Sepsis and ECMO: beware the breast milk.
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Biomedical subjects
Publications and source records attributed to S Morgan.
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The need for solid organs suitable for transplantation is an ever growing one in the United States today. It is imperative that there is ongoing interaction between the local Organ Procurement Organization and the health care professional so that a trust and a spirit of collaboration can develop. The use of the Organ/Tissue Donation Algorithm and the multidisciplinary approach has produced both positive and negative outcomes.
OBJECTIVES: To determine the effect of breathing helium-oxygen (HELIOX) mixtures on pulmonary gas exchange during severe asthma. DESIGN: A retrospective case-match control design was used to compare the changes in alveolar to arterial gradient [(A-a)gradient] in the first 2 hrs of mechanical ventilation (MV) for status asthmaticus (SA) in patients who received HELIOX with those who did not. Patients were matched for diagnosis of asthma, ventilatory failure, ventilator mode and settings, and equivalent pharmacologic therapy. SETTING: The adult and pediatric intensive care units of a tertiary-care hospital. SUBJECTS: Adult and pediatric patients undergoing MV for SA. INTERVENTIONS: Use of HELIOX or standard nitrogen-oxygen mixtures during MV. MEASUREMENTS AND MAIN RESULTS: A total of 11 patients receiving HELIOX in the first 2 hrs of MV for SA were compared with 11 case-matched controls who did not. At baseline, the HELIOX and control groups had similar (A-a)gradients (216+/-92 torr and 226+/-82 torr, respectively). The (A-a)gradient decreased significantly to 85+/-44 torr after initiation of ventilation with HELIOX (p < .0003), whereas it did not change significantly in the control group in a similar time frame and during identical treatment without HELIOX. The reduction in (A-a)gradient in the HELIOX group facilitated a reduction in F(IO)2 from 0.8+/-0.2 initially to 0.4+/-0.1 at the time of the second blood gas determination, thus permitting greater concentrations of helium to be administered. CONCLUSIONS: MV with HELIOX improves (A-a)gradient in patients with SA. Although this improvement adds little to routine therapy with supplemental oxygen, it does permit reduction in concentration of inspired oxygen to levels that maximize helium concentration and thus permit full benefits of HELIOX on lung mechanics to be realized in even the most severely ill asthmatics.
OBJECTIVE: To compare two rapid whole-blood serology tests for Helicobacter pylori and a laboratory serology assay against a gold standard. DESIGN: Prospective comparison of tests in 81 patients. SETTING: A hospital rapid access endoscopy clinic. PARTICIPANTS: Dyspeptic patients requiring assessment of H. pylori status. INTERVENTIONS: Measurement of H. pylori antibody status by Quickvue One-step, Helisal, and Premier H. pylori test; 13C urea breath test for H. pylori, and gastric biopsies for histology, culture and rapid urease test. MAIN OUTCOME MEASURE: Sensitivity and specificity of Quickvue One-step, Helisal and Premier tests, compared to a gold standard based on 13C urea breath test, biopsy culture, histology and urease test. RESULTS: The Quickvue assay has significantly greater sensitivity (81%) than Helisal (67%), but without appreciable loss of specificity (86% and 93%, respectively). The Premier laboratory assay is significantly more sensitive than both of the rapid blood tests (96%), with comparable specificity to the Quickvue assay. CONCLUSION: The rapid serology tests used in this study are quick and convenient to use, but do not approach the sensitivity of a laboratory assay in detecting H. pylori status in this group of dyspeptic patients attending an endoscopy clinic.
Between September 1995 and August 1998, the incidence and diversity of the main human rotavirus genotypes (G1, G2, G3, and G4 and P[8], P[4], P[6], and P[9]) among Irish children were determined by using established and adapted reverse transcriptase PCR-based genotyping methods. From a total of 193 rotavirus-positive specimens collected from nine hospitals we successfully identified the P type in 182 (94%) of the samples and the G type in 165 (85.5%) of the samples. Only four samples could not be assigned a G or P type. Two P types existed in Ireland, P[8] (78%) and P[4] (16%), and their relative incidence varied over the 3 years of this study. No P[6] or P[9] types were detected. G1 was the most predominant G type (55%), and the incidences of G2, G3, and G4 isolates were 15.5, 1, and 11%, respectively. Three percent of the samples tested had a mixed G type. A P and G type was assigned to 158 (81.8%) of samples. Of the typeable samples, G1 P[8] was the most prevalent (65%), whereas G2 P[4] (17%), G3 P[8] (1%), G4 P[8] (12%), and mixed types (all G1/ G4 P[8]) (4%) were detected less frequently. In the third year a significant genotypic shift from G1 P[8] to G2 P[4] and G4 P[8] was observed. During the study, we noticed that the inclusion of random primers during cDNA synthesis greatly increased the specificity of the PCR typing assays. No correlation was seen between the contributing hospitals and a specific genotype. In conclusion, the coverage of infection given by the recently licensed tetravalent vaccine would be significantly high in Ireland, although future monitoring of genotypic changes among Irish isolates should be encouraged.
The in vivo antithrombotic activity of RPR 20844, a novel synthetic coagulation factor Xa (fXa) inhibitor (Ki = 7 nM), was assessed by its ability to inhibit thrombus formation in a damaged segment of the rabbit jugular vein. Intravenous dose-response studies were performed and thrombus mass (TM), activated partial thromboplastin time (APTT), prothrombin time (PT), inhibition of ex vivo fXa activity and plasma drug levels (PDL) were determined. TM, measured at the end of a 50 min infusion, was significantly reduced (p<0.05 vs. saline-treated animals) by RPR120844 at 30 and 100 microg/kg/min. At doses of 10, 30 and 100 microg/kg/min, APTT was prolonged by 2.1, 4.2 and 6.1-fold, and PT was prolonged by 1.4, 2.2 and 3.5-fold, respectively. PDL were determined by measuring anti-fXa activity using an amidolytic assay. Peak PDL were 0.8+/-0.3, 1.5+/-0.9 and 2.4+/-0.6 microM, respectively. The drug effect was reversible with APTT, PT and PDL returning toward pretreatment values 30 min after termination of treatment. The results suggest that RPR 120844, or similar compounds, may provide an efficacious, yet easily reversible, means of inhibiting thrombus formation.
Ca2+ influxes regulate multiple events in photoreceptor cells including phototransduction and synaptic transmission. An important Ca2+ sensor in Drosophila vision appears to be calmodulin since a reduction in levels of retinal calmodulin causes defects in adaptation and termination of the photoresponse. These functions of calmodulin appear to be mediated, at least in part, by four previously identified calmodulin-binding proteins: the TRP and TRPL ion channels, NINAC and INAD. To identify additional calmodulin-binding proteins that may function in phototransduction and/or synaptic transmission, we conducted a screen for retinal calmodulin-binding proteins. We found eight additional calmodulin-binding proteins that were expressed in the Drosophila retina. These included six targets that were related to proteins implicated in synaptic transmission. Among these six were a homolog of the diacylglycerol-binding protein, UNC13, and a protein, CRAG, related to Rab3 GTPase exchange proteins. Two other calmodulin-binding proteins included Pollux, a protein with similarity to a portion of a yeast Rab GTPase activating protein, and Calossin, an enormous protein of unknown function conserved throughout animal phylogeny. Thus, it appears that calmodulin functions as a Ca2+ sensor for a broad diversity of retinal proteins, some of which are implicated in synaptic transmission.
Leukocyte adhesion under flow is preferentially mediated by the selectins. In this study we used intravital microscopy to investigate whether E-selectin may promote firm leukocyte adhesion in vivo. E-Selectin is expressed by endothelial cells activated with tumor necrosis factor-alpha (TNF-alpha) and causes slow leukocyte rolling. Microinjection of formyl-methionyl-leucyl-phenylalanine (fMLP) or macrophage inflammatory protein-2 (MIP-2) next to a venule of the TNF-alpha-treated mouse cremaster muscle significantly increased the number of adherent leukocytes. In gene-targeted mice homozygous for a null mutation in the E-selectin gene or in wild-type mice treated with an E-selectin monoclonal antibody (mAb), this response was significantly attenuated (by >80%). No such defect was seen in intercellular adhesion molecule-1 (ICAM-1)-deficient mice. E-Selectin-null mice showed more rapid leukocyte rolling than wild-type or ICAM-1-deficient mice, resulting in significantly shortened leukocyte transit times through venules. Topical application of fMLP onto the whole cremaster muscle generated the same number of adherent leukocytes in wild-type and E-selectin-deficient mice. We conclude that slow leukocyte rolling through E-selectin results in long transit times, which are essential for efficient leukocyte adhesion in response to a local chemotactic stimulus.
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The sequencing of euryarchaeal genomes has suggested that the essential protein lysyl-transfer RNA (tRNA) synthetase (LysRS) is absent from such organisms. However, a single 62-kilodalton protein with canonical LysRS activity was purified from Methanococcus maripaludis, and the gene that encodes this protein was cloned. The predicted amino acid sequence of M. maripaludis LysRS is similar to open reading frames of unassigned function in both Methanobacterium thermoautotrophicum and Methanococcus jannaschii but is unrelated to canonical LysRS proteins reported in eubacteria, eukaryotes, and the crenarchaeote Sulfolobus solfataricus. The presence of amino acid motifs characteristic of the Rossmann dinucleotide-binding domain identifies M. maripaludis LysRS as a class I aminoacyl-tRNA synthetase, in contrast to the known examples of this enzyme, which are class II synthetases. These data question the concept that the classification of aminoacyl-tRNA synthetases does not vary throughout living systems.
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An outbreak of Gram-negative septicaemia due to cross infection on an acute cardiology ward is reported. This outbreak was facilitated by two factors: first, an area originally designed for non-clinical purposes was converted into a clean utility area without consulting the infection control team, and second, changes in staff had taken place at the same time. This outbreak emphasizes the importance of continuous staff training in infection control, the involvement of the infection control team in all building alterations and the need to improve recommendations by the Department of Health in the design of clean utility areas.
In some studies the BioStar Strep A OIA (optical immunoassay) has yielded inconsistent results, although originally it was reported to be more sensitive than conventional culture for the detection of group A Streptococcus (GAS). The Group A Selective Strep Agar with 5% sheep blood (ssA) incubated anaerobically has been reported to be more sensitive than conventional culture in the detection of GAS. We compared the BioStar Strep A OIA GAS rapid antigen detection kit to anaerobic culture on ssA with and without preincubation in Todd-Hewitt broth (THB) for the detection of GAS. From September 1995 through January 1996, throat swabs were collected in duplicate from 75 children (< or = 18 years) and 188 adults (> 18 years) who presented with pharyngitis in the outpatient University of New Mexico Family Practice Clinic. Thirty-one (12%) of the 263 cases were positive for GAS by culture and/or broth. Compared with anaerobic culture on the ssA, with and without preincubation in THB, the sensitivity, specificity, positive predictive value, and negative predictive value of the BioStar Strep A OIA were 77, 62, 22, and 95%, respectively. Compared with enrichment in THB followed by subculture on ssA and anaerobic incubation, the sensitivity, specificity, positive predictive value, and negative predictive value of direct culture on ssA and anaerobic incubation were 79, 99, 98, and 96%, respectively. All isolates were serologically grouped. The BioStar Strep A OIA is as sensitive as direct culture on ssA incubated anaerobically, but the low specificity and low positive predictive value when the OIA is used in low prevalence populations could lead to unnecessary antibiotic treatment.
This project utilized constructive feedback from clients of mental health facilities as a means of facilitating student nurse learning in three clinical environments. Three questionnaires were utilized to elicit and evaluate the impact of this feedback with a sample of 43 students and 74 client participants. The inquiry demonstrated that clients are willing to participate in students learning and believe that they can contribute towards it. Students also believed that clients have a valuable role to play in their learning, although they note caution in regards to client selection.
OBJECTIVE: We aimed to assess general practice care for patients following a myocardial infarction (MI). METHOD: A structured review was carried out of general practice records of patients identified from hospital administration data. A total of 266 survivors following MI were identified from the discharge data of 13 hospitals in Southern England and registered with 71 GPs belonging to the Wessex Research Network. Median time since hospital discharge was 2.1 years. The main outcome measures were the provision of appropriate preventive care, including cardiac rehabilitation, drug therapy, and lifestyle advice for modifiable risk factors. RESULTS: Basic care was provided to nearly all patients; 253 (95.1%, 95% Cl 91.8-97.4) had blood pressure documented after their MI, 216 of 234 patients eligible for aspirin (92.3%; 88.1-95.4) had been recommended treatment, and the provision of advice on smoking cessation was documented for 27 of 33 continuing smokers (81.8%; 64.5-93.0). However, only 73 of 236 patients eligible to attend a structured rehabilitation programme (30.9%; 25.0-36.8) were documented as having received rehabilitation. Of 89 patients with heart failure following MI, 33 (37.1%; 27.1-48.0) had no record of having been offered treatment with an ACE inhibitor. Total cholesterol measurement was documented for only 144 patients (54.1%; 48.1-60.1). We estimate that there is still the potential to prevent between 4 and 9 deaths in this group of 266 surviving patients in the next 2 years by further improving the quality of follow-up care. CONCLUSIONS: Preventive care in patients with proven ischaemic heart disease in general practice remains haphazard, even among doctors enthusiastic to participate in research and to audit their quality of care. As general practitioners we should ensure that we are providing high quality preventive care to patients with clinical disease before we focus on the even more demanding task of primary prevention.
We have previously reported that nitric oxide (NO) plays an important role in protecting the renal vasculature from acute norepinephrine-induced vasoconstriction. The purpose of this study was to determine the importance of this interaction between NO and norepinephrine in long-term control of renal hemodynamics and arterial pressure. To achieve this goal, we examined the effects of an intrarenal infusion of norepinephrine (NE) (0.1 microgram.kg-1.min-1) for 7 days in conscious, chronically instrumented control dogs and in dogs pretreated with a synthesis inhibitor, L-NAME (3 micrograms.kg-1.min-1 intrarenally). Both groups of dogs also received captopril (15 micrograms.kg-1.min-1) plus angiotensin I] intravenously to clamp the renin-angiotensin system throughout the protocol. In control dogs (n = 6), intrarenal infusion of NE decreased renal plasma flow by 9% (134 +/- 10 to 122 +/- 14 mL/min) and glomerular filtration rate by 16% (49 +/- 4 to 41 +/- 5 mL/min) while having no effect on mean arterial pressure (100 +/- 3 to 98 +/- 4 mm Hg). In marked contrast, in dogs pretreated with intrarenal L-NAME (n = 9), NE decreased renal plasma flow by 37% (129 +/- 8 to 81 +/- 16 mL/min) and glomerular filtration rate by 32% (47 +/- 3 to 32 +/- 5 mL/min) while increasing mean arterial pressure from 104 +/- 5 to 113 +/- 6 mm Hg. The results of this study demonstrate that NO plays an important role in modulating the long-term actions of NE on renal function and arterial pressure.
We describe a new method for measuring autoantibodies (Ab) to the 65 kDa isoform of glutamic acid carboxylase (GAD65). In particular, GAD65 without the hydrophobic N-terminal region has been produced in yeast, purified, labelled with 125I and reacted with GAD65 Ab. Antibody bound 125I-GAD65 is then precipitated by the addition of solid phase protein A. With the assay, GAD65 Ab were detected in 59 of 71 (83%) islet cell antibody (ICA) positive IDDM patients and in 8 of 23 (35%) ICA negative IDDM patients (overall 67 of 94 (71%) of IDDM patients). Low concentrations of GAD65 Ab were also detected in 2/98 (2%) healthy blood donors and 1/27 (4%) Graves' disease patients had a high level of antibody. GAD65 Ab were not detected in any of 10 Hashimoto's thyroiditis, 20 Addison's disease or 19 myasthenia gravis sera. There was good agreement between the 125I assay and the current reference method based on 35S-labelled full-length GAD65 (produced by in vitro transcription/translation reaction) and solid phase protein A (r = 0.91, n = 108). Overall, our 125I assay showed sensitivity, precision and disease group specificity at least as good as any assay so far described. These features, combined with a simple assay protocol and the convenience of 125I counting and handling indicate that the method is suitable for routine GAD65 Ab measurements.