol logMAR visual acuity, contrast sensitivity, and stereoscopic fluorescein angiography. RESULTS: A total of 170 eyes of 159 patients were enrolled with CNV due to: 147 age-related macular degeneration (AMD) (90 classic/no occult, 21 recurrent after confluent laser, 36 predominantly classic with occult), 10 pathological myopia, and 13 others. Response to treatment (loss of < 15 letters) at 12 months was 73% overall, 76% in AMD, 70% in classic/no occult, and 89% in predominantly classic. The mean number of treatments in the first year was 2.7. Contrast sensitivity was unchanged. CONCLUSIONS: Verteporfin PDT delivered in a NHS setting can be at least as effective as and requires fewer treatments than reported in the literature.

Thorium and iodine memory effects in inductively-coupled plasma mass spectrometry.

Thorium and iodine memory effects have been characterized experimentally for inductively-coupled plasma mass spectrometry by adding ammonia gas directly to the spray chamber and nebulizing aqueous ammonia sample solutions to assess analyte memory retention sites. Thorium memory effect originates from the tendency of an unidentified thorium compound to volatilize from the spray-chamber walls, and not from Th compound adsorption to nebulizer tubing. The mass spectrometer skimmer and sampler cones, ion optics, quadrupole, and other components are not responsible for the memory effect. Unlike that of thorium the iodine memory effect originates from adsorption of iodine compounds on nebulizer tubing surfaces and from volatilization of HI and I2 from the spray-chamber walls. Addition of ammonia sample solutions or ammonia gas directly to the spray chamber eliminated the Th and I memory effects in practical analyses, and blank levels were achieved after 2 min wash-outs. Quantitative recoveries were obtained for Th and I in reference materials.

Beta radiation as an adjunct to low-risk trabeculectomy.

PURPOSE: To assess a single dose of intraoperative beta radiation used to enhance the success rate of trabeculectomy in a population of low-risk glaucoma patients in whom antimetabolites might not be indicated. METHODS: A prospective randomized trial of 65 eyes was designed, with 31 eyes receiving 750 rads of intraoperative beta radiation (group 1), and 34 eyes receiving no supplementation (group 2). RESULTS: Mean follow-up time was 24 months. Mean postoperative intraocular pressure was 12.2 mmHg in group 1, and 13.7 mmHg in group 2 (P = 0.16). Mean decrease in intraocular pressure was 10.3 mmHg in group 1, and 9.3 mmHg in group 2 (P = 0.49). The two groups were not significantly different in terms of surgical complications. CONCLUSION: For this population of low-risk patients, there was no significant difference in outcome after applications of a single intraoperative dose of beta radiation.

Kinetics of zinc metabolism: variation with diet, genetics and disease.

Kinetic studies are used to investigate metabolic processes. By adding an isotope to a system and measuring its movement in the system over time, pool sizes and transport rates can be determined by mathematically modeling the data. This approach enables rate differences to be determined in conditions that have been modified by diet, environment, genetics or disease. Kinetic studies in humans have shown that there are multiple pools of zinc that turnover from minutes to years and that processes, including zinc absorption and excretion, are regulated to maintain tissue levels when zinc intake varies. Animal studies allow for greater understanding of kinetics because more tissues can be sampled and environmental and genetic factors can be controlled. Kinetic studies in animals will provide information on the overexpression or the deletion of genes coding for specific proteins involved in zinc transport and metabolism. The advances that have been made in our understanding of the role of zinc in metabolism have been aided by the development of techniques for measuring isotopes in biological materials. In the future, the kinetics of zinc bound to different compounds will be measured. Modeling will enable this information, at the molecular level, to be integrated with knowledge of zinc metabolism at the cellular, organ and whole body level. To understand more fully the role of zinc in human health, kinetic studies are needed in healthy and disease states to identify differences in metabolic processes. This knowledge can be used as a basis for dietary and therapeutic recommendations.

Determination of some trace elements in human tooth enamel.

Determination of seven elements (Cu, Fe, Mg, Mn, Pb, Sr and Zn) in whole enamel and surface layers of extracted non-carious human teeth by FAAS, ETA AAS, ICP-AES and ICP-MS (Pb) is demonstrated. Techniques are described for obtaining whole enamel and its acid dissolution. Fifty microm width enamel layers from outer enamel surface to a 200 microm depth were successively etched in 1 mL of 3 M HClO4 for 3 min dissolution periods. Enamel samples were analyzed for populations under and over 20 years of age and enamel from Bronze Age teeth. Concentrations of microelements in the whole enamel and in the first surface layer (50 microm depth) were compared. With exception of Sr and Mg, all elements show significantly higher concentrations in the first layer than in whole enamel and higher concentration in teeth of individuals over 20 years, which demonstrate the cumulative effect of these elements. The Cu, Fe, Mn, Pb and Zn concentrations in four layers of erupted and non-erupted teeth decreased while Mg and Sr concentrations increased toward enamel-dentine junction. The concentrations of most elements were almost constant as they approached the 150 microm layer. This concentration gradient may result from interaction between saliva and teeth and supports the hypothesis that the surface de- and re-mineralization process is effective at most to 150 microm from the enamel surface.

Circulating antibodies to Saccharomyces cerevisiae (bakers'/brewers' yeast) in gastrointestinal disease.

AIM: To measure circulating antibodies to yeast organisms that could be used to characterise the yeast specific immune response in gastrointestinal disease. METHODS: A quantitative, isotype specific enzyme linked immunosorbent assay was developed to measure circulating antibodies to an aqueous extract of Saccharomyces cerevisiae (sacc). Comparisons of specific antibody concentrations were made between 224 healthy controls and 51 patients with Crohn's disease, 41 with ulcerative colitis, 24 with indeterminate colitis, 23 with chronic liver disease, 17 with coeliac disease, and seven with irritable bowel syndrome. Additional comparisons were made between Crohn's disease and ulcerative colitis patients. Within the Crohn's disease group, the dependence of antibody levels on several clinical variables was assessed. RESULTS: IgG and IgA anti-sacc antibodies were significantly raised in Crohn's disease. IgG antibodies were also raised in patients with chronic liver disease. Among patients with Crohn's disease, IgG antibody concentrations were higher in those with serum alpha 1 acid glycoprotein (AAG) above the normal range and there was a strong trend towards increased IgG anti-sacc in the presence of small bowel disease, whereas IgA anti-sacc correlated positively with disease duration. No differences were detected according to whether patients were taking steroids. Neither the Crohn's disease nor the chronic liver disease group differed from normal subjects in respect of IgG antibodies to bovine milk casein. On linear regression analysis of complete data from 39 Crohn's disease patients, AAG was found to be a significant predictor of both IgG and IgA antibodies, and male sex and disease duration to be additional predictors of IgA antibodies. There was a significant difference in IgG antibodies between Crohn's disease and ulcerative colitis. CONCLUSIONS: Raised antibodies to yeast, although not completely specific for Crohn's disease, may have a future role in diagnosis. The assays described here could be used to address this question in the context of a prospective study.

Zinc absorption, distribution, excretion, and retention by healthy preterm infants.

Zinc (Zn) is an essential nutrient for growth, but little is known about Zn absorption, distribution, excretion, and retention in preterm infants. Nine infants with gestational age 32+/-1 wk (mean+/-SE), birth weight 1.44+/-0.08 kg, postnatal age 14+/-3 d, on Zn intake of 23+/-3 micromol/kg per d via enteral feeding of preterm formula were studied. A stable Zn isotope (70Zn) was administered orally or i.v., and plasma, red blood cells, urine, and feces were sampled for up to 30 d. Samples were analyzed for Zn by inductively coupled plasma atomic emission spectrometry and for isotope enrichment by inductively coupled plasma mass spectrometry. Data were analyzed by compartmental analysis using the Simulation Analysis and Modeling program, and absorption, distribution, excretion, and retention were calculated. Absorption was 36+/-5% or 7+/-1 micromol/kg per d; distribution in plasma was 15+/-1 micromol Zn/L and in RBC was 41+/-4 micromol Zn/L; excretion in urine was 0.55+/-0.03 micromol Zn/kg per d and in feces was 17+/-3 micromol Zn/kg per d and retention was 5+/-1 microl/kg per d. Results show that healthy preterm infants with Zn intake of 23 micromol/kg per d and expected growth rates (> 15 g/kg per d) absorb and retain Zn at rates comparable to in utero accretion. The values for absorption, distribution, and excretion by this population of healthy preterm infants provide a normal range for future studies, although further studies are required to determine endogenous excretion rates in healthy preterm infants. We speculate that these values can be used to determine whether Zn kinetics are abnormal in sick infants or in infants with slow growth.

Characterization of oligosaccharides from an antigenic mannan of Saccharomyces cerevisiae.

Mannans of the yeast Saccharomyces cerevisiae have been implicated as containing the allergens to which bakers and brewers are sensitive and also the antigen recognized by patients with Crohn's disease. A fraction of S. cerevisiae mannan, Sc500, having high affinity for antibodies in Crohn's patients has been characterized by NMR spectroscopy followed by fragmentation using alkaline elimination, partial acid hydrolysis and acetolysis. The released oligosaccharides were separated by gel filtration on a Biogel P4 column and analyzed by fluorescence labeling, HPLC and methylation analysis. The relationship between structure and antigen activity was measured by competitive ELISA. The antigenic activity of the original high molecular weight mannan could be ascribed to terminal Manalpha1-->3Manalpha1-->2 sequences which are rarely found in human glycoproteins but were over-represented in Sc500 compared to other yeast mannans.

Plasma source mass spectrometry in experimental nutrition.

The development and commercial availability of plasma ion source, specifically inductively coupled plasma, mass spectrometers (ICP-MS) have significantly extended the potential application of stable isotopes for nutritional modeling. The status of research and commercial ICP-MS instruments, and their applications and limitations for stable isotopic studies are reviewed. The consequences of mass spectroscopic resolution and measurement sensitivity obtainable with quadrupole, sector, time-of-flight, and trap instruments on stable isotope analysis are examined. Requirements for reliable isotope measurements with practical biological samples including tissues and fluids are considered. The possibility for stable isotope analysis in chemically separated compounds (speciation) also is explored. On-line compound separations by chromatography or electrophoresis, for example, have been combined instrumentally with ICP-MS. Som possibilities and requirements are described for stable isotope speciation analysis.

Flight crew fatigue III: North Sea helicopter air transport operations.

We studied 32 helicopter pilots before, during, and after 4-5 d trips from Aberdeen, Scotland, to service North Sea oil rigs. On duty days, subjects awoke 1.5 h earlier than pretrip or posttrip, after having slept nearly an hour less. Subjective fatigue was greater posttrip than pretrip. By the end of trip days, fatigue was greater and mood more negative than by the end of pretrip days. During trips, daily caffeine consumption increased 42%, reports of headache doubled, reports of back pain increased 12-fold, and reports of burning eyes quadrupled. In the cockpits studied, thermal discomfort and high vibration levels were common. Subjective workload during preflight, taxi, climb, and cruise was related to the crewmembers' ratings of the quality of the aircraft systems. During descent and approach, workload was affected by weather at the landing site. During landing, it was influenced by the quality of the landing site and air traffic control. Beginning duty later, and greater attention to aircraft comfort and maintenance, should reduce fatigue in these operations.

TNFB gene polymorphism in insulin-dependent diabetes mellitus: association with HLA-DR alleles.

A polymorphism of the TNF-beta gene can be detected by restriction digestion of a PCR product with NcoI. In this study we look at the risk associated with this polymorphism in a study of 69 insulin-dependent diabetes patients and 119 healthy controls. The risk was further characterized by comparison to the HLA type of the individual, since the TNF polymorphism is in linkage disequilibrium with HLA genes.

Determination of total iodine in nutritional and biological samples by ICP-MS following their combustion within an oxygen stream.

A mineralization and determination method for total iodine in nutritional and biological samples is described. Combustion of the sample in an oxygen stream is followed by collection of the combustion products in a 5% water-soluble tertiary amine solution. Iodine is determined by inductively coupled plasma mass spectrometry. The accuracy and precision of the quantitative iodine analysis using standard addition is better than +/- 10%. A semi-quantitative analysis of four standard reference materials is evaluated. Owing to the presence of low-level iodine contaminant in the blank solution, the determination limit of the method is +/- 10 micrograms kg-1. Good agreement with certified iodine values is obtained for six reference materials. The use of the tertiary amine matrix solution permits the simultaneous determination of iodine and other trace metals of biological and toxicological importance, including Mn, Co, Ni, Cu, Zn, Rb, Cd, and Pb.

Soil ingestion estimates for children residing on a superfund site.

Soil ingestion estimates were obtained from a stratified, simple random sample of 64 children aged 1-4 years residing on a superfund site in Montana. The study was conducted during the month of September for 7 consecutive days. The study utilized a mass-balance methodology in which eight naturally occurring soil tracers (Al, Si, Ti, Ce, Nd, La, Y, and Zr) believed to be poorly absorbed by the gastrointestinal tract were employed to provide soil ingestion estimates. Food and fecal samples were analyzed on a daily basis. Soil/dust samples representative of where the children played during the study period were obtained. Very high compliance among the participants was maintained throughout the study. The identical methodology employed in the childrens' study was used in an adult study of tracer recovery in 10 subjects over 28 days of observation to provide validation that soil ingestion over the range of 20 to 500 mg/day could be detected. Soil ingestion was estimated by each soil tracer via traditional methods as well as by an improved approach using five trace elements (Al, Si, Ti, Y, and Zr), called the Best Tracer Method (BTM), which substantially corrects for error due to misalignment of tracer input and output as well as error occurring from ingestion of tracers from nonfood, nonsoil sources, while being insensitive to the particle size of the soil/dust ingested. According to the BTM, the median soil ingestion was less than 1 mg/day while the upper 95% was 160 mg/day. No significant age (1 year vs 2, vs 3) or sex-related differences in soil ingestion were observed. These estimates are lower than estimates observed in another study in Massachusetts during September and October. Significant methodological improvements in this study as compared to previously conducted soil ingestion studies include the selection of a representative sample of children, longer study duration, inclusion of dietary recommendations to reduce food tracer input and variability, use of the BTM, and a stronger adult validation study with respect to number of subjects, and duration and range of possible soil ingestion rates. Despite these methodological improvements, evidence exists that this study displays a net residual negative error, suggesting that the above estimates are below the true soil ingestion. The magnitude of this residual negative error cannot be quantified with the BTM but is likely to not affect the median by more than 40 mg/day, while the impact of such an error on the upper end of the distribution is more uncertain.

Zinc kinetics in preterm infants: a compartmental model based on stable isotope data.

Zinc is an essential nutrient for growth; however, little is known about zinc kinetics (absorption, distribution, and excretion) in preterm infants (< 38-wk gestation). Zinc kinetics were studied in two preterm infants (gestational ages, 32 and 33 wk) following oral or intravenous administration of a stable isotope (70Zn). Plasma, red blood cells (RBC), urine, and feces were sampled for up to 30 days. Isotope enrichment was measured in tissues by inductively coupled plasma (ICP)-mass spectrometry, and zinc was determined by ICP-atomic emission spectrometry. Data were analyzed by compartmental analysis using SAAM31. Zinc intake increased during the studies, and, because body zinc was not in steady state, both tracer (70Zn) and tracee (Zn) data were fitted using analogous models. A model for adults [M. E. Wastney, R. L. Aamodt, W. F. Rumble, and R. I. Henkin. Am. J. Physiol. 251 (Regulatory Integrative Comp. Physiol. 20): R398-R408, 1986] was modified to fit data from the preterm infants. RBC data were fitted using one compartment (vs. 2 in adults), and an adult RBC subsystem was included in the model to account for zinc introduced during blood transfusions. Exchange of zinc between compartments that were not sampled was based on zinc distribution in neonates. Absorption was 42 and 34%, and endogenous fecal excretion, based on intravenous data, was 15 micrograms.kg-1.day-1. The model can be used to quantify changes in zinc kinetics of preterm infants with age, weight, and zinc intake for evaluating nutritional requirements with growth.

Analytical plasma source mass spectrometry in biomedical research.

The features of inductively coupled plasma - mass spectrometry (ICP-MS) that make it unique also make possible applications in biological chemistry and biomedical research that would be otherwise difficult or impossible. High sensitivity, characterized spectral interferences, rapid mass scanning, and individual isotope measurements are now combined with sophisticated sample preparation, separations, or stable isotope additions to achieve rapid semi-quantitative analysis, element speciation, and high accuracy. The semi-quantitative analysis of various materials, the separation and detection of macromolecules in blood and other tissues, and tracking of stable isotopes added either purposely or inadvertently to children are important applications of ICP-MS. Current functional limitations and obstacles and potential development areas also are examined.

Vapour-phase acid digestion of micro samples of biological material in a high-temperature, high-pressure asher for inductively coupled plasma atomic emission spectrometry.

This vapour-phase acid decomposition of small biological samples (50-165 mg) and concurrent purification of the reagent acid were achieved in a mini-quartz sample holder inserted in a commercial high-pressure digestion vessel. A 3.1 ml volume sample contained was developed to hold the sample and to maximize the successful decomposition of a variety of biological samples. When biological standard reference materials were digested at 230 degrees C and 122 bar (1770 psi), the residual carbon content in the digested samples was less than 1.8 +/- 0.1%. Inductively coupled plasma atomic emission spectrometric analysis of the digested materials for C, Ca, Cu, Cd, Fe, Mg, Mn and Zn provided good recoveries and low reagent blank values and demonstrated complete matrix decomposition.