8†Unexpected retinopathy in a patient presenting with bilateral optic disc swelling.

A 12-year-old boy presented with 5 day history of blurry vision, 'wobbly eyes', tinnitus and difficulty seeing at night. Local ophthalmology noted bilateral optic disc swelling and referred him urgently for neurological investigations.Clinical Findings: At presentation VA was RE 0.00 and LE 0.2 with normal Ishihara colour vision. His extraocular movements were full without manifest strabismus. Fundoscopy showed bilateral optic disc swelling. Electrophysiology unexpectedly revealed a functionally cone isolated retina with markedly abnormal rod function. Pattern VEPs indicated bilateral macular pathway dysfunction affecting left eye more than right eye. Wide field imaging showed bilateral diffusely scattered yellow-white flecks in the midperiphery of each eye. His kinetic visual fields were moderately restricted bilaterally. MRI showed a Chiari 1 malformation with cerebellar tonsil herniation, but LP opening pressure was normal.Differential diagnosis included RDH5 retinopathy or vitamin A deficiency. On questioning he reported a diet restricted to only meat and biscuits. His vitamin A levels were subnormal at 0.14 umol/L (reference range 0.9-2.5umol/l) and he was started on high-dose Vitamin A supplements.Four months after supplementation retinal appearances had normalised, the rod ERGs recovered, nyctalopia and visual field restriction resolved. PVEPs had improved but an element of LE macular pathway dysfunction remained. Optic disc swelling settled leaving mild temporal pallor, particularly of the LE with some RNFL loss.It is important to recognise nutritional Vitamin A deficiency in children as prompt recognition and treatment can improve symptoms, reverse retinal pathology which we have demonstrated with electrophysiological findings.

Anoxia-induced release of colloid- and nanoparticle-bound phosphorus in grassland soils.

Particle-facilitated transport is a key mechanism of phosphorus (P) loss in agroecosystems. We assessed contributions of colloid- and nanoparticle-bound P (nPP; 1-415 nm) to total P released from grassland soils receiving biannual poultry litter applications since 1995. In laboratory incubations, soils were subjected to 7 days of anoxic conditions or equilibrated at pH 6 and 8 under oxic conditions and then the extract was size fractionated by differential centrifugation/ultrafiltration for analysis of P, Al, Fe, Si, Ti, and Ca. Selected samples were characterized by transmission electron microscopy-energy dispersive spectroscopy (TEM-EDS) and field flow fractionation (FFF-ICP-MS). Particles released were present as nanoaggregates with a mean diameter of 200-250 nm, composed of ~50-nm aluminosilicate flakes studded with Fe and Ti-rich clusters (<10 nm) that contained most of the P detected by EDS. Anoxic incubation of stimulated nPP release with seasonally saturated soils released more nPP and Fe(2+)(aq) than well-drained soils; whereas, nonreductive particle dispersion, accomplished by raising the pH, yielded no increase in nPP release. This suggests Fe acts as a cementing agent, binding to the bulk soil P-bearing colloids that can be released during reducing conditions. Furthermore, it suggests prior periodic exposure to anoxic conditions increases susceptibility to redox-induced P mobilization.

The clinical effectiveness of glucosamine and chondroitin supplements in slowing or arresting progression of osteoarthritis of the knee: a systematic review and economic evaluation.

OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of glucosamine sulphate/hydrochloride and chondroitin sulphate in modifying the progression of osteoarthritis (OA) of the knee. DATA SOURCES: Electronic databases were searched from 1950 to 2008 and included: MEDLINE and PubMed; EMBASE; Cochrane Library (including Cochrane Systematic Reviews Database, CENTRAL, DARE, NHS EED and HTA databases); Allied and Complementary Medicine (AMED); National Research Register (NRR); Web of Science Proceedings; Current Controlled Trials; and Clinical Trials.gov. Other sources included bibliographies of retrieved papers, registered but unpublished trials, internet searches and the Food Standards Agency website. REVIEW METHODS: A search was conducted for systematic reviews of randomised controlled trials (RCTs), which were used to identify RCTs of at least 12 months' duration and updated with searches for primary studies. A cost-effectiveness model was constructed using cohort simulation and drawing on available evidence. Sensitivity analysis was undertaken and value of information analysis conducted. A review of studies of mechanism of action was carried out to explore the biological plausibility of the preparations. RESULTS: Five systematic reviews and one clinical guideline met the inclusion criteria. They reported inconsistent conclusions with only modest effects on reported pain and function. A reduction in joint space narrowing was more consistently observed, but the effect size was small and the clinical significance uncertain. A separate review of eight primary trials of > 12 months' duration showed evidence of statistically significant improvements in joint space loss, pain and function for glucosamine sulphate, but the clinical importance of these differences was not clear. In two studies of glucosamine sulphate, the need for knee arthroplasty was reduced from 14.5% to 6.3% at 8 years' follow-up. For other preparations of glucosamine, chondroitin and combination therapy, there was less evidence to support a clinical effect. Cost-effectiveness modelling was restricted to glucosamine sulphate. Over a lifetime horizon the incremental cost per quality-adjusted life-year (QALY) gain for adding glucosamine sulphate to current care was estimated to be 21,335 pounds. Deterministic sensitivity analysis suggested that the cost-effectiveness of glucosamine sulphate therapy was particularly dependent on the magnitude of the quality of life (QoL) gain, the change in knee arthroplasty probability with therapy and the discount rate. At a cost per QALY gained threshold of 20,000 pounds, the likelihood that glucosamine sulphate is more cost-effective than current care is 0.43, while at a threshold of 30,000 pounds, the probability rises to 0.73. Probabilistic sensitivity analysis showed that estimates were imprecise and subject to a degree of decision uncertainty. Value of information analysis demonstrated the need for further research. Several biologically plausible mechanisms of action for glucosamine sulphate and chondroitin were proposed. CONCLUSIONS: There was evidence that glucosamine sulphate shows some clinical effectiveness in the treatment of OA of the knee. No trial data came from the UK and caution should be exercised in generalising the findings to the UK health-care setting. Cost-effectiveness was not conclusively demonstrated. There was evidence to support the potential clinical impact of glucosamine sulphate. The value of information analysis identified three research priorities: QoL, structural outcomes and knee arthroplasty. The biological mechanism of glucosamine sulphate and chondroitin remains uncertain and, in particular, the proposal that the active substance may be sulphate should be explored further.

Effect of dietary conjugated linoleic acid (CLA) on lipid composition, metabolism and gene expression in Atlantic salmon (Salmo salar) tissues.

Dietary conjugated linoleic acid (CLA) affects fat deposition and lipid metabolism in mammals, including livestock. To determine CLA effects in Atlantic salmon (Salmo salar), a major farmed fish species, fish were fed for 12 weeks on diets containing fish oil or fish oil with 2% and 4% CLA supplementation. Fatty acid composition of the tissues showed deposition of CLA with accumulation being 2 to 3 fold higher in muscle than in liver. CLA had no effect on feed conversion efficiency or growth of the fish but there was a decreased lipid content and increased protein content after 4% CLA feeding. Thus, the protein:lipid ratio in whole fish was increased in fish fed 4% CLA and triacylglycerol in liver was decreased. Liver beta-oxidation was increased whilst both red muscle beta-oxidation capacity and CPT1 activity was decreased by dietary CLA. Liver highly unsaturated fatty acid (HUFA) biosynthetic capacity was increased and the relative proportion of liver HUFA was marginally increased in salmon fed CLA. CLA had no effect on fatty acid Delta6 desaturase mRNA expression, but fatty acid elongase mRNA was increased in liver and intestine. In addition, the relative compositions of unsaturated and monounsaturated fatty acids changed after CLA feeding. CLA had no effect on PPARalpha or PPARgamma expression in liver or intestine, although PPARbeta2A expression was reduced in liver at 4% CLA feeding. CLA did not affect hepatic malic enzyme activity. Thus, overall, the effect of dietary CLA was to increase beta-oxidation in liver, to reduce levels of total body lipid and liver triacylglycerol, and to affect liver fatty acid composition, with increased elongase expression and HUFA biosynthetic capacity.

Tailoring of Atlantic salmon (Salmo salar L.) flesh lipid composition and sensory quality by replacing fish oil with a vegetable oil blend.

Atlantic salmon (Salmo salar L.) juveniles were fed either 100% fish oil (FO), 75% vegetable oil (VO), or 100% VO throughout their life cycle to harvest weight followed by a finishing diet period when all groups were fed 100% FO. The two experimental VO diets were tested at two different locations (Scotland and Norway) against the same control diet (100% FO). The VO blend was composed of rapeseed oil, palm oil, and linseed oil using capelin oil as a control for fatty acid class compositions. Flesh fatty acid profiles were measured regularly throughout the experiment, with the times of sampling determined by changes in pellet size/lipid content and fish life stage. Growth and mortality rates were not significantly affected by dietary fatty acid compositions throughout the life cycle, except during the seawater winter period in Norway when both growth and protein utilization were increased in salmon fed 100% VO compared to 100% FO. Flesh fatty acid composition was highly influenced by that of the diet, and after the finishing diet period the weekly intake recommendations of very long chain n-3 polyunsaturated fatty acid (VLCn-3 PUFA) for human health were 80 and 56% satisfied by a 200 g meal of 75% VO and 100% VO flesh, respectively. No effect on flesh astaxanthin levels was observed in relation to changing dietary oil sources. Sensory evaluation showed only minor differences between salmon flesh from the dietary groups, although prior to the finishing diet period, flesh from 100% VO had less rancid and marine characteristics and was preferred over flesh from the other dietary groups by a trained taste panel. After the finishing diet period, the levels of typical vegetable oil fatty acids in flesh were reduced, whereas those of VLCn-3 PUFA increased to levels comparable with a 100% FO fed salmon. No differences in any of the sensory characteristics were observed between dietary groups. By blending VOs to provide balanced levels of dietary fatty acids, up to 100% of the fish oil can be replaced by the VO blend without compromising growth or flesh quality. At the same time, 75% of the dietary fish oil can be replaced without compromising flesh VLCn-3 PUFA content, thereby providing a beneficial nutritional profile for human consumption.

Environmental and dietary influences on highly unsaturated fatty acid biosynthesis and expression of fatty acyl desaturase and elongase genes in liver of Atlantic salmon (Salmo salar).

Highly unsaturated fatty acid (HUFA) synthesis in Atlantic salmon (Salmo salar) was known to be influenced by both nutritional and environmental factors. Here we aimed to test the hypothesis that both these effectors involved similar molecular mechanisms. Thus, HUFA biosynthetic activity and the expression of fatty acyl desaturase and elongase genes were determined at various points during an entire 2 year production cycle in salmon fed diets containing either 100% fish oil or diets in which a high proportion (75% and 100%) of fish oil was replaced by C18 polyunsaturated fatty acid-rich vegetable oil. The results showed that HUFA biosynthesis in Atlantic salmon varied during the growth cycle with peak activity around seawater transfer and subsequent low activities in seawater. Consistent with this, the gene expression of Delta6 desaturase, the rate-limiting step in the HUFA biosynthetic pathway, was highest around the point of seawater transfer and lowest during the seawater phase. In addition, the expression of both Delta6 and Delta5 desaturase genes was generally higher in fish fed the vegetable oil-substituted diets compared to fish fed fish oil, particularly in the seawater phase. Again, generally consistent with this, the activity of the HUFA biosynthetic pathway was invariably higher in fish fed diets in which fish oil was substituted by vegetable oil compared to fish fed only fish oil. In conclusion, these studies showed that both nutritional and environmental modulation of HUFA biosynthesis in Atlantic salmon involved the regulation of fatty acid desaturase gene expression.

Clopidogrel used in combination with aspirin compared with aspirin alone in the treatment of non-ST-segment-elevation acute coronary syndromes: a systematic review and economic evaluation.

OBJECTIVES: To review systematically the clinical effectiveness and the cost-effectiveness of clopidogrel used in combination with standard therapy including aspirin, compared with standard therapy alone for the treatment of non-ST-segment elevation acute coronary syndromes (ACS). DATA SOURCES: Electronic databases. Manufacturers' submissions. REVIEW METHODS: Studies were selected using rigorous criteria. The quality of randomised controlled trials (RCTs) was assessed according to criteria based on NHS CRD Report No. 4, and the quality of systematic reviews was assessed according to the guidelines for the Database of Reviews of Effect (DARE) criteria. The quality of economic evaluations was assessed according to a specifically tailored checklist. The clinical effectiveness and cost-effectiveness of clopidogrel in combination with standard therapy compared with standard therapy alone were synthesised through a narrative review with full tabulation of the results of the included studies. In the economic evaluations, a cost-effectiveness model was constructed using the best available evidence to determine cost-effectiveness in a UK setting. RESULTS: One RCT (the CURE trial) was a randomised, double-blind, placebo-controlled trial of high quality and showed that clopidogrel in addition to aspirin was significantly more effective than placebo plus aspirin in patients with non-ST-segment elevation ACS for the composite outcome of death from cardiovascular causes, non-fatal myocardial infarction or stroke over the 9-month treatment period. However, clopidogrel was associated with a significantly higher number of episodes of both major and minor bleeding. The results from the five systematic reviews that assessed the adverse events associated with long-term aspirin use showed that aspirin was associated with a significantly higher incidence of haemorrhagic stroke, extracranial haemorrhage and gastrointestinal haemorrhage compared with placebo. Of the cost-effectiveness evidence reviewed, only the manufacturer's submission was considered relevant from the perspective of the NHS. The review of this evidence highlighted potential limitations within the submission in its use of data and in the model structure used. These limitations led to the development of a new model with the aim of providing a more reliable estimate of the cost-effectiveness from the perspective of the UK NHS. This model indicated that clopidogrel appears cost-effective compared with standard care alone in patients with non-ST-elevation ACS as long as the NHS is willing to pay GBP6078 per quality of life year (QALY). The results were most sensitive to the inclusion of additional strategies that assessed alternative treatment durations with clopidogrel. Although treatment with clopidogrel for 12 months remained cost-effective for the overall cohort, provisional findings indicate that the shorter treatment durations may be more cost-effective in patients at low risk. CONCLUSIONS: The results of the CURE trial indicate that clopidogrel in combination with aspirin was significantly more effective than placebo combined with aspirin in a wide range of patients with ACS. This benefit was largely related to a reduction in Q-wave myocardial infarction. There was no statistically significant benefit in relation to mortality. The trial data suggested that a substantial part of the benefit derived from clopidogrel is achieved by 3 months, with a further small benefit over the remaining 9 months of chronic treatment. The results from the base-case model suggest that treatment with clopidogrel as an adjunct to standard therapy (including aspirin) for 12 months, compared with standard therapy alone, is cost-effective in non-ST elevation ACS patients as long as the health service is willing to pay GBP6078 per additional QALY. However, although treatment with clopidogrel for 12 months remained cost-effective for the overall cohort, provisional findings indicate that the shorter treatment durations may be more cost-effective in patients at low risk. To estimate the exact length of time that clopidogrel in addition to standard therapy should be prescribed for patients with non-ST-segment ACS would require a prospective trial that randomised patients to various durations of therapy. This would accurately assess whether a 'rebound' phenomenon occurs in patients if clopidogrel were stopped after 3 months of treatment.

Replacement of dietary fish oil with increasing levels of linseed oil: modification of flesh fatty acid compositions in Atlantic salmon (Salmo salar) using a fish oil finishing diet.

Five groups of salmon, of initial mean weight 127 +/- 3 g, were fed increasing levels of dietary linseed oil (LO) in a regression design. The control diet contained capelin oil (FO) only, and the same oil was blended with LO to provide the experimental diets. After an initial period of 40 wk, all groups were switched to a finishing diet containing only FO for a further 24 wk. Growth and flesh lipid contents were not affected by dietary treatment. The FA compositions of flesh total lipids were linearly correlated with dietary FA compositions (r2 = 0.88-1.00, P < 0.0001). LO included at 50% of added dietary lipids reduced flesh DHA and EPA (20:5n-3) concentrations to 65 and 58%, respectively, of the concentrations in fish fed FO. Feeding 100% LO reduced flesh DHA and EPA concentrations to 38 and 30%, respectively, of the values in fish fed FO. Differences between diet and flesh FA concentrations showed that 16:0, 18:1n-9, and especially DHA were preferentially retained in flesh, whereas 18:2n-6, 18:3n-3, and 22:1n-11 were selected against and presumably utilized for energy. In fish previously fed 50 and 100% LO, feeding a finishing diet containing FO for 16 wk restored flesh DHA and EPA concentrations, to approximately 80% of the values in fish fed FO throughout. Flesh DHA and EPA concentrations in fish fed up to 50% LO were above recommended intake values for humans for these EFA. This study suggests that LO can be used as a substitute for FO in seawater salmon feeds and that any reductions in DHA and EPA can be largely overcome with a finishing diet high in FO before harvest.

Plasma ghrelin response following a period of acute overfeeding in normal weight men.

BACKGROUND: Ghrelin, a 28 amino-acid peptide secreted primarily from the stomach has been identified as the endogenous ligand for the growth hormone secretagogue receptor. Ghrelin is suppressed in the postprandial state and has been linked to both type II diabetes and obesity. AIMS: To investigate the effects of a period of overfeeding with high-fat dietary supplements on plasma ghrelin levels in nonobese men. METHODS: Six healthy males (21-34 y; BMI 21-24 kg/m(2)) underwent the dietary intervention after completing diet and exercise diaries for 7 days. For 3 further weeks subjects followed their own diet diary supplemented with 125 ml single cream and 50 g roasted peanuts (88 g fat, 15 g Protein, 8 g carbohydrate) every day. Oral fat tolerance tests (OFTT) were undertaken at baseline, 7, 14 and 21 days of fat supplementation. The diet was increased in energy by 3.9 MJ/day and from a mean of 29-45% energy intake from fat with a small weight gain noted each week (P=0.009). RESULTS: Ghrelin concentrations were significantly reduced during the baseline OFTT. The postprandial ghrelin response (AUC) was significantly reduced following 2 weeks of dietary supplementation (P=0.005) increasing the suppression of plasma ghrelin by 18% despite only a 3% increase in body weight. Plasma triacylglycerol (P=0.009) and leptin (P=0.035) concentrations were also elevated and postprandial pancreatic polypeptide levels decreased (P=0.038) following dietary-supplementation. CONCLUSIONS: These results suggest that the metabolic profile associated with obesity, including a reduction in plasma ghrelin levels, may be related to recent dietary energy intake and precedes the development of significant adiposity.

Peripheral intrapulmonary lipoma: a rare lung neoplasm.

Lipomas are common benign tumours, but intrathoracic lipomas are rare and peripheral lung lipomas exceptionally rare. Seven cases--all in men--have been described in the world literature, diagnosed after thoracotomy and excision. We report a case of a peripheral intrapulmonary lipoma in a woman presenting as an opacity on a routine chest radiograph. The CT characteristics and the finding of the same lesion on reviewing a barium enema film from 12 years earlier allowed a confident diagnosis, avoiding the need for surgical excision. This is the first reported case of peripheral lung lipoma in a woman and highlights the value of reviewing previous radiographs.

Altered fatty acid compositions in atlantic salmon (Salmo salar) fed diets containing linseed and rapeseed oils can be partially restored by a subsequent fish oil finishing diet.

Atlantic salmon postsmolts were fed a control diet or one of 9 experimental diets containing various blends of two vegetable oils, linseed (LO) and rapeseed oil (RO), and fish oil (FO) in a triangular trial design, for 50 wk. After sampling, fish previously fed 100% FO, LO and RO were switched to a diet containing 100% FO for a further 20 wk. Fatty acid compositions of flesh total lipid were linearly correlated with dietary fatty acid compositions (r = 0.99-1.00, P < 0.0001). Inclusion of vegetable oil at 33% of total oil significantly reduced the concentrations of the highly unsaturated fatty acids, eicosapentaenoate [20:5(n-3)] and docosahexaenoate [22:6(n-3)], to approximately 70 and 75%, respectively, of the values in fish fed 100% FO. When vegetable oil was included at 100% of total dietary lipid, the concentrations of 20:5(n-3) and 22:6(n-3) were significantly reduced to approximately 30 and 36%, respectively, of the values in fish fed FO. Transfer of fish previously fed 100% vegetable oil to a 100% FO diet for 20 wk restored the concentrations of 20:5(n-3) and 22:6(n-3) to approximately 80% of the value in fish fed 100% FO for 70 wk, although the values were still significantly lower. However, in fish previously fed either 100% LO or RO, concentrations of 18:2(n-6) remained approximately 50% higher than in fish fed 100% FO. This study suggests that RO and LO can be used successfully to culture salmon through the seawater phase of their growth cycle; this will result in reductions in flesh 20:5(n-3) and 22:6(n-3) concentrations that can be partially restored by feeding a diet containing only marine FO for a period before harvest.

The esterification and modification of n-3 and n-6 polyunsaturated fatty acids by hepatocytes and liver microsomes of turbot (Scophthalmus maximus).

The present study was undertaken to establish whether the formation of 22:6n-3 from 18:3n-3 and/or 20:5n-3 can occur in turbot liver and if this conversion is consistent with the operation of a Delta4 desaturase-independent pathway. At the same, time the effects of feeding a diet devoid of long chain polyunsaturated fatty acids (PUFA) on the patterns of esterification and modification of 18:3n-3, 20:5n-3 and 18:2n-6 by turbot hepatocytes and liver microsomes were examined. For this purpose, two groups of fish (25-30 g) were employed: one was fed a commercial diet containing fish oil (FO) and thus rich in long chain n-3 PUFA and the other was fed an experimental diet based on olive oil (OO). After 5 months of feeding, hepatocytes and liver microsomes isolated from individuals in the two groups of fish were incubated with [1-(14)C]-PUFA [either 18:3n-3, 20:5n-3 or 18:2n-6]. After 3 h of incubation, most radioactivity from all three radiolabelled substrates incorporated into lipids by hepatocytes and microsomes was recovered in the original substrate. The formation of desaturation products of n-3 radiolabelled substrates was higher in hepatocytes isolated from OO-fed than FO-fed fish. Small amounts of radiolabelled 22:6n-3 were formed from [1-(14)C]18:3n-3 and [1-(14)C]20:5n-3, but only by hepatocytes from fish fed OO, which also synthesised a small amount of radiolabelled 24:6n-3 from 14C-20:5n-3. Elongation products predominated over desaturation products in hepatic microsomes from both groups of fish studied, particularly in microsomes from fish fed FO. The results confirm that regardless of the long chain PUFA content of the diet, the production of 22:6n-3 in turbot liver from 18:3n-3 and/or 20:5n-3, and of 20:4n-6 from 18:2n-6, is very limited. The presence of radiolabelled 24:6n-3 in microsomes coupled with the absence of radiolabelled 22:6n-3 suggests that the formation of 22:6n-3 that does occur in turbot liver cells, may involve C24 intermediates and peroxisomal beta-oxidation.

Substituting fish oil with crude palm oil in the diet of Atlantic salmon (Salmo salar) affects muscle fatty acid composition and hepatic fatty acid metabolism.

Supplies of marine fish oils (FO) are limited and continued growth in aquaculture production dictates that substitutes must be found that do not compromise fish health and product quality. In this study the suitability of crude palm oil (PO) as a replacement for FO in diets of Atlantic salmon was investigated. Duplicate groups of Atlantic salmon post-smolts were fed four practical-type diets in which the added lipid was either 100% FO and 0% crude PO (0% PO); 75% FO and 25% PO (25% PO); 50% FO and 50% PO (50% PO); and 100% PO, for 30 wk. There were no effects of diet on growth rate or feed conversion ratio nor were any histopathological lesions found in liver, heart or muscle. Lipid deposition was greatest in fish fed 0% PO and was significantly greater than in fish fed 50% and 100% PO. Fatty acid compositions of muscle total lipid were correlated with dietary PO inclusion such that the concentrations of 16:0, 18:1(n-9), 18:2(n-6), total saturated fatty acids and total monoenoic fatty acids increased linearly with increasing dietary PO. The concentration of eicosapentaenoic acid [20:5(n-3)] was reduced significantly with increasing levels of dietary PO but the concentration of docosahexaenoic acid [22:6(n-3)] was significantly reduced only in fish fed 100% PO, compared with the other three treatments. Similar diet-induced changes were seen in liver total lipid fatty acid compositions. Hepatic fatty acid desaturation and elongation activities were approximately 10-fold greater in fish fed 100% PO than in those fed 0% PO. This study suggests that PO can be used successfully as a substitute for FO in the culture of Atlantic salmon in sea water. However, at levels of PO inclusion above 50% of dietary lipid, significant reductions in muscle 20:5(n-3), 22:6(n-3) and the (n-3):(n-6) PUFA ratio occur, resulting in reduced availability of these essential (n-3) highly unsaturated fatty acids to the consumer.

Oxygen measurements in brain stem slices exposed to normobaric hyperoxia and hyperbaric oxygen.

We previously reported (J Appl Physiol 89: 807-822, 2000) that < or =10 min of hyperbaric oxygen (HBO(2); < or = 2,468 Torr) stimulates solitary complex neurons. To better define the hyperoxic stimulus, we measured PO(2) in the solitary complex of 300-microm-thick rat medullary slices, using polarographic carbon fiber microelectrodes, during perfusion with media having PO(2) values ranging from 156 to 2,468 Torr. Under control conditions, slices equilibrated with 95% O(2) at barometric pressure of 1 atmospheres absolute had minimum PO(2) values at their centers (291 +/- 20 Torr) that were approximately 10-fold greater than PO(2) values measured in the intact central nervous system (10-34 Torr). During HBO(2), PO(2) increased at the center of the slice from 616 +/- 16 to 1,517 +/- 15 Torr. Tissue oxygen consumption tended to decrease at medium PO(2) or = 1,675 Torr to levels not different from values measured at PO(2) found in all media in metabolically poisoned slices (2-deoxy-D-glucose and antimycin A). We conclude that control medium used in most brain slice studies is hyperoxic at normobaric pressure. During HBO(2), slice PO(2) increases to levels that appear to reduce metabolism.

The impact of ferrous ion reduction of chlorite ion on drinking water process performance.

The use of chlorine dioxide (ClO2) as a primary disinfectant and pre-oxidant in drinking water treatment is being explored as an alternative to chlorine for reducing disinfection by-product formation and to assure compliance with United States Environmental Protection Agency's Stage 1 Disinfection/ Disinfection By-Products Rule. However, the ClO2 by-product chlorite ion (ClO2-) is also regulated by the same regulation. Ferrous iron (Fe(II)) has been shown to effectively reduce chlorite ion to chloride ion (Cl-) and this study was conducted to evaluate the impact on overall treatment process performance due to the ferric hydroxide solids that form from the reaction. Ferrous iron application was explored at three different points in a pilot-scale water treatment system: pre-rapid mix. pre-settling and pre-filter. Chlorite ion concentrations were effectively reduced from 2mg/L to less than 0.3mg/L using an Fe(II) dose of approximately 6mg/L for all trials. Fe(II) addition at the rapid mix caused no adverse effects and, in fact, allowed for reduction of the alum dose due to the newly formed ferric hydroxide acting as a supplemental coagulant. An increase of 241 and 247% of total suspended solids influent to the filter process was observed when Fe(II) was applied at the pre-settling and pre-filter locations. Pilot-scale filter runs during these trials were less than 2 h and never obtained true steady state conditions. Jar testing was performed to better understand the nature of the ferric hydroxide solids that are formed when Fe(II) was oxidized to Fe(III) and to explore the effectiveness of Fe(II) addition at intermediate stages in the flocculation process.

Hyperbaric oxygen depolarizes solitary complex neurons in tissue slices of rat medulla oblongata.

Hyperbaric oxygen (HBO2) at approximately 3 atmospheres absolute (ATA) pressure is toxic to the mammalian CNS due to excessive O2 free radical production. No study has ever determined the effects of < or = 3 ATA of O2 on the membrane potential and firing rate of neurons in the mammalian brainstem. Likewise, no study has ever determined the effects of < or = 3 ATA pressure per se on brainstem neurons. Accordingly, we initiated intracellular recordings at 1 ATA in solitary complex neurons in slices (300 microns) of rat caudal medulla oblongata that were maintained inside a 72 liter hyperbaric chamber. Helium, which is inert and without narcotic effect at moderate levels of hyperbaria, was used to hydrostatically compress the submerged brain slice to determine the effects of pressure per se. Tissue oxygen tension and extracellular pH were also measured during exposure to hyperbaric gases. Six of 19 neurons were affected by hyperbaric helium; 5 cells were depolarized and 1 cell was hyperpolarized. Input resistance (Rin) either increased (n = 1) or decreased (n = 3). When control perfusate (0.95 ATA O2) was switched to perfusate saturated with 98% O2 (balance CO2, pH = 7.3-7.4, pO2 = 2.5-3.4 ATA; 2-18 minutes of exposure) in a separate pressure vessel, 8 of 13 neurons were depolarized and 5 neurons were insensitive. In the 8 O2-responsive neurons, Rin either increased (n = 5), decreased (n = 2) or was unchanged (n = 1). Three of 8 neurons depolarized by HBO2 were also depolarized by hyperbaric helium, usually with an additional change in Rin. We conclude that hydrostatic (helium) pressure and HBO2 independently increase excitability in certain solitary complex neurons. We hypothesize that these responses contribute, in part, to neural events that either precede or occur during CNS O2 toxicity.

Bone mineral content and body composition in children and young adults with cystic fibrosis.

With dual energy X-ray absorptiometry (DEXA), it is possible to quantitate important aspects of growth in children with cystic fibrosis (CF), supplementing the usual measures of height and weight. Of particular concern during growth is the accumulation of bone mineral, since osteoporosis and fractures are well-recognized problems in end-stage disease. Various measures of growth and body composition were examined in 40 children and young adults (ages 5.7-20.3 years, mean 11.9 years) and compared to age-, gender-, and race-matched normal controls. The mean (+/- SE) weight Z-score of the 40 CF patients was -0.70 +/- 0.11, and the mean height Z-score was -0.66 +/- 0.15. Relative to their matched normal controls, the CF patients had a deficit in total body bone mineral averaging 19.1% +/- 3.0%. The deficits in total body bone mineral correlated with pulmonary and nutritional measures of disease severity. Serum vitamin D levels, calcium intake, age, gender, use of steroids, and CF genotype were not found to be significant factors. In this group of children and young adults with CF, height and weight measures of growth were not dramatically reduced (mean Z-scores = -0.7), yet large deficits in total body bone mineral averaging nearly 20% were identified.

Longitudinal evaluation of bone mineral density in children receiving chemotherapy.

PURPOSE: Some children who survive a childhood malignancy have diminished bone mineral density (BMD). The purpose of this study is to assess when, and perhaps why, this problem develops. PATIENTS AND METHODS: BMD was longitudinally monitored in 37 children for a minimum of 1 year (mean, 23.4 months; range, 12 to 41 months) during and, in some cases, after chemotherapy. Evaluations included serum analyses (vitamin D, calcium, and alkaline phosphatase), assessment of calcium intake, and measures of growth and nutrition (height, weight, and skinfolds). RESULTS: BMD was already diminished at the start of treatment in some patients; 6 of 13 patients (46%) had a BMD z score in the hip or spine of < -1.0. However, only 1 patient (8%) was < -2.0. Most patients did not have a significant drop in BMD z scores during chemotherapy, but one in four did decrease at least 0.5 standard deviations. Age greater than 10 years, a drop in height z score, and treatment with cranial irradiation correlated with a drop in BMD z scores during treatment. In the year immediately after completion of chemotherapy, no consistent "catch-up" was observed in BMD z scores. CONCLUSIONS: In some patients, BMD z scores are diminished at the time of diagnosis and a drop may occur during treatment in others. Multiple factors related to the disease process and treatment likely contribute to these observations. Cranial irradiation, perhaps by impacting on growth hormone homeostasis, is one such factor. Fortunately, most survivors of a childhood malignancy will not have large deficits in BMD later in life.

The effect of home training with direct blood pressure biofeedback of hypertensives: a placebo-controlled study.

BACKGROUND: Home training in self-lowering of blood pressure using continuous blood pressure feedback has not previously been reported. Enhancement of laboratory-learned skills was hypothesized on the basis of outcomes from other intellectual, emotional and physical endeavours. OBJECTIVE: To examine the supplementary effect of home blood pressure biofeedback training. DESIGN: Thirty unmedicated, mild hypertensives participated in a randomized, double-blinded, modified contingency placebo-controlled study. METHOD: After suitable screening and baseline blood pressure measurements subjects undertook eight laboratory biofeedback sessions and then 12 home training sessions over 4 weeks using continuous finger blood pressure monitoring. RESULTS: In the laboratory those being administered active therapy (n=16) lowered systolic pressures by 5 +/- 5.4 mmHg compared with a lowering of 4 +/- 4.2 mmHg with placebo (NS). During the fourth week at home lowering for the active group (11 +/- 8 mmHg) was greater than that with placebo (4 +/- 6.2 mmHg, P=0.017). Arm-cuff blood pressures were not statistically different for groups and with time but that of the active group was lower by 9 +/- 15.4/7 +/- 10.2 mmHg, which is a clinically relevant change, after home biofeedback. CONCLUSIONS: The efficacy of self-lowering of systolic blood pressure in mild hypertensives by continuous feedback was enhanced by 6 mmHg with 4 weeks of practice at home. Standard arm-cuff blood pressure was reduced by a clinically relevant amount. The home environment proved cost effective for this 'high-tech' approach.

Effect of feedback signal and psychological characteristics on blood pressure self-manipulation capability.

Blood pressure presentation mode and personality are likely to influence biofeedback outcome. Thirty-six normotensive subjects were randomly assigned to visual or auditory continuous systolic feedback. "Distracting speech" and "broad band noise" were also superimposed and the effect on the biofeedback response was investigated. Psychological influence was also investigated. Systolic pressure reduction of 4 +/- 4.3 mmHg (visual, p = .04) and 5 +/- 5.5 mmHg (visual + auditory, p = .03) were achieved compared with auditory feedback (2 +/- 4.7 mmHg), which was less effective. The addition of noise or speech had no effect on the systolic response, but speech adversely affected diastolic reduction (p = .04). Mood (p = .003) was associated with systolic lowering, whereas increased trait anxiety (p = .06) and expectation (p = .03) had trends for opposite effects. Increased anger-hostility, state-anxiety, and expectation (p = .06) had links with systolic raising capability. We conclude that feedback modality and psychological characteristics have implications for studies investigating blood pressure manipulation capability.