An Experimental and Numerical Investigation of CO2 Distribution in the Upper Airways During Nasal High Flow Therapy.

Nasal high flow (NHF) therapy is used to treat a variety of respiratory disorders to improve patient oxygenation. A CO2 washout mechanism is believed to be responsible for the observed increase in oxygenation. In this study, experimentally validated Computational Fluid Dynamics simulations of the CO2 concentration within the upper airway during unassisted and NHF assisted breathing were undertaken with the aim of exploring the existence of this washout mechanism. An anatomically accurate nasal cavity model was generated from a CT scan and breathing was reproduced using a Fourier decomposition of a physiologically measured breath waveform. Time dependent CO2 profiles were obtained at the entrance of the trachea in the experimental model, and were used as simulation boundary conditions. Flow recirculation features were observed in the anterior portion of the nasal cavity upon application of the therapy. This causes the CO2 rich gas to vent from the nostrils reducing the CO2 concentration in the dead space and lowering the inspired CO2 volume. Increasing therapy flow rate increases the penetration depth within the nasal cavity of the low CO2 concentration gas. A 65% decrease in inspired CO2 was observed for therapy flow rates ranging from 0 to 60 L min(-1) supporting the washout mechanism theory.

Altered hippocampal circuit function in C3H alpha7 null mutant heterozygous mice.

The alpha7 subtype of nicotinic receptor is highly expressed in the hippocampus where it is purported to modulate release of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The alpha7 receptor-mediated release of GABA is thought to contribute to hippocampal inhibition (gating) of response to repetitive auditory stimulation. This hypothesis is supported by observations of hippocampal auditory gating deficits in mouse strains with low levels of hippocampal alpha7 receptors compared to strains with high levels of hippocampal alpha7 receptors. The difficulty with comparisons between mouse strains, however, is that different strains have different genetic backgrounds. Thus, the observed interstrain differences in hippocampal auditory gating might result from factors other than interstrain variations in the density of hippocampal alpha7 receptors. To address this issue, hippocampal binding of the alpha7 receptor-selective antagonist alpha-bungarotoxin as well as hippocampal auditory gating characteristics were compared in C3H wild type and C3H alpha7 receptor null mutant heterozygous mice. The C3H alpha7 heterozygous mice exhibited significant reductions in hippocampal alpha7 receptor levels and abnormal hippocampal auditory gating compared to the C3H wild type mice. In addition, a general increase in CA3 pyramidal neuron responsivity was observed in the heterozygous mice compared to the wild type mice. These data suggest that decreasing hippocampal alpha7 receptor density results in a profound alteration in hippocampal circuit function.

Schizophrenia trials in China: a survey.

OBJECTIVE: China's biomedical research activity is increasing and this literature is becoming more accessible online. Our aim was to survey all randomized control schizophrenia trials (RCTs) in one Chinese bibliographic database. METHOD: Chinese Academic Journals was electronically searched for RCTs and all relevant citations were also sought on PubMed to ascertain global accessibility. RESULTS: The search identified 3275 records, of which 982 were RCTs relevant to schizophrenia. A total of 71% (699) could be found by using English phrases. All the main body of text of the 982 papers was in Mandarin. On average, these trials involved about 100 people, with interventions and outcome measures familiar to schizophrenia trialists worldwide. Four of the 982 records (<1%) were identified on PubMed. CONCLUSION: Those undertaking systematic reviews should search the Chinese literature for relevant material. Failing to do this will leave the results of systematic reviews prone to random error or bias, or both.

Treatability of chloro-s-triazines by conventional drinking water treatment technologies.

Recent research shows that herbicide atrazine (ATZ), simazine (SIM), and propazine (PROP), as well as their three chlorinated degrades-desethylatrazine (DEA), deisopropylatrazine (DIA), and didealkylatrazine (DDA)-may cause a common toxic effect in terms of endocrine disruption. The US Environmental Protection Agency (EPA) is currently considering a regulatory trigger based on the sum of these concentrations of these six chloro-s-triazines. While limited removal data exists for the parent compounds, little information is available for the degrades formed biologically and/or chemically in the environment and in the treatment plants. It is therefore critical to assess the removal efficiency in a typical water plant of the parent herbicides, as well as the daughter products. In this work, conventional drinking water treatment technologies were evaluated under typical water treatment plant conditions to determine their effectiveness in removing six chloro-s-triazines: ATZ, SIM, PROP, DEA, DIA, and DDA. Experiments were conducted using synthetic solutions prepared by spiking both distilled water and Missouri River water with the study compounds. Two powder activated carbons (PAC)--Calgon WPH and Norit HDB-were shown to be partially effective in removing the studied chloro-s-triazines. Ozonation efficiency varied, depending on different water sources, with respect to the removal of atrazine and didealkylatrazine. Coagulation/flocculation/sedimentation with alum and iron salts, excess lime/soda ash softening, and disinfection by free chlorine were all ineffective methods for removing chloro-s-triazines. It appears that chloro-s-triazine compounds are not readily removed by most conventional drinking water treatment processes, with the exception of use of activated carbon.

Women's beliefs about "natural" hormones and natural hormone replacement therapy.

OBJECTIVE: To assess women's beliefs about natural hormones, including what they believe the term "natural" means, and their beliefs about the risks, side effects, and efficacy of natural hormone replacement compared to standard hormone replacement. DESIGN: Eighty-two women completed a 20-item survey available at a local compounding pharmacy. Respondents were white (100%), middle-aged (mean age, 47.22 years), and college educated (95.1%); 32.9% were perimenopausal, and 50.0% were postmenopausal; 58.5% were currently using hormone replacement therapy and, of those, 77.1% were using human bio-identical hormones. RESULTS: Ninety percent of the respondents ( n = 74) reported that they had heard about natural hormones. Of those, most believed natural meant plant-derived (44.6%) and/or not synthesized or made without chemicals (50.0%). Most reported hearing about natural hormones from a healthcare provider (66.2%) and/or magazines and books (55.4%). When compared with standard hormone replacement, most respondents endorsed the beliefs that natural hormones have fewer or no risks (71.4%), have fewer or no side effects (69.0%), and are equally or more effective for managing menopause symptoms (61.8%). In addition, many endorsed the beliefs that natural hormone replacement is equally or more effective than standard hormone replacement for protection against osteoporosis (47.1%) and heart disease (40.0%), although many endorsed "don't know" for bone (45.7%) and heart (54.3%) protection. CONCLUSIONS: Among women responding to a survey in a compounding pharmacy, most believed that, compared with standard hormones, natural hormones are safer, cause fewer side effects, and are equally or more effective for symptom management. Many believed natural hormone replacement is equally or more effective for long-term bone and heart protection. Educating women on the nature, risks, and benefits of natural hormone therapy is recommended.

Clinical diagnostic and intervention studies of children with semantic-pragmatic language disorder.

The diagnosis of semantic-pragmatic language disorder (SPLD) has been the subject of a number of research studies over the last two decades. Classification and diagnostic debates, while illuminating, have done little to develop tools to improve services to these children. In this paper, two children whose communication difficulties are suggestive of an SPLD diagnosis but who have differing profiles are studied. Using existing models of psycholinguistics and pragmatics to guide assessment and intervention, the diversity of language and social communicative behaviours that are covered by the label SPLD are exemplified. Consideration is given to whether the term SPLD is appropriate for both children or whether Bishop's revision of the diagnosis to 'pragmatic language impairment' might be more useful. Methods of intervention and evaluation for semantic and pragmatic deficits in these two cases are described. It is argued that existing tools can enable accurate explanation and modelling of the communication of children with SPLD and that there is a role for intervention studies in helping to refine those tools, to improve therapies and to understand the nature of the condition more fully.

Anticipation of increasing monetary reward selectively recruits nucleus accumbens.

Comparative studies have implicated the nucleus accumbens (NAcc) in the anticipation of incentives, but the relative responsiveness of this neural substrate during anticipation of rewards versus punishments remains unclear. Using event-related functional magnetic resonance imaging, we investigated whether the anticipation of increasing monetary rewards and punishments would increase NAcc blood oxygen level-dependent contrast (hereafter, "activation") in eight healthy volunteers. Whereas anticipation of increasing rewards elicited both increasing self-reported happiness and NAcc activation, anticipation of increasing punishment elicited neither. However, anticipation of both rewards and punishments activated a different striatal region (the medial caudate). At the highest reward level ($5.00), NAcc activation was correlated with individual differences in self-reported happiness elicited by the reward cues. These findings suggest that whereas other striatal areas may code for expected incentive magnitude, a region in the NAcc codes for expected positive incentive value.

The benefits of integrated nursing teams in primary care.

This article reports a study in which a literature search, questionnaire study and interviews were used to measure the costs and benefits to patients and professionals when nurses work in integrated nursing teams in primary care. Our study showed that there are significant benefits for the nurses' employers, the primary health-care team, the nurses and the patients. Compared with traditional models, delivery by integrated nursing teams can offer a much higher quality service. Patients can expect to be cared for by a team in which morale is high, communication is good and care is efficient and effective. The team can also offer many specialist services that were not previously available. Integrated nursing teams are most effective when the management savings are used by the teams to meet their professional and client needs. Financial savings, therefore, cannot be expected. The difficulties that arise when such teams are set up should be short-term and surmountable, but will be influenced by the motivation of the team members and the efficiency of the human resource management.

Head protection in England before the first World War.

Man has sought to protect himself from physical injury resulting either from the vicissitudes of an arbitrary natural environment or from the calculated activity of his fellow creatures since at least the beginning of recorded time. The earliest substantial British evidence of this activity dates from shortly after the Roman invasion of 55 BC. The head has always been seen by both assailant and defender as a region of particular vulnerability, where an incapacitating blow might most effectively be landed. We present an overview of the evolution and development of English military head protection through the ages, with particular reference to the advances made in metallurgical technology at Greenwich through the course of the 16th century. Much of this represents original research by the authors (particularly ARW), published here for the first time. We include the first metallographic data on armor excavated from the Wisby grave-pits (1361), the first scientific analysis of the textile composition of medieval helmet linings from the Wallace Collection, and the first metallurgical study of the Windsor Castle suit, the personal armor of King Henry VIII, perhaps England's most famous monarch. We combine this with our own experimental data, also previously unpublished, relating to the attack energy available from ancient weaponry (whose technology determines the design of defenses, then as now) in an attempt to assess the effectiveness of helmets. Finally, we set this in the context of contemporary medical technology. The latter is found to be woefully inadequate when presented with serious head injuries. Nevertheless, mortality from battlefield injury has been reduced from ancient times to the present day, despite advances in weapons technology.

Inhibition of nitric oxide synthase prevents alpha 7 nicotinic receptor-mediated restoration of inhibitory auditory gating in rat hippocampus.

The hippocampus rapidly inhibits its response to repetitive auditory stimulation, an example of an auditory sensory gating mechanism involved in human psychopathology. The neuronal basis of this inhibitory gating mechanism has been investigated in rats. Activation of the alpha 7 nicotinic receptor is required. alpha 7 nicotinic receptor activation also releases nitric oxide in the hippocampus and blockade of nitric oxide synthase reduces inhibitory gating of auditory response. There has not been a direct demonstration that blockade of nitric oxide synthase specifically prevents alpha 7 nicotinic receptor activation of the inhibition of auditory response. Therefore, the goal of the present study was to determine whether this functional effect of alpha 7 receptor activation requires release of nitric oxide. Lesions of the fimbria-fornix disrupt auditory gating by preventing cholinergic stimulation of the hippocampus. Following recovery from this surgery, rats were administered 3-(2,4-dimethoxybenzylidene) anabaseine (DMXB-A; 10 mg/kg, sc), an agonist at the alpha 7 receptor. DMXB-A restored auditory gating in the fimbria-fornix-lesioned rats, indicating that activation of the alpha 7 nicotinic receptor alone is sufficient to restore auditory gating following lesions of the fimbria-fornix. However, intracerebroventricular infusion of N(omega)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, blocked the DMXB-A-mediated restoration of auditory gating; infusion of the inactive D-enantiomer did not. Restoration of auditory gating by DMXB-A in the fimbria-fornix-lesioned rats was blocked by intracerebroventricular infusion of alpha-bungarotoxin, but not by mecamylamine or dihydro-beta-erythroidine. Together, these data support the hypothesis that nitric oxide mediates alpha 7 nicotinic receptor activation of gating of auditory response in rat hippocampus.

Paradoxical stimulation of a DEG/ENaC channel by amiloride.

Extracellular amiloride inhibits all known DEG/ENaC ion channels, including BNC1, a proton-activated human neuronal cation channel. Earlier studies showed that protons cause a conformational change that activates BNC1 and exposes residue 430 to the extracellular solution. Here we demonstrate that, in addition to blocking BNC1, amiloride also exposes residue 430. This result suggested that, like protons, amiloride might be capable of activating the channel. To test this hypothesis, we introduced a mutation in the BNC1 pore that reduces amiloride block, and found that amiloride stimulated these channels. Amiloride inhibition was voltage-dependent, suggesting block within the pore, whereas stimulation was not, suggesting binding to an extracellular site. These data show that amiloride can have two distinct effects on BNC1, and they suggest two different interaction sites. The results suggest that extracellular amiloride binding may have a stimulatory effect similar to that of protons in BNC1 or extracellular ligands in other DEG/ENaC channels.

Kainic acid lesions in adult rats as a model of schizophrenia: changes in auditory information processing.

Previous studies have suggested that intracerebroventricular kainic acid injections alter brain anatomy and neurochemistry in a manner similar to what is observed in schizophrenic patients. Disturbances in sensory information processing are one of the major symptoms of schizophrenia. Thus, the present experiments were designed to evaluate the hypothesis that hippocampal damage, induced by administration of kainic acid, would alter the processing of auditory stimuli in a paired-click paradigm. Adult male Sprague-Dawley rats were implanted for surface recording of auditory evoked potentials. At the time of electrode implantation, the rats also received bilateral injections of either kainic acid or the vehicle solution. In vehicle-treated rats, the midlatency N40 component of the auditory evoked potential was diminished in amplitude by approximately 60% in response to the second of a pair of clicks delivered 0.5 s apart. By contrast, no reduction of the N40 wave evoked by the second click was observed in kainate-treated rats. Further, administration of haloperidol, a prototypical neuroleptic agent, did not improve this auditory processing dysfunction in kainate-treated animals. Loss of auditory filtering in the paired-click paradigm and a lack of response to haloperidol in this test are typically observed in schizophrenic humans. Thus, the present results demonstrate that kainate-lesioned rats possess a functional schizophrenia-like abnormality, further reinforcing the utility of this model system for studying the basic neurobiology of schizophrenia-induced sensory processing deficits.

Intercessory Prayer for ill Health: A Systematic Review.

OBJECTIVES: To review the effectiveness of prayer as an additional intervention for those with health problems already receiving standard medical care. SEARCH STRATEGY: Electronic Searches of Biological Abstracts, CINAHL, The Cochrane Controlled Trials Register, EM-BASE, MEDLINE, PsycLIT, and Sociofile were undertaken. All references of articles selected were searched for further relevant trials. SELECTION CRITERIA: Randomised and quasi-randomised trials of personal, focused, committed and organised intercessory prayer on behalf of anyone with a health problem were considered. Outcomes such as achievement of desired goals, death, illness, quality of life and well-being for the recipients of prayer, those praying and the caregivers were sought. DATA COLLECTION AND ANALYSIS: Studies were reliably selected and assessed for methodological quality. Data were extracted by 4 reviewers working independently. Dichotomous data were analysed on an intention-to-treat basis, and continuous data with over 50% completion rate are presented. MAIN RESULTS: There was no evidence that prayer affected the numbers of people dying from leukaemia or heart disease (OR 0.64, CI 0.32-1.27), or that it decreased coronary care complications (OR 1.05, CI 0.49-2.26) or the time participants stayed in hospital. There were significantly fewer 'intermediat//poor outcomes' for those with heart disease in the prayed-for group (OR 0.49, CI 0.30-0.80), and this finding was robust to some changes in definition. CONCLUSIONS: This review provides no guidance for those wishing to uphold or refute the effect of intercessory prayer on the outcomes studied in the available trials. Therefore, in the light of the best available data, there are no grounds to change current practices. There are very few completed trials of the value of intercessory prayer. The evidence presented so far is interesting enough to justify further study. If prayer is seen as a human endeavour it may or may not be beneficial, and further trials could uncover this. It could be the case that any effects are due to elements beyond present scientific understanding that will, in time, be understood. If any benefit derives from God's response to prayer it may be beyond any such trials to prove or disprove.

Interaction between nutrition and Eimeria acervulina infection in broiler chickens: diet compositions that improve fat digestion during Eimeria acervulina infection.

Previously an experimental infection model was developed in which broiler chickens were inoculated with sporulated Eimeria acervulina oocysts at an age of 18 d. The infection resulted in adverse performance results and reduced nutrient digestion. In two new experiments with the infection model effects of diet adjustments on fat digestion were investigated. In the first experiment addition of 0.4 g cholic acid/kg to a diet rich in animal fat resulted in increased fat digestion during the infection. In the second experiment replacing animal fat by coconut oil resulted in improved fat digestion during the coccidiosis infection. However, replacement of animal fat by soybean oil did not improve fat digestion.

Randomized controlled trials in the Journal of Psychosomatic Research; 1956-1993: a prevalence study.

RCTs are the gold standard for the evaluation of mental health care [WHO Scientific Group on Treatment of Psychiatric Disorders, 1991]. All RCTs in the Journal of Psychosomatic Research to date (October 1993) were identified. A profile of the geographical origin, content, interventions under investigation, and methodological quality (as measured by reporting of randomization) of every trial is described. The prevalence of trials from Europe in the Journal is increasing. The frequency of trials regarding the psychotherapies in this journal is also increasing whilst that of drug trials is constant. High quality reporting of randomization is rare. This pilot study generates many disturbing questions regarding the content and quality of RCTs within psychosomatic medicine that urgently need to be answered. Trials in this journal may well not be representative of all RCTs relevant to psychosomatic medicine. If all such trials are to be made accessible to those interested in evidence-based practice, however, much methodical searching must be undertaken, and this study can then be repeated and the questions answered with more authority.

Phosphorus-31 magnetic resonance spectra reveal prolonged intracellular acidosis in the brain following subarachnoid hemorrhage.

Subarachnoid hemorrhage may be complicated by cerebral ischemia which, though reversible initially, can progress to an irreversible neurological deficit. 31P magnetic resonance spectroscopy, which can determine intracellular pH and thus detect areas of ischemia noninvasively, was applied to 10 patients on 30 occasions, at various times after subarachnoid hemorrhage. In 5 of them, there were focal areas of the brain in which the intracellular pH was reduced to < 6.8 compared with the normal range of 7.05 +/- 0.05. Consciousness was impaired in 4 of these patients. Repeat studies in these 4 patients showed that intracellular pH remained abnormally low for several days but eventually returned toward normal. The return of intracellular pH to normal paralleled an improvement in clinical condition in each case. In the fifth patient with lowered regions of intracellular pH, there had been an impaired level of consciousness and a transient focal deficit prior to the single study. In the other 5 patients there were no areas of reduced pHi even though in 3 of them there was intraventricular or cisternal blood shown on brain computerized tomography. In 2 of these 3 patients there were no abnormal neurological signs at the time of the magnetic resonance study. The third patient had a dense and persistent hemiparesis. The remaining two patients had no abnormal neurological signs at any stage. We suggest that the areas of acidosis may reflect ischemia which is potentially reversible. Since the technique is noninvasive, sequential 31P magnetic resonance spectroscopy of the brain offers a method of detecting cerebral ischemia and, more importantly, of assessing methods of treatment.

Improving spatial and temporal resolution in evoked EEG responses using surface Laplacians.

Spline generated surface Laplacian temporal wave forms are presented as a method to improve both spatial and temporal resolution of evoked EEG responses. Middle latency and the N1 components of the auditory evoked response were used to compare potential-based methods with surface Laplacian methods in the time domain. Results indicate that surface Laplacians provide better estimates of underlying cortical activity than do potential wave forms. Spatial discrimination among electrode sites was markedly better with surface Laplacian than with potential wave forms. Differences in the number and latencies of peaks, and their topographic distributions, were observed for surface Laplacian, particularly during the time period encompassing the middle latency responses. Focal activities were observed in surface Laplacian wave forms and topographic maps which were in agreement with previous findings from auditory evoked response studies. Methodological issues surrounding the application of spline methods to the time domain are also discussed. Surface Laplacian methods in the time domain appear to provide an improved way for studying evoked EEG responses by increasing temporal and spatial resolution of component characteristics.

Sources of neostriatal cholecystokinin in the cat.

The objective of this study was to determine the sources of cholecystokinin within the neostriatum of the cat. Cholecystokinin-immunoreactive cells and fibers were detected by means of the peroxidase antiperoxidase immunohistochemical technique. This method was combined with intrastriatal injections of the retrograde marker horseradish peroxidase conjugated with wheat-germ agglutinin to survey the possible afferent sources of cholecystokinin to the feline neostriatum. Intrinsic, apparently aspiny cholecystokinin-immunoreactive neurons organized in a pericapsular pattern were found within both the caudate and putamen of the cat. In addition, both thalamostriatal and mesostriatal projections containing cholecystokinin were observed. These results indicate that cholecystokinin within the neostriatum of the cat arises from both intrinsic and extrinsic sites.

Non-isotopic RNA probes. Comparison between different labels and detection systems.

Several studies have shown the use of non-radioactive labelled DNA probes for in situ hybridisation, mainly to identify cellular DNA. In this study mRNA in situ hybridisation was performed on rat pituitary with biotinylated complementary (c) RNA probes for rat prolactin and growth hormone (GH), and compared with radioactive 35S-radiolabelled probes. Biotinylated cRNA probes were labelled with either biotin-11-UTP or with allylamine-UTP, the latter method being able to produce a higher yield of labelled RNA. Different detection systems were tested, and hybridisation signal was seen in cells of anterior pituitary with both types of biotinylated probes. The signals were detected using either avidin-biotin-complex with peroxidase (ABC), peroxidase-anti-peroxidase (PAP) or gold-silver methods. ABC peroxidase detected using glucose oxidase-diaminobenzidine (DAB)-nickel solution appeared to be the best method for detecting labelled RNA probes, with very strong signal and low background. The biotinylated probes were comparable in sensitivity to the radiolabelled probes in detecting prolactin and GH mRNAs in the anterior lobe of the rat pituitary. These results indicate an alternative methods of labelling and detection of biotinylated probes which could have a potential role in research and diagnostic techniques.