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Improving the sensitivity and ultimately the range of particle sizes that can be detected with a single pore extends the versatility of the Coulter counting technique. Here, to enable a pore to have greater sensitivity, we have developed and tested a novel differential resistive pulse sensing (DiS) system for sizing particles. To do this, the response was generated through a time shift approach utilizing a “self-servoing regime” to enable the final signal to operate with a zero background in the absence of particle translocation. The detection and characterization of a series of polystyrene particles, forced to translocate through a cylindrical glass microchannel (GMC) by a suitable static pressure difference using this approach, is demonstrated. An analytical response, which scales with the size of the particles employed, was verified. Parasitic capacitive effects are discussed; however, translocations on the millisecond time scale can be detected with high sensitivity and accuracy using the approach described.

A simple benchtop method of fabricating glass-sealed nanometer-sized Au and Pt disk electrodes, glass nanopore electrodes, and glass nanopore membranes is reported. The synthesis of all three structures is initiated by sealing the tips of electrochemically sharpened Au and Pt microwires into glass membranes at the end of a soda lime or lead glass capillary. Pt and Au nanodisk electrodes are obtained by hand polishing using a high-input impedance metal oxide semiconductor field effect transistor (MOSFET)-based circuit to monitor the radius of the metal disk. Proper biasing of the MOSFET circuit, based on a numerical analysis of the polishing circuit impedance, allows for the reproducible fabrication of Pt disk electrodes of radii as small as 10 nm. Significantly smaller background currents in voltammetric measurements are obtained using lead glass capillaries, a consequence of the lower mobility of Pb(2+) (relative to Na(+)) in the glass matrix. Glass nanopore electrodes and glass nanopore membranes are fabricated, respectively, by removal of part or all of the metal sealed in the glass membranes. The nanostructures are characterized by atomic force microscopy, steady-state voltammetry, and ion conductivity measurements.

A study was initiated to investigate the relationship between soil test P and depth of soil sampling with runoff losses of dissolved molybdate reactive phosphorus (DMRP). Rainfall simulations were conducted on two noncalcareous soils, a Windthorst sandy loam (fine, mixed, thermic Udic Paleustalf) and a Blanket clay loam (fine, mixed, thermic Pachic Argiustoll), and two calcareous soils, a Purves clay (clayey, smectitic, thermic Lithic Calciustoll) and a Houston Black clay (fine, smectitic, thermic Udic Haplustert). Soil (0- to 2.5-, 0- to 5-, and 0- to 15-cm depths) and runoff samples were collected from each of the four soils in permanent pasture exhibiting a wide range in soil test P levels (as determined by Mehlich III and distilled water extraction) due to prior manure applications. Simulated rain was used to produce runoff, which was collected for 30 min. Good regression equations were derived relating soil test P level to runoff DMRP for all four soil types, as indicated by relatively high r2 values (0.715 to 0.961, 0- to 5-cm depth). Differences were observed for the depth of sampling, with the most consistent results observed with the 0- to 5-cm sampling depth. Runoff DMRP losses as a function of the concentration of P in soil were lower in calcareous soils (maximum of 0.74 mg L(-1)) compared with noncalcareous soils (maximum of 1.73 mg L(-1)). The results indicate that a soil test for environmental P could be developed, but it would require establishing different soil test P level criteria for different soils or classes of soils.

Management practices for biomass production of bioenergy grasses may differ from management for forage. Our objective was to determine the yield and stand responses of Alamo' switchgrass (Panicum virgatum L.) to N and P fertilization as affected by row spacing. A combination of five rates each of N and P were applied to plots during 1992 to 1998 at Stephenville, TX and 1993 to 1995 at Beeville, TX. Three row-spacing treatments were applied as subplots. Biomass production was determined each year with a single harvest in late summer. Tiller density and tiller mass were measured during 1993 to 1996 at Stephenville. Biomass production was not influenced by the addition of P. Biomass production response to N at Beeville was greater in narrow rows than wide rows during the establishment year only. Biomass production responses to N were quadratic in 5 of 7 yr at Stephenville and linear at Beeville. A maximum yield of 22.5 Mg ha -1 occurred during 1995 at Stephenville at 168 kg N ha -1 . Lodging occurred at both locations but only at the 224 kg N ha -1 rate. Tiller density and mass increased as row width increased. Tiller mass also increased with increasing N fertility at Stephenville. This response was more important in determining biomass production than was tiller density. Average biomass production at 168 kg N ha -1 yr -1 was 14.5 and 10.7 Mg ha -1 yr -1 at Stephenville and Beeville, respectively. Biomass production without applied N tended to decline over the years. Our data indicated that switchgrass biomass production is sustainable at Stephenville only with the application of at least 168 kg N ha -1 yr -1 , but P application and row spacing are not crucial.

Dexmedetomidine–propofol pharmacodynamic interaction was evaluated in nine healthy subjects in a crossover design. Dexmedetomidine/placebo was infused using a computer‐controlled infusion pump (CCIP) to maintain a pseudo‐steady‐state plasma concentration of 0.66 ± 0.080 or 0 ng/mL, respectively. Forty‐five minutes after the dexmedetomidine/placebo infusion was started, propofol was infused using a second CCIP to achieve a stepwise logarithmically ascending propofol concentration (1.00 to 13.8 μg/mL) profile. Each propofol step lasted 10 min. Blood was sampled for plasma concentration determination, and pharmacodynamic endpoint assessments were made during the study. Propofol and dexmedetomidine/placebo infusions were terminated when three endpoints (subjects were too sedated to hold a syringe, followed by loss of eyelash reflex, followed by loss of motor response to electrical stimulation) were achieved sequentially. The concentration of propofol associated with 50% probability of achieving a pharmacodynamic endpoint in the absence of dexmedetomidine (EC 50 ; placebo treatment) was 6.63 μg/mL for motor response to electrical stimulation and ranged from 1.14 to 1.98 μg/mL for the ability to hold a syringe, eyelash reflex, and sedation scores. The apparent EC 50 values of propofol (EC 50APP ; concentration of propofol at which the probability of achieving a pharmacodynamic endpoint is 50% in the presence of dexmedetomidine concentrations observed in the current study; dexmedetomidine treatment) were 0.273, 0.544–0.643, and 3.89 μg/mL for the ability to hold a syringe, sedation scores, and motor response, respectively. Dexmedetomidine reduced propofol concentrations required for sedation and suppression of motor response. Therefore, the propofol dose required for sedation and induction of anesthesia may have to be reduced in the presence of dexmedetomidine. © 2001 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:172–181, 2001

The anaesthetic-sparing activity of dexmedetomidine during isoflurane anaesthesia was examined, using the end-point of lack of response to tetanic nerve stimulation. Nine subjects were given two doses of dexmedetomidine (target plasma concentrations of 0.3 ng ml-1 and 0.6 ng ml-1, respectively) and saline on separate occasions. We measured auditory (AER) and somatosensory (SER) evoked responses at end-tidal isoflurane concentrations of 0.2-1.4%. Pa and P25-N35 amplitudes increased as isoflurane concentration was reduced (P0.001). Dexmedetomidine had no significant effect on this relationship. In contrast, P15-N20 (SER) amplitude increased (P0.001) as isoflurane concentration was reduced. The dose of dexmedetomidine had a significant interaction with this trend (P0.002). Decreasing the concentration of isoflurane at the high dose of dexmedetomidine had less impact on P15-N20 amplitude than decreasing isoflurane at the low dose or with saline. The mechanism by which dexmedetomidine spares isoflurane is discussed in the light of these evoked response changes.

Clonidine has proved to be a clinically useful adjunct in clinical anaesthetic practice as well as in chronic pain therapy because it has both anaesthetic and analgesic-sparing activity. The more selective alpha-2 adrenoceptor agonists, dexmedetomidine and mivazerol, may also have a role in providing haemodynamic stability in patients who are at risk of peri-operative ischaemia. The side-effects of hypotension and bradycardia have limited the routine use of alpha-2 adrenoceptor agonists. Investigations into the molecular pharmacology of alpha-2 adrenoceptors have elucidated their role in the control of wakefulness, blood pressure and antinociception. We discuss the pharmacology of alpha-2 adrenoceptors and their therapeutic role in this review. The alpha-2 adrenoceptor agonists are agonists at imidazoline receptors which are involved in central blood pressure control. Selective imidazoline agonists are now available for clinical use as antihypertensive agents and their pharmacology is discussed.

A high power oscillator circuit, designed to power radio-frequency (rf) ion guides and traps, is described. The rf circuit is directly coupled to the guide/trap electrodes, and no frequency or impedance matching is required. The design provides precisely adjustable rf amplitudes from ∼50 to 600 V, either under manual or computer control. The operating frequency can be varied from

Application of manure on cropland in association with large confined animal feeding operations, such as large drylot dairies, has raised concern about nutrient contamination of surface and groundwaters. Our objective was to determine the yield and nutrient uptake of 'Coastal' bermudagrass (Cynodon dactylon L. Pers.) and a bermudagrass sod interseeded with winter wheat (Triticum aestivum emend Thell cv. Wintex) treated with dairy waste, the fate of manure N and P in the soil, and nitrate N in soil solution. Four rates of dairy manure (target rates of 0, 100, 200, and 400 lb N/acre) were surface applied to each system from 1992 to 1995. We measured N and P harvested in forage, changes in extractable N and P concentrations in the soil, nitrate N levels in soil water, and N volatilization from surface-applied manure. Yield increased linearly with increasing manure rate each year. Only 25% of manure N and 20% or less of P were recovered in forage during the 4 yr. Analysis of soil water samples collected at 18 or 36 in. below the soil surface on 54 dates indicated < 3 ppm of nitrate N in plots treated with up to 60 tons/acre of solid dairy manure during 4 yr. The primary adverse effect of manure application to forage crops was a sixfold increase in extractable P in the surface 6 in. of soil at the highest manure rate. Nitrogen losses to the atmosphere from surface-applied dairy waste increased from 20 to a maximum of 35% as moisture content of the manure increased to 40%. Most of the N loss occurred within 6 h of waste application. These data indicate that solid dairy manure from confinement lots should be applied at rates less than 20 tons/acre per year to reduce risks of soil P buildup and nitrate N leaching.

Hot weather, limited rainfall during the growing season, and low soil fertility limit corn (Zea mays L.) production for silage in south central USA (e.g., Texas). Our objective was to examine the effects of supplemental irrigation, plant density, and N rate on quality of forage maize. Pioneer brand hybrid 3165 was planted at four densities (7 250, 14 500, 29 000, and 58 000 plants/acre) in rows spaced 3-ft apart in 1987, 1988, and 1989. Nitrogen was applied at 0, 160, or 320 lb/acre each year. Plots were either not irrigated or received supplemental irrigation when plants exhibited leaf rolling. Treatments were arranged as split-split plots randomized in four complete blocks. Water treatments were whole plots, N rates subplots, and plant densities were sub-subplots. Plots were harvested at dent stage of grain (33 to 37 % dry matter). Whole plants, leaf blades, and stalks were analyzed for in vitro true digestibility (IVTD), acid detergent fiber (ADF), cellulose, and acid detergent lignin (ADL; except leaf blades) via near infrared reflectance spectroscopy (NIRS). In 1987, concentrations of ADF, ADL, and cellulose increased by 20 to 40 %, whereas IVTD was reduced by 4 to 6 % in all components with increased plant density when 160 or 320 ld N/acre was applied, whereas under 0 N fiber concentrations and IVTD changed little, if any, with increased plant density. Supplemental irrigation did not affect whole-plant forage quality, whereas IVTD of leaf blades and stalks from irrigated plots was reduced by 3 to 5 %, respectively, with applied N in 1988 but not in 1987 or 1989. Quality of corn forage may have to be considered in plant density recommendations

Relocation of large dairy operations into the south central USA during the mid-1980s created the need for local production of large quantities of high-quality forage. Corn (Zea mays L.) silage was recognized as a forage for meeting this need, but production information was limited. Corn was grown at Stephenville, TX, on Windthorst fine sandy loam (fine, mixed, thermic Udic Paleustalf) soil during 1987, 1988, and 1989 to determine optimum fertilizer N rate and plant density, and to compare dryland production with supplemental irrigation. Dry matter yield, partitioning of dry matter to morphological components (ear, stalk, and leaf), forage quality, stalk diameter, and production economics were studied. Water treatment was either dryland or dryland plus supplemental irrigation. Nitrogen rates were 0, 160, and 320 lb/acre annually. Plant densities were 7 300, 14 500, 29 000, and 58 000 plants/acre. Supplemental irrigation increased dry matter yield in 1987 and 1988, increased digestible dry matter yield all years, reduced leaf percentage in 1987 and 1988, decreased stalk percentage in 1987, and increased ear percentage in 1987. Dry matter yield increased as plant density increased at the 160 and 320 N rates each year and at 0 N in 1989. Digestible dry matter yield increased with increasing plant density. Ear percentage decreased at 160 and 320 lb N/acre as stalk and leaf percentage increased. Stalk diameter increased at 160 lb N/acre each year. Increasing plant density for all N rates and water regimes reduced stalk diameter. Economically, the highest return occurred at 160 lb N/acre and a plant density of 29 000 (dryland corn; $138.56/ acre) to 58 000 (irrigated corn; $154.06/acre) plants/acre. The difference in net return between dryland and irrigated corn at optimum N rate and plant density was $15.50/acre (not accounting for labor and fixed costs). We conclude that dryland corn fertilized with 160 lb N/acre and grown at a plant density of 29 000 plants/acre produced the optimum dry matter yield and profit. Less costly water could improve profitability of supplemental irrigation

Background: ANQ 9040 is an experimental nondepolarizing neuromuscular relaxant. Initial investigations in animals had indicated a rapid onset of action comparable to that of succinylcholine. The purpose of this study was to assess the safety and potency of ANQ 9040 in humans. Methods: ANQ 9040 was assessed in 41 male volunteers. Anesthesia was induced with propofol and maintained with a propofol infusion and 60% N 2 O/40% O 2 . Neuromuscular function was measured by mechanomyography using train-of-four stimulation of the ulnar nerve every 12 s. After an initial pilot study, 23 volunteers received a single dose of ANQ 9040 of between 0.5 and 1.1 mg/kg to determine the dose-response relationship. The final 10 volunteers were given twice the estimated ED 95 of ANQ 9040 as a single bolus dose. Results: The estimated ED 50 and ED 95 of ANQ 9040 were 0.6 and 1.3 mg/kg, respectively. Apart from an increase in heart rate, no important adverse effects were noted after ANQ 9040 administration in the dose range 0.5-1.1 mg/kg. In the volunteers who received 2.6 mg/kg ANQ 9040, a substantial increase in plasma histamine was observed. This was associated with a 12% decrease in mean arterial pressure and a 49% increase in heart rate. In this group, the mean onset time to neuromuscular block was 51.3 s. Conclusions: ANQ 9040 is a rapid-onset neuromuscular blocking agent. However, twice the ED 95 dose is associated with significant histamine release and tachycardia. This finding suggests that this drug will not be useful in clinical practice

Stand maintenance of alfalfa (Medicago sativa L.) relies on the persistence of the original plants. Yield (yield per plant, yield per shoot) and stand components (plants per square meter, shoots per square meter, shoots per plant) were studied in two experiments designed to determine yield response to P on a low P soil (Windthorst fine sandy loam; fine, mixed, thermic, Udic Paleustalfs) near Stephenville, TX. Three preplant incorporated rates of P (0, 29, and 59 kg ha-1) and five annual surface broadcast rates of P (0, 7, 15, 29, 59 kg ha-1) were applied to two field experiments established in September 1988 and 1989. The experimental design was a split plot in four randomized blocks. Whole plots were incorporated P rates and subplots were annual broadcast P rates. Plants and shoots per square meter were counted 4 and 8 wk after planting in 1988 and 1989, at each harvest in 1989 and 1990, and at the beginning and end of the season in 1991. Relative distribution of root mass to a 90-cm depth was determined in the fall of 1990 and 1991 for selected treatments. Phosphorus incorporated before planting increased alfalfa dry matter (DM) yields more efficiently than did broadcast P. Plant and shoot densities did not differ among treatments; thus, low yields at low P levels were a function of reduced yield per shoot. Delayed application of P on fall-planted alfalfa did not affect plant density. Under O-P, root mass was concentrated in the upper 20 cm of soil, whereas under adequate to high P, more root mass was distributed throughout the upper 40 to 50 cm.

SUMMARY Ten healthy unpremedicated male volunteers were exposed to an average inspired concentration of 3.6% desflurane (1–653) in oxygen for 89 (SD 17) min. Standard haematological and biochemical tests were performed before (control) and immediately after exposure and at 4, 24, 72 and 192 h. Liver function was assessed at these times by determining total and unconjugated (indirect) bilirubin, and plasma concentrations of aspartate amino transferase, alanine amino transferase, γglutamyl transpeptidase and alkaline phosphatase. Renal function was assessed by examining the urine microscopically for leucocytes, red blood cells, casts and crystals at these times, and creatinine clearance and urine concentrating ability were determined before and 24 and 72 h after exposure. Two additional and sensitive tests of renal integrity were performed before and 4 and 24 h after anaesthesia: measurement of urinary retinol-binding protein and β-N-acetyl-D-glucosaminidase. Serum inorganic fluoride was determined immediately before and 1, 4, 24, 48, 72 and 192 h after anaesthesia. Urinary inorganic and organic fluoride concentration and excretion rate were determined before and 24, 48, and 72 h after anaesthesia. There were no significant changes in any measured haematological or biochemical variable (other than an increase in total white cell count from 5.9 (1.3) to 8.3 (1.1) × 109 litre−1 immediately after exposure) nor in liver or renal function tests. There was no increase in serum or urinary inorganic fluoride or urinary non-volatile organic fluoride concentrations.

The new volatile anaesthetic, desflurane (1–653), was administered to 10 healthy, unpremedicated young male volunteers in order to determine its cardiorespiratory effects and the characteristics and acceptability of its inhalation. All volunteers breathed either sub-anaesthetic (1.8% inspired) or anaesthetic (5.4% inspired) concentrations of the anaesthetic without coughing, breath-holding, salivation or other untoward respiratory response. Respiratory minute volume and alveolar ventilation decreased and ventilatory rate increased. Systemic arterial pressure decreased (diastolic more than systolic) and heart rate remained unchanged. Cardiac rhythm remained unaltered, except in one volunteer who experienced a single premature atrial contraction. Volunteers stated that the odour of desflurane was not irritating or unpleasant. Exposure to the agent for approximately 90 min resulted in rapid and clear-headed recovery.

The hepatotoxicity of halothane is now well known, but only became apparent after several years of use. The nephrotoxicity of methoxyflurane was not realized immediately, but once identified, led to its withdrawal from use. Therefore, when new agents that appear to offer significant advantages over established drugs become available, exhaustive testing and monitoring is necessary to ensure their safety. Sevoflurane, recently available in the UK and the USA but used for some time in Japan, has been subjected to considerable scrutiny.

Patients who smoke cigarettes suffer increased postoperative morbidity. A prospective, controlled trial was designed to evaluate the effectiveness of written pre-operative advice to stop smoking before admission for elective surgery and to record the duration of abstinence immediately before the operation. Although the advice was ineffective in persuading patients to stop smoking, it was associated with a reduction in the amount of tobacco consumed. Nicotine and carbon monoxide have important short-term adverse effects but 15% of all patients continued to smoke within an hour of surgery. If patients are unable to give up cigarette smoking completely, it is still worthwhile stopping on admission to hospital.

Manure use on cropland has raised concern about nutrient contamination of surface and ground waters. Warm-season perennial grasses may be useful in filter strips to trap manure nutrients and as biomass feedstock for nutrient removal. We explored the use of 'Alamo' switchgrass (Panicum virgatum L.) in a biomass production-filter strip system treated with dairy manure. We measured changes in extractable P in the soil, NO3 -N in soil water, and changes in total reactive P and chemical oxygen demand (COD) of runoff water before and after a switchgrass filter strip. Five rates of dairy manure (target rates of 0, 50, 100, 150, and 200 kg N ha(-1) from solid manure in 1995; 0, 75, 150, 300, and 600 kg N ha(-1) from lagoon effluent in 1996 and 1997) were surface-applied to field plots of switchgrass (5.2 by 16.4 m) with a 5.2- by 16.4-m switchgrass filter strip below the manured area. Yield of switchgrass from the manured area increased linearly with increasing manure rate in each year. Soil water samples collected at 46 or 91 cm below the soil surface on 30 dates indicated < 3 mg L(-1) of NO3-N in all plots. Concentrations of total reactive P in surface runoff water were reduced an average of 47% for the 150 kg N rate and 76% for the 600 kg N rate in 1996 and 1997 after passing through the strip. Manure could effectively substitute for inorganic fertilizer in switchgrass biomass production with dual use of the switchgrass as a vegetative filter strip.

Dexmedetomidine is a highly selective alpha 2-adrenoceptor agonist with anaesthetic-sparing effects. We have determined the pharmacodynamic and pharmacokinetic interactions between dexmedetomidine and isoflurane in volunteers. Nine male subjects were allocated randomly to receive isoflurane anaesthesia preceded by infusion of dexmedetomidine on three separate occasions, 2 weeks apart. Dexmedetomidine target plasma concentrations were 0.0 (placebo), 0.3 ng ml-1 (low-dex) and 0.6 ng ml-1 (high-dex). End-tidal isoflurane concentrations at which gross purposeful movement and response to verbal commands occurred were identified. In the recovery period, sedation scores and digit symbol substitution tests were recorded. Venous blood samples were obtained before, during and after anaesthesia at predetermined intervals for measurement of plasma concentrations of dexmedetomidine and calculation of standard pharmacokinetic indices (AUC, Cl, Vss, T1/2 alpha, T1/2 beta). The end-tidal isoflurane concentration at which 50% of subjects first responded to the tetanic stimulus was 1.05% in the placebo group, 0.72% in the low-dex group and 0.52% in the high-dex group. We conclude that dexmedetomidine decreased isoflurane requirements in a dose-dependent manner and reduced heart rate, systolic and diastolic arterial pressures. Sedation and slight impairment of cognitive function persisted for several hours after anaesthesia and the end of infusion of dexmedetomidine. Isoflurane did not appear to influence the pharmacokinetics of dexmedetomidine.

New anaesthetic agents are continually being developed in an effort to prepare the ideal agent. Isoflurane is the first choice of many anaesthetists, although it clearly falls short of the ideal on a number of counts. The need and place for any new agent depends on comparing the properties of a theoretically ideal agent with those of isoflurane and the new agent. Desflurane is a step towards a more ideal inhaled agent ; however, there is still the need to synthesise and evaluate new chemical entities in order that the ideal can more nearly be approached.

The characteristics of neuromuscular block induced by doxacurium were compared in patients with and without renal function. Seventeen patients with end stage chronic renal failure and 18 patients with normal renal function were anaesthetized with 0.5% halothane and nitrous oxide in oxygen and received doxacurium in an initial dose of 25 micrograms kg-1 (estimated from available data as an ED95 dose), with incremental doses of 5 micrograms kg-1. At the end of surgery, residual neuromuscular block was antagonized with either edrophonium 1.0 mg kg-1 or neostigmine 0.08 mg kg-1. There was no significant difference between the mean maximum blocks achieved with doxacurium: 17.4% (renal failure group) and 11.6% (control group) of control twitch heights, or between the mean times to achieve maximum block (10.9 min and 10.8 min, respectively). The mean duration of action of doxacurium, indicated by the time for twitch height to recover to 25% of control, was longer in the renal failure group (120.8 min vs 66.7 min in the control group) (ns). Similarly, the mean duration of action of increments was longer in the renal failure group (27.4 min vs 20.5 min in the control group). The rate of spontaneous recovery from doxacurium as indicated by the time for twitch height to recover from 0 to 5%, 5 to 10% and 10 to 25%, was not significantly different in the two groups. Antagonism of doxacurium was achieved more reliably with neostigmine than with edrophonium in both groups. The administration of doxacurium was associated with minimal cardiovascular effects.

We report the design and construction details for a very simple radio-frequency (rf) generator, suitable for driving ion guides, traps, or any capacitive load in the few to few hundred picofarad range. The design is a simple high voltage tube oscillator, and the frequency can be step adjusted by changing capacitors. An optional TTL-triggered keying circuit is provided for applications where the rf needs to be turned off and on under external control.

The purpose of this study was to measure the serum fluoride concentration after enflurane or sevoflurane anesthesia and to compare the effects of prolonged anesthesia with these drugs on renal concentrating function in male volunteers. The study was subdivided into three stages; an ascending dose study of 3.0 and 6.0 minimum alveolar anesthetic concentration (MAC) hours of sevoflurane alone, a 6.0-MAC-hour comparison of enflurane and sevoflurane, and a 9.0-MAC-hour comparison of enflurane and sevoflurane. Renal concentrating function was assessed by an 18-h period of fluid deprivation and the serum fluoride concentration was measured at intervals until 60 h postanesthesia. The maximum serum fluoride concentration was greater in the volunteers exposed to sevoflurane and reached a peak in the 9-MAC-hour sevoflurane group of 36.6 microM (SD 4.3) compared with 27.5 microM (SD 2.6) in the 9-MAC-hour enflurane group. However, the rapid decrease in the serum fluoride concentration after sevoflurane was such that there was no difference between the areas under the fluoride concentration-time curves. There were no significant differences between the median maximum urine osmolalities after enflurane or sevoflurane anesthesia. Prolonged anesthesia with enflurane or sevoflurane is not associated with impaired renal concentrating function despite an increase in the serum fluoride concentration.

We have compared, in 51 ASA II and III patients undergoing coronary artery bypass surgery, an inhaled anaesthetic technique based on desflurane, supplemented with low-dose (10 micrograms kg-1) fentanyl, with an i.v. technique using high-dose (50 micrograms kg-1) fentanyl with midazolam for induction. Satisfactory records were available for analysis in 50 patients. There were no differences between groups in operating time, cardiopulmonary bypass time, aortic cross-clamp time or duration of stay in the intensive care unit after surgery. Desflurane maintained mean systemic arterial pressure at the awake level during incision and sternotomy (end-tidal concentrations 3.7% and 4.6%, respectively) but decreased it significantly at all other times. With fentanyl, mean systemic arterial pressure was unchanged from awake values during induction and laryngoscopy but increased significantly at incision and sternotomy by 8% and 12.8%, respectively, to exceed the desflurane group at sternotomy by 20 mm Hg (P0.001). With desflurane, heart rate remained at 60-67 beat min-1 at all times before cardiopulmonary bypass. This was always lower than the fentanyl group by 5-15 beat min-1 and the difference was significant at induction, during skin preparation and before aortic cannulation. In comparison with the desflurane group, cardiac index was significantly greater in the fentanyl group at induction, laryngoscopy and during skin preparation, but was significantly less before aortic cannulation. The need for vasodilator intervention was significantly more common in the fentanyl group before, during and after cardiopulmonary bypass and for beta adrenoceptor block before cardiopulmonary bypass.(ABSTRACT TRUNCATED AT 250 WORDS)

The ability to evoke reversal of dense vecuronium- and pancuronium-induced paralysis (T1 10% of control) with edrophonium 1.0 mg · kg-1 was studied using train-of-four nerve stimulation and electromyographic monitoring. Two different end-points, train-of-four ratios of 0.5 and 0.7, were used to define “adequate reversal”, and the results for both relaxants were compared. Reversal was reliable and rapid for vecuronium if either ratio was used with times of 2.8 (1.5) and 9 (3) min required to achieve ratios of 0.5 and 0.7, respectively. However, if the block was due to pancuronium, reversal was unreliable with 2 of 9 and 4 of 9 patients not achieving ratios of 0.5 and 0.7, respectively. Reversal was also markedly prolonged in this group with a mean time of 37 (23) min to achieve a ratio of 0.7, and in almost half these patients a supplementary dose of edrophonium was required.

Summary The anaesthetic problems we have encountered in eight patients with the mucopolysaccharidoses are described and the pathophysiology of this group of clinically progressive inherited diseases is reviewed with emphasis on the aspects of importance to the anaesthetist.

The role of two recently introduced muscle relaxants--atracurium and vecuronium--in contemporary anaesthetic practice is assessed. Recent advances in the physiology of neuromuscular transmission, particularly the roles of calcium and calmodulin, are reviewed, and new ideas concerning the reversal and monitoring of neuromuscular blockade are discussed.

Summary Two patients presenting for removal of phaeochromocytoma are described. Vecuronium was used to provide neurornuscular blockade by two different methods of administration: an infusion and a large bolus dose. Both gave satisfactory results and we suggest that vecuroniurn may be the neuromuscular blocking agent of choice for patients with phaeochromocytoma.

The external nares rarely close completely during positive pressure lung filling in Bufo marinus. Simultaneous measurement of airflow at the nares and transnarial pressure revealed continuous airflow (out) during lung emptying (nares open) and the subsequent lung filling (nares partially closed). Expiratory minute volume (VE) measured at the nares is consistently greater than VE from the lungs because the buccal contents are being simultaneously forced into the lungs and out the partially closed nares. The relation between narial resistance and ventilatory parameters during hypercapnia was investigated to determine if control of the narial aperture is an important variable related to the volume of air transferred to and from the lungs and buccal chamber. Buccal frequency decreased (from 73 to 30/min) and buccal TE (time for expiratory air flow at the nares) increased (from 0.28 to 0.41 sec) when breathing 2% CO2. Mean narial resistance was 0.40 cm H2O/L . min, maximum narial resistance was 0.44 cm H2O/L . min, and both were uninfluenced by CO2. Lung ventilation frequency increased with 2% CO2 (from 5.3 to 20.8/min). TE of lung ventilation cycles remained constant (about 0.45 sec) while VTE (expiratory tidal volume at the nares) increased from 0.73 to 0.90 ml/100 g. Mean narial resistance during lung ventilations decreased from 3.80 to 1.76 cm H2O/L . min with 2% CO2. Maximum narial resistance during lung ventilations was unchanged. It is concluded that the nares may remain open for a longer proportion of each lung ventilation cycle during hypercapnic hyperpnea.

1. 1. Bufa woodhousei . a terrestrial toad, and Hyla cadarerina , a terrestrial treefrog, accumulate and tolerate high concentrations of urea in the body fluids during dehydration or reduced water turnover (up to 280 mM urea in B. woodhousei , 140 mM urea in H. cadaverina ). 2. 2. In contrast to Rana cancrivora . Xenopus laevis and Scaphiopus couchi (considered to be unusual in their ability to handle osmotic stress), B. woodhousei and H. cadaverina do not increase the rate of urea synthesis and therefore the rate of urea accumulation in the body fluids in response to dehydration. 3. 3. Hepatic activity of CPS-I. the first enzyme of the urea-ornithine cycle, is correlated with a greater proportion of N waste being formed as urea rather than as NH 3 during times of reduced water turnover or osmotic stress. This results in preferential accumulation of urea rather than of NH 3 in the body fluids. 4. 4. CPS-I activity is also correlated with the increased N waste production that follows from increased dietary N intake.

The characteristics of the train-of-four response during neuromuscular blockade with two agents, atracurium and vecuronium, have been compared. During onset of blockade, at 75% depression of the initial twitch, atracurium was associated with significantly more fade than was vecuronium, and larger doses of atracurium were associated with less fade than smaller doses of the same agent. In addition, with both agents, the degree of fade at a given amount of initial twitch depression was significantly less during onset than during spontaneous offset of action. The degree of train-of-four fade bears no fixed relationship to depression of the initial twitch.

(1) Batrachoseps attenuatus and B. major were successfully acclimated to 600 m-osmol NaCl and 400 m-osmol sucrose solutions. (2) Accumulation of sodium and an increased rate of synthesis of urea provide substantial increases in plasma concentrations of these solutes. Sodium concentrations in excess of 230 mM and urea concentrations in excess of 200 mM indicate that these are the two major solutes (plus anions) responsible for elevation of osmotic concentration in Batrachoseps. (3) Batrachoseps exhibits a water balance response upon dehydration (greater than twofold increase in cutaneous uptake, 50% reduction in urine production). Urine production, estimated from bladder contents, was significantly reduced in salamanders acclimated to sucrose solutions compared to animals acclimated to tap water or saline of equivalent osmotic concentration. (4) Plasma urea concentration was equivalent to urine urea concentration when Batrachoseps was kept in tap water and during short term saline acclimation. After long term saline acclimation, urine urea concentration was one-fourth the plasma urea concentration.

Scaphiopus couchi newly emerged from natural dormancy produce urea at a greater rate than dormant toads kept in moist soil. Energy budgets during dormancy of Scaphiopus couchi and S. multiplicatus were calculated by measuring protein, carbohydrate, lipid, ash, and DNA content of newly emerged toads and toads near the end of the natural activity period. Scaphiopus couchi uses 17% of the protein, 36% of the lipid, and 28% of the total energy reserves available at the start of dormancy, and S. multiplicatus uses 32% of the protein, 62% of the lipid, and 51% of the total energy reserves. If all of the nitrogen derived from protein catabolism were accumulated as urea, the minimum difference in body fluid concentrations before and after dormancy would be 167 mM for S. couchi and 341 mM for S. multiplicatus. Because these predicted increases are greater than normally observed in the body fluids of spadefoots at the end of dormancy, the toads apparently are obtaining sufficient part of their nitrogen wastes. Simultaneous O2 consumption, CO2 production, and nitrogen waste production measurements provide evidence for a shift from lipid to protein metabolism in S. couchi when osmotically stressed. During osmotic stress, S. couchi does not simultaneously achieve the reduced levels of O2 consumption associated with dormancy, and increased protein catabolism and urea synthesis. Feeding experiments show that protein, carbohydrate, and lipid and replenished in newly emerged. S. couchi in proportion to their representation in the diet.

Scaphiopus couchi and S. multiplicatus larvae develop in ephemeral ponds, which may dry before the larvae complete development. Measurement of nitrogen excretion rates throughout larval development shows that urea becomes the predominant nitrogen waste before metamorphosis in both species. Scaphiopus multiplicatus becomes ureotelic at an earlier development stage than S. couchi, but due to the slower development of S. multiplicatus (21-30 days to metamorphosis, 10 days for S. couchi), both species may start to excrete predominantly urea at the same time when developing in the same pond. Larvae of S. multiplicatus accumulated urea in the body fluids when noncutaneous water uptake was restricted, and survived for 48 h out of water in the field. Ureotelism apparently enables Scaphiopus larvae to survive for short periods out of water, allowing either metamorphosis or additional time for refilling of the pond by the erratic summer rains.

For rapid cutaneous water uptake upon dehydration, newly metamorphosed and juvenile Scaphiopus couchi toadlets possess a specialized pelvic region (5% of the total surface area) which is not found in adults of this species. The surface specific rate of water uptake across the pelvic region of S. couchi toadlets increases fifteenfold, from 18.4 to 322 mg/cm² per hour, in response to dehydration, and the increase in total cutaneous water uptake upon dehydration may be confined to this region. The specialized pelvic area is responsible for 50% of the total water uptake of dehydrated toadlets. The ability of toadlets but not adults to absorb water from a specialized pelvic region is correlated with the activity patterns of the two age groups and may extend the foraging time available to toadlets into the hotter parts of the day.

Summary The effects of three different anaesthetic carrier gases on middle-ear pressure in the operative and postoperative periods was assessed. Patients receiving oxygen and oxygen-enriched air did not have significant changes in middle-ear pressure. The changes associated with the use of nitrous oxide as the carrier gas were reversed with return of pharyngeal reflexes or after prolonged inhalation of 100% oxygen. In patients undergoing middle-ear surgery or those with pre-existing middle-ear disease, we suggest that oxygen-enriched air is the anaesthetic carrier gas of choice.

The management of the period after hypothermic cardiopulmonary bypass has been compared in a group of patients maintained on nifedipine therapy, a group who had the drug withdrawn at least 24 hours prior to cardiac surgery, and a control group who had never received calcium antagonists. Patients in the drug withdrawal group were significantly more likely to need vasodilator intervention than the treated (p less than 0.001) or the control (p less than 0.05) groups. Although nifedipine withdrawal appeared to reduce the need for inotropic support, compared to treated (p less than 0.001) and control groups (p less than 0.005), this may be at the cost of increasing systemic vascular resistance. This observation, coupled with reports of a rebound phenomenon following abrupt withdrawal of calcium antagonist therapy, suggests that nifedipine should be continued up to the time of surgery.

The organisation of research in the Department of Anesthesiology at the University of Michigan is described and the comments of a British Senior Registrar working within the system are recorded.

The anaesthetized, heparinized health adult dogs were infused with protamine sulphate 3 mg X kg-1 and plasma ionized calcium was measured. A significant (p less than 0.01) decrease in ionized calcium occurred which preceded the maximal reduction in cardiac output and systemic arterial pressure. The clinical implications of these results are discussed.

Summary A case of multiple endocrine adenopathy type I associated with a solitary carcinoid tumour is described. During anaesthesia the characteristic syndrome consisting of hypertension, tachycardia and flushing occurred. The possible mechanisms for this are discussed. It is generally agreed that the presence of hepatic metastases is necessary for the development of the typical carcinoid syndrome.’S2 Most carcinoids of the mid-gut secrete a variety of vasoactive substances but detoxication of these products usually occurs in the liver. When hepatic metastases are present, however, vasoactive substances are able to gain access to the suprahepatic circulation. This case report describes the occurrence of a typical ‘malignant’ carcinoid attack occurring during anaesthesia, in a patient not previously suspected of having a carcinoid tumour, but who was known to have multiple endocrine adenopathy (MEA).

There are a number of factors to consider in choosing a muscle relaxant for patients with a phaeochromocytoma. It has been suggested that pancuronium is the muscle relaxant of choice.1-3 This report describes a severe hypertensive response associated with pancuronium in a patient undergoing surgery for the removal of a phaeochromocytoma.