Comparative yield of positive brain computed tomography after implementing the NICE or SIGN head injury guidelines in two equivalent urban populations.

AIMS: To compare the yield of positive computed tomography (CT) brain examinations after the implementation of the National Institute for Clinical Excellence (NICE) or the Scottish Intercollegiate Guidance Network (SIGN) guidelines, in comparable urban populations in two teaching hospitals in England and Scotland. MATERIALS AND METHODS: Four hundred consecutive patients presenting at each location following a head injury who underwent a CT examination of the head according to the locally implemented guidelines were compared. Similar matched populations were compared for indication and yield. Yield was measured according to (1) positive CT findings of the sequelae of trauma and (2) intervention required with anaesthetic or intensive care unit (ICU) support, or neurosurgery. RESULTS: The mean ages of patients at the English and Scottish centres were 49.9 and 49.2 years, respectively. Sex distribution was 64.1% male and 66.4% male respectively. Comparative yield was 23.8 and 26.5% for positive brain scans, 3 and 2.75% for anaesthetic support, and 3.75 and 2.5% for neurosurgical intervention. Glasgow Coma Score (GCS) <13 (NICE) and GCS ≤ 12 and radiological or clinical evidence of skull fracture (SIGN) demonstrated the greatest statistical association with a positive CT examination. CONCLUSION: In a teaching hospital setting, there is no significant difference in the yield between the NICE and SIGN guidelines. Both meet the SIGN standard of >10% yield of positive scans. The choice of guideline to follow should be at the discretion of the local institution. The indications GCS <13 and clinical or radiological evidence of a skull fracture are highly predictive of intracranial pathology, and their presence should be an absolute indicator for fast-tracking the management of the patient.

Small cell lung carcinoma presenting with acute disseminated encephalomyelitis.

Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease characterised by subcortical high-signal white matter lesions on T2 weighted MRI. It most commonly occurs in children following an acute viral illness. We present a case study in which ADEM was the presenting condition in an adult female with small cell lung carcinoma. We discuss the evidence in the literature suggesting that ADEM may be viewed as a paraneoplastic syndrome.

High yield and rapid growth of Neoparamoeba pemaquidensis in co-culture with a rainbow trout gill-derived cell line RTgill-W1.

Neoparamoeba pemaquidensis is an ubiquitous amphizoic marine protozoan and has been implicated as the causative agent for several diseases in marine organisms, most notably amoebic gill disease (AGD) in Atlantic salmon. Despite several reports on the pathology of AGD, relatively little is known about the protozoan and its relationship to host cells. In this study, an in vitro approach using monolayers of a rainbow trout gill cell line (RTgill-W1, ATCC CRL-2523) was used to rapidly grow large numbers of N. pemaquidensis (ATCC 50172) and investigate cell-pathogen interactions. Established cell lines derived from other tissues of rainbow trout and other fish species were also evaluated for amoeba growth support. The amoebae showed preference and highest yield when grown with RTgill-W1 over nine other tested fish cell lines. Amoeba yields could reach as high as 5 x 10(5) cells mL(-1) within 3 days of growth on the gill cell monolayers. The amoebae caused visible focal lesions in RTgill-W1 monolayers within 24 h of exposure and rapidly proliferated and spread with cytopathic effects destroying the neighbouring pavement-like cells within 48-72 h after initial exposure in media above 700 mOsm kg(-1). Disruption of the integrity of the gill cell monolayers could be noted within 30 min of exposure to the amoeba suspensions by changes in transepithelial resistance (TER) compared with control cell monolayers maintained in the exposure media. This was significantly different by 2 h (P < 0.05) compared with control cells and remained significantly different (P < 0.01) for the remaining 72 h that the TER was monitored. The RTgill-W1 cell line is thus a convenient model for growing N. pemaquidensis and for studying host-pathogen interactions in AGD.

Structure of the carboxy-terminal PH domain of pleckstrin at 2.1 Angstroms.

Pleckstrin is an important intracellular protein involved in the phosphoinositide-signalling pathways of platelet activation. This protein contains both N- and C-terminal pleckstrin-homology (PH) domains (N-PH and C-PH). The crystal structure of C-PH was solved by molecular replacement and refined at 2.1 Angstroms resolution. Two molecules were observed within the asymmetric unit and it is proposed that the resulting dimer interface could contribute to the previously observed oligomerization of pleckstrin in resting platelets. Structural comparisons between the phosphoinositide-binding loops of the C-PH crystal structure and the PH domains of DAPP1 and TAPP1, the N-terminal PH domain of pleckstrin and a recently described solution structure of C-PH are presented and discussed.

Dry Matter Production and Rate of Change of Harvest Index at High Temperature in Peanut.

The concept of a linear increase in harvest index, dHI/dt, has proven very useful for crop simulation modeling. The effect of high temperature on the response of dHI/dt of pods and seeds of peanut (Arachis hypogaea L.) has not been described. The objectives of this work were to determine (i) whether dHI/dt was linear at high temperature, (ii) whether high temperature affected dHI/dt and/or the timing of the linear phase of increase in HI, and (iii) whether there was genotypic variation in the response of dHI/dt to high temperature. Four peanut genotypes varying in heat tolerance were grown in pots at either 28/22 or 38/22 degrees C from 21 to 90 d after planting (DAP). Plants were harvested on 10 occasions starting 27 DAP and total dry matter accumulation and partitioning measured. High temperature reduced total dry weight by 20 to 35%, seed HI by 0 to 65%, and seed dry weight by 23 to 78%. At 28/22 degrees C, dHI/dt for pods and seeds was linear and varied from 0.0058 to 0.0109 d(-1). At 38/22 degrees C, dHI/dt of pods and seeds was also linear and varied from 0.0028 to 0.0089 d(-1). There were genotypic differences in response to temperature. High temperature had no effect on dHI/dt in moderately tolerant genotypes 796 and 47-16. In susceptible genotypes ICGV 86016 and ICGV 87282, however, the start of pod and seed filling was delayed by 5 to 9 d and dHI/dt reduced by 20 to 65% at 38/22 degrees C. Reductions in pod and seed dry weight at 38/22 degrees C were therefore due to reductions in total dry matter and dHI/dt, depending on the heat tolerance of the genotype. Crop models need to account for genotypic differences in the response of timing and rate of dHI/dt to high temperature to successfully simulate yields in warmer environments.

Effects of short episodes of heat stress on flower production and fruit-set of groundnut (Arachis hypogaea L.).

Groundnuts (Arachis hypogaea L.) are an important crop of the semi-arid tropics where they are often exposed to maximum temperatures of > 40 degrees C for short periods during the growing season. The objectives of this study were to determine: (i) the effects of short periods of exposure to high temperature on flower production (FN), the proportion of flowers forming fruits (fruit-set) and the number of pegs and pods per plant (RNt); (ii) whether fruit-set is affected by high temperature during different periods of daylight in each diurnal cycle; and (iii) whether responses to temperature were qualitative or quantitative. Plants of cv. ICGV 86015 were grown in controlled environments at a day/night temperature of 28/22 degrees C from sowing until 9 d after flowering (DAF). Then, cohorts of plants were: (a) exposed to day temperature of 28, 34, 42 or 48 degrees C for 2, 4 or 6 d; or were (b) exposed to 34, 42 or 48 degrees C for 6 d either throughout a 12 h day (08.00 to 20.00 h, WD), or only during the first 6 h (AM) or second 6 h (PM) of the day. Values of RNt were significantly reduced by high temperature, by duration of exposure, and by timing of exposure. Variation in FN was quantitatively related to floral bud temperatures during the day over the range 28-43 degrees C. In contrast, only floral bud temperatures > 36 degrees C during AM and WD significantly reduced fruit-set and hence RNt, whereas high PM temperature had no effect on fruit-set. These findings indicate that the response of RNt to day temperature is quantitative and can be modelled by combining the responses of FN and fruit-set to temperature.

Radiosurgery for arteriovenous malformations: the University of Toronto experience.

BACKGROUND: From July 1989 to February 1996, 130 patients underwent stereotactic radiosurgery. We report the results of the first 50 patients eligible for a minimum of three years of follow-up. METHODS: Twenty women and 30 men, (mean age: 37.5 years) were treated by dynamic rotation on a 6 MV linear accelerator. Prior treatment was embolization in seventeen, surgery in three and embolization and surgery in six. All had DSA and enhanced CT scanning, while some had MRI. Forty-seven treatments used a single isodose. Restricting eloquent normal tissue to 15 Gy, margin doses (at 50-90% isodose) were 12 Gy (one patient); 15 Gy (sixteen patients); 20 Gy (31 patients); 25 Gy (two patients). Maximum diameters were: < 1.5 cm (12 patients); < 2.0 cm (nine patients); < 2.5 cm (twelve patients); < 3.0 cm (thirteen patients; 3.0 cm (four patients). RESULTS: Forty-five patients were evaluable at three years, with thirty-nine having angiography. Twenty-five had angiographically confirmed obliterations; two had parenchymal AVMs obliterated but with residual dural components; four had MRI evidence of obliteration (refused angiography). One patient acutely had a seizure; one patient (with hemorrhages, resection, and embolizations preceding two applications of radiosurgery, separated by 3.5 years) had worsening of memory. CONCLUSIONS: Our uncorrected (five patients unevaluable at three years) and corrected angiographically confirmed obliteration rates are 54% and 60% respectively. Our follow-up (98% accounting of cohort; 78% angiographic rate) and explicit derivation of denominators help delineate the efficacy of radiosurgery at these doses.

Use of field observations to characterise genotypic flowering responses to photoperiod and temperature: a soyabean exemplar.

Thirty-nine accessions of soyabean [Glycine max (L.) Merrill] and 1 of wild annual soyabean (Glycine soja L.) were sown at two sites in Taiwan in 1989 and 1990 and on six occasions during 1990 at one site in Queensland, Australia. On two of the occasions in Australia additional treatments extended natural daylengths by 0.5 h and 2 h. The number of days from sowing for the first flower to appear on 50% of the plants in each treatment was recorded (f), and from these values the rate of progress towards flowering (1/f) was related to temperature and photoperiod. In photoperiod-insensitive accessions it was confirmed that the rate is linearly related to temperature at least up to about 29°C. In photoperiod-sensitive genotypes this is also the case in shorter daylengths but when the critical photoperiod (P c) is exceeded flowering is delayed. This delay increases with photoperiod until a ceiling photoperiod (P ce) is reached. Between P c and P ce, 1/f is linearly related to both temperature (positive) and photoperiod (negative), but in photoperiods longer than P ce there is no further response to either factor. The resulting triple-intersecting-plane response surface can be defined by six genetically-determined coefficients, the values of which are environment-independent but predict time to flower in any environment, and thus quantify the genotype x environment interaction. By this means the field data were used to characterise the photothermal responses of all 40 accessions. The outcome of this characterisation in conjunction with an analysis of the world-wide range of photothermal environments in which soyabean crops are grown lead to the following conclusions: (1) photoperiod-insensitivity is essential in soyabean crops in temperate latitudes, but such genotypes flower too rapidly for satisfactory yields in the tropics; (2) photoperiod-sensitivity appears to be essential to delay flowering sufficiently to allow adequate biomass accumulation in the warm climates of the tropics; (3) contrary to a widely held view, some degree of photoperiod-sensitivity is also needed in the tropics if crop-duration homeostasis is required where there is variation in sowing dates (this is achieved through a photoperiod-controlled delay in flowering which counteracts the seasonal increase in temperature that is correlated with increase in day-length); and (4) a greater degree of photoperiod-sensitivity is necessary to provide maturity-date homeostasis for variable sowing dates - a valuable attribute in regions of uncertain rainfall. Since the triple-intersecting-plane response model used here also applies to other species, the use of field data to characterise the photothermal responses of other crops is discussed briefly.

Characterization of photothermal flowering responses in maturity isolines of soyabean [Glycine max (L.) Merrill] cv. Clark.

All eight isolines of three maturity genes (E(1)/e(1), E(2)/e(2), and E(3)/e(3)) of soyabean [Glycine max (L.) Merrill] cv. Clark were grown in widely different combinations of photoperiod and temperature. Under the more inductive conditions, i.e. in a warm mean temperature (30 degrees C) when daylengths were less than the critical value (i.e. less than about 13 h), the isolines flowered at similar times (23-24 d). The responses of all isolines to temperature were also similar, if not identical. Increase in daylength above the critical photoperiod progressively delayed flowering until the time taken to flower (f) reached a maximum at the ceiling photoperiod. The relations between the rate of progress towards flowering (1/f) and photoperiod (between the critical and ceiling values) were linear. The coefficient characterizing the slope of the response (photoperiod sensitivity) varied amongst the isolines. These responses could be grouped into three categories of increasing sensitivity: (1) least sensitive, e(1)e(2)e(3), e(1)E(2)e(3), e(1)e(2)E(3); (2) intermediate, E(1)e(2)e(3), e(1)E(2)E(3), and (3) most sensitive, E(1)E(2)e(3), E(1)e(2)E(3), E(1)E(2)E(3). Thus, in the Clark cultivar genetic background, E(1) induces greater photoperiod sensitivity but neither E(2) nor E(3) on their own have any effect. However, both E(2) and E(3) together induce photoperiod sensitivity comparable to that induced by E(1) alone. Furthermore, in addition to this epistasis, either E(2) or E(3) has considerable epistatic effect on E(1), further increasing photoperiod sensitivity. The effects of these genes and their epistasis were also reflected in the extent of the maximum delays to flowering which occur when the ceiling photoperiod is exceeded, and also possibly in earliness in circumstances when photoperiods were below the critical value.

Variation in the durations of the photoperiod-sensitive and photoperiod-insensitive phases of development to flowering among eight maturity isolines of soyabean [Glycine max (L.) Merrill].

In soyabean [Glycine max (L.) Merrill] the period between sowing and flowering is comprised of three successive developmental phases--pre-inductive, inductive and post-inductive--in which the rate of development is affected, respectively, by temperature only, by photoperiod and temperature, and then again by temperature only. A reciprocal-transfer experiment (carried out at a mean temperature of 25 degrees C) in which cohorts of plants were transferred successively between short and long photoperiods and vice-versa showed that eight combinations of three pairs of maturity alleles (E(1)/e(1), E(2)/e(2), E(3)/e(3)) had their greatest effect on the duration of the inductive phase in long days. This phase was increased with the increasing photoperiod sensitivity induced by the different gene combinations, and ranged from about 27 to 54 d according to genotype. In a short day regime (11.5 h d(-1)), less than the critical photoperiod, the duration of the inductive phase was brief-requiring about 11 photoperiodic cycles in the less photoperiod-sensitive genotypes and only about seven cycles in the more sensitive ones. The maturity genes also affected the duration of the two photoperiod-insensitive phases; these durations were positively correlated with the photoperiod-sensitivity potential of the gene combinations. The largest effect was on the pre-inductive phase which varied from 3 to 11 d, while the post-inductive phase varied from about 13 to 18 d. As a consequence of these nonphotoperiodic effects of the maturity genes, even in the most inductive regimes (daylengths less than the critical photoperiod) the time taken to flower by the less photoperiod-sensitive combinations of maturity genes was somewhat less than in the more sensitive combinations-ranging from about 28 to 34 d. The genetic and practical implications of these findings are discussed.

Field evaluation of a model of photothermal flowering responses in a world lentil collection.

A model to predict flowering time in diverse lentil genotypes grown under widely different photothermal conditions was developed in controlled environments. The present study evaluated that model with a world germ plasm collection of 369 accessions using two field environments in Syria and two in Pakistan. Photoperiod alone accounted for 69% of the variance in 1/f, the reciprocal of time (d) from sowing to flower. In contrast, temperature alone did not account for a significant proportion of variation in flowering time due to the exposure of plants to supra-optimal temperatures in the late-sown Syrian trial. With the model mean pre-flowering values of photoperiod and temperature combined additively to account for 90.3% of the variance of 1/f over accessions. The correlation of field-derived estimates of temperature sensitivity of accessions to glass-house-derived estimates was significant at P = 0.05, but the equivalent correlation for estimates of photoperiodic sensitivity was higher at P < 0.01. Flowering in the field was better measured as time from sowing to 50% plants in flower rather than time to first bloom or its node number. Dissemination of the lentil crop following domestication in West Asia to the lower latitudes such as Ethiopia and India has depended on selection for intrinsic earliness and reduced sensitivity to photoperiod. Movement from West Asia to the higher latitudes accompanied by spring sowing has resulted in a modest reduction in photoperiod sensitivity and an increase in temperature sensitivity.

Characterization of responses to temperature and photoperiod for time to flowering in a world lentil collection.

The times from sowing to first flowering (f) of 231 accessions of lentil (Lens culinaris Medik.), comprising germ plasm from eight countries and breeding lines from ICARDA in Syria, were recorded in four glasshouse environments; two photoperiods (16 and 13 h/day) combined with warmer (24°/13°C) and cooler (18°/9°C) day/night temperatures. The linear model 1/f=a+bT + cP (where T is mean diurnal temperature and P is photoperiod) provided an average fit over the 231 accessions of r (2)=0.852. Since there is no interaction term in this linear model, the flowering responses of an accession to temperature and photoperiod are independent. The values of the constants b and c indicate relative responsiveness of rate of progress towards flowering (1/f) to temperature and photoperiod, respectively. Comparison among the 231 accessions showed a weak, but significant, negative correlation between the values of b and c (r=-0.291, P<0.01). Since the proportion of the variance of b not attributed to its linear regression on c was >0.91, we conclude that these phenological responses are under separate control and that there is considerable scope for selection of any combination of sensitivities to temperature and photoperiod in lentil. Just as a large proportion of the variation among accessions in mean time to first flowering was attributed to country of origin, so also was variability in the values of the constants a, b, and c. In particular, sensitivity to photoperiod (i.e., the value of constant c) was dependent upon latitude of origin. Breeding lines from ICARDA were equally variable in a, b, and c as were germ plasm accessions from elsewhere, while the mean values were similar to those of accessions from neighboring Jordan. A single accession of wild lentil (L. culinaris subsp. orientalis) from Turkey showed flowering responses to T and P similar to the mean value of accessions of cultivated lentil from that country. Results from diverse environments for the Argentinian cv Precoz show that the use of this linear model facilitates predictions of time to flowering in any environment (within wide limits) of known mean temperature and photoperiod. The model, then, minimizes the need for multisite evaluations of phenology, since predictions of pre-flowering duration in any environment, and characterization of flowering responses to photoperiod and temperature, can now be achieved by screening germ plasm in a few, carefully selected locations.

Alfentanil infusions on the intensive therapy unit.

We have investigated the use of alfentanil by infusion to sedate 14 patients during controlled ventilation on the intensive therapy unit (ITU). An initial rate of 24 micrograms.kg-1.h-1 was chosen and altered thereafter according to patient response. Incremental doses of midazolam (2.5-5.0 mg) were given intravenously (i.v.) if indicated. In 4 patients, the use of a muscle relaxant was necessary to allow adequate controlled ventilation of the patient. The mean duration of infusion was 27.9 h (range 10-141 h), and the mean total dose of alfentanil was 69.3 mg (12.5-240 mg). Spontaneous ventilation was rapidly achieved in 11 patients after stopping the infusion. The mean arterial carbon dioxide tension (PaCO2) was 5.38 kPa, 15-30 min after stopping the infusion. The clinical condition of 2 patients necessitated a change in sedation technique and one patient died during the alfentanil infusion. Alfentanil by infusion caused no major cardiovascular effects and did not influence the plasma cortisol response to trauma. There was no major alteration in blood biochemistry or haematology during the infusions of alfentanil. The plasma concentrations of alfentanil during infusion showed a wide variability. These probably relate to both changes in the volume of distribution of the drug and in hepatic clearance.

Fluradoline and aspirin for orthopedic postoperative pain.

Fluradoline (150 or 300 mg), a novel tricyclic with both antidepressant and analgesic properties in animals, was compared with aspirin, 650 mg, and placebo when given orally for postoperative orthopedic pain in a double-blind, single-dose, parallel-group study. Analgesic measurements were made by two trained nurse observers using standard verbal rating and visual analogue scales. Aspirin was statistically superior to placebo on all analgesic measures, demonstrating assay sensitivity. Fluradoline, 300 mg, was distinguished from placebo and fluradoline, 150 mg, but not from aspirin, 650 mg. Overall, fluradoline, 300 mg, was equivalent to aspirin, 650 mg. Fluradoline, 300 mg, produced a significant elevation in mood score. Neither aspirin, 650 mg, nor fluradoline caused untoward side effects, but fluradoline, 300 mg, increased blood pressure.

Is alfentanil by infusion useful for sedation on the ITU?

Methods of sedation in the ITU have changed considerably over the last few years. Whereas the use of muscle relaxants to control ventilation was a frequent feature of those ITUs reviewed by Merriman, a more recent study by Gast and colleagues revealed a far greater use of narcotics and/or hypnotics, or combinations of the two. Alfentanil has many of those ideal properties needed of a sedative drug in the ITU--its use is associated with marked cardiovascular stability, it is a potent ventilatory depressant, has a high therapeutic ratio, minimal immunological or metabolic effects, and has an appropriate kinetic profile (low liposolubility, small volume of distribution, short half-life). The present paper describes the use of an infusion of alfentanil, in combination with increments of midazolam, to provide sedation and control of ventilation in patients admitted to a general ITU.

Ketorolac and acetaminophen for orthopedic postoperative pain.

In a double-blind, single-dose, parallel-group study, ketorolac (5, 10, or 20 mg) was compared with acetaminophen (500 or 1000 mg) when taken by mouth for postoperative orthopedic pain. Analgesic measurements were made by trained nurse observers who used standard verbal rating and visual analog scales. Acetaminophen, 1000 mg, was statistically superior to 500 mg acetaminophen, demonstrating assay sensitivity. Ketorolac, 20 mg, was distinguished from 500 mg acetaminophen, 5 mg ketorolac, and 10 mg ketorolac, but not from 1000 mg acetaminophen. The higher doses of ketorolac induced a longer lasting peak analgesic effect than did acetaminophen, but the magnitude of the peak pain relief was changed little by an increased ketorolac dose. Overall, 10 mg ketorolac appeared equivalent to 1000 mg acetaminophen. Acetaminophen, 500 mg, induced less sedation than the higher doses of ketorolac, but neither drug caused untoward side effects.