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An alternative to the use of synthetic pesticides is to exploit the natural defense chemicals produced by cereals. An important class of allelochemicals is cyclic hydroxamic acids and related benzoxazolinones. A prolonged degradation experiment of the allelochemical compound from rye 2-benzoxazolinone (BOA) was carried out for up to 90 d at 15 degrees C at three different concentration levels, 3, 3000, and 30,000 nmol BOA g soil(-1), respectively, in a sandy loam soil. Two main degradation products, 2-amino-(3H)-phenoxazin-3-one (APO) and 2-acetylamino-(3H)-phenoxazin-3-one (AAPO), were identified and quantified by LC-ESI-MS-MS. The half-life of BOA increased with higher levels of BOA added to the soil. Half-lives of BOA, APO, and AAPO were determined by fitting a single first-order model to the degradation data. Half-life of BOA was determined to be 0.6 d in the 3 nmol BOA g soil(-1) treatment. Half-lives of BOA, APO, and AAPO were 3.1, 2.7, and 2.1 d, respectively, in the 3000 nmol BOA g soil(-1) treatment. In the 30,000 nmol BOA g soil(-1) treatment, the half-lives were 31 d for BOA and 45 d for APO. The microbial community structure was not affected by addition of BOA to the soil as investigated by analysis of signature fatty acids. The results suggest that the exploitability of BOA for crop protection is dependent on the existing concentration of BOA in the soil and the timing of incorporation of hydroxamic acid synthesizing crops into the soil.

Ptaquiloside (PTA) is a carcinogenic norsesquiterpene glucoside produced by Bracken in amounts up to at least 500 mg m(-2). The toxin is transferred from Bracken to the underlying soil from where it may leach to surface and groundwater's impairing the quality of drinking water. The objectives of the present study were to characterize the solubility, degradation and retention of PTA in soils in order to evaluate the risk for groundwater contamination. PTA was isolated from Bracken. The logarithmic octanol-water and ethyl acetate-water partitioning coefficients for PTA were -0.63 and -0.88, respectively, in agreement with the high water solubility of the compound. PTA hydrolysed rapidly in aqueous solution at pH 4 or lower, but was stable above pH 4. Incubation of PTA with 10 different soils at 25 degrees C showed three different first order degradation patterns: (i) rapid degradation observed for acid sandy soils with half life's ranging between 8 and 30 h decreasing with the soil content of organic matter, (ii) slow degradation in less acid sandy soils with half-lives of several days, and (iii) fast initial degradation with a concurrent solid phase-water partitioning reaction observed for non-acid, mostly clayey soils. The presence of clay silicates appears to retard the degradation of PTA, possibly through sorption. Degradation at 4 degrees C was generally of type (iii) and degradation rates were up to 800 times lower than at 25 degrees C. Sorption isotherms for the same set of soils were almost linear and generally showed very low sorption affinity with distribution coefficients in the range 0.01-0.22 l kg(-1) at a solution concentration of 1 mg l(-1) except for the most acid soil; Freundlich affinity coefficients increased linearly with clay and organic matter contents. Negligible sorption was also observed in column studies where PTA and a non-sorbing tracer showed almost coincident break-through. Leaching of PTA to the aqueous environment will be most extensive on sandy soils, having pH >4 and poor in organic matter which are exposed to high precipitation rates during cold seasons.

1,2,4-Thiadiazine derivatives, like 3-methyl-7-chlorobenzo-4H-1,2,4-thiadiazine 1,1-dioxide, diazoxide and 7-chloro-3-isopropylamino-4H-benzo-1,2,4-thiadiazine 1,1-dioxide, BPDZ 73, are potent openers of Kir6.2/SUR1 K(ATP) channels. To explore the structure-activity relationship of this series of K(ATP) openers, 4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide and N-(2-cyanomethylsulfonylphenyl)acylamide derivatives were synthesized from 2-acetylamino-5-chloro-benzenesulfonic acid pyridinium salt or 2-aminobenzenethiols. The 4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide derivatives (e.g., 7-chloro-3-isopropylamino-4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide, 3f) were found to activate K(ATP) channels as indicated by their ability to hyperpolarize beta cell membrane potential, to inhibit glucose-stimulated insulin release in vitro and to increase ion currents through Kir6.2/SUR1 channel as measured by patch clamp. The potency and efficacy of, for example, 3f is however significantly reduced compared to the corresponding 4H-1,2,4-benzothiadiazine 1,1-dioxide derivatives. Opening of the 4H-1,2,4-thiadiazine ring to get (e.g., 2-cyanomethylsulfonyl-4-fluorophenyl) carbamic acid isopropyl ester (4c) gives rise to compounds, which are able to open K(ATP) channels but with considerable reduced potency compared to, for example, diazoxide. Compound 3a, 7-chloro-3-methyl-4H-1,4-benzothiazine-2-carbonitrile 1,1-dioxide, which inhibits insulin release in vitro from beta cells and rat islets, reduces plasma insulin levels and blood pressure in anaesthetized rats upon intravenous administration.

The relationship between sorption strength and degradation kinetics has been studied for the pesticide MCPA in a sandy top- and subsoil. After adding two types of sorbents (crushed peat and activated carbon) in various amounts to the sandy soils, sorption, desorption, and mineralization of 14C-MCPA were measured. The obtained Freundlich constants (KF) varied between 0.7 and 27.2 mg(1-nF) x L(nF)/kg, and the first-order mineralization rate constants varied between 0.001 and 0.128 d(-1). The results showed an inverse relationship between sorption strength and mineralization. A higher KF value corresponded to a smaller mineralization rate and less mineralization. A correlation coefficient of r2 = 0.934 between the log-transformed Freundlich desorption coefficient (K(F,des)) and the log-transformed mineralization rate constant (k) was obtained. After 7, 14, 22, and 35 days of incubation, soil samples were consecutively extracted by water, methanol, and 5 M NaOH to separate the remaining 14C into 3 different pools. The extractions showed that the mineralization only proceeded from the water extractable pool of MCPA. Thin-layer chromatography revealed a formation of small amounts of metabolites; <7% of initially added 14C was present as other compounds than 14C-MCPA in the water and methanol extractable pools. The study showed mineralization to be strongly correlated with sorption, represented by the desorption coefficient, and hence stresses the significance of bonding strength for estimating pesticide degradation in soil.

Flow through artificial macropores may occur as a water film along the macropore walls (film flow) or as moving water segments separated by air bubbles (pulse flow). To investigate the effect of macropore flow pattern (i.e., film and pulse flow) on the interaction of solutes with macropore walls, we studied orthophosphate (P) transport and sorption in artificial macropores. The experimental setup consisted of a column (height = 20 cm, diameter = 20 cm) homogenously packed with glass beads and fitted at outflow with a vertical artificial macropore placed below the column. The artificial macropore consisted of ceramic tubes (3 or 8 mm i.d.; 31.5 cm long) coated on the inside with iron oxide serving as phosphate sorbents. An orthophosphate solution containing 0.04 mg P L(-1) was applied at a rate of 9 to 12 mm h(-1) to the column, eventually causing macropore flow. In the 8-mm-i.d. tubes only film flow occurred. Pulse flow was dominating in the 3-mm-i.d. tubes. Generally, the flow patterns were reproducible and seldom did pulse flow replaced film flow or vice versa. During film flow, a significantly larger decrease in macropore P concentration per tube was observed relative to that with pulse flow events. However, pulse and film flow lead to almost the same amounts of P sorbed per unit surface area when exposed to the same solute P concentration. Comparison with P sorption capacity experiments indicated that the sorption rate, rather than the sorption capacity, controls the amount of sorbed P during macropore flow in the studied system.

Electronic medical records (EMR) can both replace the paper clinical chart and perform scheduling and billing tasks. EMRs are currently used in only a small proportion of medical practices; however, EMR adoption is expected to soar in a few years. Governmental and industry concerns about safety and quality, along with medical practice needs for increased productivity, are fueling this transition. Medical practices are likely to consider transitioning to EMRs. At this point, the marketplace is fragmented in terms of suppliers, and refinement of the software is continuing. Transitioning to an EMR is a step that offers enormous benefits to interventional pain management physicians, in terms of compliance, the ability to maintain quality, and the ability to manage practices, including larger and more complex practices. Transitioning to an EMR is also a major effort in terms of time and expense: the goal is to settle on a specific EMR and continue to use it. This review focuses on (1) why physicians are or are not transitioning to EMRs; (2) the benefits of a transition; and (3) factors to consider in evaluating the various competing software products. Although EMR technology continues to develop, the review also considers areas in which future development is necessary. The most important areas are seen in document management, data input, and outcomes analysis and decision support capability. The EMR market is evolving rapidly. However, this review should in no way serve as an endorsement of any particular system, vendor, or technology.

Beta-thujaplicin (beta-TH) is a toxic tropolone derivative present in the heartwood of western red cedar (Thuja plicata) and is used as a preservative and antimicrobial additive in a number of commercial goods. beta-TH released from western red cedar timber used outdoor and from other products containing beta-TH may transfer to soil and leach to groundwater and surface waters. The objective of this study was to quantify the adsorption of beta-TH to goethite as a typical model for geosorbents. Adsorption was studied using pH-adjusted goethite suspensions with solid:solution ratios of 1:500, 0.01 M NaNO(3) electrolyte, and 20 degrees C. beta-TH was determined using a new capillary zone electrophoresis (CZE) method providing a detection limit of 0.21 microM. Near-sorption equilibrium was attained within 48 h. beta-TH showed maximum adsorption at low pH (3.8) and a 70% drop in adsorption from pH 6.2 to 8.8. The Langmuir type adsorption isotherm at pH 5.5 approached a maximum adsorption of 220 micromol/g (= 6.2 micromol/m(2)), which is more than twice the amount of phosphate adsorbed under similar conditions. The affinity of beta-TH for goethite is low as compared with organic ligands such as citrate, oxalate, and 2,4-dihydroxybenzoate. The adsorption data and FTIR analyses indicate that beta-TH is most likely adsorbed as monodentate mononuclear surface complexes at the surface of goethite. Hydrophobic adsorption is thought to contribute to the adsorption, in particular at low pH. The strong adsorption of beta-TH to goethite suggests low mobility in most soil environments, the risk of contamination increasing in soils with high pH (calcareous material), low contents of iron and aluminum oxides, phyllosilicates, and organic matter.

Environmental risk assessment of heavy metals in soil frequently involves testing of freshly spiked soils kept under stable humidity conditions, but it has been questioned whether these assessments are representative of the field situation. Furthermore, the poor correspondence that is often found between total metal content and metal toxicity calls for integrated chemical and biological analysis. The aim of this work was to determine time- and moisture-dependent changes in total water-extractable Cu as well as bioavailable Cu in soil water extracts. Measurements of total water-extractable copper ([Cu]tot) were performed using furnace atomic absorption spectrometry. An in vitro assay employing a Cu-specific Pseudomonas fluorescens reporter strain was used to estimate Cu that was biologically available to the reporter strain. We refer to this copper fraction as "bioavailable," [Cu]bio. We found a time-dependent decrease in [Cu]tot and [Cu]bio during incubation for up to 220 d at field capacity. Hence the [Cu]bio was reduced to between 32 and 40% of the initial values. Furthermore, the [Cu]bio to [Cu]tot ratio correlated positively with the amount of added Cu and tended to increase with time. The moisture content of the soil was important for Cu retention. Dry soil had higher [Cu]tot concentrations than humid soil, but the [Cu]bio to [Cu]tot, ratio was lower in the dry soil. Alternating drying and wetting did not lead to a more rapid Cu retention than observed under constant humid conditions. Our observations underline the need for considering both time and moisture effects when interpreting short-term toxicity studies and when making predictions concerning possible long-term effects of Cu in the soil environment.

Degradation and mobility of the surfactants linear alkylbenzene sulfonate (LAS) and nonylphenol (NP) were investigated in a lysimeter study using a sandy loam soil and 45-cm soil columns. Anaerobically digested sewage sludge was incorporated in the top-15-cm soil layer to an initial content of 38 mg LAS and 0.56 mg NP kg(-1) dry wt., respectively. Spring barley (Hordeum vulgare L.) was sown onto the columns. The lysimeters were placed outdoors and therefore received natural precipitation, but were also irrigated to a total amount of water equivalent to 700 mm of precipitation. Leachate and soil samples from three soil layers were collected continuously during a growth period of 110 d. Leachate samples and soil extracts were concentrated by solid-phase extraction (SPE) and analyzed using high performance liquid chromatography (HPLC) with fluorescence detection. The concentrations in the top-15-cm soil layer declined to 25 and 45% of the initial contents for LAS and NP, respectively, within the first 10 d of the study. At the end of the study, less than 1% LAS was left, while the NP content was below the detection limit. Assuming first-order degradation kinetics, half-lives of 20 and 37 d were estimated for LAS and NP, respectively. The surfactants were not measured in leachate samples in concentrations above the analytical detection limits of 4.0 and 0.5 microg L(-1) for LAS and NP, respectively. In addition, neither LAS nor NP were measured in concentrations above the detection limits of 150 and 50 microg kg(-1) dry wt., respectively, in soil layers below the 15 cm of sludge incorporation, indicating negligible downward transport of the surfactants in the lysimeters.

The effects of washing, storing, boiling, peeling, coring and juicing on pesticide residue were investigated for field-sprayed Discovery and Jonagold apples. Residues of chlorpyrifos, cypermethrin, deltamethrin, diazinon, endosulfan, endosulfan sulfate, fenitrothion, fenpropathrin, iprodione, kresoxim-methyl, lambda-cyhalothrin, quinalphos, tolylfluanid and vinclozolin in the processed apples were analysed by gas chromatography. Statistical analysis showed that reductions of 18-38% were required to obtain significant effects of processing practices, depending on pesticide and apple variety. Juicing and peeling the apples significantly reduced all pesticide residues. In the case of detectable pesticide residues, 1-24% were distributed in the juice and in the peeled apple. None of the pesticide residues was significantly reduced when the apples were subject to simple washing or coring. Storing significantly reduced five of the pesticide residues: diazinon, chlorpyrifos, fenitrothion, kresoxim-methyl and tolylfluanid, by 25-69%. Residues of the metabolite endosulfan sulfate were increased by 34% during storage. Boiling significantly reduced residues of fenitrothion and tolylfluanid by 32 and 81%, respectively. Only a few of the observed effects of processing could be explained by the physical or chemical characteristics of the pesticides. No differences in effect of processing due to apple variety were identified.

Peptidase-catalyzed formation of macrocyclic lactams on solid phase identifies ring systems that are favorably bound in the enzyme active site. We evaluated several cyclic peptide motifs linked by ester bonds between the P2 and P1' or the P1 and P2' side chains. The depsipeptide represented by structure 5 was readily generated by a variety of peptidases from precursor omega-amino acids or omega-amino esters. This strategy for identifying ring systems for potential macrocyclic transition state analogues was demonstrated with the serine peptidases trypsin and chymotrypsin, with the aspartic peptidase pepsin, and with the zinc peptidase thermolysin.

Controlled substance abuse has increased at an alarming rate. However, available evidence suggests a wide variance in the use of controlled substances, as documented by different medical specialties, medical boards, advocacy groups, and the Drug Enforcement Administration. The primary objective of controlled substance guidelines by American Society of Interventional Pain Physicians (ASIPP) is to provide guidance for the use of controlled substances for the treatment of chronic pain. It is anticipated that these practical guidelines will improve quality of care, patient access, and quality of life. Additional benefits include improved treatment efficiency and efficacy, and cost containment by improving the risk-benefit ratio of treating patients with chronic pain. Further goals of this manuscript are to bring consistency in opioid philosophy among the many diverse groups involved, to improve the treatment of chronic pain patients with medically appropriate controlled substances, and to reduce the incidence of drug diversion. These guidelines also reinforce the need for systematic evaluation and ongoing care of patients with chronic or persistent pain. ASIPP controlled substance guidelines also provide a discussion of the epidemiology of chronic pain, the role of controlled substances in treating chronic pain, various aspects of drug abuse, pharmacological considerations, clinical effectiveness of controlled substances, options for treatment monitoring and drug testing and a review of terminology used in addiction medicine. These guidelines do not constitute inflexible treatment recommendations. It is expected that a provider will establish a plan of care on a case-by-case basis, taking into account an individual patient's medical condition, personal needs, and preferences, and the physician's experience. Based on an individual patient's needs, controlled substance prescribing and treatment different from that outlined here may be warranted. These guidelines do not represent "standard of care."

Epidural injections with or without steroids are used extensively in the management of chronic spinal pain. However, evidence is contradictory with continuing debate about the value of epidural steroid injections in chronic spinal syndromes. The objective of this systematic review is to determine the effectiveness of epidural injections in the treatment of chronic spinal pain. Data sources include relevant literature identified through searches of MEDLINE, EMBASE (Jan 1966- Mar 2003), manual searches of bibliographies of known primary and review articles, and abstracts from scientific meetings. Both randomized and non-randomized studies were included in the review based on the criteria established by the Agency for Healthcare Research and Quality (AHRQ). Studies were excluded from the analysis if they were simply review or descriptive and failed to meet minimum criteria. The results showed that there was strong evidence to indicate effectiveness of transforaminal epidural injections in managing lumbar nerve root pain. Further, evidence was moderate for caudal epidural injections in managing lumbar radicular pain. The evidence in management of chronic neck pain, chronic low back pain, cervical radiculopathy, spinal stenosis, and post laminectomy syndrome was limited or inconclusive. In conclusion, the evidence of effectiveness of transforaminal epidural injections in managing lumbar nerve root pain was strong, whereas, effectiveness of caudal epidural injections in managing lumbar radiculopathy was moderate, while there was limited or inconclusive evidence of effectiveness of epidural injections in managing chronic spinal pain without radiculopathy, spinal stenosis, post lumbar laminectomy syndrome, and cervical radiculopathy.

Mycotoxins are secondary metabolites, formed by the action of fungi on agricultural crops in the field or during storage. These metabolites are highly toxic to animals and humans and high levels have been measured in agricultural crops. In order to evaluate human risks due to ingestion of mycotoxin-contaminated food different methods have been developed for analysis of mycotoxins in cereals and maize. In this project the focus was on mycotoxins in agricultural soil and the fate of these toxins in the soil-water-plant system. Two different mycotoxins were selected in the study: zearalenone (ZON) produced by species of Fusariumor Aspergillusand ochratoxin A (OTA) produced by species of Penicillium. We developed a method for analysis of these toxins in soil. Soil samples were extracted with methanol-water (9:1) and purified by solid-phase extraction (SPE, C8-columns). The final extract was analysed using high-pressure liquid chromatography (HPLC) with fluorescence detection. A Phenyl Hexyl column was used to separate the toxins. The detection limits obtained were 0.1 and 1.0 microg kg(-1) dry weight (dw) for OTA and ZON, respectively. The developed method has been used for analysis of different soils in connection with growth chamber experiments. The soil types used in the growth chamber experiments were a sandy soil, a sandy clay soil, and a soil with high content of organic matter. The recovery was determined as 85.8 and 93.4% and the repeatability to 5.1 and 12.8% for OTA and ZON, respectively. The reproducibility obtained was 8.5 and 15.0% for soil samples, representing concentration levels from 0.2-30 microg kg(-1) dw (OTA) and from 1.0-100 microg kg(-1) dw (ZON).

Bracken (Pteridium aquilinum (L.) Kuhn) is a common fern found on all continents except Antarctica. It is under suspicion of causing cancer among people who utilizes it as food. The main carcinogenic compound is thought to be the water-soluble compound ptaquiloside. Ptaquiloside-uptake may occur not only through food, but also via drinking water as ptaquiloside might leach from plant material. The purpose of the study was to identify environmental parameters that correlate with the ptaquiloside-content in fronds, and to quantify the amount of ptaquiloside in the soil environment. The ptaquiloside-content in fronds, Oi/Oe-, and Oa/A-horizons was quantified at end of the growth season at 20 sites in Denmark. The fronds had ptaquiloside-contents between 108 and 3795 microgg(-1). The Oi/Oe-horizons had contents between 0.09 and 7.70 microgg(-1), while Oa/A-horizons had contents between 0.01 and 0.09 microgg(-1). The ptaquiloside-content in the standing biomass, which could be transferred to the soil by the end of the growing season, ranged between 10 and 260 mgm(-2), with nine sites having ptaquiloside loads over 100 mgm(-2). The carbon-content in the O-horizon, the precipitation, the amount of Bracken-litter, the turnover rate and the size of Bracken-stands determined the ptaquiloside-content in the soil materials while the content in fronds was found to be a function of the frond-height and the light-exposure in the ecosystem.

The use of sacroiliac joint injection has been a steadily increasing for therapeutic and diagnostic purposes in the United States. Because of the conceivably easy accessibility of sacroiliac joint and reported low incidence of morbidity, the sacroiliac joint injection is felt to be a procedure that maybe performed easily in the office based setting. While this procedure may be common, the sacroiliac joint injection is not performed accurately without the aide of imaging. Further complicating the issue of sacroiliac joint injections is the lack of specific and reliable diagnostic testing. Clinical evaluation and imaging studies are often unreliable and practitioners often mistakenly assume that pain over the posterior superior iliac spine is pathognomonic for sacral joint pain. In addition, referral patterns are unreliable and bedside testing is often non-diagnostic. Sixty patients undergoing sacroiliac joint injections were studied. Sacroiliac joint injections were placed blindly then examined under fluoroscopy for accurate needle placement. The needle was placed by a single this experienced spinal injectionist. Results of blind needle placement revealed that only 5 of 60 patients were felt to have needle placement approximating a therapeutic point of contact with the sacroiliac joint. Furthermore, the posterior superior iliac spine, was found to be a poor indicator of sacroiliac joint anatomic access. The results of this study show that accurate placement of sacroiliac joint injections is successful without fluoroscopy in only 12% of the patients, even in experienced hands.

The distribution of ptaquiloside (PTA) was studied in four Danish bracken populations in order to evaluate the transfer of PTA from ferns to soil. Populations showed statistically significant differences in PTA contents of fronds and rhizomes despite large in-site variations. The highest concentrations were encountered in fronds with concentrations ranging between 213 and 2145 microg/g, while rhizomes had concentrations between 11 and 902 microg/g. PTA was present in soil materials in amounts of 0.22-8.49 microg/g but apparently with no correlation with PTA contents of fronds or rhizomes. Laboratory tests showed that water could leach PTA from bracken fronds, which is in support of the high soil contents observed at sites exposed to heavy showers just before sampling. The observed soil contents correspond to estimated soil solution concentrations of 200-8500 microg/liter, demonstrating a substantial risk of PTA contamination of surface water and groundwater.

Evidence-based practice guidelines for interventional techniques in the management of chronic spinal pain are systematically developed and professionally derived statements and recommendations that assist both physicians and patients in making decisions about appropriate health care in the diagnosis and treatment of chronic or persistent pain. The guidelines were developed utilizing an evidence-based approach to increase patient access to treatment, to improve outcomes and appropriateness of care, and to optimize cost-effectiveness. All types of relevant and published evidence and consensus were utilized. The guidelines include a discussion of their purpose, rationale, and importance, including descriptions of the patient population served, the methodology, and the pathophysiologic basis for intervention. Multiple diagnostic and therapeutic interventional techniques are included in this document. Strong evidence was shown for diagnostic facet joint blocks for the diagnosis of facet joint pain, and lumbar provocative discography for discogenic pain. Moderate evidence was shown for sacroiliac joint blocks in the diagnosis of sacroiliac joint pain, and for transforaminal epidural injections in the preoperative evaluation of patients with negative or inconclusive imaging studies, but with clinical findings of nerve root irritation. Moderate to strong evidence was shown for multiple therapeutic interventional techniques including medial branch blocks and medial branch neurotomy; caudal epidural steroid injections and transforaminal epidural steroid injections; lumbar percutaneous adhesiolysis; and implantable therapies. These guidelines do not constitute inflexible treatment recommendations. It is expected that a provider will establish a plan of care on a case-by-case basis, taking into account an individual patient's medical condition, personal needs, and preferences, and the physician's experience. Based on an individual patient's needs, treatment different from that outlined here could be warranted. These guidelines do not represent "standard of care."

Healthcare decisions are increasingly being made on research-based evidence, rather than on expert opinion or clinical experience alone. Consequently, the process by which the strength of scientific evidence is evaluated and developed by means of evidence-based medicine recommendations and guidelines has become crucial resulting in the past decade in unprecedented interest in evidence-based medicine and clinical practice guidelines. Systematic reviews, also known as evidence-based technology assessments, attempt to minimize bias by the comprehensiveness and reproducibility of the search for and selection of articles for review. Evidence-based medicine is defined as the conscientious, explicit and judicious use of the current best evidence in making decisions about the care of individual patients. Thus, the practice of evidence-based medicine requires the integration of individual clinical expertise with the best available external evidence from systematic research. To arrive at evidence-based medicine decisions all valid and relevant evidence should be considered alongside randomized controlled trials, patient preferences and resources. However, many systematic reviews in interventional pain management fail to follow evidence-based medicine principles. Clinical practice guidelines are systematically developed statements that assist clinicians, consumers and policy makers to make appropriate healthcare decisions. The complex processes of guideline development depend on integration of a number of activities, from collection and processing of scientific literature to evaluation of the evidence, development of evidence-based recommendations or guidelines and implementation and dissemination of the guidelines to relevant professionals and consumers. Guidelines are being designed to improve the quality of healthcare and decrease the use of unnecessary, ineffective or harmful interventions. This review describes various aspects of evidence-based medicine, systematic reviews in interventional pain management, evaluation of the strength of scientific evidence, differences between systematic and narrative reviews, rating the quality of individual articles, grading the strength of the body of evidence and appropriate methods for searching for the evidence.

Specific hydroxy groups of the terminal disaccharide unit of globotriaosyl ceramide (Gb(3)Cer) were identified from binding studies with deoxyGb(3)Cer and verotoxins (VTs) [Nyholm, Magnusson, Zheng, Norel, Binnington-Boyd and Lingwood (1996) Chem. Biol. 3, 263-275]. Four such hydroxy groups (2", 4", 6" and 6') were each substituted with an amino group and the corresponding deoxyamino globotrioses were conjugated to a ceramide-like aglycone which contained an adamantyl group instead of an acyl chain. Such aglycone modification significantly enhanced the water-solubility of the glycoconjugates [Mylvaganam and Lingwood (1999) Biochem. Biophys. Res. Commun. 257, 391-394]. The inhibitory potential of these soluble aminodeoxy conjugates on the binding of VT(1) to Gb(3)Cer immobilized on an ELISA plate was evaluated. Only the 2" and the 6' deoxyamino conjugates were effective inhibitors (IC(50) 10 microM); the 4" and 6" conjugates were ineffective up to 10 mM. To evaluate the importance of incorporating a rigid adamantyl hydrocarbon group into the ceramide aglycone, globotriaose was conjugated to a t- butylacetamido or an adamantaneacetamido aglycone. By similar ELISAs, only the adamantaneacetamido conjugate inhibited the binding of VT(1) to Gb(3)Cer. When deoxyamino conjugates were adsorbed to silica on TLC plates, only the 2" and 6" conjugates bound VT(1) and VT(2). By a similar TLC assay, acetamido derivatives of 2" and 6' deoxyamino conjugates showed less binding to VT(1) and VT(2). Neither the crystallographically determined structure of the VT(1)-globotriaose complex nor modelling studies fully explain the binding patterns shown by these deoxyamino glycoconjugates. Enhanced solvation of the ammonium group of the deoxyamino conjugate could enforce greater constraints in the binding interactions.

Sorption to mineral surfaces may be important for retention and degradation of hydrophobic pesticides in subsoils and aquifers poor in organic matter. In this work the title pyrethroids have been used to investigate selective interactions with the surfaces of four minerals. Sorption of the four pyrethroids was quantified in batch experiments with initial pyrethroid concentrations of 1-100 microg/l. Sorption to centrifuge tubes used in the batch experiments accounted for 25-60% of total sorption. Net sorption was obtained from total sorption after subtracting the amounts of pyrethroids sorbed to centrifuge tubes used. All isotherms could be fitted by the Freundlich equation with n ranging between 0.9 and 1.1. Bonding affinities per unit surface area decreased in the order: corundum > quartz > montmorillonite approximately equal kaolinite. A similar sequence as found for the total surface tension of the minerals. All minerals showed the same selectivity order with respect to sorption affinity of the four pyrethroids: lambda-cyhalothrin > deltamethrin > cypermethrin > fenvalerate, which shows that the most hydrophobic compound is sorbed most strongly. Stereochemical properties of the four pyrethroid formulations may also contribute to the selectivity pattern.

We evaluated midterm functional outcome after endovascular occlusion of aneurysms in patients with subarachnoid haemorrhage (SAH) and determined the incidence of late rebleeding as an additional prognostic parameter. We treated 79 consecutive patients with SAH from an intracranial aneurysm admitted from a neurological intensive care unit by the endovascular route between 1993 and 1997 and 52 survivors were followed up in 1999-2000. The mean interval between SAH and follow-up was 41 months (range 13-74 months). Outcome was determined by the Glasgow outcome (GOS) and Rankin (RS) scales and by questions concerning neuropsychological disorders. The patients were analysed according to Hunt and Hess (H & H) grades I-III or IV-V on admission. We observed two episodes of rebleeding (3%) with impact on outcome at 907 and 2010 days after SAH, respectively. A complete recovery (GOS 5) was achieved in 53% of H & H grade I-III and 17% of grade IV-V patients; with death rates 19% and 50%, and morbidity according to the RS (5-2) 18% and 29%, respectively. Midterm morbidity after endovascular therapy is thus low. Rebleeding with an impact on outcome can be observed up to 2010 days after SAH, suggesting that long-term angiographic follow-up is indispensable.

The pH-dependent release of cadmium, copper, and lead from soil materials was studied by use of a stirred flow cell to quantify their release and release rates, and to evaluate the method as a test for the bonding strength and potential mobility of heavy metals in soils. Soil materials from sludge-amended and nonamended A horizons from a Thai coarse-textured Kandiustult and a Danish loamy Hapludalf were characterized and tested. For each soil sample, release experiments with steady state pH values in the range 2.9 to 7.1 and duration of 7 d were performed. The effluent was continuously collected and analyzed. Release rates and total releases were higher for the Hapludalf than the Kandiustult and higher for the sludge-amended soils than the nonamended soils. With two exceptions the relative release rates (release rate/total content of metal in soil) plotted vs. steady state pH followed the same curves for each metal, indicating similar bonding strengths. These curves could be described by a rate expression of the form: relative release rate = k[H+]a, with specific a (empirical constant) and k (rate constant) parameters for each metal demonstrating that metal release in these systems can be explained by proton-induced desorption and dissolution reactions. With decreasing pH, pronounced increases in release rates were observed in the sequence cadmium > lead > copper, which express the order of metal lability in the soils. The flow cell system is useful for comparison of metal releases as a function of soil properties, and can be used as a test to rank soils with respect to heavy metal leaching.

Zygapophysial or facet joints have been implicated as cause of low back, mid back, upper back and neck pain with referred pain. Cervical, thoracic and lumbar facet joints are innervated by the medial branches of the dorsal rami. Zygapophysial (facet) joints have been implicated as the source of chronic pain in 15% to 45% of the patients with chronic low back pain, 54% to 60% of the patients with chronic neck pain and 48% of the patients with thoracic pain. A systematic review of the evidence of effectiveness of radiofrequency denervation in the management of chronic spinal pain was undertaken. This review included randomized clinical trials, as well as non-randomized or observational studies in the analysis. Literature search included MEDLINE, EMBASE, systematic reviews, narrative reviews, cross-references to the reviews and various published trials; and peer reviewed abstracts from scientific meetings during the past two years. An algorithmic approach was followed in study evaluation with a description of inclusion and exclusion criteria. A set of high-performing scales or checklists pertaining to randomized clinical trials and observational trials derived from the Agency for Healthcare Research and Quality (AHRQ) was utilized; Systems to Rate the Strength of Scientific Evidence. Qualitative analysis was conducted, using five levels of evidence for effectiveness of medial branch neurotomy. Our search strategy identified over 1,000 citations as the result of electronic and manual screening. A total of 7 randomized trials of radiofrequency neurotomy for spinal pain were identified. However, only 4 related to medial branch neurotomy. Two of the four met the inclusion criteria. Among the multiple observational studies considered for inclusion, 4 prospective evaluations were included in the systematic review. In addition, 3 retrospective evaluations were also included. Two randomized trials comprised of 27 patients receiving active treatment. The first study consisted of cervical facet joint pain and the second consisted of lumbar facet joint pain. Both studies showed positive results. Similar to randomized trials, prospective, as well as retrospective evaluations showed positive evidence, both in short-term and long-term. The results of this systematic review of 2 well-designed randomized trials, 4 prospective well-designed trials without randomization and 3 retrospective evaluations provided strong evidence that radiofrequency denervation offers short-term relief and moderate evidence of long-term pain relief of facet joint origin.

Septic encephalopathies rapidly affect brain function without the involvement of a specific area causing a broad range of reversible neurologic symptoms. Capillary leakage including dysfunction of the blood-brain barrier has been proposed as a potential pathogenic mechanism in this entity. We tested the hypothesis that oxidative stress measured in plasma and cerebrospinal fluid (CSF) of patients suffering from septic encephalopathy could be linked to the neurologic symptoms of the disease. The neurologic symptoms of eleven patients with septic encephalopathy were described semiquantitatively through a score system. The ascorbate levels were significantly lower in both plasma and CSF from patients with septic encephalopathy than controls, and in CSF but not plasma this decrease correlated with the severity of neurologic symptoms. No significant changes were found for alpha-tocopherol. Our findings suggest that the short-term oxidative stress may be an important factor in the development of septic encephalopathy, possibly through dysregulation of the blood-brain barrier.

Incorporation of chlorpyrifos into starch matrices was achieved by thermal gelatinization. The level of amylose content in the starch matrices (10 and 52%) and the addition of auxiliary agents, i.e. solvent, emulsifiers or both, were varied and eight different formulations were prepared. According to differential scanning calorimetry (DSC) and X-ray diffraction measurements, chlorpyrifos was partly present in a crystalline form in all the starch formulations. The formulations had controlled release properties, and the release rate into water could be described by a linear model. In a bioassay, the formulations killed all larvae of the cabbage root fly at a dosing of 1.4 kg a.i. per ha. The degradation of chlorpyrifos in soil from the starch formulations could be described in a non-linear logistic model and the half-life was predicted to be 88 days. Differences in the amount of amylose in the starch as well as the addition of solvent and emulsifiers in the preparation procedure had no systematic influence on the release rate, the insecticidal effect and the degradation rate. No correlation between release rate into water and degradation in soil could be established. Two commercial chlorpyrifos formulations Lorsban 15 G (granular) and Cyfos 500 gl(-1) (emulsifiable concentrate), were included in the study for comparison.

The prevalence of Salmonella serovars and their antimicrobial resistance patterns were investigated among Danish turkeys between 1995 and 2000, by sampling the flocks approximately 14 days before they were slaughtered. Within the flocks, the prevalence of salmonella varied from 7.1 per cent to 25 per cent, and 24 different serovars were detected. The five most prevalent, which accounted for 58.5 per cent of the isolates were Salmonella Heidelberg (16.2 per cent of the isolates), Salmonella Agona (15.8 per cent), Salmonella Derby (12.4 per cent), Salmonella Muenster (7.3 per cent) and Salmonella Anatum (6.8 per cent). In addition, a few rough isolates and isolates belonging to the antigenically incomplete formulae 6,7:-:- and 4,12:b:- were found. The level of antimicrobial resistance was low; the highest resistance was recorded to ampicillin (13.7 per cent) and streptomycin (9.0 per cent) followed by tetracycline (8.5 per cent), sulphonamides (7.7 per cent) and spectinomycin (4.7 per cent). Resistance to quinolones was very low: four isolates were resistant to nalidixic acid, and only one was resistant to enrofloxacin. No resistance was recorded to colistin, apramycin, ceftiofur, florfenicol, or amoxycillin with clavulanic acid. Only 24 isolates were resistant to two or more compounds in various combinations of up to six compounds; one Salmonella Havana isolate was resistant to six compounds. Six isolates were serovar Typhimurium, but none of them belonged to phage type DT104.

Suction cups made of poly(tetrafluorethene) (PTFE) are widely used for sampling of soil solution. A brand (Prenart) of PTFE cups was tested for adsorption of Cd, Cu, Ni, and Zn at low concentrations under different conditions. In a laboratory experiment adsorption from a 10 microg L(-1) heavy metal solution with a 0.01 M NaCl background electrolyte was investigated at pH 3.6, 4.5, and 5.8 by pumping the solutions through the cups. The effect of three different ionic compositions was also investigated using 0.01 M CaCl2, 0.01 M NaCl, and no background electrolyte at pH 4.5. In 0.01 M NaCl electrolyte at pH 5.8 the cups acted as effective filters. At pH 3.6 after 300 mL of solution had passed through the cup, equivalence between the Cd and Ni concentrations in influent and effluent was found. No equivalence between effluent and influent concentrations was found for Zn and Cu at pH 4.5 and 5.8. With Ca as the electrolyte, no adsorption of Cd, Ni, or Zn was found. In Na electrolyte, equivalence between influent and effluent concentrations for Cd, Ni, and Zn was reached. The difference between effluent and influent concentrations of Zn, Ni, and Cd remained significant in the absence of electrolyte. For all pH values and electrolytes the difference between effluent and influent concentrations of Cu was significant. It is concluded that PTFE cups affect the concentrations of heavy metals sampled at low soil solution concentrations. Cadmium, Cu, Ni, and Zn adsorb to the cup at pH > 4.5 and low ionic strength.

We have used a cell-based functional assay to define the pharmacological profiles of a wide range of central nervous system active compounds as agonists, competitive antagonists, and inverse agonists at almost all known monoaminergic G-protein-coupled receptor (GPCR) subtypes. Detailed profiling of 40 antipsychotics confirmed that as expected, most of these agents are potent competitive antagonists of the dopamine D2 receptor. Surprisingly, this analysis also revealed that most are potent and fully efficacious 5-hydroxytryptamine (5-HT)2A receptor inverse agonists. No other molecular property was shared as universally by this class of compounds. Furthermore, comparisons of receptor potencies revealed that antipsychotics with the highest extrapyramidal side effects (EPS) liability are significantly more potent at D2 receptors, the EPS-sparing atypical agents had relatively higher potencies at 5-HT2A receptors, while three were significantly more potent at 5-HT2A receptors. Functional high-throughput screening of a diverse chemical library identified 530 ligands with inverse agonist activity at 5-HT2A receptors, including several series of compounds related to known antipsychotics, as well as a number of novel chemistries. An analog of one of the novel chemical series, AC-90179, was pharmacologically profiled against the remaining monoaminergic GPCRs and found to be a highly selective 5-HT2A receptor inverse agonist. The behavioral pharmacology of AC-90179 is characteristic of an atypical antipsychotic agent.

We assessed the outcome of surgical and endovascular treatment in patients in poor (Hunt & Hess IV or V) grade following subarachnoid haemorrhage due to anterior circulation aneurysm (ACA). There were 41 patients, treated surgically (20), by the endovascular route (20) or both (1). The aneurysms were clipped in 20 patients, wrapped in one; 19 were treated with Guglielmi detachable coils (GDC), one by parent vessel occlusion using detachable balloons. One GDC treatment was interrupted and the aneurysm was surgically clipped instead. We treated five patients surgically to evacuate accompanying intracerebral clots. We treated 14 (66%) patients by the endovascular route and 15 (71%) surgically within 72 h of the haemorrhage. The frequency of delayed ischaemic neurological deficit and/or cerebral infarct due to vasospasm did not differ significantly between the endovascular and surgical groups. We had one surgical and three endovascular procedure-related complications with clinical manifestations. Outcome was evaluated after 6 months. After GDC treatment, angiographic follow-up was carried out between 8 and 26 months (mean 17 months). Good outcomes were achieved in six (29%) of the surgically treated patients (40% of the survivors) and six (30%) of the endovascular treatment patients (60% of the survivors). Outcome was similar after surgical and endovascular approaches. The decision as to which treatment to chosen is influenced mainly by clinical factors such as cerebral haematoma or age.

Objective: To determine the ability of somatosensory evoked potentials (SEP) compared with clinical findings to monitor and predict recovery in patients suffering from closed head injury with predominantly diffuse axonal injury (DAI)., Design: Prospective cohort study., Setting: Neurologic intensive care unit (ICU) of a university hospital., Patients: Serial SEP recordings were obtained from 31 consecutive patients with closed head injury. The first SEP was recorded within 48 hrs after trauma, followed by recordings after another 2 days, after which the time interval for each consecutive recording was doubled. Clinical examinations were performed every 6 hrs during the ICU stay and daily after transfer to a general neurologic ward., Interventions: None., Measurements and Main Results: Twenty-three of 31 patients demonstrated pathologic SEP findings at initial examination. Of these patients, 11 recovered clinically, two remained vegetative, and ten died. In all 11 patients with clinical recovery, SEP also recovered. In 8 of 31 patients, initial SEPs were normal and remained normal until discharge, all eight had a good outcome. Initial SEP findings were related with outcome at 6 months (p = .02), and follow-up studies increased the predictive value of SEP studies (p = .009). Other factors related to outcome included age, severity of DAI, and length of ICU/hospital stay. In the 11 patients with SEP and clinical recovery, early (day 2) and late (>or=2 months) recovery was documented. Early and reliable SEP indicators of improvement included N20-P25-Amplitudes (mean recovery, 8.5 days) and central conduction time (9.6 days). Pupillary light reaction (6.4 days), Babinski reflex (12.4 days), and Glasgow Coma Score (9.6 days) were the most valuable clinical findings. Recovery of the Glasgow Coma Score frequently coincided with reduction of sedatives. In most patients, recovery was detected with SEP before clinical recovery (7/11 patients, time difference 1 wk)., Conclusions: Initial SEP findings correlate with long-term outcome in patients with closed head injury with DAI. Initial bilaterally absent cortical responses in the SEP reliably predicted death, whereas completely normal SEP findings predicted good long-term outcome. Early recovery after DAI can be detected with serial SEP recordings despite sedative medications. Electrophysiologic recovery frequently precedes clinical recovery.

A flexible, multistep parallel synthesis of spiperone analogues is described. A library of 4-substituted piperidines, assembled utilizing reductive amination and acylation protocols, was alkylated either homogeneously or heterogeneously, exploiting a product release only concept, to afford an oxa-series of spiperone analogues. Screening of the products at 5-HT2 and D2 receptors revealed 5-HT2A antagonists with improved selectivity compared to spiperone and AMI-193.

Fifteen patients at our neurological intensive care unit were monitored with continuous EEG (cEEG: 10 channels EEG and ECG) for a total of 109 days. Primary indications for monitoring were nonconvulsive seizures in patients with altered consciousness (AC, n = 9) and control of therapy in generalized/partial status epilepticus (SE, n = 5). The cEEG findings influenced therapeutic management of patients in almost 50% of monitoring days (50/109), with decisive decisions (changes in medication) being made in 31/109 days. In 5/9 patients with AC, cEEG revealed findings that could not be demonstrated in previous EEG recordings. Identification of repetitive, nonepileptic, involuntary movements was guided by cEEG in four patients. Aside from the established application of cEEG monitoring in SE, the usefulness of clarifying the differential diagnosis in patients with AC was demonstrated particularly by the finding of nonconvulsive seizures in three patients. In two of these, intermittent EEG recordings did not demonstrate the seizures.

Background: Development of elevated intracranial pressure (ICP) in hepatic failure indicates poor prognosis. Its detection by invasive methods poses methodological problems. We applied ultrasound studies of the optic nerves to noninvasively estimated ICP status., Methods: A total of 22 pediatric patients with hepatic failure were examined by serial B scan ultrasound and followed up clinically. Outcome was scored as survival or death due to multiorgan failure (MOF) or raised ICP. In 18 patients, transplantations were performed., Results: Four patients died before transplantation was possible (raised ICP: n=3, MOF: n=1). After OLT there were 10 survivors and 8 patients died (MOF: n=3, raised ICP: n=5). In 10 patients we found optic nerve sheath diameter (ONSD) above normal limits. Eight patients died, mostly because of raised ICP (n=7). Only 2 of the 10 survivors experienced a transient ONSD increase, steadily normalized after transplantation. Preoperatively, normal ONSD was detected in four of seven patients. The outcome of these four cases was clearly superior (three survivors and one MOF) compared with abnormal pre-OLT ultrasound findings (raised ICP: n=3)., Conclusion: Patients with poor prognosis related to raised ICP in pediatric liver failure can be identified by ultrasound measurement of ONSD without the disadvantages of invasive procedures. Although the exact intracranial pressure level cannot be deduced from single examinations, ONSD trends can reflect the evolution of ICP in hepatic encephalopathy.

Bioisosteric replacement of the isoxazole heterocycle in (3-methyl-5-isoxazolyl)methylene-azacyclic compounds with pyridine, oxadiazole, or an acyl group resulted in ligands with high to moderate affinity for the central nicotinic cholinergic receptors (IC50 = 2.0 to IC50 > 1000 nM) labeled by [3H]methylcarbamylcholine. Additionally, further support of an important distance parameter for high-affinity nicotinic compounds has been provided.

Gabapentin, an antiepileptic agent, is a safe and versatile medication also used in the adjunctive treatment of painful disorders. These include neuropathic pain, such as postherpetic neuralgia, diabetic neuropathy, and the pain of reflex sympathetic dystrophy. Interstitial cystitis, a painful disease entity, shares many common features of these chronic pain states, and the use of gabapentin can assist in pain control. Gabapentin, as an adjunctive agent, may reduce use of cotherapeutics such as narcotics. Two patients with interstitial cystitis improved functional capacity within their activities of daily living and received adequate pain control with the addition of gabapentin to their medication regimen.

Four aminodeoxy analogs of globotriosylceramide (6"-, 4"-, 2"-, and 6'-aminodeoxy) were synthesized by glycosylation of 3-O-benzoylated azidosphingosine with the corresponding aminodeoxy-globotriose trichloroacetimidate, followed by reduction of the azido group, N-acylation with 1-adamantaneacetic acid, and removal of the protecting groups.

Background and Purpose: The most common cause of poor treatment outcome in patients suffering aneurysmal subarachnoid hemorrhage is cerebral vasospasm, especially in cases of poor Hunt and Hess grades (IV and V). A further prognostic factor in surgically treated patients is aneurysm localization. The aim of the present retrospective study is to compare the endovascular treatment outcome in such poor-grade patients according to aneurysm localization in either the anterior (AC) or posterior (PC) circulation., Methods: Forty poor-grade patients admitted between 1993 and July 1998 were treated by endovascular approach within 23 days after aneurysm rupture. Eighteen had aneurysms in the AC, 22 in the PC. Mean treatment delay was 4 days after rupture and median, 2 days. One patient showed multiple aneurysms. In 36 cases, aneurysms were occluded by Guglielmi detachable coils; in 4 cases, by parent vessel balloon occlusion., Results: The incidence of delayed ischemic neurological dysfunction or cerebral infarct due to vasospasm did not differ significantly between the AC and PC groups. Two procedure-related complications with clinical effect were observed in each group. At 6 months' follow-up, the result was good in 5 patients and poor in 13 in the AC group and good in 11 patients and poor in 11 in the PC group., Conclusion: Given comparable incidence of vasospasm in poor-grade patients, a tendency toward better treatment outcome was found in patients with aneurysms in the posterior circulation (chi(2)=2.04; P=0.15) than in the anterior circulation. Endovascular therapy for poor-grade patients is recommended, as are further studies to determine treatment differences.

Object: The effect of increased intracranial pressure (ICP) on cerebral venous blood flow has been the subject of very few clinical and experimental studies. The authors assessed the usefulness of venous transcranial Doppler (TCD) ultrasonography as a noninvasive monitoring tool for predicting raised ICP., Methods: Serial venous TCD studies of the basal vein of Rosenthal and the straight sinus (SS) were prospectively performed in 30 control volunteers and 25 patients with raised ICP. Correlations with ICP data were calculated using a multivariate regression model. Venous blood flow velocities (BFVs) in the basal vein of Rosenthal showed, within a certain range, a linear relationship between mean ICP and maximal venous BFV (r = 0.645; p<0.002). Moreover, a linear relationship was found for maximal venous BFVs in the SS and mean ICP (r = 0.928; p<0.0003)., Conclusions: Venous TCD studies may provide an additional noninvasive monitoring tool for raised ICP and give further insights into the cerebral venous hemodynamics present during raised ICP.

The epidemiology of an outbreak of Newcastle disease in a population of approximately 12,000 free-living pheasants (Phasianus colchicus) on the island of Faenø in Denmark in 1996 is described. The mortality during the epizootic was 56%. The spread of the disease between 7 groups of pheasants could be demonstrated over an observation period of 3 weeks. A total of 70 avian paramyxovirus serotype 1 (APMV-1) isolates was made from the flock. The intra cerebral pathogenicity indices of the 4 isolates tested were in the range 1.78-1.88. By means of immunoperoxidase monolayer assay with murine monoclonal antibodies and sequence analysis of an RT-PCR amplified segment of the F0 viral protein it was found, that the virus belonged to the highly virulent C1 antigenic group and that the amino acid sequence at the F0 cleavage site corresponded with the sequences of virulent APMV-1 strains. Based on the epidemiological circumstances it is believed that the virus was transmitted to the pheasants by feral birds.

The burst-suppression (BS) pattern of the EEG occurs in a rather limited number of conditions. It has been observed in deep stages of general anesthesia and in conjunction with sedative overdoses. It is also known to occur in the wake of cardiorespiratory arrest. Undercutting of the cortex has been found to result in BS activity. Rare neonatal epileptic encephalopathies also give rise to BS. Our personal interest was prompted by the consistent finding of BS activity in rats following cerebral anoxia (nitrogen inhalation, airway obstruction): after periods of EEG flatness, BS activity developed, followed by periodic bursts and diffuse slowing. On the other hand, earlier literature (before 1960) showed virtually no observation of BS, neither in anoxic patients, nor in animal experiments. It is likely that the introduction of modern intensive care treatment has engineered episodes of BS activity, probably due to modifications of the anoxic cerebral pathology.

Ikaite, calcium carbonate hexahydrate, has by means of X-ray diffraction analyses of frozen samples been identified as the mineral component of the white spots formed in the shell of frozen shrimp during storage. When the shrimp thaw and the shell material is dried and kept at room temperature, ikaite rapidly transforms into a mixture of anhydrous calcium carbonate forms. X-ray diffraction analyses and Raman spectra of synthetic ikaite as well as the dehydration product confirm the assignments, and the rate constant for dehydration is approximately 7 x 10(-)(4) s(-)(1) at ambient temperature. Differential scanning calorimetry showed that dehydration of synthetic ikaite is an entropy-driven, athermal process and confirms that a single first-order reaction is rate-determining. Ikaite is found to be stable in aqueous solution at temperatures below 5 degrees C and in the shell of frozen shrimps but decomposes on thawing to form anhydrous calcium carbonates.

Congestive myelopathy, formerly referred to as varicosis spinalis or Foix-Alajouanine syndrome, is caused by a spinal dural arteriovenous fistula (SDAVF). So far, the blood supply from the meningeal arteries draining through the fistula into the medullary venous system can only be verified by spinal angiography. Patients predominantly male and over the age of 60 are afflicted. Initially reversible functional disorders caused by the congestion of the spinal cord veins eventually become irreversible, the most common symptom being an increasingly paretic gait disorder, the signs of which generally begin symmetrically and progress from distal to proximal signs. Simultaneously, predominantly transverse sensory dysfunctions develop, as well as bladder and bowel dysfunctions, most often leading to incontinence. MRI typically shows a central medullary signal enhancement with slight swelling of the afflicted region, initially indicative of a reversible congestive edema and later of an irreversible infarction, and extended perimedullar vessels. Thus, if the clinical course and the characteristic MRI findings suggest the possibility of disease related to congestive myelopathy, spinal angiography becomes indispensable. Since ensuing the success of therapy and prognosis depends on rapid determination of the extent of the illness, a speedy diagnostic reaction is mandatory to institute the treatment necessary to prevent paraplegia.

A patient is presented who suffered a lateral brainstem infarction which selectively abolished pain and temperature sensitivity in the lower right limb. One year later central post-stroke pain had developed in the affected limb with touch and cold allodynia. P40m dipoles calculated from magnetoencephalographic fields after electrical stimulation of both tibial nerves were localized in SI as is seen in normal subjects. However, stimulation of the affected side caused deep pain sensations and elicited a large N80m component, best explained by an additionally active dipole in cingulate cortex. This early co-activation in a limbic structure suggests peripheral Abeta-fiber mediation and lemniscal projection. Abnormal link to the pain system may be due to sensitization and reorganization above the level of nociceptive deafferentation.

The conversion of EEG findings and the evolution of clinical signs was investigated in 7 CJD patients who underwent serial EEG recordings along the course. At the onset of PSWC (mean 8.7 weeks), 5 patients had already progressed to akinetic mutism (characterized by loss of verbal contact and directed responses); and a CJD-typical-movement disorder (myoclonia, exaggerated startle reaction or focal dyskinesia) had started in 5 patients. When akinetic mutism commenced (on average at 7.5 weeks), runs of frontal intermittent non-peaked rhythmical delta activity (FIRDA) were found in all cases. These were later replaced by PSWC in 6 patients (interval 1 to 3 weeks). Occurrence of PSWC was often negatively related to external stimuli (2 of 6 cases), and sedative medication (all patients tested). We conclude that the selection of EEG recording dates to detect PSWC in CJD-candidates should be guided by detailed information about movement disorders and conscious level. Regarding the short survival time after their onset (average 8 weeks), PSWC usually mark the terminal stage of CJD. To detect PSWC, especially, EEG registrations in advanced stages are often necessary. In earlier disease stages, FIRDA-like EEG activities should be regarded as compatible with this diagnosis, and encourage further EEG studies for the demonstration of PSWC in a more advanced stage of CJD.