Susceptibility in vitro of canine methicillin-resistant and -susceptible staphylococcal isolates to fusidic acid, chlorhexidine and miconazole: opportunities for topical therapy of canine superficial pyoderma.

OBJECTIVES: Increasing multidrug resistance amongst canine pathogenic staphylococci has renewed interest in topical antibacterial therapy for skin infections in the context of responsible veterinary prescribing. We therefore determined the activity in vitro of three clinically relevant topical agents and synergism between two of them against Staphylococcus pseudintermedius and Staphylococcus aureus. METHODS: The MICs of fusidic acid (n = 199), chlorhexidine (n = 198), miconazole (n = 198) and a 1:1 combination of miconazole/chlorhexidine (n = 198) were determined for canine isolates [50 MRSA and 49 methicillin-resistant S. pseudintermedius (MRSP), 50 MSSA and 50 methicillin-susceptible S. pseudintermedius (MSSP)] collected from the UK and Germany using an agar dilution method (CLSI VET01-A4). Fractional inhibitory concentration (FIC) indices were calculated to assess the interaction of miconazole with chlorhexidine. RESULTS: MICs of each drug/combination were significantly (P < 0.0005) higher for S. aureus when compared with S. pseudintermedius. Most strains (n = 172) had an MIC of fusidic acid of ≤0.03 mg/L (MIC ≥64 mg/L, n = 5 MRSA). All strains had MICs of chlorhexidine of 0.5-4 mg/L, except for one MRSA (MIC = 8 mg/L). All but four strains had MICs of miconazole of 1-4 mg/L (MIC = 16 mg/L, n = 3; MIC = 256 mg/L, n = 1). Miconazole/chlorhexidine (1:1 ratio) had a synergistic effect against 49/50 MRSA, 31/50 MSSA, 12/49 MRSP and 23/49 MSSP. CONCLUSIONS: Since the majority of these staphylococci, including methicillin-resistant isolates, had MICs that should be readily exceeded by topical skin application of these agents, their therapeutic efficacy for canine superficial pyoderma should be assessed. The synergistic interaction shown in vitro supports further clinical evaluation of miconazole/chlorhexidine combination therapy for staphylococcal infection.

Beat note stabilization of mode-locked lasers for quantum information processing.

We stabilize a chosen radio frequency beat note between two optical fields derived from the same mode-locked laser pulse train in order to coherently manipulate quantum information. This scheme does not require access or active stabilization of the laser repetition rate. We implement and characterize this external lock, in the context of two-photon stimulated Raman transitions between the hyperfine ground states of trapped 171Yb(+) quantum bits.

Primary carbonatite melt from deeply subducted oceanic crust.

Partial melting in the Earth's mantle plays an important part in generating the geochemical and isotopic diversity observed in volcanic rocks at the surface. Identifying the composition of these primary melts in the mantle is crucial for establishing links between mantle geochemical 'reservoirs' and fundamental geodynamic processes. Mineral inclusions in natural diamonds have provided a unique window into such deep mantle processes. Here we provide experimental and geochemical evidence that silicate mineral inclusions in diamonds from Juina, Brazil, crystallized from primary and evolved carbonatite melts in the mantle transition zone and deep upper mantle. The incompatible trace element abundances calculated for a melt coexisting with a calcium-titanium-silicate perovskite inclusion indicate deep melting of carbonated oceanic crust, probably at transition-zone depths. Further to perovskite, calcic-majorite garnet inclusions record crystallization in the deep upper mantle from an evolved melt that closely resembles estimates of primitive carbonatite on the basis of volcanic rocks. Small-degree melts of subducted crust can be viewed as agents of chemical mass-transfer in the upper mantle and transition zone, leaving a chemical imprint of ocean crust that can possibly endure for billions of years.

Coherent error suppression in multiqubit entangling gates.

We demonstrate a simple pulse shaping technique designed to improve the fidelity of spin-dependent force operations commonly used to implement entangling gates in trapped ion systems. This extension of the Mølmer-Sørensen gate can theoretically suppress the effects of certain frequency and timing errors to any desired order and is demonstrated through Walsh modulation of a two qubit entangling gate on trapped atomic ions. The technique is applicable to any system of qubits coupled through collective harmonic oscillator modes.

Hysteretically reversible phase transition in a molecular glass.

Pressure induced densification in a molecular arsenic sulfide glass is studied at ambient temperature using x-ray scattering, absorption and Raman spectroscopic techniques in situ in a diamond anvil cell. The relatively abrupt changes in the position of the first sharp diffraction peak, FSDP, and the pressure-volume equation of state near ∼2 GPa suggest a phase transition between low- and high-density amorphous phases characterized by different densification mechanisms and rates. Raman spectroscopic results provide clear evidence that the phase transition corresponds to a topological transformation between a low-density molecular structure and a high-density network structure via opening of the constituent As(4)S(3) cage molecules and bond switching. Pressure induced mode softening of the high density phase suggests a low dimensional nature of the network. The phase transformation is hysteretically reversible, and therefore, reminiscent of a first-order phase transition.

Nature of phase transitions in crystalline and amorphous GeTe-Sb2Te3 phase change materials.

The thermodynamic nature of phase stabilities and transformations are investigated in crystalline and amorphous Ge(1)Sb(2)Te(4) (GST124) phase change materials as a function of pressure and temperature using high-resolution synchrotron x-ray diffraction in a diamond anvil cell. The phase transformation sequences upon compression, for cubic and hexagonal GST124 phases are found to be: cubic → amorphous → orthorhombic → bcc and hexagonal → orthorhombic → bcc. The Clapeyron slopes for melting of the hexagonal and bcc phases are negative and positive, respectively, resulting in a pressure dependent minimum in the liquidus. When taken together, the phase equilibria relations are consistent with the presence of polyamorphism in this system with the as-deposited amorphous GST phase being the low entropy low-density amorphous phase and the laser melt-quenched and high-pressure amorphized GST being the high entropy high-density amorphous phase. The metastable phase boundary between these two polyamorphic phases is expected to have a negative Clapeyron slope.

Tenascin-X deficiency and Ehlers-Danlos syndrome: a case report and review of the literature.

Tenascin-X is a large extracellular matrix glycoprotein that is widely distributed within connective tissues and is associated with an autosomal recessive type of Ehlers-Danlos syndrome (EDS). Tenascin-X represents the first EDS susceptibility gene that does not code for a fibrillar collagen or collagen-processing enzyme. We describe a paediatric case of tenascin-X deficiency and review the literature.

A novel instrument for separating large DNA molecules with pulsed homogeneous electric fields.

A new instrument has been developed for the electrophoretic separation of large DNA molecules that can independently regulate the voltage of each of 24 electrodes and allow the magnitude, orientation, homogeneity, and duration of the electric field to be precisely controlled. Each parameter can be varied at any time during the electrophoretic process. Thus distinct sets of conditions can be combined to optimize the separation of various fragment sizes in a single run. Independent control of electrode voltage allows all of the fields to be generated with electrodes arranged in a closed contour, independent of a particular geometry. This device increases both the resolution in any size range and the speed of separation, especially for DNA molecules larger than 3 megabases.

Biological microscopy: the emergence of digital microscopy.

The past few years have seen a tremendous renaissance in biological optical microscopy, mainly as a result of the application of digital image processing and video imaging techniques. We review recent developments in microscopy that are permitting unprecedented views of biological structure and function.

Reduced febrile responses to peripheral and central administration of pyrogen in aged squirrel monkeys.

There is long-standing controversy as to whether fever capacity is reduced in aged man. Although loss of this cardinal sign of disease would be an impediment to diagnosis and treatment, there has been no previous research on altered febrile responses using aged primate models. In the present experiments the febrile reaction to IV Salmonella typhosa endotoxin was reduced in monkeys over 14 years old and in one-third of those 10-14 years of age compared with that of younger animals. In response to injections of endotoxin into the lateral cerebral ventricle (ICV), animals over 10 years old showed small or no fevers. Injections of probenecid (ICV), an inhibitor of central inactivation of leukocytic pyrogen and prostaglandin, augmented fever caused by IV and ICV endotoxin and hyperthermia caused by ICV PGE2 in animals under 10 years of age. However, in older animals probenecid increased fever caused by ICV endotoxin only, although the increased response was still less than one quarter that of younger animals. The results indicate that old squirrel monkeys have decreased febrile responses that may be traced to alterations in central sensitivity to pyrogens.

Automation of dideoxynucleotide DNA sequencing reactions using a robotic workstation.

We report here a system for automation of the dideoxynucleotide DNA sequencing method. The system consists of a Beckman Biomek 1000 robotic workstation which has been modified by the addition of a thin heater/cooler block directly on the instrument table. The heater/cooler block, which is regulated by a user-specified program integrated into the Biomek software, facilitates the use of both single- and double-stranded DNA sequencing procedures. Using this system, we are able to perform 24 sets of dideoxynucleotide DNA sequencing reactions in approximately 45 min. The reactions are performed in 96-well microtiter plates, using a prepared reagent pack which includes primer, enzyme, nucleotide mixes and radioactive label. Using standard gel electrophoresis technology, we are able to resolve over 500 nucleotides per sequencing reaction in about 5 h. Currently, we are able to perform three runs of 24 samples each, with subsequent gel analysis per 8-h period. Excluding autoradiography, this represents a daily data output of 36,000 base pairs.

Innominate artery compression of the trachea. Treatment by reimplantation of the innominate artery.

The standard treatment of innominate artery compression of the trachea has been innominate artery suspension, but the syndrome can recur when this technique is used. From October 1985 until March 1991, 29 infants and children were treated for this syndrome by innominate artery reimplantation. In all patients severe anterior vascular compression of the trachea was demonstrated preoperatively by bronchoscopy and in 17 the diagnosis was confirmed by magnetic resonance imaging scanning. Indications for operation included apneic episodes in 17 (58.6%), severe stridor in seven (24.1%), recurrent bronchopulmonary infections in four (13.8%), and exercise-induced stridor in one (3.4%). Through a median sternotomy, the innominate artery was reimplanted more proximally on the ascending aorta and to the right of the trachea. In this new position, the innominate artery no longer crosses the trachea anteriorly, and the anatomic cause of tracheal obstruction is completely eliminated. There were no early or late deaths, and 27 of the 29 patients (93%) had complete resolution of symptoms. Partial resolution of symptoms was seen in two patients (7%). Reimplantation of the innominate artery offers a unique method by which the anatomic cause of tracheal compression is eliminated. It is a safe and effective means of treating symptomatic compression of the trachea by the innominate artery.

Fetal cardiac bypass: improved placental function with moderately high flow rates.

Prenatal correction of certain cardiac lesions with a poor prognosis may have advantages over postnatal repair. For this to be done, safe and effective support of the fetal circulation must be devised. Studies involving fetal cardiac bypass have demonstrated progressive fetal hypoxemia, hypercapnia, and acidosis, indicating placental dysfunction. We performed fetal cardiac bypass in 18 fetal lambs (126 to 140 days' gestation) to assess the effect of flow rate on fetal oxygenation and metabolism and function of the placenta as an in vivo oxygenator. Fetal cardiac bypass was done for a 30-minute study period at normothermia in all fetuses. During the study period the fetal aorta was cross-clamped and cold cardioplegia was administered to the heart so there was no fetal cardiac contribution to systemic output. Nine fetuses underwent studies at low flow rates (109 +/- 20 mL.kg-1.min-1) and 9 at higher flow rates (324 +/- 93 mL.kg-1.min-1). At the lower flow rate, mean aortic pressure, arterial pH, and oxygen tension decreased whereas carbon dioxide tension and lactate levels increased when compared with prebypass levels. At the higher flow rate mean aortic pressure, pH, oxygen tension, carbon dioxide tension, and lactate levels remained similar to prebypass levels during the 30-minute study period. When the animals were weaned from the bypass circuit after studies at high flow rates, arterial oxygen tension and pH decreased whereas carbon dioxide tension increased to levels similar to those in the low-flow group.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of diazepam on body temperature of the aged squirrel monkey.

Hypothermia was produced by IM administration of diazepam (0.125-0.5 mg/kg) to squirrel monkeys of various ages (2-16 years) in a thermoneutral (23 +/- 0.5 degrees C) environment with animals over eight years of age having slightly greater responses. Hypothermia caused by an intermediate dose (0.25 mg/kg) was augmented in a cold environment (15 degrees C), especially in the older animals. There was no marked alteration in the temperature change/age regression after 0.25 mg/kg diazepam in a hot environment (30 degrees C) compared with the control response. Injections of diazepam (1.25-5.0 microgram) into the lateral cerebral ventricle in a thermoneutral environment produced hyperthermia rather than hypothermia in all animals, and the magnitude of the induced hyperthermia was smaller in older monkeys. The results support previous case reports in man and suggest that this commonly used drug can induce hypothermia, especially in older primates exposed to cold. The drug action responsible for this temperature change appears to take place peripherally rather than within the brain.

Effects of morphine on body temperature of squirrel monkeys of various ages.

Increased sensitivity to certain drugs is believed to contribute to dysthermia in the elderly. To learn whether the temperature-altering effects of an opiate are increased in aged primates, injections of morphine sulfate (0.5-4 mg/kg) were given SC in randomly assigned order to squirrel monkeys ranging in age from 3.5 to over 17 years. Hyperthermia was the predominant response with no clear relationship to age, although hypothermic and biphasic responses also occurred, most commonly after the highest dose. Lateral cerebral ventricular injections of 0.625 and 1.25 micrograms morphine sulfate evoked hyperthermia in monkeys over 8 years of age but did not affect the temperature of animals less than 5 years old. Doses of 2.5 and 5 micrograms usually elicited hyperthermia regardless of age, but 10 micrograms induced hypothermia in a majority of monkeys. Naloxone was given intraventricularly to several monkeys to limit the degree of hypothermia after high doses of morphine given peripherally or centrally. Thus in these primates, as in other species such as the rat, lower doses of morphine usually evoked hyperthermia, but sufficiently high doses caused body temperature to fall. Unlike the case in the squirrel monkey with diazepam and with endogenous substances such as leukocytic pyrogen and taurine, there was not a strong or consistent relationship between age and morphine-induced temperature changes.

Exercise in the reduction of cardiovascular events. Lessons from epidemiologic trials.

In conclusion, much has been learned about the effects of exercise in reducing events in those with CHD. Some data are confusing, however, and some gaping holes exist in our understanding. Hopefully, new data forthcoming in the next 5 to 10 years will clear up this picture significantly. Meanwhile, cardiovascular exercise, coupled with other risk factor reduction, has been firmly established as a lifesaving and life-improving tool in those who have developed manifestations of CHD.

Parasitization of humans in West Virginia by Ixodes cookei (Acari: Ixodidae), a potential vector of Lyme borreliosis.

In 32 collections, two larvae, 33 nymphs, and one adult female Ixodes cookei Packard were collected from humans in West Virginia from August 1987 to May 1990. Most were attached. The ticks were found in 14 counties and were the most abundant Ixodes found biting humans. One nymphal I. cookei was removed from the left axilla of a 39-yr-old woman who lives and works in Monongalia and Marion counties, W. Va. The bite was the center of an expanding erythematous lesion reaching 4 cm in diameter, clearing centrally, and typical of erythema migrans. This association and the near absence of Ixodes dammini Spielman, Clifford, Piesman & Corwin from the state suggests the possibility that I. cookei may be an important vector of Lyme borreliosis in West Virginia. In five separate collections, five nymphal Ixodes dentatus Marx were removed from humans in four counties, implicating this species as a potential minor vector of Lyme borreliosis in West Virginia.

Hypersensitive dentin: testing of procedures for mechanical and chemical obliteration of dentinal tubuli.

This study examined by scanning electron microscopy the effect of various mechanical and chemical procedures in obliterating dentinal tubuli. Dentin blocks containing open, cross-sectioned dentinal tubuli were separated into one experimental and one control area. The mechanical treatments consisted of 20 seconds of continuous instrumentation with sharp and dull curets, finely textured inserts for the EVA reciprocating handpiece, metal and plastic inserts for a sonic scaler, and metal inserts for an ultrasonic scaler. Chemical treatments included a light-cured dental resin and active obliterating agents including sodium, stannous and hydrogen fluorides, potassium oxalate, glycerin, ferric oxalate, and potassium nitrate. These substances were applied to the test surfaces for 2 minutes and allowed to dry. One half of the chemically treated specimens were then sprayed with water in order to evaluate the retention of the obliterating agents. The results revealed that among the mechanical treatments, the sharp curet gave the most consistent and complete obliteration of the tubuli. The plastic inserts had no tubular occluding effects. Among the chemical procedures, the light-cured resin resulted in the most complete obliteration of the tubuli, while the fluoride agents and glycerin had no effect. It can be hypothesized that combining instrumentation with a sharp curet causing a heavy smear layer and occlusion of tubuli apertures, followed by application of a light body resin, may prove to be a rational method of desensitizing hypersensitive dentin surfaces. However, this combined treatment should be evaluated in clinical trials.