Comment on "Reconstructing past climate from noisy data"

von Storch et al. (Reports, 22 October 2004, p. 679) criticized the ability of the "hockey stick" climate field reconstruction method to yield realistic estimates of past variation in Northern Hemisphere temperature. However, their conclusion was based on incorrect implementation of the reconstruction procedure. Calibration was performed using detrended data, thus artificially removing a large fraction of the physical response to radiative forcing.     

Pharmacokinetics and pharmacodynamics of intravenous medetomidine in the horse

ObjectiveTo describe the pharmacodynamics and pharmacokinetics following an intravenous (IV) bolus dose of medetomidine in the horse.Study designProspective experimental trial.AnimalsEight, mature healthy horses age 11.7 ± 4.6 (mean ± SD) years, weighing 557 ± 54 kg.MethodsMedetomidine (10 μg kg^?1) was administered IV. Blood was sampled at fixed time points from before drug administration to 48 hours post administration. Behavioral, physiological and biochemical data were obtained at predetermined time points from 0 minutes to 24 hours post administration. An algometer was also used to measure threshold responses to noxious stimuli. Medetomidine concentrations were determined by liquid chromatography-Mass Spectrometry and used for calculation of pharmacokinetic parameters using noncompartmental and compartmental analysis.ResultsPharmacokinetic analysis estimated that medetomidine peaked (8.86 ± 3.87 ng mL^?1) at 6.4 ± 2.7 minutes following administration and was last detected at 165 ± 77 minutes post administration. Medetomidine had a clearance of 39.6 ± 14.6 mL kg^?1 minute^?1 and a volume of distribution of 1854 ± 565 mL kg^?1. The elimination half-life was 29.1 ± 12.5 minutes. Glucose concentration reached a maximum of 176 ± 46 mg dL^?1 approximately 1 hour post administration. Decreased heart rate, respiratory rate, borborygmi, packed cell volume, and total protein concentration were observed following administration. Horses lowered their heads from 107 ± 12 to 20 ± 10 cm within 10 minutes of drug administration and gradually returned to normal. Horse mobility decreased after drug administration. An increased mechanical threshold was present from 10 to 45 minutes and horses were less responsive to sound.Conclusion and clinical relevance Behavioral and physiological effects following intravenous administration positively correlate with pharmacokinetic profiles from plasma medetomidine concentrations. Glucose concentration gradually transiently increased following medetomidine administration. The analgesic effect of the drug appeared to have a very short duration.     

Effects of hypercapnic hyperpnea on recovery from isoflurane or sevoflurane anesthesia in horses

Objective To test the hypothesis that hypercapnic hyperpnea produced using endotracheal insufflation with 5–10% CO₂ in oxygen could be used to shorten anesthetic recovery time in horses, and that recovery from sevoflurane would be faster than from isoflurane. Study design Randomized crossover study design. Animals Eight healthy adult horses. Methods After 2 hours’ administration of constant 1.2 times MAC isoflurane or sevoflurane, horses were disconnected from the anesthetic circuit and administered 0, 5, or 10% CO₂ in balance O₂ via endotracheal tube insufflation. End‐tidal gas samples were collected to measure anesthetic washout kinetics, and arterial and venous blood samples were collected to measure respiratory gas partial pressures. Horses recovered in padded stalls without assistance, and each recovery was videotaped and evaluated by reviewers who were blinded to the anesthetic agent and insufflation treatment used. Results Compared to isoflurane, sevoflurane caused greater hypoventilation and was associated with longer times until standing recovery. CO₂ insufflation significantly decreased anesthetic recovery time compared to insufflation with O₂ alone without significantly increasing PaCO₂. Pharmacokinetic parameters during recovery from isoflurane with CO₂ insufflation were statistically indistinguishable from sevoflurane recovery without CO₂. Neither anesthetic agent nor insufflation treatment affected recovery quality from anesthesia. Conclusions and clinical relevance Hypercapnic hyperpnea decreases time to standing without influencing anesthetic recovery quality. Although the lower blood gas solubility of sevoflurane should favor a shorter recovery time compared to isoflurane, this advantage is negated by the greater respiratory depression from sevoflurane in horses.     

Molecular characterization of low pathogenic avian influenza viruses, isolated from food products imported into Singapore

We have completed the genetic characterization of all eight gene segments for four low pathogenic avian influenza (LPAI) viruses. The objective of this study was to detect the presence of novel signatures that may serve as early warning indicators of the conversion of LPAI viruses to high pathogenic avian influenza (HPAI) viruses. This study included three H5N2 and one H5N3 viruses that were isolated from live poultry imported into Singapore as part of the national avian influenza virus (AIV) surveillance program. Based on the molecular criterion of the World Organisation for Animal Health (OIE), sequence analysis with the translated amino acid (aa) sequence of the hemagglutinin (HA) gene revealed the absence of multibasic aa at the HA cleavage site, identifying all four virus isolates as LPAI. Detailed phylogenetic tree analyses using the HA and neuraminidase (NA) genes clustered these isolates in the Eurasian H5 lineage, but away from the HPAI H5 subtypes. This analysis further revealed that the internal genes clustered to different avian and swine subtypes, suggesting that the four isolates may possibly share their ancestry with these different influenza subtypes. Our results suggest that the four LPAI isolates in this study contained mainly avian signatures, and the phylogenetic tree for the internal genes further suggests the potential for reassortment with other different circulating avian subtypes. This is the first comprehensive report on the genetic characterization of LPAI H5N2/3 viruses isolated in South-East Asia.     

Sedative effects of propofol in horses

Objective  We hypothesized that propofol can produce rapidly-reversible, dose-dependent standing sedation in horses.
Study design  Prospective randomized, blinded, experimental trial.
Animals  Twelve healthy horses aged 12 ± 6 years (mean ± SD), weighing 565 ± 20 kg, and with an equal distribution of mares and geldings.
Methods  Propofol was administered as an intravenous bolus at one of three randomized doses (0.20, 0.35 and 0.50 mg kg⁻¹). Cardiovascular and behavioral measurements were made by a single investigator, who was blinded to treatment dose, at 3 minute intervals until subjective behavior scores returned to pre-sedation baseline values. Continuous data were analyzed over time using repeated-measures anova and noncontinuous data were analyzed using Friedman tests.
Results  There were no significant propofol dose or temporal effects on heart rate, respiratory rate, vertical head height, or jugular venous blood gases (pH_v, P_vO₂, P_vCO₂). The 0.35 mg kg⁻¹ dose caused mild sedation lasting up to 6 minutes. The 0.50 mg kg⁻¹ dose increased sedation depth and duration, but with increased ataxia and apparent muscle weakness.
Conclusions and clinical relevance  Intravenous 0.35 mg kg⁻¹ propofol provided brief, mild sedation in horses. Caution is warranted at higher doses due to increased risk of ataxia.     

Effects of alpha2-adrenergic receptor agonists on urine production in horses deprived of food and water

OBJECTIVE: To quantitate the dose- and time-related effects of IV administration of xylazine and detomidine on urine characteristics in horses deprived of feed and water. ANIMALS: 6 horses. PROCEDURE: Feed and water were withheld for 24 hours followed by i.v. administration of saline (0.9% NaCI) solution, xylazine (0.5 or 1.0 mg/kg), or detomidine (0.03 mg/kg). Horses were treated 4 times, each time with a different protocol. Following treatment, urine and blood samples were obtained at 15, 30, 60, 120, and 180 minutes. Blood samples were analyzed for PCV and serum concentrations of total plasma solids, sodium, and potassium. Urine samples were analyzed for pH and concentrations of glucose, proteins, sodium, and potassium. RESULTS: Baseline (before treatment) urine flow was 0.30 +/- 0.03 mL/kg/h and did not significantly change after treatment with saline solution and low-dose xylazine but transiently increased by 1 hour after treatment with high-dose xylazine or detomidine. Total urine output at 2 hours following treatment was 312 +/- 101 mL versus 4,845 +/- 272 mL for saline solution and detomidine, respectively. Absolute values of urine concentrations of sodium and potassium also variably increased following xylazine and detomidine administration. CONCLUSIONS AND CLINICAL RELEVANCE: Xylazine and detomidine administration in horses deprived of feed and water causes transient increases in urine volume and loss of sodium and potassium. Increase in urine flow is directly related to dose and type of alpha2-adrenergic receptor agonist. Dehydration in horses may be exacerbated by concurrent administration of alpha2-adrenergic receptor agonists.     

Effects of ventilation and isoflurane end-tidal concentration on intracranial and cerebral perfusion pressures in horses

OBJECTIVE: To measure the effects of isoflurane end-tidal concentration and mode of ventilation (spontaneous vs controlled) on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in horses. ANIMAL: adult horses of various breeds. PROCEDURES: Anesthesia was induced and maintained with isoflurane in O2 in 6 healthy, unmedicated, adult horses. Using a subarachnoid strain gauge transducer, ICP was measured. Blood gas tensions and carotid artery pressures also were measured. Four isoflurane doses were studied, corresponding to the following multiples of the minimum alveolar concentration (MAC): 1.0 MAC, 1.2 MAC, 1.4 MAC, and 1.6 MAC. Data were collected during controlled ventilation and spontaneous ventilation at each dose. RESULTS: increasing isoflurane end-tidal concentration induced significant dose-dependent decreases in mean arterial pressure (MAP) and CPP but no change in ICR Hypercapnic spontaneous ventilation caused significant increases in MAP and ICR compared with normocapnic controlled ventilation; no change in CPP was observed. CONCLUSIONS AND CLINICAL RELEVANCE: Hypercapnia likely increases cerebral blood flow (CBF) by maintaining CPP in the face of presumed cerebral vasodilation in healthy anesthetized horses. The effect of isoflurane dose on CBF however, remains unresolved because it depends on the opposing influences of a decrease in CCP and cerebral vasodilation.     

Effects of duration of isoflurane anesthesia and mode of ventilation on intracranial and cerebral perfusion pressures in horses

OBJECTIVE: To test the hypothesis that isoflurane-anesthetized horses during controlled ventilation and spontaneous ventilation exhibit temporal changes in cerebral hemodynamics, as measured by intracranial pressure and cerebral perfusion pressure, that reflect temporal changes in systemic arterial pressure. ANIMALS: 6 healthy adult horses. PROCEDURE: Horses were anesthetized in left lateral recumbency with 1.57% isoflurane in O2 for 5 hours in 2 experiments by use of either controlled ventilation (with normocapnia) or spontaneous ventilation (with hypercapnia) in a randomized crossover design. Intracranial pressure was measured with a subarachnoid strain-gauge transducer. Carotid artery pressure, central venous pressure, airway pressures, blood gases, and minute ventilation also were measured. RESULTS: Intracranial pressure during controlled ventilation significantly increased during constant dose isoflurane anesthesia and thus contributed to decreasing cerebral perfusion pressure. Intracranial pressure was initially higher during spontaneous ventilation than during controlled ventilation, but this difference disappeared over time; no significant differences in cerebral perfusion pressures were observed between horses that had spontaneous or controlled ventilation. CONCLUSIONS AND CLINICAL RELEVANCE: Cerebral hemodynamics and their association with ventilation mode are altered over time in isoflurane-anesthetized horses and could contribute to decreased cerebral perfusion during prolonged anesthesia.     

Effects of iron modulation on growth and viability of Rhodococcus equi and expression of virulence-associated protein A

OBJECTIVE: To determine the importance of iron for in vitro growth of Rhodococcus equi, define potential iron sources in the environment and mechanisms by which R equi may obtain iron from the environment, and assess expression and immunogenicity of iron-regulated proteins. SAMPLE POPULATION: 10 virulent and 11 avirulent strains of R equi. PROCEDURE: In vitro growth rates and protein patterns of R equi propagated in media with normal, excess, or limited amounts of available iron were compared. Immunoblot analyses that used serum from foals naturally infected with R equi and monoclonal antibody against virulence-associated protein (Vap)A were conducted to determine immunogenicity and identity of expressed proteins. RESULTS: Excess iron did not alter growth of any R equi strains, whereas growth of all strains was significantly decreased in response to limited amounts of available iron. Virulent R equi were able to use iron from ferrated deferoxamine, bovine transferrin, and bovine lactoferrin. Only virulent R equi expressed an iron-regulated, immunogenic, surface-associated protein identified as VapA. CONCLUSIONS AND CLINICAL RELEVANCE: Iron is required for the growth and survival of R equi. Sources of iron for R equi, and mechanisms by which R equi acquire iron in vivo, may represent important virulence factors and novel targets for the development of therapeutic and immunoprophylactic strategies to control R equi infection in foals. Expression of VapA is substantially upregulated when there is a limited amount of available iron.