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For 12 months the surgical staff at Hope Hospital have operated a form of audit. The monitored information included work load, methods of treatment, complications, misdiagnoses, and deaths. The method described is suitable for any district general or teaching hospital provided adequate secretarial help is available. In addition to helping to maintain standards, an audit of this type has a positive educational role.
BACKGROUND: Patients with asthma routinely exhibit elevated levels of fractionated exhaled nitric oxide (FE(NO)), and this observation has led to studies investigating FE(NO) as a potential marker of airway inflammation. FE(NO) has been shown to enhance the diagnosis of asthma, detect deterioration in control of patients with asthma, and monitor response to anti-inflammatory therapy. OBJECTIVES: The aim of this work was to determine if FE(NO) measurement provides a noninvasive, well-tolerated, and standardized technique to monitor airway inflammation, and if it has the potential to complement standard asthma monitoring tools (eg, symptom diaries, control questionnaires, and pulmonary function testing) and to improve asthma control and patient outcomes. METHODS: Thirteen experts in the diagnosis and treatment of asthma met to discuss the use of FE(NO) in the diagnosis and management of patients with asthma. Participants were selected by Aerocrine, a medical, technical company with headquarters in Stockholm, Sweden, in consultation with their medical education partner Cadent Medical Communications located in Irving, Texas, to represent a diversity of specialists, including both clinicians and investigators, in the fields of allergy, immunology, and pulmonology. All participants were nominally compensated for their time to attend this closed scientific roundtable discussion. The meeting was supported by an educational grant from Aerocrine. This report represents the overall consensus reached by the participants on the clinical applicability of this technique. RESULTS: Our understanding of asthma has expanded so that investigators are now focusing on inflammation in addition to airway obstruction and hyper-reactivity. Whereas patient history, symptoms, and pulmonary function testing can assist in diagnosing asthma, they are not direct measures of the extent of airway inflammation. Elevated FE(NO) levels have been shown to reflect airway inflammation and to occur together with other conventional markers used to detect inflammation. Studies have confirmed increased levels of FE(NO) in both adults and children with asthma. In most studies, FE(NO) was found to be elevated 2- to 3-fold compared with normal controls. There are many determinants of FE(NO) levels, however, and factors other than inflammation must be considered when FE(NO) measurement is used to diagnose and monitor asthma. FE(NO) measurement alone is not sufficient for diagnosing or monitoring asthma, but it can be a valuable addition to current clinical tools. CONCLUSIONS: FE(NO) measurement is a noninvasive and reproducible test that is a surrogate measure of airway inflammation in patients with asthma. The test has demonstrated utility in diagnosing and managing asthma and in predicting response to therapy and, therefore, may be an important tool to incorporate into clinical care.
Evidence suggests that NMDA receptors may have a differential role in the modulation of visceral and somatic pain. Specifically, animal data indicate an analgesic role of NMDA-R antagonists in acute visceral but not acute somatic pain. In humans analgesic effects are documented in acute somatic pain, while the role of NMDA-R antagonists in acute visceral pain is still questionable. We, therefore, conducted a study in humans comparing the analgesic effects of ketamine in an experimental model of visceral and cutaneous pain. In a double-blind, randomized, cross-over study, 11 healthy volunteers (3M, 8F) participated in two experimental sessions in which they evaluated perceptions induced by balloon distention of the distal esophagus and contact heat on the upper chest during continuous computer-controlled i.v. infusion of either ketamine (60 and 120 ng/mL) or saline. Two stimulus intensities producing non-painful and painful sensation were used for each stimulus modality. Subjects reported maximum pain intensity and unpleasantness on visual analog scales (VAS). For noxious visceral stimulation, low dose ketamine produced significant attenuation of both pain intensity and unpleasantness. In contrast, for noxious cutaneous stimulation, ketamine reduced pain unpleasantness, but not perceived intensity. In addition, ketamine did not alter the perception of innocuous stimuli in either modality. Our results confirm the analgesic effects of low-dose ketamine, with minimal side effects, on acute visceral pain and indicate a similar but smaller effect on acute cutaneous pain. A decrease in the unpleasantness but not in the intensity of cutaneous pain may reflect the differential effect of NMDA-R antagonists for the two pain states observed in animal models.
Combination B is a malaria vaccine that comprises recombinant Plasmodium falciparum (P. falciparum) blood-stage proteins MSP1, MSP2 and RESA, formulated with the adjuvant Montanide ISA 720. A phase I-IIb double-blind randomised placebo-controlled trial was undertaken in 120 children aged 5-9 years. Subjects were randomised in four groups: (i) No sulphadoxine-pyrimethamine (SP)+vaccine, (ii) No SP+placebo, (iii) SP+vaccine, (iv) SP+placebo. 15 microg of each protein were given in the thigh, at both first and second injection (4 weeks apart). The placebo was adjuvant emulsified with saline. No serious or severe AEs occurred. Moderate AEs were seen in 3% of the vaccine and 3% of the placebo recipients after first injection and in 12 and 10% after second injection. The vaccine induced significant antibody responses to all three antigens but triggered an IFN-gamma response to MSP1 only. At Week 12, the IFN-gamma response to MSP1 was substantially higher in the vaccine group where No SP had been given. Combination B proved to be safe and immunogenic in children aged 5-9 years. Vaccine immunogenicity was neither impaired by circulating parasites nor increased after pre-treatment with SP and pre-treatment is not advisable in future trials of malaria vaccines, at least for those including blood-stage antigens.
1. Two characteristic properties of the specific high-affinity steroid-binding proteins or receptors, their ability to bind to DNA-cellulose and their relatively acidic isoelectric point, have been exploited as a means of purification. These two fundamental properties distinguish the receptors from the steroid-binding proteins in serum and the non-specific low-affinity steroid-binding proteins in hormone-responsive cells. 2. A significant degree of purification of both cytoplasmic and nuclear steroid-receptor complexes can be achieved with practical facility by these procedures. The purity of the receptor complexes is sufficient to enable studies on their possible control of metabolic processes to be investigated in the future. 3. After extensive purification the physicochemical properties of the cytoplasmic androgen-receptor complex, such as sedimentation coefficient, were unchanged. Further, the purified complex fully retained at least one of its fundamental physiological properties, namely the ability to transfer 5alpha-dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) into chromatin in vitro. 4. The methods may also be employed for studying the changes in the structure and properties of the receptor complexes that are an essential prerequisite for the transfer of cytoplasmic receptor complexes into nuclear chromatin. The temperature-dependence of the binding of androgen-receptor complexes into chromatin is essentially due to a major change in cytoplasmic receptor complex before its attachment to nuclear chromatin. 5. The resolution of these analytical procedures was sufficient to enable a critical comparison of the receptor proteins from different male accessory glands to be undertaken. From these studies, no substantial evidence in support of the tissue specificity of androgen receptors could be established; rather the receptors from different androgen-dependent glands were remarkably similar in physicochemical properties. 6. Although the methods were initially developed for the partial purification of androgen-receptor complexes, they are equally suitable for the prompt and extensive purification of oestrogen-receptor and progesterone-receptor complexes.
OCT embedded cryostat sections of stored pathological specimens of non-Hodgkin's lymphoma were used to provide RNA. After reverse transcription to produce cDNA, the polymerase chain reaction was performed with primers for standard and variant forms of the CD44 molecule. Using Southern transfer and hybridisation with a probe specific for exon 4 of the CD44 gene, both standard and variant forms were visualised by autoradiography. This method was shown to be applicable to other gene products by using primers specific for the abl and bcr genes. This technique permits retrospective analysis of RNA from small amounts of stored pathological samples.
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Controlling for the effects of socioeconomic disadvantage is commonplace in epidemiologic studies. In New Zealand, the Elley Irving scale is used to classify individuals into socioeconomic groups. In this study, data from the control group of a large population based case-control study were used to examine the extent to which indicators of socioeconomic disadvantage vary between ethnic groups, within socioeconomic strata. In each of the commonly constructed socioeconomic strata, the proportion of subjects with car access was significantly lower in the Maori/Pacific Island group than in the nonMaori/Pacific Island group. Similarly, apart from in the highest socioeconomic stratum, where the numbers in the Maori/Pacific Island group were small, the proportion of subjects who were owner occupiers was significantly lower in the Maori/Pacific Island group compared with the nonMaori/Pacific Island group, in each stratum. The Elley Irving scale has limited utility as a measure of material well being. Its widespread use in epidemiologic research, to control for the effects of socioeconomic disadvantage must therefore be questioned.
A case is reported of successful conception and completion of pregnancy in a patient with intestinal failure due to Crohn's disease, nourished entirely by home parenteral nutrition. The nutritional regimen included both dextrose and lipid as calorie sources, together with synthetic amino acids and appropriate additives. Nutritional status was monitored by blood biochemistry, anthropometry, urinary nitrogen losses, and measured resting energy expenditure. Obstetric progress was monitored by standard methods, including abdominal ultrasound, maternal weight gain, and measurement of plasma hormone levels. Herein, particular attention is given to the use of intravenous lipid in pregnancy.
Taurine is one of the most abundant amino acids in mammals and there is increasing evidence for the importance of taurine during development. Plasma taurine kinetics in a rhesus monkey was studied using [1,2-13C2]taurine. Taurine in plasma was derivatized to its dimethylaminomethylene methyl ester, separated on a gas chromatographic column, and the [M+2+H]+/[M+H]+ ion ratio was measured by ammonia chemical ionization mass spectrometry. The results were comparable to those obtained from the simultaneous radioisotope tracer study using [35S]taurine. This stable isotope method requires only 200 microliters of plasma for precise and accurate determination and is suitable for taurine kinetic studies in human infants.
AIM: To determine the success and complication rates of percutaneous nephrostomies (PCNs) performed at a UK training centre over a one-year period by different groups of operators. MATERIALS AND METHODS: During 2002, a total of 276 PCNs were performed in 190 patients by operators of varying experience. We employed two different techniques: (1) a "Seldinger" technique (ultrasound-guided puncture with a 19G sheathed needle followed by guide-wire insertion and track dilatation to accommodate 8-12F nephrostomy catheters), with or without fluoroscopic guidance, and (2) an ultrasound-guided "one-stab" technique using a 6F Bonanno catheter. Selection of technique was according to configuration of the collecting system and whether the procedure was performed out of hours. RESULTS: There were 218 procedures using the Seldinger technique and 62 using the one-stab technique. The Seldinger technique and one-stab technique were compared: primary technical success rate was 98 versus 93%, the major complication rate was 4.1 versus 3.2%, the minor complication rate was 5 versus 13%, and tube complications, such as drainage catheter dislodgement and blockage, were 29.5 versus 17.7%, respectively. The 30-day mortality was 4.3%, none of which were procedure related. CONCLUSION: Based on data from the USA, proposed targets for primary technical success rates are 88-99%, major complications 4-8%, and minor complications 3-15%, and the results were within these target ranges. The ultrasound-guided one-stab technique is a quick and safe procedure in selected cases, and we recommend this method for temporary urinary diversion in cases with moderate to severe degrees of pelvicalyceal system dilatation. These data may help to form a baseline for outcome targets in the UK.
Interaction between iron(II) and acetohydroxamic acid (Aha), alpha-alaninehydroxamic acid (alpha-Alaha), beta-alaninehydroxamic acid (beta-Alaha), hexanedioic acid bis(3-hydroxycarbamoyl-methyl)amide (Dha) or desferrioxamine B (DFB) under anaerobic conditions was studied by pH-metric and UV-Visible spectrophotometric methods. The stability constants of complexes formed with Aha, alpha-Alaha, beta-Alaha and Dha were calculated and turned out to be much lower than those of the corresponding iron(II) complexes. Stability constants of the iron(II)-hydroxamate complexes are compared with those of other divalent 3d-block metal ions and the Irving-Williams series of stabilities was found to be observed. Above pH 4, in the reactions between iron(II) and desferrioxamine B, the oxidation of the metal ion to iron(III) by the ligand was found. The overall reaction that resulted in the formation of the tris-hydroxamato complex [Fe(HDFB)]+ and monoamide derivative of DFB at pH 6 is: 2Fe2+ + 3H4DFB+ = 2[Fe(HDFB)]+ + H3DFB-monoamide+ + H2O + 4H+. Based on these results, the conclusion is that desferrioxamine B can uptake iron in iron(III) form under anaerobic conditions.
SimPlate for coliforms and Escherichia coli (CEc) is a new method for the detection and quantification of coliforms and E. coli in food. Internal validation of the method was carried out at IDEXX Laboratories (Westbrook, ME) with 180 food samples representing a variety of different food matrices and compared against three-tube MPN (most probable number), VRBA (violet red bile agar) + MUG, and Petrifilm (E. coli count) methods. SimPlate CEc was highly correlated with each of these methods for the quantification of coliform bacteria (r > or = 0.90). An insignificant number of food samples were found to contain E. coli; therefore, no meaningful correlation data could be generated. Four hundred forty-four additional food samples were tested at five collaborating laboratories for the presence of coliforms E. coli using SimPlate CEc and either VRBA + MUG or Petrifilm (E. coli count). Regression analysis of data from SimPlate for CEc versus Petrifilm E. coli count plates generated correlation coefficients (r) of at least 0.89 for total coliforms and at least 0.90 for generic E. coli. Correlation coefficients between SimPlate for CEc and VRBA + MUG data were at least 0.90 for coliforms and at least 0.86 for E. coli. SimPlate for CEc demonstrated better recovery of E. coli than Petrifilm when high populations of bacteria were present. E. coli was not detected in 20 or 50 (40%) raw milk samples tested by the Petrifilm method due to the presence of interfering coliform and noncoliform bacteria. It is concluded that SimPlate for CEc is a suitable alternative for determining numbers of coliform bacteria and E. coli in food.
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In 19 anesthetized piglets 3 ventilatory modes were studied after inducing pulmonary insufficiency by bronchoalveolar lavage by the method of Lachmann. The lavage model was considered suitable for reproduction of severe respiratory distress. This model was reproducible and stable with respect to alveolar collapse, decrease in static chest-lung compliance and increase in extravascular lung water. The ventilatory modes studied were volume-controlled intermittent positive-pressure ventilation (IPPV), pressure-controlled inverse ratio ventilation (IRV), and pressure-controlled high-frequency positive-pressure ventilation (HFPPV). The 3 ventilatory modes were used in random sequence for at least 30 min to produce a ventilatory steady state. Ventilation with no PEEP, permitting alveolar collapse, was interposed between each experimental mode. The ability to open collapsed alveoli, i.e. alveolar recruitment, was different. The recruitment rate for IPPV was 74%, but for IRV and HFPPV it was 95%, respectively. Although IRV provided the best PaO2, this was at the expense of high airway pressures with circulatory interference and reduced oxygen transport. In contrast to this, HFPPV provided lower airway pressures, less circulatory interference and improved oxygen transport. In the clinical setting there might be negative effects on vital organs and functions unless the ventilatory modes are continuously and cautiously adapted to the individual requirements in different phases of severe respiratory distress. Therefore, one ventilatory strategy could be to "open the airways" with IRV, but then switch to HFPPV in an attempt to maintain the airways open with lesser risk of barotrauma and with improved oxygen transport.
Plasma protein binding of oxybutynin (OXY) was investigated quantitatively and enantioselectively using high-performance frontal analysis (HPFA). An on-line HPLC system which consists of HPFA column, extraction column and analytical column was developed to determine the unbound concentrations of OXY enantiomers in human plasma, in human serum albumin (HSA) solutions, and in human alpha1-acid glycoprotein (AGP) solutions. OXY is bound in human plasma strongly and enantioselectively. The bound drug fraction in human plasma containing 2-10 microM (R)- or (S)-OXY was higher than 99%, and the unbound fraction of (R)-OXY was 1.56 times higher than that of (S)-isomer. AGP plays the dominant role in this strong and enantioselective plasma protein binding. The total binding affinities (nK) of (R)- and (S)-OXY to AGP were 6.86 x 10(6) and 1.53 x 10(7) M(-1), respectively, while the nK values of (R)- and (S)-OXY to HSA were 2.64 x 10(4) and 2.19 x 10(-4) M(-1), respectively. The binding affinity of OXY to AGP is much higher than that to HSA, and shows high enantioselectivity (SIR ratio of nK values is 2.2). It was found that both enantiomers are bound competitively at the same binding site on an AGP molecule. The binding property between OXY and low density lipoprotein (LDL) was investigated by using the frontal analysis method incorporated in high-performance capillary electrophoresis (HPCE/FA). It was found the binding is non-saturable and non-enantioselective.
The ability to rapidly recognize methicillin-resistant Staphylococcus aureus by use of two automated instrument systems, the MS-2 system (Abbott Laboratories, Diagnostics Division, Irving, Tex.) and the AutoMicrobic system (Vitek Systems, Hazelwood, Mo.), was evaluated on a collection of 95 methicillin-resistant S. aureus isolates recovered from at least six geographical areas of the United States. Isolates were simultaneously tested with both systems, and the results were compared with MIC tests performed by the National Committee for Clinical Laboratory Standards agar dilution method. Methicillin-resistant S. aureus isolates were defined as those with a methicillin MIC greater than or equal to 8 micrograms/ml by the reference procedure. Overall, with the AutoMicrobic system, 94.7% of 95 methicillin-resistant S. aureus isolates were detected, and with the MS-2 system, 91.6% of the isolates were detected. Isolates with methicillin MICs greater than or equal to 32 micrograms/ml were readily detected with both systems (41 of 42 isolates). Of 53 isolates from three locales with methicillin MICs of 8 or 16 micrograms/ml, 90.6% (48) were detected by the AutoMicrobic system, whereas 86.8% (46) were detected by the MS-2 system. A program update which has been added to the MS-2 system prints a warning message indicating possible methicillin-resistant S. aureus with isolates which demonstrate multiple antibiotic resistance (greater than or equal to four drugs other than methicillin). This warning message would have provided presumptive recognition of six of eight isolates with discrepant results for methicillin by the MS-2 system.
The transjugular intrahepatic portosystemic stent-shunt is a non-surgical method for creating a portosystemic shunt. Early reports suggest that it is effective for treating portal hypertension and variceal bleeding. This review describes the technique and discusses the indications and complications.