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A letter to the editor is presented in response to the article "Chiropractic Manipulation for Childhood Asthma," by Balon and colleagues in the October 8, 1999 issue.

Background: Congenital diaphragmatic hernia (CDH) is a frequently lethal birth defect and, despite advances, extracorporeal life support (ie, extracorporeal membrane oxygenation [ECMO]) is commonly required for severely affected patients. Published data suggest that CDH survival after 2 weeks on ECMO is poor. Many centers limit duration of ECMO support. Study Design: We conducted a single-institution retrospective review of 19 years of CDH patients treated with ECMO, designed to evaluate which factors affect survival and duration of ECMO and define how long patients should be supported. Results: Of two hundred and forty consecutive CDH patients without lethal associated anomalies, 96 were treated with ECMO and 72 (75%) survived. Eighty required a single run of ECMO and 65 survived (81%), 16 required a second ECMO run and 7 survived (44%). Of patients still on ECMO at 2 weeks, 56% survived, at 3 weeks 46% survived, and at 4 weeks, 43% of patients still on ECMO survived to discharge. After 5 weeks of ECMO, survival had dropped to 15%, and after 40 days of ECMO support there were no survivors. Apgar score at 1 minute, Apgar score at 5 minutes, and Congenital Diaphragmatic Hernia Study Group predicted survival all correlated with survival on ECMO, need for second ECMO, and duration of ECMO. Lung-to-head ratio also correlated with duration of ECMO. All survivors were discharged breathing spontaneously with no support other than nasal cannula oxygen if needed. Conclusions: In patients with severe CDH, improvement in pulmonary function sufficient to wean from ECMO can take 4 weeks or longer, and might require a second ECMO run. Pulmonary outcomes in these CDH patients can still be excellent, and the assignment of arbitrary ECMO treatment durations <4 weeks should be avoided. [Copyright &y& Elsevier]

Abstract: Objective: Ordinal patterns analysis such as permutation entropy of the EEG series has been found to usefully track brain dynamics and has been applied to detect changes in the dynamics of EEG data. In order to further investigate hidden nonlinear dynamical characteristics in EEG data for differentiating brain states, this paper proposes a novel dissimilarity measure based on the ordinal pattern distributions of EEG series. Methods: Given a segment of EEG series, we first map this series into a phase space, then calculate the ordinal sequences and the distribution of these ordinal patterns. Finally, the dissimilarity between two EEG series can be qualified via a simple distance measure. A neural mass model was proposed to simulate EEG data and test the performance of the dissimilarity measure based on the ordinal patterns distribution. Furthermore, this measure was then applied to analyze EEG data from 24 Genetic Absence Epilepsy Rats from Strasbourg (GAERS), with the aim of distinguishing between interictal, preictal and ictal states. Results: The dissimilarity measure of a pair of EEG signals within the same group and across different groups was calculated, respectively. As expected, the dissimilarity measures during different brain states were higher than internal dissimilarity measures. When applied to the preictal detection of absence seizures, the proposed dissimilarity measure successfully detected the preictal state prior to their onset in 109 out of 168 seizures (64.9%). Conclusions: Our results showed that dissimilarity measures between EEG segments during the same brain state were significant smaller that those during different states. This suggested that the dissimilarity measure, based on the ordinal patterns in the time series, could be used to detect changes in the dynamics of EEG data. Moreover, our results suggested that ordinal patterns in the EEG might be a potential characteristic of brain dynamics. Significance: This dissimilarity measure is a promising method to reveal dynamic changes in EEG, for example as occur in the transition of epileptic seizures. This method is simple and fast, so might be applied in designing an automated closed-loop seizure prevention system for absence epilepsy. [Copyright &y& Elsevier]

This research evaluated five case studies of patients with psoriasis following a dietary regimen. There is no cure for psoriasis and the multiple treatments currently available only attempt to reduce the severity of symptoms. Treatments range from topical applications, systemic therapies, and phototherapy; while some are effective, many are associated with significant adverse effects. There is a need for effective, affordable therapies with fewer side effects that address the causes of the disorder. Evaluation consisted of a study group of five patients diagnosed with chronic plaque psoriasis (two men and three women, average age 52 years; range 40-68 years) attending a 10-day, live-in program during which a physician assessed psoriasis symptoms and bowel permeability. Subjects were then instructed ofn continuing the therapy protocol at home for six months. The dietary protocol, based on Edgar Cayce readings, included a diet of fresh fruits and vegetables, small amounts of protein from fish and fowl, fiber supplements, olive oil, and avoidance of red meat, processed foods, and refined carbohydrates. Saffron tea and slippery elm bark water were consumed daily. The five psoriasis cases, ranging from mild to severe at the study onset, improved on all measured outcomes over a six-month period when measured by the Psoriasis Area and Severity Index (PASI) (average pre- and post-test scores were 18.2 and 8.7, respectively), the Psoriasis Severity Scale (PSS) (average pre- and posttest scores were 14.6 and 5.4, respectively), and the lactulose/mannitol test of intestinal permeability (average pre- and post-test scores were 0.066 and 0.026, respectively). These results suggest a dietary regimen based on Edgar Cayce's readings may be an effective medical nutrition therapy for the complementary treatment of psoriasis; however, further research is warranted to confirm these results. [ABSTRACT FROM AUTHOR]

Introduction: Sprint interval training (SIT), characterized by brief bouts of 'supramaximal' exercise interspersed with recovery periods, increases peak oxygen uptake ( V ˙ O 2 peak ) despite a low total exercise volume. Per the Fick principle, increased V ˙ O 2 peak is attributable to increased peak cardiac output ( Q ˙ peak ) and/or peak arterio-venous oxygen difference (a-vO2diff). There are limited and equivocal data regarding the physiological basis for SIT-induced increases in V ˙ O 2 peak , with most studies lasting ≤ 6 weeks. Purpose: To determine the effect of 12 weeks of SIT on Q ˙ peak , measured using inert gas rebreathing, and the relationship between changes in Q ˙ peak and V ˙ O 2 peak . Methods: 15 healthy untrained adults [6 males, 9 females; 21 ± 2 y (mean ± SD)] performed 28 ± 3 training sessions. Each session involved a 2-min warm-up at 50 W, 3 × 20-s 'all-out' cycling bouts (581 ± 221 W) interspersed with 2-min of recovery, and a 3-min cool-down at 50 W. Results: Measurements performed before and after training showed that 12 weeks of SIT increased Q ˙ peak (17.0 ± 3.7 vs 18.1 ± 4.6 L/min, p = 0.01, partial η2 = 0.28) and V ˙ O 2 peak (2.63 ± 0.78 vs 3.18 ± 1.1 L/min, p < 0.01, partial η2 = 0.58). The changes in these two variables were correlated (r2 = 0.46, p < 0.01). Calculated peak a-vO2diff also increased after training (154 ± 22 vs 174 ± 23 ml O2/L; p < 0.01) and was correlated with the change in V ˙ O 2 peak (r2 = 0.33, p = 0.03). Exploratory analyses revealed an interaction (p < 0.01) such that Q ˙ peak increased in male (+ 10%, p < 0.01) but not female participants (+ 0.6%, p = 0.96), suggesting potential sex-specific differences. Conclusion: Twelve weeks of SIT increased Q ˙ peak by 6% in previously untrained participants and the change was correlated with the larger 21% increase in V ˙ O 2 peak . [ABSTRACT FROM AUTHOR]

The article analyzes the impact of acute ingestion of a commercial (R)-3-hydroxybutyl (R)-3-hydroxybutyrate ketone monoester (KE) supplement on exercise responses and performance in endurance-trained participants. It has been hypothesized that nutritional ketosis induced by actue KE ingestion would decrease indices of cardiorespiratory and perceived stress and improves time-trial performance.

Background: Most low-risk obstetric patients do not have crossmatched blood available to treat unexpected postpartum hemorrhage. An emergency-release blood transfusion (ERBT) program is critical for hospitals with obstetrical services. We performed a retrospective analysis of obstetrical ERBTs administered in our multihospital system.Design and Methods: We collected data from the past 8 years at all Intermountain Healthcare hospitals on every ERBT after postpartum hemorrhage; logging circumstances, number and type of transfused products, and outcomes.Results: Eighty-nine women received ERBT following 224,035 live births, for an incidence of 3.97 transfused women/10,000 births. The most common causally-associated conditions were: uterine atony (40%), placental abruption/placenta previa (16%), retained placenta (11%), and uterine rupture (5%). The mean number of total units transfused was 7.9 (range 1-76). The mean number of red blood cells (RBCs) transfused was 4.8, the median 4, and SD was ±4.4. Massive transfusion protocols (MTPs) for trauma recommend using a ratio of 1:1:1 or 2:1:1 of RBC:FFP:Platelets, however the ratios varied widely for postpartum hemorrhage. Only 1.5% received a 1:1:1 ratio and 7.5% received a 2:1:1 ratio. Nineteen percent (17/89) of women underwent hysterectomy, 7% (6/89) had uterine artery embolization, 36% (32/89) had an intensive care unit admission, and 1% (1/89) died.Conclusion: Emergency transfusion for postpartum hemorrhage occurred after 1/2500 births. Most women received less FFP and platelets than recommended for traumatic hemorrhage. A potentially better practice for postpartum hemorrhage would be a balanced ratio of blood products, transfusion of low-titer, group O, cold-stored, whole blood, or inclusion in a MTP. [ABSTRACT FROM AUTHOR]

Use of marginal liver grafts, especially those from donors after circulatory death (DCD), has been considered as a solution to organ shortage. Inferior outcomes have been attributed to donor warm ischaemic damage in these DCD organs. Here we sought to profile the metabolic mechanisms underpinning donor warm ischaemia. Non-targeted Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry metabolomics was applied to biopsies of liver grafts from donors after brain death (DBD; n = 27) and DCD (n = 10), both during static cold storage (T1) as well as post-reperfusion (T2). Furthermore 6 biopsies from DBD donors prior to the organ donation (T0) were also profiled. Considering DBD and DCD together, significant metabolic differences were discovered between T1 and T2 (688 peaks) that were primarily related to amino acid metabolism, meanwhile T0 biopsies grouped together with T2, denoting the distinctively different metabolic activity of the perfused state. Major metabolic differences were discovered between DCD and DBD during cold-phase (T1) primarily related to glucose, tryptophan and kynurenine metabolism, and in the post-reperfusion phase (T2) related to amino acid and glutathione metabolism. We propose tryptophan/kynurenine and S-adenosylmethionine as possible biomarkers for the previously established higher graft failure of DCD livers, and conclude that the associated pathways should be targeted in more exhaustive and quantitative investigations. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Understanding the transition of brain activity towards an absence seizure is a challenging task. In this paper, we use recurrence quantification analysis to indicate the deterministic dynamics of EEG series at the seizure-free, pre-seizure and seizure states in genetic absence epilepsy rats. Methods: The determinism measure, DET, based on recurrence plot, was applied to analyse these three EEG datasets, each dataset containing 300 single-channel EEG epochs of 5-s duration. Then, statistical analysis of the DET values in each dataset was carried out to determine whether their distributions over the three groups were significantly different. Furthermore, a surrogate technique was applied to calculate the significance level of determinism measures in EEG recordings. Results: The mean (±SD) DET of EEG was 0.177±0.045 in pre-seizure intervals. The DET values of pre-seizure EEG data are significantly higher than those of seizure-free intervals, 0.123±0.023, (P <0.01), but lower than those of seizure intervals, 0.392±0.110, (P <0.01). Using surrogate data methods, the significance of determinism in EEG epochs was present in 25 of 300 (8.3%), 181 of 300 (60.3%) and 289 of 300 (96.3%) in seizure-free, pre-seizure and seizure intervals, respectively. Conclusions: Results provide some first indications that EEG epochs during pre-seizure intervals exhibit a higher degree of determinism than seizure-free EEG epochs, but lower than those in seizure EEG epochs in absence epilepsy. Significance: The proposed methods have the potential of detecting the transition between normal brain activity and the absence seizure state, thus opening up the possibility of intervention, whether electrical or pharmacological, to prevent the oncoming seizure. [Copyright &y& Elsevier]

Mucopolysaccharidosis Type VII (MPS VII) is a lysosomal storage disease caused by a deficiency of the enzyme, β-glucuronidase. MPS VII has a wide variation in phenotypic expression, including presentation in the neonatal period with nonimmune hydrops fetalis. We report a neonate with MPS VII who initially presented with marked isolated ascites not associated with hydrops fetalis. This appears to be a novel finding in patients with MPS VII. Journal of Perinatology (2003) 23, 73–75 doi:10.1038/sj.jp.7210844 [ABSTRACT FROM AUTHOR]

To improve the outcome of orthotopic liver transplantation (OLT), knowledge of early molecular events occurring upon ischemia/reperfusion is essential. Powerful approaches for profiling metabolic changes in tissues and biofluids are now available. Our objective was to investigate the applicability of two technologies to a small but well-defined cohort of patients undergoing OLT: consecutive liver biopsies by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and microdialysates of extracellular fluid by coulometric electrochemical array detection (CEAD). FT-ICR MS detected reproducibly more than 4,000 peaks, revealing hundreds of significant metabolic differences between pre- and postreperfusion grafts. These included increased urea production, bile acid synthesis and clearance of preservation solution upon reperfusion, indicating a rapid resumption of biochemical function within the graft. FT-ICR MS also identified successfully the only graft obtained by donation-after-cardiac-death as a "metabolic outlier." CEAD time-profile analysis showed that there was considerable change in redox-active metabolites (up to 18 h postreperfusion), followed by their stabilization. Collectively these results verify the applicability of FT-ICR MS and CEAD for characterizing multiple metabolic pathways during OLT. The success of this proof-of-principle application of these technologies to a clinical setting, considering the potential metabolic heterogeneity across only eight donor livers, is encouraging.

3-Nitrotyrosine (3-NT) is formed by the reaction of peroxynitrite with either free or protein-bound tyrosine residues and has been proposed as a biomarker of oxidative stress caused by reactive nitrogen species. This study describes the development of an HPLC electrochemical detection assay for free 3-NT capable of measuring this metabolite at the very low (nanomolar) levels encountered physiologically. We employed a dual-cell coulometric approach in which 3-NT is first reduced at an upstream cell to 3-aminotyrosine, which itself is then oxidized at the downstream cell. The method was shown to be linear over the range of 1-500 nM (r = 0.999), with a detection limit (signal/noise ratio of 3) of 0.5 nM (25 fmol on column). Ten consecutive injections of 2 and 20 nM 3-NT standards produced coefficients of variation of 5.88 and 1.87%, respectively. Validation of the identity of the 3-NT peak was confirmed by coelution with authentic standards and by the in vitro production of 3-NT by incubation of 3-morpholinylsydnoneimine (SIN-1, 100 microM), a molecule releasing nitric oxide and superoxide in solution at a pH of 7.0 or higher with tyrosine (10 microM). Using this method, 3-NT was detected in human liver microdialysate (levels up to 2.6 nM), although levels in rat spinal cord dialysate were below the limit of detection.

The amino acid content of hourly microdialysis samples from nine severely head-injured children was examined. Of particular interest was the measurement of the excitatory amino acid glutamate, as high levels of this substance, which are associated with the excitotoxicity cascade, have been linked to high intracranial pressure and poor outcome in a similar study in adults. Interpretation of these data is complicated by many clinical and methodological factors and these are discussed in relation to the findings. Our findings from this pilot study in children confirm the associations between glutamate levels, intracranial pressure and outcome, but fail to corroborate the correlation between excitatory and structural amino acid levels seen in adult patients, that was interpreted as evidence of non-specific leakage of amino acids through damaged cell membranes. In addition, we have shown that the role of glutamine in glutamate homeostasis is an important consideration and that estimation of the extracellular glutamine/glutamate ratio may have some prognostic value in head trauma cases as there is evidence of links to clinical outcome.

Absence epilepsy is characterised by recurrent periods of physical and mental inactivity coupled to bilateral, synchronous spike and wave discharges (SWDs) on the electroencephalogram. The mechanism of action of ethosuximide (ETX), a drug specific for absence seizures, is believed to involve a reduction in the low threshold T-type Ca(2+) current in thalamocortical and nucleus reticularis thalami (NRT) neurones, although other electrophysiological data have questioned this. Here, we employed a genetic rat model of absence seizures to investigate the effects of directly administering ETX to the thalamus.SWDs were immediately and substantially reduced (approximately 90%) by systemic administration of ETX (177-709 micromol/kg), or by bilateral microinfusion into the thalamus of the GABA(B) antagonist, CGP 36742 (5-27 nmol per side). However, infusion of ETX (1-200 nmol per side) into the ventrobasal complex or the NRT resulted in a reduction of SWDs that was delayed (30-60 min) and less marked (approximately 50%). Administration of ETX (0.2 mM to 1M) to a greater volume of thalamus by reverse microdialysis also produced significant but delayed reduction of SWDs at concentrations >1mM. Only at 5mM were seizures significantly reduced (approximately 70%) within 30 min of administration. These results suggest that targeting of the thalamus alone may be insufficient for an immediate and full anti-absence action for ETX. Concomitant or exclusive actions in the cortex remain a possibility.

Objective: To determine, using a microdialysis technique, the extracellular levels of glutamate and non-transmitter amino acids in the brain of children with severe head injuries., Methods: A microdialysis probe was inserted along side the intracranial pressure (ICP) bolt in 9 children (age range 2-14 years) with severe head injuries (Glasgow coma scale<8). Dialysate samples were collected hourly and analysed, using High Performance Liquid Chromatography (HPLC), for glutamate, glutamine and various structural amino acids. Clinical monitoring parameters were also correlated with amino acid concentrations., Conclusions: Mean glutamate concentrations in the dialysate varied from very low (<5 micro M) to very high (>30 micro M). No correlation with outcome at discharge was demonstrated. Structural amino acid levels did not follow the glutamate fluctuations. Low glutamine/glutamate ratio was associated with increased morbidity, while a high ratio was associated with clinical improvement. Glutamate metabolism may have a more significant role in the pathophysiology of paediatric head injury than has already been recognised.