Intensive care doctors' preferences for arterial oxygen tension levels in mechanically ventilated patients.

BACKGROUND: Oxygen is liberally administered in intensive care units (ICUs). Nevertheless, ICU doctors' preferences for supplementing oxygen are inadequately described. The aim was to identify ICU doctors' preferences for arterial oxygenation levels in mechanically ventilated adult ICU patients. METHODS: In April to August 2016, an online multiple-choice 17-part-questionnaire was distributed to 1080 ICU doctors in seven Northern European countries. Repeated reminder e-mails were sent. The study ended in October 2016. RESULTS: The response rate was 63%. When evaluating oxygenation 52% of respondents rated arterial oxygen tension (PaO2 ) the most important parameter; 24% a combination of PaO2 and arterial oxygen saturation (SaO2 ); and 23% preferred SaO2 . Increasing, decreasing or not changing a default fraction of inspired oxygen of 0.50 showed preferences for a PaO2 around 8 kPa in patients with chronic obstructive pulmonary disease, a PaO2 around 10 kPa in patients with healthy lungs, acute respiratory distress syndrome or sepsis, and a PaO2 around 12 kPa in patients with cardiac or cerebral ischaemia. Eighty per cent would accept a PaO2 of 8 kPa or lower and 77% would accept a PaO2 of 12 kPa or higher in a clinical trial of oxygenation targets. CONCLUSION: Intensive care unit doctors preferred PaO2 to SaO2 in monitoring oxygen treatment when peripheral oxygen saturation was not included in the question. The identification of PaO2 as the preferred target and the thorough clarification of preferences are important when ascertaining optimal oxygenation targets. In particular when designing future clinical trials of higher vs lower oxygenation targets in ICU patients.

Simultaneous quantitation of homocysteine, cysteine and methionine in plasma and urine by liquid chromatography-tandem mass spectrometry.

BACKGROUND: A method utilizing liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) has been developed and evaluated for the determination of total homocysteine, cysteine and methionine in plasma and urine. The simultaneous measurement of homocysteine and methionine concentrations may help explain the underlying mechanism responsible for hyperhomo-cysteinaemia. METHODS: Samples were prepared by simple protein precipitation after reduction of disulphides by dithiothreitol. Reduced analyte signal caused by ionization suppression effects, seen with plasma samples, was compensated for with matrix-matched standards, and the use of isotopically labelled internal standards. Recovery for each analyte was better than 94%. RESULTS: Concentrations of plasma homocysteine determined by LC-MS/MS were compared with those obtained by two automated commercially available FDA-approved procedures: (i) high-performance liquid chromatography (HPLC) with pre-column derivatization and fluorescence detection and (ii) by fluorescence polarization immunoassay (FPIA). Agreement with the LC-MS/MS method is given by the Deming regression equations LC-MS/MS = 1.062 HPLC-0.01 and LC-MS/MS = 1.104 FPIA-0.43. CONCLUSION: Low reagent costs together with the relative simplicity of sample preparation make the LC-MS/MS method well suited, not only for research work but also in those laboratories with a tandem mass spectrometer, for the measurement of routine clinical samples.

Behavioural and psychological symptoms of Alzheimer type dementia are not correlated with plasma homocysteine concentration.

BACKGROUND/AIMS: Vitamin B12 and folate deficiencies have been associated with cognitive impairment and various psychiatric symptoms but not specifically with behavioural and psychological symptoms of dementia (BPSD). A limitation of previous studies in dementia was lack of concurrent homocysteine measurement especially as it may provide a better indicator of tissue activities of these vitamins. This study was designed to clarify whether a relationship exists between plasma homocysteine concentration and BPSD. METHODS: Plasma homocysteine, serum vitamin B12 and folate were measured in 23 Alzheimer's disease (AD) patients with BPSD and 27 AD patients without BPSD as determined through the use of the Neuropsychiatric Inventory (NPI). Blood levels of measured substances were also correlated with individual NPI scores and with cumulative NPI scores for different cluster of symptoms. RESULTS: There was no significant difference (p = 0.956) in the mean plasma homocysteine levels between AD patients with BPSD (17.48 micromol/l) and AD patients without BPSD (17.34 micromol/l). Similarly, there was no significant difference between the two groups in the mean serum B12 (382.61 and 391.60 pg/ml, respectively) and folate (7.95 and 10.02 ng/ml, respectively). Mean levels for both vitamins were well within the laboratory reference range. Neither individual nor cluster NPI scores correlated significantly with plasma homocysteine. CONCLUSION: This study shows for the first time that BPSD are not associated with hyperhomocysteinaemia in Alzheimer dementia. Although previous studies have identified homocysteine as an independent risk factor in AD, the results reported here do not lend weight to an aetiological role for homocysteine specifically in BPSD.

Does routine blood bone biochemistry predict vitamin D insufficiency in elderly patients with low-velocity fractures?

PURPOSE: Vitamin D deficiency impairs bone mineralisation and can predispose individuals to fractures. This study aimed at testing whether measurement of plasma calcium, alkaline phosphatase, and phosphate levels could detect vitamin D insufficiency. METHODS: During a 10-week winter period from December 2000 to February 2001, all elderly patients presenting to a general hospital in Brighton--British seaside town--with a fracture of the proximal femur and without known bone mineralisation problems were invited to participate in the study. RESULTS: 23 (63.9%) of the 36 eligible patients had insufficient levels of vitamin D, with a plasma concentration of less than 30 nmol/L. The mean parathyroid hormone level was 56 pg/mL (range, 12-193 pg/mL). 11 of the 36 patients had an elevated level of parathyroid hormone were insufficient in vitamin D. The mean plasma concentration of calcium was 2.30 mmol/L (range, 2.05-2.98 mmol/L). The mean phosphate level was 0.98 mmol/L (range, 0.40-1.79 mmol/L), and the mean alkaline phosphatase level was 91 IU/L (range, 46-127 IU/L). There was poor correlation between vitamin D insufficiency and plasma calcium, alkaline phosphatase, or phosphate levels. CONCLUSION: Plasma calcium, alkaline phosphatase, and phosphate testing cannot detect vitamin D insufficiency. We recommend that vitamin D and calcium supplementation be considered for patients with low-energy hip fractures.

Limitation of the Vitros dry-slide technique in measuring high concentrations of salicylate in plasma.

The linearity of the Vitros dry-slide method for plasma salicylate was assessed in two ways: serial concentrations of sodium salicylate were added to fresh lithium heparin plasma, and the salicylate was determined both neat and in dilution. Vitros salicylate results submitted to the Heathcontrol External Quality Assessment Scheme were compared to the spike value. Similar loss of linearity was observed in both cases. Serious salicylate overdosage requiring specific clinical treatment may have been underestimated.

Phylogeography and population history of Atlantic mackerel (Scomber scombrus L.): a genealogical approach reveals genetic structuring among the eastern Atlantic stocks.

Despite the resolving power of DNA markers, pelagic and migratory marine fish species generally show very little geographical population structuring. In mackerel (Scomber scombrus L.) population differentiation has been detected only at a transatlantic scale. By applying two regions in mitochondrial DNA (mtDNA) (D-loop and cytochrome b (cytb)) in combination with genealogical and frequency-based statistical approaches, our data suggest population differentiation among eastern Atlantic spawning stocks. In contrast, and indicative of homing behaviour, no genetic structuring was observed among shoals of individuals outside the spawning season. Among spawning stocks, mtDNA D-loop sequences detected differentiation within the eastern Atlantic, while the cytb gene detected transatlantic differentiation. The impact of recurrent events (e.g. gene flow restricted by isolation by distance) and historic events (e.g. population range expansions) among spawning stocks was investigated applying a nested cladistic analysis of geographical distribution of cytb haplotype lineages. In the eastern Atlantic, historical population range expansion, presumably in connection with recolonization of northern areas after the last glaciation, is suggested to be the main factor determining mtDNA lineage distribution. This was supported by estimates of mtDNA nucleotide diversity, where the highest diversity was observed for the stock spawning in the Bay of Biscay, for which the size estimate is only 15% of the largest stock (Celtic Sea). In addition to revealing population differentiation, our data demonstrate the importance of sampling strategy and the power of applying statistical methods addressing both ongoing and historical population processes.

The acceptability of resin therapy to patients attending a hospital lipid clinic.

Low dose cholestyramine ('Questran A') and colestipol ('Colestid Orange') were compared in a blinded two period crossover study of 55 patients attending a hospital lipid clinic. Colestipol was rated higher on a combined acceptability/palatability score. Both treatments reduced low density lipoprotein (LDL) cholesterol to a similar extent.

Direct measurement of low density lipoprotein in whole blood by silver-enhanced gold-labelled immunoassay.

A competitive silver-enhanced gold-labelled immunoassay has been developed for the direct measurement of low density lipoprotein (LDL) in whole blood. Immobilized LDL and sample LDL compete for added antibody. Quantitation of the bound antibody/antigen complex is achieved by the addition of gold-labelled anti-immunoglobulin G followed by enhancement of absorbance by addition of silver ions. Whole-blood samples from fasting patients were assayed directly for LDL by the procedure and the corresponding plasma samples were assayed for total cholesterol, high density lipoprotein and triglycerides followed by the indirect calculation of LDL cholesterol. The correlation between the two methods was good (r = 0.82) and the SEGLISA exhibited good precision.

Diagnosis of familial hypercholesterolaemia using DNA probes for the low-density lipoprotein (LDL) receptor gene.

Familial hypercholesterolaemia (FH) is one of the most commonly inherited diseases. It is characterised by an abnormal LDL receptor resulting in a selective elevation of serum LDL and cholesterol levels. The correlation between FH and premature heart disease means that these patients contribute significantly to the number of individuals presenting with coronary heart disease. In the work described here cDNA probes to LDL-receptor were used to assess the usefulness of recombinant DNA technology to diagnose familial hypercholesterolaemia. A 3' probe to the LDL-receptor which detects a restriction fragment length polymorphism (RFLP) in linkage disequilibrium with normal and mutant LDL-receptor genes, was found to be potentially informative in 20% of the families studied. In addition a 5' probe to the LDL-receptor may be capable of directly detecting mutations in some 6% of families. We suggest that until further work has established other RFLP's or oligonucleotide probes are synthesised to directly detect mutant LDL-receptor genes, recombinant DNA technology is only of limited value for diagnosing familial hypercholesterolaemia.

Increased free-radical activity in alcoholics.

The identification of the main dieneconjugated "free-radical marker" in human serum led to a study of free-radical activity in chronic alcoholics. 66 patients were investigated immediately after alcohol withdrawal and over 1-4 weeks' follow-up. The control groups were 76 normal subjects, 78 patients with liver disease, 30 patients on long-term antiepileptic drug treatment, 9 pregnant women, and 99 unselected hospital patients. 82% of chronic alcoholics had a significantly higher than normal level of phospholipid-esterified 9,11 linoleicacid isomer in blood collected within 24 h of their last alcoholic drink. The levels fell to normal over the next 2-4 days but continued to decline within the normal range for 2-3 weeks. There was no rise in the level of the isomer in normal controls after an acute alcohol load. The results suggest that chronic alcoholism may induce a specific detoxifying mechanism which is activated by alcohol and which entails or depends on greatly increased free-radical activity.

A method for the measurement of a diene-conjugated derivative of linoleic acid, 18:2(9,11), in serum phospholipid, and possible origins.

A method is described for the measurement of a diene-conjugated derivative of linoleic acid, 18:2(9,11), in the phospholipid fraction of serum. The method is based on enzymatic hydrolysis, solid-phase sample preparation, and high-performance liquid chromatography (HPLC). Phospholipid esterified 18:2(9,11) can be detected in serum from normal individuals, and a provisional normal range is provided. The possible origins of 18:2(9,11) and the potential application of this method to the measurement of free radical damage to linoleic acid in vivo is discussed.

An altered ratio of 18:2 (9,11) to 18:2 (9,12) linoleic acid in plasma phospholipids as a possible predictor of pre-eclampsia.

As a part of a larger study, 15 healthy primigravidas were studied from 28 weeks gestation until 3 days after deliver. In 6 of these women pre-eclampsia (PET) developed; the remaining 9 subjects, who were age matched had normal pregnancies. Plasma phospholipid-esterified 18:2(9,11):18:2(9,12)fatty acids were measured by high performance liquid chromatography (HPLC). The ratio of 18:2(9,11):18:2(9,12)linoleic acid was significantly higher in the PET group than in the normotensive group at 28 weeks' gestation--that is before the onset of symptoms and signs of PET. The ratio remained significantly higher in the PET group than in the normotensive group until deliver, except at 30 weeks when the difference between the ratios just failed to reach statistical significance. It is suggested that measurement of the ratio of 18:2(9,11) to 18:2(9,12)linoleic acid in plasma phospholipids may be useful as a predictor of the likely development of PET.

Unsuspected caffeine toxicity complicating theophylline therapy.

A 58-year-old man with a history of alcoholic liver disease and chronic airflow obstruction presented with heart failure and acute bronchitis. Plasma methylxanthines were estimated as a guide to further theophylline therapy and serious caffeine accumulation was noted in the presence of a subtherapeutic concentration of theophylline. After 3 weeks on a caffeine-free diet theophylline and caffeine challenge tests were performed which demonstrated the ease with which caffeine could accumulate. The importance of caffeine accumulation during theophylline therapy is discussed.

Identification of a diene conjugated component of human lipid as octadeca-9,11-dienoic acid.

The predominant diene conjugated acyl residue in triacylglycerols, cholesteryl esters and phospholipids in human serum was identified by high performance liquid chromatography and capillary gas chromatography-mass spectrometry. It is an octadeca -9,11-dienoic acid.

The nature of diene conjugation in human serum, bile and duodenal juice.

Diene-conjugated lipids have been located by HPLC in serum, bile and duodenal juice. Whether esterified or not the same predominant fatty acid is responsible for most of the diene conjugation in all of these biological fluids. Initial attempts to generate this fatty acid in pure lipid by classical lipid peroxidation in vitro were unsuccessful. Ultraviolet irradiation of free fatty acids in the presence of protein produced diene-conjugated lipids similar to those found in vivo. The predominant diene-conjugated fatty acid in vivo is an isomerised C18:2 compound.