How hospitals can adapt to managing ESRD patient care.
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Biomedical subjects
Publications and source records attributed to M Thompson.
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Septic shock is a complex pathophysiologic state which often leads to multiple organ dysfunction, multiple organ failure, and death. This review summarizes current views on the molecular biology of three aspects of septic shock: recognition of bacterial invasion and induction of the cytokine response; genetic variability among humans and their predispositions toward pathologic inflammatory responses; and the signal transduction mechanisms which account for the transfer of molecular signals from cytokine receptors on the plasma membrane to cytokine-responsive genes in the nucleus. In particular, the review summarizes the pathway involved in tumor necrosis factor signaling through nuclear factor-kappaB, and elucidates the molecular signals involved in inflammatory responses and apoptosis.
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PURPOSE: Postoperative infection remains one of the most serious complications of implantation of penile prostheses. Attempts to reduce the rate of infection by spraying the prosthesis with an antibiotic solution prior to implantation, along with perioperative antibiotics, have failed to eradicate infection. No published studies have evaluated the effect of antibiotic coating of penile prostheses. In this study, we evaluate the antibacterial effect of antibiotic-coated silicone strips as a surrogate for the penile prosthesis. MATERIALS AND METHODS: Strips coated with several different antibiotics were dipped in bacterial solutions containing Staphylococcus epidermidis or S. aureus and implanted subcutaneously in adult Sprague-Dawley rats. After a week, the strips were removed, and the number of bacteria on the strips and in the surrounding tissue were determined. The in vitro antibiotic activity of the antibiotic-coated strips against the same organisms was also determined. RESULTS: In the group of rats that received silicone strips contaminated in vitro with S. epidermidis, six of nine control rats yielded strips and tissues containing heavy bacterial growth. None of six strips coated with rifampin/minocycline yielded bacterial growth, nor did any of the seven strips coated with vancomycin. One of seven rats that received amikacin-coated strips had infection of the strip. The tissue results were similar to the strip results. In the group using S. aureus as the contaminating bacterium, the strips and tissues from eight of nine control rats yielded bacteria. None of the six rifampin/minocycline-coated strips yielded bacteria, while two of seven vancomycin-treated strips and two of six amikacin-coated strips were infected with S. aureus. The difference in bacterial growth between controls and antibiotic-coated strips reached a level of statistical significance for the rifampin/minocycline and vancomycin groups and was highly significant for the rifampin/minocycline groups. CONCLUSION: The experimental results presented here suggest that coating silicone graft material with antibiotics, particularly rifampin/minocycline, can reduce the incidence of graft colonization in contaminated wounds in rats, even in the absence of systemic antibiotics. These graft materials may prove useful in preventing the infection of penile prostheses.
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BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate the efficacy of epicardially delivered laser energy to ablate induced ventricular tachycardia in a post-infarction canine model. STUDY DESIGN/MATERIALS AND METHODS: In 13 canines, the left anterior wall myocardial infarction was created. Five days later, 240 plunged electrodes were inserted into the heart. Three-dimensional ventricular activation sequences were analyzed on line by a computerized mapping system. RESULTS: Sixteen sustained monomorphic ventricular tachycardias were reproducibly induced in 10 canines. Epicardially contacted Nd:YAG laser irradiated the areas of the final pathway in macro-reentrant activation and the impulse origin in focal excitation. Linear photocoagulation lesions (11-16 x 50-72 mm) were created. Seven macro-reentrant circuits and six of nine focal origins were eliminated (success rate 81%). Pathology showed that laser photocoagulation involved all surviving subepicardial and intramural fibers. CONCLUSION: Epicardially delivered laser energy in conjunction with electrical activation mapping has a high probability of ablating post-infarction ventricular tachycardia.
UNLABELLED: A video telecommunication network was established to transmit coronary images between a cardiac catheterization laboratory and a remote core laboratory. In 40 patients during interventional procedures, cine angiograms, live fluoroscopy, intravascular ultrasound studies, and images of the cath lab were transmitted in real time over a T1 line at 768 kbits/second at 15 frames/second. RESULTS: Measurements of angiographic and intravascular ultrasound parameters were very close between the original studies and the transmitted images. The telecommunication link up during the interventional procedures had a significant affect in 58% of cases.
Data characterizing the endocrine stress response to burn injury in children are sparse. We have measured the levels of the stress hormones arginine vasopressin, catecholamines-adrenaline, noradrenaline and dopamine-atrial natriuretic peptide and hormones of the renin-angiotensin-aldosterone system in admission blood samples taken from 35 children admitted to the burns unit of the regional children's hospital. Hormone levels were compared with the size of burn injury. With the exception of adrenaline, there were significant positive correlations between vasopressin (r = 0.707, p < 0.0001), plasma renin activity (r = 0.721, P < 0.0001), angiotensin II (r = 0.512, P = 0.002), aldosterone (r = 0.620, P < 0.0001), noradrenaline (r = 0.430, P = 0.0189), dopamine (r = 0.627, P = 0.0024) and percentage burn surface area, and a negative correlation between atrial natriuretic peptide (r = 0.548, P = 0.0008) and burn surface area. It is concluded that the hormones which react to stress are very sensitive to burn injury in children, and that the magnitude of their response is closely related to the size of the burn surface area.
International approaches to defining the scope of nursing practice are many and varied. Some attempts to do this have produced models which are cumbersome lists of tasks or behaviours, or statements which do not clearly articulate the scope of practice. Others have provided processes for the extension of the scope of nursing practice without clearly identifying what is being extended. This paper explores relevant conceptual and professional issues which may assist nurses to address this important issue for nursing in Australia. These issues will be discussed in terms of boundaries limiting practice, borders being extended and balloons being flexible and shaped by forces and events internal and external to them.
BACKGROUND: Previous research has suggested that behavioural problems displayed during the pre-school years are best understood as undifferentiated difficulties in manageability. The present study explored this issue, by examining the structure of British parents' ratings of their pre-school children's behavioural problems. METHOD: The 19-item Behavioural Checklist (BCL; Richman, 1977) was completed by 1047 parents of 3-year-old children taking part in an epidemiological survey of child development. RESULTS: Factor analysis revealed six factors representing poor social adjustment, poor emotional adjustment, sleep problems, over-activity/inattention, eating problems and soiling. When these scores were used as a basis for cluster analysis, problem types clustered around six centres. The first, and largest, grouping was of children with no problems. Three further large groupings displayed specific but moderate problems (over-active, timid, and naughty children). The final two groupings displayed more extreme problems including anti-social behaviour. In one group these were accompanied by severe emotional problems and in the other by signs of hyperactivity. The reliability and validity of these clusters was supported. Parental ratings of behaviour problems taken when the children were 8-years-old suggested that the children in the hyperactive/conduct group were likely to have continued difficulties. CONCLUSION: This paper argues against the homogeneity of pre-school behaviour problems but supports the idea that problems of a clinically significant level are likely to be co-morbid, with either problems of emotional regulation (neurotic) or those of behavioural regulation (hyperactive) accompanied by problems of conduct.
1. 4-Amino-7-hydroxy-2-methyl-5,6,7,8,-tetrahydrobenzo[b]thieno[2,3-b]pyrid ine-3-carboxylic acid, but-2-ynyl ester (SB-205384) and other gamma-aminobutyric acid(A) (GABA(A)) receptor modulators were tested for their effects on GABA-activated chloride currents in rat cerebellar granule cells by use of the whole-cell patch clamp technique. 2. The major effect of SB-205384 on GABA(A)-activated current was an increase in the half-life of decay of the response once the agonist had been removed. This is in contrast to many GABA(A) receptor modulators that have previously been shown to potentiate GABA-activated currents. 3. This profile could be explained if SB-205384 stabilizes the channel in open and desensitized states so that channel closing is dramatically slowed. Such a modulatory profile may produce a novel behavioural profile in vivo.
1. Earlier optimization of structure-activity relationships in a novel series of 4-(benzoylamino)-benzopyrans, led to the discovery of SB-204269 (trans-(+)-6-acetyl-4S-(4-fluorobenzoylamino)-3,4-dihydro-2, 2-dimethyl-2H-benzo[b]pyran-3R-ol, hemihydrate), a potent orally-active anticonvulsant in the mouse maximal electroshock seizure threshold (MEST) test. 2. Studies have now been undertaken to determine the effects of SB-204269 in a range of seizure models and tests of neurological deficits in rats. In addition, the compound has been evaluated in a series of in vitro mechanistic assays. 3. SB-204269 proved to be an orally-effective anticonvulsant agent, at doses (0.1-30 mg Kg-1) devoid of overt behavioural depressant properties, in models of both electrically (MEST and maximal electroshock (MEST)) and chemically (i.v. pentylenetetrazol (PTZ) infusion)-evoked tonic extension seizures. However, the compound did not inhibit PTZ-induced myoclonic seizures at doses up to 30 mg kg-1, p.o. 4. SB-204269 also selectively reduced focal electrographic seizure activity in an in vitro elevated K+ rat hippocampal slice model at concentrations (0.1-10 microM) that had no effect on normal synaptic activity and neuronal excitability. 5. In all of these seizure models, SB-204269 was equivalent or better than the clinically established antiepileptic drugs carbamazepine and lamotrigine, in terms of anticonvulsant potency and efficacy. 6. Unlike SB-204269, the corresponding trans 3S,4R enantiomer, SB-204268, did not produce marked anticonvulsant effects, an observation in accord with previous findings for other related pairs of trans enantiomers in the benzopyran series. 7. In the rat accelerating rotarod test, a sensitive paradigm for the detection of neurological deficits such as sedation and motor incoordination, SB-204269 was inactive even at doses as high as 200 mg kg-1, p.o. This was reflected in the excellent therapeutic index (minimum significantly effective dose in the rotarod test/ED50 in the MES test) for SB-204269 of > 31, as compared to equivalent values of only 7 and 13 for carbamazepine and lamotrigine, respectively. 8. At concentrations (> or = 10 microM) well above those required to produce anticonvulsant activity in vivo (i.e. 0.1 microM in brain), SB-204269 did not interact with many of the well known mechanistic targets for established antiepileptic drugs (e.g. Na+ channels or GABAergic neurotransmission). Subsequent studies have shown that the anticonvulsant properties of SB-204269 are likely to be mediated by a novel stereospecific binding site present in the CNS. 9. The overall efficacy profile in rodent seizure models, together with a minimal liability for inducing neurological impairment and an apparently unique mechanism of action, highlight the therapeutic potential of SB-204269 for the treatment of refractory partial and generalized tonic-clonic seizures.
1. SB-204269 (trans-(+)-6-acetyl-4S-(4-fluorobenzoylamino)-3, 4-dihydro-2,2-dimethyl-2H-benzol[b]pyran-3R-ol, hemihydrate) shows potent anticonvulsant activity in a range of animal seizure models, with a lack of neurological or cardiovascular side-effects. The profile of the compound suggests that it may have a novel mechanism of action. This study describes the characteristics of a binding site for [3H]-SB-204269 in rat forebrain membranes. 2. Specific [3H]-SB-204269 binding was saturable and analysis indicated binding to a homogenoeous population of non-interacting binding sites with a dissociation constant (KD) of 32 +/- 1 nM and a maximum binding capacity (Bmax) of 253 +/- 18 fmol mg-1 protein. Kinetic studies indicated monophasic association and dissociation. Binding was similar in HEPES or Tris-HCl buffers and was unaffected by Na+, K+, Ca2+ or Mg2+ ions. Specific binding was widely distributed in brain, but was minimal in a range of peripheral tissues. 3. Specific [3H]-SB-204269 binding was highly stereoselective, with a 1000 fold difference between the affinities of SB-204269 and its enantiomer SB-204268 for the binding site. The affinities of analogues of SB-204269 for binding can be related to their activities in the mouse maximal electroshock seizure threshold (MEST) test of anticonvulsant action. 4. None of the standard anticonvulsant drugs, phenobarbitone, phenytoin, sodium valproate, carbamazepine, diazepam and ethosuximide, or the newer anticonvulsants, lamotrigine, vigabatrin, gabapentin and levetiracetam, showed any affinity for the [3H]-SB-204269 binding site. A wide range of drugs active at amino acid receptors, Na+ or K+ channels or various other receptors did not demonstrate any affinity for the binding site. 5. These studies indicate that SB-204269 possesses a specific CNS binding site which may mediate its anticonvulsant activity. This binding site does not appear to be directly related to the sites of action of other known anticonvulsant agents, but may have an important role in regulating neuronal excitability.
The adsorption of the proteins, bovine serum albumin, fibrinogen, avidin and neutravidin (non-glycosylated form of avidin) to a variety of surfaces imposed on thickness shear mode sensors in examined in a flow-injection analysis format. In all cases, adsorption of these moieties was essentially irreversible, although the magnitude of adsorption was dependent on surface free energy and functional group chemistry. Also described is the direct, real-time detection of the binding of peptides to HIV-1 TAR RNA bound on a thickness-shear mode (TSM) sensor surface. The results clearly indicate that responses are discriminatory for two different peptides. In order to provide a theoretical backcloth for the experimental measurements, a new model for the operation of the TSM in liquids is presented.
Eight different conducting polymer films formed from pyrrole and N-substituted pyrrole derivatives were characterized by cyclic voltammetry, X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy. In particular, the XPS of poly[N-butylpyrrole], poly[N-(2-carboxyethyl)pyrrole], poly[N-(6-hydroxyhexyl)pyrrole] and poly[N-(6-tetrahydropyranylhexyl)pyrrole] is reported for the first time. The vapour sorption properties of these films were also examined by forming the films onto the electrodes of thickness-shear mode acoustic wave sensors. The influence of the pendant side chain is apparent in both the electrochemical behaviour, composition, doping level, morphology and the nature and extent of polymer-vapour interactions. The latter can be rationalized by consideration of vapour physical properties and solvatochromic parameters.
OBJECTIVE: The purpose of this study was to assess the efficacy of Borg's rating of perceived exertion (RPE) scale to predict maximal exercise levels to control exercise intensity in patients taking atenolol for the treatment of essential hypertension. Normally, a standard formula (220-age) is used for calculating a percentage of exercise intensity, but beta blockade can cause reductions in maximal heart rate of between 20 and 30%. METHODS: Patients were split into a control group-10 men and 10 women, aged 50 (SD 12) and 46 (9) respectively, who had risk factors for cardiovascular disease but were not taking any drugs, and a treatment group-11 men and 11 women, aged 53 (13) and 55 (13) respectively, who were established on 25-100 mg of atenolol. All patients performed two submaximal tests on a cycle ergometer. Test 1 was an estimation test, during which the RPE was reported for each increment in work rate. Test 2 was an RPE production test, during which the patient regulated the work rate according to his/her perception of effort at four predetermined points on the RPE scale (RPE 9, 13, 15, 17). RESULTS: In both tests the individual correlations (r) between RPE, heart rate, and work rate ranged from 0.96 to 0.99. Analysis of variance showed no significant difference in maximal heart rate and maximal power output for the control group when predicted from the regression lines of RPE versus heart rate and RPE versus power output in the estimation test. However, the prediction of maximal power output was lower in the women in the control group and patients in the treatment group when this was predicted from the effort production protocol (P < 0.01). When exercise intensity at each RPE was expressed relative to maximal power output there were no differences between treatment and control groups. CONCLUSION: The findings from this study confirmed the strong positive relation between RPE, heart rate, and work rate in these patients in both passive effort estimation and active effort production protocols. However, caution in applying these procedures is required because the prediction of maximal exercise levels may be lower when effort production procedures are used.
The absolute right to refuse medical treatment, even if the reasons are irrational, is confined to competent adults. Children under 16 years can give legal consent to treatment in the absence of consent from those with parental responsibility. Children under 18 years do not, however, have an absolute right to consent, or refuse to consent, to treatment. The views of children assume increasing importance with age and maturity. Accident and emergency medical and nursing staff may face difficult decisions when children, or those with parental responsibility, refuse to consent to medical treatment. This paper presents guidelines designed to guide the decision making process in immediately or potentially life threatening conditions and in non-life-threatening conditions.