Multiplate and TEG platelet mapping in a population of severely injured trauma patients.

OBJECTIVES: The objectives of this study were to compare thromboelastography platelet mapping (TEG PM) with impedance aggregometry (Multiplate, MP) in a single trauma population and relate their results clinically. BACKGROUND: Platelet function as measured by thromboelastography and impedance aggregometry demonstrates significant reductions that persist for days following traumatic injury. However, no study compares these devices and the correlation between them is not known. METHODS: In level 1 trauma patients, TEG PM and MP were conducted at their initial presentation to the emergency department. Within-device repeatability and between-device association were determined using correlation analyses. Demographic variables, Injury Severity Score, blood product transfusion, laboratory test results and mortality rate were recorded. RESULTS: Ninety-two patients were enrolled. Within-device repeatability was high for TEG PM and MP for arachidonic acid (AA) and adenosine diphosphate (ADP) activation pathways. When comparing TEG PM with MP, results correlated poorly in the ADP pathway (Spearman's rho = 0·11, P = 0·44) and moderately in the AA pathway (Spearman's rho = 0·56, P < 0·0001). TEG PM was predictive of blood product transfusion and correlated with increased base deficit, whereas MP was only predictive of mortality. CONCLUSIONS: Intra-device variability was low for TEG PM and MP, but the two point-of-care devices measuring platelet function correlate poorly with each other in injured trauma patients. Each device also had different clinical associations.

Synchronous bidirectional endoscopy for iron deficiency anaemia: is it appropriate for patients under 50?

BACKGROUND: UK guidelines1 suggest investigation with bidirectional endoscopy (BDE) (upper endoscopy and colonoscopy) in the same sedative episode is a reasonable approach for the investigation of iron deficiency anaemia. There are few data regarding such investigation for iron deficiency anaemia (IDA) in young men. OBJECTIVE: To assess the use of synchronous BDE for IDA in men and in women <50; and to compare the effectiveness of synchronous BDE in the investigation of iron deficiency anaemia in patients <50 years with those >50 years. METHODS: Our endoscopy database was searched for all synchronous bidirectional endoscopies that were undertaken for the indication of iron deficiency anaemia between 2003 and 2009. Age, gender and endoscopic findings were retrieved for each procedure. Significant findings were defined as cancer, grade 3 oesophagitis (Savory Miller classification), oesophageal stricture, Barrett's oesophagus, ulcer, arteriovenous malformation, colitis, and colonic polyps >1 cm. RESULTS: 558 patients underwent synchronous BDE for iron deficiency anaemia between 2003 and 2009. A significant finding in those >50 years was found in 24.6% vs 11.3% of patients <50 years (OR 2.5, 95% CI 1.3 to 5.0). In men under 50 years a significant finding was present in 20.6%. Dual pathology was present in 1.5% of patients over 50 vs 1.3% under 50 years. CONCLUSIONS: Our findings suggest that synchronous BDE is an appropriate means of investigation for iron deficiency anaemia in patients >50 and for men <50 years old.

Effect of carbon monoxide and high oxygen modified atmosphere packaging and phosphate enhanced, case-ready pork chops.

The objective of this study was to evaluate the effects of CO-MAP compared to traditional high oxygen MAP (HiOx-MAP) packaging and enhanced with different phosphate on enhanced pork quality. Pork loins were enhanced to 10.5% over initial weight to contain 0.3% salt and 0.4% phosphate (either sodium tripolyphosphate [STP] or a blend of STP and sodium hexametaphosphate) on a finished weight basis. Chops were cut, packaged in atmospheres containing 0.4% CO/30.0% CO(2)/69.6% N(2) (CO-MAP) or 80% O(2)/20% CO(2) (HiOx-MAP), aged in the dark, then placed in a lighted retail display case for 48h. Chops packaged in CO-MAP were redder (higher Minolta a(∗) values) and darker (lower Minolta b(∗) values) than chops packaged in HiOx-MAP. Based on sensory scores, the CO-MAP chops were pinker than the HiOx chops after cooking. CO-MAP chops also experienced less purge loss than chops in HiOx-MAP. Results indicate that CO-MAP had no effect on flavor or consumer acceptability and only minimal effects on other characteristics.

Colonoscopy services in the United Kingdom.

BACKGROUND AND STUDY AIMS: Provision of a reasonable colonoscopy service requires approximately 160 procedures per 100000 population per year. The aim of the present study was to document current levels of colonoscopy service, the use of guidelines in surveillance practice and the capacity for expansion in endoscopy units throughout the United Kingdom. MATERIAL AND METHODS: A postal questionnaire was sent to 294 endoscopy units. RESULTS: Replies were received from 164 units (60 %). Of the units, 49 % have reached the calculated target figure. In units not meeting the target, 22% have only one colonoscopist, and 31% have one colonoscopy session a week. Overall, 50 % of units are working at full capacity. Out of all units, 70 % are unable to expand their service further, because of lack of nursing support in 81%, non-availability of endoscopist in 72 % and lack of physical space in 51%. Guidelines for surveillance colonoscopy were a problem: 51% of units reported that guidelines were available for surveillance of ulcerative colitis, 28 % for Crohn's disease, 59 % for polyp follow-up, and 44 % for follow-up of resected colorectal cancer. The majority of units (>70%) had no protocols for their surveillance practice. Nonetheless, 92% of units performed surveillance colonoscopy for ulcerative colitis, 34% for Crohn's disease, and 76% for resected colorectal cancer. CONCLUSIONS: The colonoscopy service has expanded, but there are constraints on further growth. There is a pressing need for national guidelines on surveillance colonoscopy.

Fatal acute fulminant liver failure due to clozapine: a case report and review of clozapine-induced hepatotoxicity.

Clozapine-induced hepatotoxicity is not well known and is usually of no clinical significance. This report describes fatal acute fulminant liver failure caused by clozapine in a 39-year-old man with chronic paranoid schizophrenia. The hepatotoxicity of clozapine is reviewed. Asymptomatic elevation of transaminase levels is observed most commonly, affecting between 30% and 50% of patients. Icteric hepatitis is uncommon, noted in 84 of 136,000 patients (0.06%). Fatal acute fulminant hepatitis has been documented in 2 patients (0.001%). The mechanism of clozapine hepatotoxicity is unknown. Although serious toxicity is rare, prescribers of clozapine should be aware of the hepatotoxic potential.

Chronic neuropathic pain and its control by drugs.

The medical treatment and some currently known aspects of the aetiology of five neurogenic pain states are discussed. Neurogenic pain can be described as pain resulting from noninflammatory dysfunction of the peripheral or central nervous system without nociceptor stimulation or trauma. The enormity of the field has limited this review to post-herpetic neuralgia, complex regional pain syndromes, phantom pain, trigeminal neuralgia and diabetic neuralgia. Evidence suggests that many neurogenic pain states are not effectively controlled. This may be due in part to a lack of understanding of the aetiology of these conditions and to the lack of high quality studies evaluating existing treatments. A compact review of the literature is presented with some treatment options and possible future directions. Where appropriate surgical management and physical therapy have been discussed; however, a thorough appraisal of nondrug treatments was not the main priority of this review.

Reversible blockade of retrograde axonal transport in the rat sciatic nerve by vincristine.

Altered axoplasmic transport has been implicated as a contributing factor in neuropathic pain states. Treatments which produce transient axoplasmic transport blockade have shown initial promise as therapeutic procedures in the management of chronic neuropathic pain. The present study evaluated the capacity of the vinca alkaloid, vincristine to produce reversible blockade of retrograde axoplasmic transport. Results indicated that intraneural administration of 10(-5)M vincristine resulted in blockade of retrograde axoplasmic transport of [3H]leucine 24 h following administration. Importantly, the effect reversed over the next four days and axoplasmic transport was re-instated fully at day five. The implications of these results are discussed in relation to the potential use of axoplasmic transport blocking agents in the management of chronic neuropathic pain.

Endoscopic retrograde cholangiography in the diagnosis and endoscopic management of biliary complications after liver transplantation.

OBJECTIVE: Biliary reconstruction in orthotopic liver transplantation is increasingly being performed without T tube drainage. This increases the difficulty of diagnosing subsequent biliary tract problems, with a greater reliance placed on endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis of biliary tract complications. The usefulness of ERCP was evaluated in patients who underwent liver transplant where biliary reconstruction was not done with T tube drainage. DESIGN AND PARTICIPANTS: A retrospective study of the case notes of 90 patients who underwent liver transplantation, and in whom the biliary reconstruction was by end to end choledochocholedochostomy without T tube splintage. RESULTS: ERCP was performed as the primary procedure to investigate a suspected biliary complication in 30 patients (33%). The procedure was successful in 26 patients (87%), and showed a biliary stricture in 12 patients and a bile leak in six patients. ERCP was normal in seven patients and demonstrated dilated ducts alone in one patient. Six of the biliary strictures were successfully dilated endoscopically (50%), but none of the bile leaks resolved with endoscopic drainage. CONCLUSION: This study confirms the diagnostic role of ERCP post liver transplant. The therapeutic role requires clearer evaluation with a controlled trial.

A quantitative analysis of matrix alignment in ligament scars: a comparison of movement versus immobilization in an immature rabbit model.

This investigation quantified the alignment of fibrillar matrix in normal rabbit medial collateral ligaments (MCLs) and in healing MCLs from animals treated with or without knee immobilization. Twenty-four immature female rabbits were given complete midsubstance injuries to their right MCLs. Fifteen of them had that knee pin immobilized in flexion, while the remaining nine were allowed unrestricted cage activity. Animals were sacrificed in groups of three at intervals of 3, 6, or 14 weeks after injury, and both healing MCLs and unoperated contralateral controls were fixed in situ for subsequent removal, freeze-fracture, and preparation for scanning electron microscopy (SEM). A random sampling of SEM photographs followed by automated, statistically validated image processing was used to quantify alignment of matrix in all samples. Results showed that nonimmobilized MCL scars in this model do remodel over 14 weeks of healing, returning to normal alignment values in that time. Surprisingly, MCL scars in immobilized knees were even better, with mean matrix alignments falling statistically within normal MCL limits at all healing intervals studied. If not due to an unknown sampling or fixation artifact, these results suggest that gross knee flexion and extension is not a prerequisite for scar matrix alignment in this immature model of ligament healing.

Ascorbic acid prevents the dose-dependent inhibitory effects of polyphenols and phytates on nonheme-iron absorption.

The effects of maize-bran phytate and of a polyphenol (tannic acid) on iron absorption from a white-bread meal were tested in 199 subjects. The phytate content was varied by adding different concentrations of phytate-free and ordinary maize bran. Iron absorption decreased progressively when maize bran containing increasing amounts of phytate phosphorous (phytate P) (from 10 to 58 mg) was given. The inhibitory effect was overcome by 30 mg ascorbic acid. The inhibitory effects of tannic acid (from 12 to 55 mg) were also dose dependent. Studies suggested that greater than or equal to 50 mg ascorbic acid would be required to overcome the inhibitory effects on iron absorption of any meal containing greater than 100 mg tannic acid. Our findings indicate that it may be possible to predict the bioavailability of iron in a diet if due account is taken of the relative content in the diet of the major promoters and inhibitors of iron absorption.

Dietary iron overload in southern African rural blacks.

A survey conducted in rural southern African black subjects indicated that dietary iron overload remains a major health problem. A full blood count, erythrocyte sedimentation rate, serum concentrations of iron, total iron-binding capacity, ferritin, C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and serological screening for hepatitis B and human immunodeficiency virus (HIV) infections were carried out in 370 subjects (214 inpatients and 156 ambulatory Mozambican refugees). The fact that the geometric mean (SD range) serum ferritin concentration was much higher in the male hospital patients than in subjects living in the community [1,581 micrograms/l (421-5,944 micrograms/l) and 448 micrograms/l (103-1,945 micrograms/l) respectively] suggested that dietary iron overload was not the only factor raising the serum ferritin concentration. The major additional factor appeared to be inflammation, since the geometric mean (SD range) serum CRP was significantly higher in male hospital patients [21 mg/l (8-53 mg/l)] than in subjects in the community [3 mg/l (1-5 mg)]. Alcohol ingestion, as judged by history and by serum GGT concentrations, was also associated with significantly raised serum ferritin concentrations. This finding was ascribed to the fact that traditional brews are not only associated with alcohol-induced hepatic damage but are also a very rich source of highly bio-available iron. The role of iron overload in the genesis of the raised serum ferritin concentrations are confirmed in the diagnostic liver biopsy study. The majority of biopsies showed heavy siderosis, with varying degrees of hepatic damage.(ABSTRACT TRUNCATED AT 250 WORDS)

The promotive effect of soy sauce on iron absorption in human subjects.

The effects on iron absorption of a traditionally fermented Japanese soy sauce added to soy and rice meals were assessed. The addition of soy sauce to a soy flour meal could not overcome the strong inhibition of iron absorption (geometric mean absorption 7.2 per cent with soy sauce vs. 8.7 per cent without, P = 0.5). However, soy sauce added to a rice meal instead of soy flour significantly improved the geometric mean iron absorption (13.9 per cent with soy sauce vs. 5.2 per cent with soy flour, P = 0.002) and had a promotory effect on absorption from a rice meal alone (11.4 per cent with soy sauce vs. 3.5 per cent without, P = 0.0002). Although soy sauce contains appreciable amounts of organic acids, the addition of 340 mg lactic acid to rice did not enhance iron absorption (3.1 per cent with lactic acid vs. 2.2 per cent without, P = 0.11). The promotory effect of soy sauce on iron absorption appears to be due not only to its lack of soy protein content but may also be due to the presence of fermentation products other than organic acids.

Effect of traditional oriental soy products on iron absorption.

The effect of a variety of traditional oriental unfermented and fermented soy products on iron absorption was evaluated in 242 Indian women. When compared with a soy-flour meal containing an equal amount of protein, iron absorption was found to be significantly improved with silken tofu, natto, tempeh, rice miso, barley miso, and soybean miso. This improvement could not be adequately explained except with reference to changes in the protein composition of the products. The protein fraction profiles of the soy products were obtained by size-exclusion high-performance liquid chromatography. An inverse relationship between food iron absorption and the high-molecular-weight fraction of the soy products was demonstrated (r = 0.66, p = 0.01). However, anomalous results obtained with three products (sufu, tempeh, and fully hydrolyzed isolated soy protein) did not make it possible to reach firm conclusions concerning the effect of the protein fraction of soy on iron bioavailability.

Factors involved in the regulation of iron transport through reticuloendothelial cells.

The effects of various maneuvers on the handling of 59Fe-labeled heat-damaged red cells (59Fe HDRC) by the reticuloendothelial system were studied in rats. Raising the saturation of transferrin with oral carbonyl iron had little effect on splenic release of 59Fe but markedly inhibited hepatic release. Splenic 59Fe release was, however, inhibited by the prior administration of unlabeled HDRC or by the combination of carbonyl iron and unlabeled HDRC. When carbonyl iron was administered with unlabeled free hemoglobin, the pattern of 59Fe distribution was the same as that observed when carbonyl iron was given alone. 59Fe ferritin was identified in the serum after the administration of 59Fe HDRC but the size of the fraction was not affected by raising the saturation of transferrin. Sizing column analyses of tissue extracts from the spleen at various times after the administration of 59Fe HDRC revealed a progressive shift from hemoglobin to ferritin, with only small amounts present in a small molecular weight fraction. The small molecular weight fraction was greater in hepatic extracts, with the difference being marked in animals that had received prior carbonyl iron. The increased hepatic retention of 59Fe associated with a raised saturation of transferrin was reduced by a hydrophobic ferrous chelator (2,2'-bipyridine), a hydrophilic ferric chelator (desferrioxamine), and an extracellular hydrophilic ferric chelator (diethylene-triaminepentacetic acid). Transmembrane iron transport did not seem to be a rate-limiting factor in iron release, since no differences in 59Fe membrane fractions were noted in the different experimental settings. These findings are consistent with a model in which RE cells release iron from catabolized red cells at a relatively constant rate. When the saturation of transferrin is raised, a significant proportion of the iron is transported from the spleen to the liver either in small molecular weight complexes or in ferritin. Although a saturated transferrin had no effect on the release of iron from reticuloendothelial cells, prior loading with HDRC conditions them to release less iron.

Nutritional iron requirements and food iron absorption.

To prevent nutritional iron deficiency, sufficient iron must be absorbed from the diet to meet the normal physiological requirements. Daily iron losses in males are about 1 mg (14 micrograms kg-1), while the average additional requirements incurred in women include menstruation (0.6 mg), pregnancy (2.7 mg) and lactation (less than 0.3 mg). Requirements during pregnancy are not evenly distributed and increase to between 5-6 mg in the last trimester of pregnancy, which is more than can be absorbed from even an optimal diet. While the amounts absorbed are affected by the iron content of the diet, the composition of the latter is even more relevant. About one-quarter of the iron in haem proteins is absorbed regardless of the other components in the diet, while non-haem iron absorption is subject to the interplay of promoting and inhibiting substances in the diet. Thus diets rich in enhancers of non-haem iron absorption, chiefly meat and/or ascorbic acid, have high iron bioavailability (about 3 mg d-1) while diets in which inhibitors, such as polyphenols and phytates, predominate are poor sources of iron (less than 1 mg d-1). Examination of the relative proportions of promoters and inhibitors of iron absorption in individual foodstuffs and the measured iron absorption from them may be useful in predicting the overall iron bioavailability from mixed diets.

Iron metabolism in normal and hemochromatotic macrophages.

Certain metabolic pathways of iron were studied in macrophages (cultured human monocytes) obtained from normal and hemochromatotic subjects. The relative abilities of the hydrophobic ferrous chelator 2,2' bipyridine and the hydrophilic ferric chelators desferrioxamine (DFO) and diethylenetriaminepenta-acetic acid (DTPA) to release iron from normal and hemochromatotic macrophages which had previously been loaded with diferric transferrin were tested but there were no differences between the two groups. The relative affinity of the macrophages for diferric transferrin was next studied. Although the hemochromatic macrophages had a somewhat lower affinity for diferric transferrin iron than normal macrophages (Kd 4.7 x 10(-8) M vs. 3.0 x 10(-8)M) the difference did not reach statistical significance (t = 2.01013; P less than 0.07). In a further experiment there was no evidence that apotransferrin was directly involved in the release of iron from hemochromatotic macrophages. A clue to the nature of postendocytotic trans-membrane transport of iron was provided by the finding that it was inhibited by the hydrophobic ferrous chelator 2,2' bipyridine. However, the degree of inhibition was similar in both normal and hemochromatotic macrophages. In summary, none of the metabolic processes examined in the present study was abnormal in cultured human blood monocytes from hemochromatotic subjects.

Effect of ferrous and ferric chelators on transferrin-iron-macrophage interactions.

A study was done to evaluate the effect of ferrous and ferric chelators on the interaction between transferrin-iron and cultured human blood monocytes. This interaction has been previously shown to involve a specific receptor and vesicle protonation. Transferrin-iron uptake was significantly inhibited by the hydrophobic ferrous chelator 2,2' bipyridine, and the inhibition was shown not to be a consequence of the mobilisation of intracellular iron by the chelator. Chase experiments and prolonged incubation studies suggested that the chelator prevented the iron released from transferrin from negotiating the unit membrane. The iron and transferrin then appeared to be returned independently to the incubation medium. In contrast, a hydrophilic ferrin chelator, desferrioxamine, had only a very modest effect on the interaction. These findings are compatible with the hypothesis that transferrin-iron is reduced to the ferrous state during its uptake by the culture human blood monocyte.

Effect of lupines, a protein-rich legume, on iron absorption.

The absorption of iron from lupines, a protein-rich legume, was assessed in 35 parous Indian women. Iron bioavailability was shown to be as low for lupines as soybeans (geometric mean absorptions 0.9 and 1.7 per cent respectively, P less than 0.005). The addition of 30 mg of ascorbic acid moderately improved the geometric mean iron absorption from 1.0 to 5.3 per cent (P less than 0.0001), and 60 mg ascorbic acid from 0.7 to 6.9 per cent (P less than 0.0001). The phytate and polyphenol content of lupines was negligible. The demonstration of poor iron bioavailability from a legume of otherwise rich nutritional potential has important implications in nutritional planning programmes for developing countries.