The effect of induction with propofol or ketamine and diazepam on quality of anaesthetic recovery in dogs.

OBJECTIVE: To evaluate the quality of recovery in dogs undergoing elective orthopaedic surgery induced with either propofol or a combination of ketamine and diazepam. MATERIALS AND METHODS: Sixty client-owned dogs undergoing single-limb elective orthopaedic procedures were enrolled. Dogs were randomly assigned to receive induction with propofol (4 mg/kg) (group P) or ketamine (5 mg/kg) with diazepam (0.25 mg/kg) (group KD) to which all scorers were blinded. The recovery monitoring period lasted for 1 hour following extubation. The recovery period was video-recorded for blinded scoring at a later time. Scoring for quality of recovery was carried out using three different systems (lower numbers=better quality): a simple descriptive scale (1 to 5), a visual analogue scale (0 to 10 cm) and a numeric rating scale (0 to 10). Videos were reviewed by three ACVAA board-certified anaesthesiologist raters. RESULTS: Five dogs were deemed to be ineligible. The mean (±SD) duration of anaesthesia was 260.4 ±57.84 minutes in group KD and 261.1 ±51.83 minutes in group P. There was no difference between groups for time to extubation, head lift or sternal recumbency. The number of dogs having a recovery that was scored overall as bad (mean simple descriptive scale > 4, mean visual analogue scale or numeric rating scale > 5) was not different between groups. Dogs in group KD had significantly lower scores than group P dogs (simple descriptive scale P=0.01, numeric rating scale P=0.03, visual analogue scale P=0.03). CLINICAL SIGNIFICANCE: Induction with ketamine and diazepam resulted in a smoother recovery from anaesthesia than induction with propofol.

Modeling the effect of analyte and reference bandwidths on signal and noise magnitudes in spectrophotometric assays.

In spectrophotometric assays, it has been well established that the recorded absorption, and therefore the experimentally determined extinction coefficient, decreases as a function of detected bandwidth. This manuscript presents an expression for the extinction coefficient as a function of the critical parameter detected bandwidth per transition linewidth. Calculations for both single channel and multichannel photodetection are presented; the derived expressions are shown to be in good agreement with experimental results. It is important to realize that this systematic bias is present in dilute solutions of low absorptivity, and the experimentally recorded extinction coefficient for a molecular standard such as caffeine can vary approximately 4% or more, depending upon choice of research instrumentation. The magnitude of this bias may be sufficient to effect method robustness, cause interlaboratory discrepancies, and fail system suitability requirements for spectrophotometric assays. The signal to noise ratio, for example as analyzed in HPLC/UV-VIS detected chromatograms, is also a function of the detected bandwidths of both the analyte and reference channels. It is shown here that use of a reference can only increase the baseline noise.

Outcomes following unilateral uterine artery embolisation.

Uterine artery embolisation has been described as successful only when both arteries are embolised. However, results in patients with one congenitally absent or previously ligated artery are unknown. Women suffering from symptomatic uterine myomata were treated at a university teaching hospital, a community hospital and an outpatient surgery centre. Retrospective review of patient response to embolisation was assessed by chart review and questionnaire. Uterine and dominant fibroid size response was assessed by comparing pre- and post-embolisation ultrasound examinations. This study analysed three patient groups within the general population: those who underwent unilateral embolisation because of technical failure, those who ultimately underwent bilateral embolisation after initial technical failure and those who underwent unilateral embolisation because of an absent uterine artery. 12 patients underwent unilateral embolisation, 4 of whom underwent this procedure because of an absent uterine artery. Three of these four patients had a congenitally absent uterine artery arising from the internal iliac artery and all three experienced successful outcomes. The fourth patient had a previously ligated internal iliac artery and her symptoms worsened after the procedure. Eight patients had unilateral embolisation due to technical failure. Five of these patients underwent a subsequent procedure during which the contralateral uterine artery was embolised. Four of these five patients had successful outcomes and one was lost to follow-up. Another of the eight patients suffered an arterial injury leading to technical failure, and was lost to follow-up. Of the two remaining patients with unilateral technical failure, only one had a successful outcome. This study concluded that patients who undergo unilateral embolisation for technical reasons should be offered a second embolisation procedure shortly after the initial procedure. Patients with a congenitally absent uterine artery may respond with similar success to those who underwent bilateral embolisation. In contrast, the patient with a previously ligated internal iliac artery failed. The numbers in this study are too small for statistical analysis and subsequent studies should be performed to confirm these findings.

Purification and identification of an impurity in bulk hydrochlorothiazide.

Hydrochlorothiazide (6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide) (HCTZ) 1 is a widely used diuretic and anti-hypertensive. Recently, the Pharmeuropa recognized a new impurity initially thought to be an HCTZ dimer 6, which consists of the active drug (HCTZ) linked via the former beta-ring methylene to a known degradate, 5-chloro-2,4-disulfamylaniline 2. In an effort to meet a new requirement, an analytical high-pressure liquid chromatography method was developed that was selective and sensitive to the subject impurity. The impurity was concentrated and purified using a combination of solid phase extraction and reverse-phase high-pressure liquid chromatography. Subsequently, the impurity has been identified as a specific HCTZ-CH2-HCTZ isomer utilizing a variety of analytical techniques, including hydrolysis, ultraviolet spectroscopy, liquid chromatography/mass spectrometry, and 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. The data resulting from the application of these analytical techniques confirm the identity of the impurity as a methylene bridged pair of HCTZ molecules; however, a total of six possible isomers 7a-f exist because of the presence of three reactive amines/sulfonamides on each HCTZ molecule. One unique molecular structure (4-[[6-chloro-3,4,-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide]-methyl]-chloro-3-hydro-H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide) 7f was identified using two-dimensional COSY, NOESY, and TOCSY 1H NMR experiments.

Stability and compatibility of tirofiban hydrochloride during simulated Y-site administration with other drugs.

The stability and compatibility of tirofiban hydrochloride injection during simulated Y-site administration with various other drugs were studied. Tirofiban hydrochloride, dobutamine, epinephrine hydrochloride, furosemide, midazolam hydrochloride, and propranolol hydrochloride injections were each prepared from their respective concentrates in both 0.9% sodium chloride injection and 5% dextrose injection at both the minimum and maximum concentrations normally administered. The high-concentration solutions of midazolam hydrochloride and furosemide were used as is. Morphine sulfate was diluted in 5% dextrose injection only. Nitroglycerin premixed infusions, atropine sulfate injection, and diazepam injection were used as is. Tirofiban hydrochloride solutions were combined 1:1 with each of the secondary drug solutions in separate glass containers. Samples were stored for four hours at room temperature under ambient fluorescent light and were assayed for drug content and degradation by high-performance liquid chromatography and for pH, appearance, and turbidity. All mixtures except those containing diazepam remained clear and colorless, with no visual or turbidimetric indication of physical instability. Mixing of tirofiban hydrochloride and diazepam solutions resulted in immediate precipitation. all remaining mixtures remained clear. There was no significant loss of any of the drugs tested, no increase in known degradation products, and no appearance of unknown drug-related peaks. The pH of all test solutions remained constant. Tirofiban hydrochloride injection 0.05 mg/mL was stable for at least four hours when combined 1:1 in glass containers with atropine sulfate, dobutamine, epinephrine hydrochloride, furosemide, midazolam hydrochloride, morphine sulfate, nitroglycerin, and propranolol hydrochloride at the concentrations studied. Tirofiban hydrochloride was incompatible with diazepam.

Auditory working memory in HIV-1 infection.

We evaluated auditory working memory in 41 HIV-seropositive (HIV+) and 37 HIV-seronegative (HIV-) male drug users, employing a modified version of the Letter-Number Span Task developed by Gold and colleagues. We added a control condition to the standard task in order to evaluate more directly the contribution of the processing component to the working memory deficits with the effects of storage demands minimized. HIV+ subjects performed significantly more poorly compared to controls on an index of working memory processing derived from raw scores obtained under the two testing conditions. These findings are consistent with our previous reports that HIV-related working memory deficits are evident across multiple informational domains; further, the deficit appears to involve multiple-component functions of working memory. Converging findings from recent working memory studies and from primate and neuroimaging investigations suggest that functional abnormalities of prefrontal cortex should receive greater emphasis in models of neurocognitive aspects of HIV-1 infection, which have typically emphasized "subcortical" deficits.

Liquid chromatography-mass spectrometry and proton nuclear magnetic resonance characterization of trace level condensation products formed between lactose and the amine-containing diuretic hydrochlorothiazide.

Trace levels of condensation products between lactose and the amine-containing diuretic hydrochlorothiazide are formed when a mixture of the two solids containing 30% weight water is heated at 60 degrees C for 2 weeks. The two most abundant condensation products were characterized by liquid chromatography-mass spectrometry (LC-MS) and proton nuclear magnetic resonance ((1)H NMR) spectroscopy. Under these relatively mild conditions of formation, the amine-lactose reaction products are limited to those involving the elimination of only a single molecule of water, rather than the multiple-water eliminations associated with later stages of the Maillard reaction. The spectroscopic data clearly show that the primary condensation products are cyclic N-substituted glycosylamines rather than Schiff base, 1,2-enolic forms, or Amadori rearrangement products of identical mass. In solution, the two most abundant N-substituted glycosylamines are shown to be in a kinetically slow equilibrium with each other, most likely through a mutarotation involving the intermediate formation of the acyclic Schiff base.

Compatibility of tirofiban HCl with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride during simulated Y-site administration.

OBJECTIVE: To study the compatibility of tirofiban HCl injection 0-05 mg/ml with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride infusion solutions during simulated Y-site administration. METHOD: Tirofiban HCl, dopamine HCl, famotidine, lidocaine HCl and potassium chloride infusions were each prepared from their respective concentrates as per current clinical preparation instructions in both 0.9% sodium chloride and 5% dextrose solutions at both the minimum and maximum concentrations normally administered. Sodium heparin premixed infusion solutions in 5% dextrose and 0-45% sodium chloride were used as-is. Tirofiban HCl solutions were combined 1:1 (simulated Y-site administration) with the dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride solutions in separate glass containers and polyvinylchloride Y-site infusion lines. Samples were held for 4 h at room temperature under ambient fluorescent light and were assayed for changes in drug content, degradation, pH, appearance and turbidity. Activity of sodium heparin solutions was measured using an aPTT coagulation assay. RESULTS: All mixtures remained clear and colourless with no visual indication of instability, i.e. precipitation. Clarity of solutions was confirmed by turbidometric analysis. There was no significant loss of drug, increase in known degradates, or appearance of unknown drug-related peaks as determined by HPLC. The activity of heparin in heparin-containing solutions remained unchanged. The pH of all test-solutions remained constant. CONCLUSION: Tirofiban HCl injection 0.05 mg/ml can be co-infused by Y-site administration with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride injection solutions.

The release and detection of endotoxin from liposomes.

Incorporation of lipopolysaccharide (LPS) into liposomes dramatically reduces its ability to coagulate Limulus amebocyte lysate (LAL). The coagulation of LAL is commonly used to signal the presence of endotoxin in vitro. This study demonstrates a simple method to release masked endotoxin from liposomal dispersions using moderate amounts of detergent to form mixed micelles containing lipid, detergent, and LPS. Several parameters were found to affect the degree of liposome solubilization and/or the sensitivity of the LAL assay. These included detergent type and concentration, temperature for solubilization, lipid composition, liposome morphology, and time for test incubation. The nonionic detergent polyoxyethylene 10 lauryl ether (C12E10) proved to be unique in its ability to solubilize liposomes and minimally interfere with endotoxin detection. The LAL endotoxin detection limit for samples dispersed in C12E10 varied with the phospholipid component; the sensitivity decreased in the order DSPC > DPPC = EPC >> DMPC. Cholesterol lowered the solubility limit of the liposomes, but did not appear to affect the LAL assay sensitivity once the liposomes were completely solubilized. The presence of negatively charged phospholipids, DSPG and Pops, also lowered the solubility limit. Pops, but not DSPG, at 10 mol% further decreased the LAL endotoxin detection limit. This detergent-solubilization method should be useful in liposomal LPS immunological studies or in other situations where accurate determination of endotoxin concentration is important.

The use of inferior vena cava filters in pediatric patients for pulmonary embolus prophylaxis.

PURPOSE: To report our experience with inferior vena cava (IVC) filters in pediatric patients. METHODS: Over a 19-month period, eight low-profile percutaneously introducible IVC filters were placed in four male and four female patients aged 6-16 years (mean 11 years). Indications were contraindication to heparin in six patients, anticoagulation failure in one, and idiopathic infrarenal IVC thrombosis in one. Six of the eight devices placed were titanium Greenfield filters. One LGM and one Bird's Nest filter were also placed. Two of the filters were introduced via the right internal jugular vein by cutdown, and the remainder were placed percutaneously via the right internal jugular vein or the right common femoral vein. Patients received follow-up abdominal radiographs from 2 to 13 months after IVC filter placement. RESULTS: All filters were inserted successfully without complication. Three of the patients died during the follow-up period: two due to underlying brain tumors at 2 and 12 months and a third at 6 weeks due to progressive idiopathic renal vein and IVC thrombosis. The remaining five patients were all alive and well at follow-up without evidence of IVC thrombosis, pulmonary emboli, or filter migration. CONCLUSION: IVC filter placement using available devices for percutaneous delivery is technically feasible, safe, and effective in children.

Properties of ganglioside GM1 in phosphatidylcholine bilayer membranes.

Gangliosides have been shown to function as cell surface receptors, as well as participating in cell growth, differentiation, and transformation. In spite of their multiple biological functions, relatively little is known about their structure and physical properties in membrane systems. The thermotropic and structural properties of ganglioside GM1 alone and in a binary system with 1,2-dipalmitoyl phosphatidylcholine (DPPC) have been investigated by differential scanning calorimetry (DSC) and x-ray diffraction. By DSC hydrated GM1 undergoes a broad endothermic transition TM = 26 degrees C (delta H = 1.7 kcal/mol GM1). X-ray diffraction below (-2 degrees C) and above (51 degrees C) this transition indicates a micellar structure with changes occurring only in the wide angle region of the diffraction pattern (relatively sharp reflection at 1/4.12 A-1 at -2 degrees C; more diffuse reflection at 1/4.41 A-1 at 51 degrees C). In hydrated binary mixtures with DPPC, incorporation of GM1 (0-30 mol%; zone 1) decreases the enthalpy of the DPPC pretransition at low molar compositions while increasing the TM of both the pre- and main transitions (limiting values, 39 and 44 degrees C, respectively). X-ray diffraction studies indicate the presence of a single bilayer gel phase in zone 1 that can undergo chain melting to an L alpha bilayer phase. A detailed hydration study of GM1 (5.7 mol %)/DPPC indicated a conversion of the DPPC bilayer gel phase to an infinite swelling system in zone 1 due to the presence of the negatively charged sialic acid moiety of GM1. At 30-61 mol % GM1 (zone 2), two calorimetric transitions are observed at 44 and 47 degrees C, suggesting the presence of two phases. The lower transition reflects the bilayer gel --> L alpha transition (zone 1), whereas the upper transition appears to be a consequence of the formation of a nonbilayer, micellar or hexagonal phase, although the structure of this phase has not been defined by x-ray diffraction. At > 61 mol % GM1 (zone 3) the calorimetric and phase behavior is dominated by the micelle-forming properties of GM1; the presence of mixed GM1/DPPC micellar phases is predicted.

Creating a healing environment by design.

This article focuses on offering a methodology that goes beyond creating a noninstitutional environment to one intended to assist in the development of a healing environment, one that influences patients' responses to the environment, and one that offers patients opportunities to cope. This article does not advocate a formula for design that, by its nature, would be antihetical to the dynamic proposed. Instead, this article suggests a methodology that allows and recommends flexibility in design. While the article discusses design issues for outpatient oncological centers and offers specific examples as demonstrations of implementation, the methodology is not limited to outpatient cancer care centers. Ambulatory care centers in general would benefit from application of these principles.

The 2.4 A crystal structure of cholera toxin B subunit pentamer: choleragenoid.

Cholera toxin, a heterohexameric AB5 enterotoxin released by Vibrio cholera, induces a profuse secretory diarrhea in susceptible hosts. Choleragenoid, the B subunit pentamer of cholera toxin, directs the enzymatic A subunit to its target by binding the GM1 gangliosides exposed on the luminal surface of intestinal epithelial cells. The crystal structure of choleragenoid has been independently solved and refined at 2.4 A resolution by combining single isomorphous replacement with non-crystallographic symmetry averaging. The structure of the B subunits, and their pentameric arrangement, closely resembles that reported for the intact holotoxin, choleragen, the heat-labile enterotoxin from Escherichia coli, and for a choleragenoid-GM1 pentasaccharide complex. In the absence of the A subunit the central cavity of the B pentamer is a highly solvated channel. The binding of choleragenoid to the A subunit or to its receptor pentasaccharide modestly affects the local stereochemistry without perceptibly altering the subunit interface.

Recommended methods for the disposal of sanitary wastes from temporary field medical facilities.

Emergency field medical facilities constructed after a disaster are frequently managed by medical staff even though many of the day-to-day problems of hospital management are unrelated to medicine. In this paper we discuss the short-term management of one of these problems, namely the control and disposal of sanitary wastes. It is aimed at persons in the medical profession who may find themselves responsible for a temporary hospital and have little or no previous experience of managing such situations. The wastes commonly generated are excreta, sullage and refuse. In addition, surface water must also be considered because its inadequate disposal is a potential health hazard. The paper concentrates on short-term measures appropriate for the first six months of the hospital or clinic's existence. Facilities expected to last longer are recommended to install conventional waste management systems appropriate to the local community and conditions. In most situations, wastes should be disposed of underground either by burial (for solids) or infiltration (for liquids). The design, construction and management of appropriate disposal systems are described.

Orientation of cholera toxin bound to model membranes.

The orientation of cholera toxin bound to its cell-surface receptor, ganglioside GM1, in a supporting lipid membrane was determined by electron microscopy of negatively stained toxin-lipid samples. Image analysis of two dimensional crystalline arrays has shown previously that the B-subunits of cholera toxin orient at the membrane surface as a pentameric ring with a central channel (Reed, R. A., J. Mattai, and G.G. Shipley. 1987. Biochemistry. 26:824-832; Ribi, H. O., D. S. Ludwig, K. L. Mercer, G. K. Schoolnik, and R. D. Kornberg. 1988. Science (Wash, DC). 239:1272-1276). We recorded images of negatively stained cholera toxin and isolated B-pentamers oriented perpendicular to the lipid surface so that the pentamer ring is viewed from the side. The pentamer dimensions, estimated from the average of 100 molecules, are approximately 60 by 30 A. Images of side views of whole cholera toxin clearly show density above the pentamer ring away from the lipid layer. On the basis of difference maps between averages of side views of whole toxin and B-pentamers, this density above the pentamer has been identified as a portion of the A-subunit. The A-subunit may also extend into the pore of the pentamer. In addition, Fab fragments from a monoclonal antibody to the A-subunit were mixed with the toxin prior to binding to GM1. Density from the Fab was localized to the region of toxin above the pentamer ring confirming the location of the A-subunit. The structure determined for the homologous heat-labile enterotoxin from Escherichia coli shows that the A-subunit lies mostly on one face of this pentamer with a small region penetrating the pentamer pore (Sixma, T. K., S. E. Pronk, K. H. Kalk, E. S. Wartna, B. A. M. van Zanten, B. Witholt,and W. G. J. Hol. 1991. Nature (Lond.). 351:371-377). The putative GM1 binding sites are located on the opposite face of the B-pentamer. Cholera toxin, therefore appears to bind to a model membrane with its GM1 binding surface adjacent to the membrane. Low resolution density maps were constructed from the x-ray coordinates of the E. coli toxin and compared with the electron microscopy-derived maps.

Prevalence of infection following hepatic chemoembolization with cross-linked collagen with administration of prophylactic antibiotics.

PURPOSE: The authors present their experience with 494 hepatic chemoembolization (HCE) procedures in 236 patients with administration of a mixture of cross-linked collagen and chemotherapeutic agents. The prevalence of infectious complications was compared in patients who did and did not receive prophylactic administration of antibiotics as part of the HCE procedure. PATIENTS AND METHODS: Fourteen HCE procedures in nine patients were performed without prophylactic antibiotics (PA). These patients underwent embolization with cross-linked collagen alone or with low-dose cisplatinum. All of the remaining 480 procedures in 227 patients were performed with PA. RESULTS: One of the nine patients (11%) who did not receive PA experienced fatal sepsis within 24 hours of HCE. Of the 227 patients who did receive antibiotics, six (2.6%) developed hepatic abscess and no fatal sepsis was encountered. CONCLUSION: Use of PA decreases the prevalence of infectious complications following HCE.

Portal venous branch targeting with a platinum-tipped wire to facilitate transjugular intrahepatic portosystemic shunt (TIPS) procedures.

We describe a technique to aid in technically difficult transjugular intrahepatic portosystemic shunt (TIPS) procedures by sonographically guided transabdominal fine-needle portal vein puncture for placement of a 0.018-inch platinum-tipped target guidewire within an appropriate portal venous branch.

In vitro flow phantom analysis and clot-capturing ability of incompletely opened Vena Tech-LGM vena caval filters.

It has been shown recently that Vena Tech-LGM (B. Braun Vena Tech, Evanston, IL) filters inserted into the inferior vena cava via the jugular route may be deployed sometimes in an incompletely opened (IO) position. The flow characteristics and clot capturing ability of IO Vena Tech-LGM filters are not clearly understood. Using a vena cava flow phantom, the clot-capturing abilities of the IO and opened Vena Tech-LGM filters were assessed. For 5 x 5-mm clots, the IO Vena Tech-LGM filter captured only 40% of thrombi compared with a 90% capture rate for the opened filter. The capture rates were 90 and 100% for the IO and opened filter, respectively, for larger 5 x 15-mm clots. It was found that the IO filter could capture 2-7 x 25 mm thrombi prior to the development of a turbulent bypass channel which prevented subsequent clot capture. Using 5 x 15 mm clots, this same phenomenon occurred with the capture of 6 and 11 thrombi by the IO and opened Vena Tech-LGM filters, respectively. Our results suggest a significantly reduced filtering efficiency for the IO Vena Tech-LGM device. However, there is a high rate of clot capture with the opened Vena Tech-LGM filter.

Microcatheter embolization of non-neurologic traumatic vascular lesions.

PURPOSE: The authors report their experience over a 28-month period with embolization of 23 non-neurologic traumatic vascular lesions in 21 patients with use of a coaxial microcatheter coil delivery system. PATIENTS AND METHODS: The injuries included pseudoaneurysms (n = 17), arteriovenous fistulas (n = 3), and sites of extravasation (n = 3) and were caused by gunshot, shotgun, and stab wounds, as well as motor vehicle accidents and iatrogenic trauma. All microcatheter embolizations except one were performed with 2.2-F Tracker-18 catheters inserted coaxially through 5.0-5.5-F guiding catheters. In one case, a coaxial 3-F Teflon catheter was used. In all cases platinum microcoils (almost all non-fibril) and/or straight platinum embolization wires (with fibrils) were used. RESULTS: Twenty-one (91%) of 23 vascular lesions were successfully occluded with use of the microcatheter system. The two cases in which microcatheter embolization failed were successfully managed by using larger catheters and steel coils. Two patients with hepatic vascular lesions (one site of extravasation and a pseudoaneurysm) and one patient with a lower extremity arteriovenous fistula required two procedures each for successful treatment. Procedures were life-saving in at least two patients. Two lesions recurred during follow-up ranging from 3 days to 17 months. Both of these recurrences were successfully treated with transcatheter embolization, in one case with use of microcatheters. CONCLUSION: Microcatheter embolization with platinum coils and wires is an effective means for treating traumatic vascular lesions. A coaxial microcatheter system allows for easier, more rapid coil/wire delivery to smaller, spasm-prone arteries in such cases.