Search Results - (Author, Cooperation:J. L. Moran)

2014-01-28

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Autistic Disorder/genetics ; Calcium Channels/genetics ; Cytoskeletal Proteins/genetics ; DNA Copy Number Variations/genetics ; Female ; Fragile X Mental Retardation Protein/metabolism ; Genome-Wide Association Study ; Humans ; Intellectual Disability/genetics ; Intracellular Signaling Peptides and Proteins/genetics ; Male ; Membrane Proteins/genetics ; Multifactorial Inheritance/*genetics ; Mutation/*genetics ; Nerve Tissue Proteins/genetics ; Receptors, N-Methyl-D-Aspartate/genetics ; Schizophrenia/*genetics

2014-01-28

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Child Development Disorders, Pervasive/genetics ; Cytoskeletal Proteins/metabolism ; Exome/genetics ; Fragile X Mental Retardation Protein/metabolism ; Humans ; Intellectual Disability/genetics ; *Models, Neurological ; Mutation/*genetics ; Mutation Rate ; Nerve Net/*metabolism/physiopathology ; Nerve Tissue Proteins/metabolism ; Neural Pathways/*metabolism/physiopathology ; Phenotype ; RNA, Messenger/genetics/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; Schizophrenia/*genetics/metabolism/*physiopathology ; Substrate Specificity ; Synapses/*metabolism

1432-1238

Cortisol ; Septic shock ; Hypoadrenalism ; Inotropes ; Haemodynamics ; Stepwise logistic regression

Springer Online Journal Archives 1860-2000

Medicine

Abstract Objective To characterise the plasma cortisol profile and adreno-cortial responsiveness (short Synacthen test) of patients in septic shock. Design Retrospective assessment using case-notes and ICU charts. Setting University teaching hospital ICU. Patients 68 septic shock patients with plasma cortisol and/or short Synacthen test measured at ICU-admission or onset of shock post ICU-admission. Patients were identified from a total population of 155 patients who had PCL and/or SST measured over a 4.5 year period. Intervention None. Measurements and results Patients with septic shock had a plasma cortisol ranging from 210–8900 nmol/l and mortality of 56%. There were 22 (32%) below (low) and 46 (68%) above (high) a ‘critical’ plasma cortisol of 500 nmol/l. Using stepwise logistic regression, mortality was adequately predicted by and increased with, increasing plasma cortisol and onset of shock remote from ICU-admission. Short Synacthen tests were available in 33 patients: 11 responders (cortisol increment 〉200 nmol/l above baseline 30 min after 0.25 mg intravenous Synacthen) and 22 hypo-responders. Mortality in patients was adequately predicted by and increased with a decrease in cortisol increment post-Synacthen. Thirteen patients (plasma cortisol 606±[SD] 297 nmol/l) had complete haemodynamic profiles before inotropic therapy; no relationship was demonstrated between plasma cortisol and circulatory variables. Follow-up revealed no cases of Addison's disease. Conclusions In septic shock, ‘hypocortisolaemia’ is not uncommon and does not predict a high mortality; adrenocortical hypo-responsiveness may be associated with poor outcome.

Electronic Resource

1432-1211

Key words Nonhuman primate ; Spondyloarthropathy ; Reactive arthritis ; Autoimmunity ; Major histocompatibility locus

Springer Online Journal Archives 1860-2000

Biology

Medicine

Abstract  The human major histocompatibility complex (MHC) class I gene, HLA-B27, is a strong risk factor for susceptibility to a group of disorders termed spondyloarthropathies. Rodents that express HLA-B27 develop spondyloarthropathies, implicating HLA-B27 in the etiology of these disorders. To determine whether an HLA-B27-like molecule was associated with spondyloarthropathies in nonhuman primates, we analyzed the MHC class I cDNAs expressed in a cohort of rhesus macaques that developed reactive arthritis after an outbreak of shigellosis. We identified several cDNAs with only limited sequence similarity to HLA-B27. Interestingly, one of these MHC molecules had a B pocket identical to that of HLA-B39. Pool sequencing of radiolabeled peptides bound by this molecule demonstrated that, like HLA-B27 and HLA-B39, it could bind peptides with arginine at the second position. However, extensive analysis of the MHC class I molecules in this cohort revealed no statistically significant association between any particular MHC class I allele and susceptibility to reactive arthritis. Furthermore, none of the rhesus MHC class I molecules bore a strong resemblance to HLA-B27, indicating that reactive arthritis can develop in this animal model in the absence of an HLA-B27-like molecule. Surprisingly, there was a statistically significant association between the rhesus macaque MHC A locus allele, Mamu-A*12, and the absence of reactive arthritis following Shigella infection.

Electronic Resource

1432-1238

Weaning ; Extubation ; Indices ; Subjective ; Critically ill ; Mechanical ventilation ; CPAP ; Pressure support

Springer Online Journal Archives 1860-2000

Medicine

Abstract Objective To assess the outcome of a clinical judgementbased approach to weaning and extubation and to adduce the predictive accuracy of various mechanical respiratory indices measured in parallel. Design Prospective study. Setting Multidisciplinary intensive care unit at a university teaching hospital. Patients 163 consecutive mechanically ventilated patients, excluding tracheotomy, for weaning trial and extubation. Interventions Using bedside clinical assessment, aided by arterial gas analysis, patients were weaned from mechanical ventilation to spontaneous ventilation via the continuous positive airway pressure (CPAP) circuit (with pressure support) of a microprocessor-controlled ventilator. Extubation occurred from the CPAP circuit at 7 cmH2O pressure support, fractional inspired oxygen (FIO2)≤0.5 and CPAP level of ≤5 cmH2O, such that the partial pressure of oxygen in arterial blood (PaO2) was ≥65 mmHg. Before extubation, observation for a 1-h (T0 and T60) trial period allowed measurement of vital capacity (VC), expired minute volume (VE), respiratory rate/tidal volume (f/VT) and maximal inspiratory pressure (MIP) using a one-way valve technique over 25 s. Measurements and main results Over 7 months, 163 patients (62 females and 101 males; mean(SD) age 64(15) years) were considered. There were 91 surgical (18 with chronic obstructive pulmonary disease; COPD) and 72 medical (28 with COPD) patients. Ventilation was for ≥1 day (median 5 days, range 1–31) in 115 [group I; APACHE II score 23(8)] and ≤1 day in 48 [Group II; APACHE II score 17(6)]. Three patients (all Group I: 2 surgical, 1 medical) were reintubated within 24 h, an overall extubation failure rate of 1.8%. In group I, at T0, PaO2/FIO2 was 238(65), f/VT 50(26), MIP 44(21) cmH2O, VE 10.6(3.7) l/min, VC 13(5) ml/kg. Cardiorespiratory variables did not change significantly in either group, T0 to T60. For prediction of reintubation (n=163), only VE (threshold 〉10 l/min) and f/VT (threshold 〉100) demonstrated moderate sensitivity and specificity at T60∶67 and 52% and 33 and 94%, respectively. Conclusions Bedside clinicla judgement of weaning and extubation produces satisfactory outcomes. As a routine, mechanical predictive indices have limited utility.

Electronic Resource

1432-1238

Inspiratory work ; CPAP ; Inspiratory flow ; Endotracheal tube

Springer Online Journal Archives 1860-2000

Medicine

Abstract Inspiratory work imposed by Continuous Positive Airway Pressure (CPAP) machines has been a matter of concern. The imposed inspiratory work of CPAP machine circuits (Wcir) and the effect of the total breathing apparatus with endotracheal tube (ETT) and connector included in the circuit (Wapp), were measured in three continuous flow (CF) and various configurations of three demand flow (DF) CPAP machines. The performance was assessed at 0, 5, 10 and 15 cmH2O CPAP using a Michigan Instruments Test Lung Model 1600, internal compliance set at 50 ml/cmH2O, driven at square wave inspiratory flows ( $$\dot V$$ I) of 20, 40 and 60 l/min at a tidal volume of 500 ml. Work, expressed in mJ/l, was calculated from the area of pressure-volume loops. Inspiratory work, Wcir and Wapp, was dependent upon the particular CPAP machine, $$\dot V$$ I and ETT size, but not upon CPAP level, being maximum at $$\dot V$$ I 601/min and with ETT 7.0 mm i.d. Work values (Wcir) varied from 50 to 325 mJ/l with both CF and DF machines and up to 1100 mJ/l with ETT and connector (Wapp). No consistent advantage of CF over DF machines was demonstrated. There was little advantage of high gas flows (〉5 l/min) in various DF circuits. Within an individual machine maximum negative pressures generated during inspiration correlated with both Wcir and Wapp.

Electronic Resource

1432-1238

Key words Weaning ; Extubation ; Indices ; Subjective ; Critically ill ; Mechanical ventilation ; CPAP ; Pressure support

Springer Online Journal Archives 1860-2000

Medicine

Abstract Objective: To assess the outcome of a clinical judgement-based approach to weaning and extubation and to adduce the predictive accuracy of various mechanical respiratory indices measured in parallel. Design: Prospective study. Setting: Multidisciplinary intensive care unit at a university teaching hospital. Patients: 163 consecutive mechanically ventilated patients, excluding tracheotomy, for weaning trial and extubation. Interventions: Using bedside clinical assessment, aided by arterial gas analysis, patients were weaned from mechanical ventilation to spontaneous ventilation via the continuous positive airway pressure (CPAP) circuit (with pressure support) of a microprocessor-controlled ventilator. Extubation occurred from the CPAP circuit at 7 cmH2O pressure support, fractional inspired oxygen (FIO2) ≤0.5 and CPAP level of ≤5 cmH2O, such that the partial pressure of oxygen in arterial blood (PaO2) was ≥65 mmHg. Before extubation, observation for a 1-h (T0 and T60) trial period allowed measurement of vital capacity (VC), expired minute volume (VE), respiratory rate/tidal volume (f/VT) and maximal inspiratory pressure (MIP) using a one-way valve technique over 25 s. Measurements and main results: Over 7 months, 163 patients (62 females and 101 males; mean(SD) age 64(15) years) were considered. There were 91 surgical (18 with chronic obstructive pulmonary disease; COPD) and 72 medical (28 with COPD) patients. Ventilation was for ≥1 day (median 5 days, range 1–31) in 115 [group I; APACHE II score 23(8)] and ≤1 day in 48 [Group II; APACHE II score 17(6)]. Three patients (all Group I: 2 surgical, 1 medical) were reintubated within 24 h, an overall extubation failure rate of 1.8%. In group I, at T0, PaO2/FIO2 was 238(65), f/VT 50(26), MIP 44(21) cmH2O, VE 10.6(3.7) l/min, VC 13(5) ml/kg. Cardiorespiratory variables did not change significantly in either group, T0 to T60. For prediction of reintubation (n=163), only VE (threshold 〉10 l/min) and f/VT (threshold 〉 100) demonstrated moderate sensitivity and specificity at T60: 67 and 52% and 33 and 94%, respectively. Conclusions: Bedside clinical judgement of weaning and extubation produces satisfactory outcomes. As a routine, mechanical predictive indices have limited utility.

Electronic Resource

1432-1238

CPAP ; Turbine ; High flow ; Work of breathing ; Mobile

Springer Online Journal Archives 1860-2000

Medicine

Abstract A continuous high flow CPAP system incorporating a turbine blower is described. The system achieves inspiratory flow rates of 150l/min or more by means of reticulated gas flow and inspired oxygen fractions of 0.21–0.95. Positive airway pressure is provided by weighted disc valves and a modified aviationtype CPAP face mask provides electronic communication with the patient. The mobility of the system also enables its use as an intermittent physiotherapy aid. Work of breathing of the system, as assessed by total pressure fluctuations, is at a minimum.

Electronic Resource

1432-1238

Procainamide ; Amiodarone ; Antiarrhythmics ; Atrial tachyarrhythmias ; Critically ill

Springer Online Journal Archives 1860-2000

Medicine

Abstract Objective To compare the efficacy and safety of intravenous (IV) amiodarone and procainamide for the treatment of atrial tachyarrhythmias (AT) in the critically ill. Design In this prospective study, patients were allocated to drug treatment on the basis of hospital identification number, even for procainamide and odd for amiodarone. Setting Patients were recruited from a teaching hospital ICU and did not include postoperative cardiac patients. Patients and participants 26 patients with AT sustained for at least 1 h and failure to respond to correction of possible precipitating factors were entered in the study. Exclusion criteria were systolic blood pressure (SBP)〈80 mmHg, and known hypersensitivity to either drug. Two patients with chronic atrial fibrillation (who received amiodarone) were later excluded from the analysis. In the final analysis, 14 patients received procainamide and 10 amiodarone. Interventions IV amiodarone (3 mg/kg followed by 10 mg/kg/24h, with repeat dose of 3 mg/kg at 1 h if no response) or IV procainamide (10 mg/kg at 1 mg/kg/min followed by infusion of 2–4 mg/min for 24 h, with repeat dose of 5 mg/kg at 1 h if no response). Measurements and results In the procainamide group 10/14 (71%) and in the amiodarone group 7/10 (70%) had converted to sinus rhythm by 12 h. There was no significant difference in response between the groups. SBP was not significantly different from baseline after administration of either drug. Conclusions Procainamide and amiodarone appear to be safe and equally effective in the treatment of AT in the critically ill.

Electronic Resource

1432-1238

Shock ; Dopamine ; Dobutamine ; Isoproterenol

Springer Online Journal Archives 1860-2000

Medicine

Abstract Twelve patients in shock, defined as being present if the mean arterial blood pressure was less than 60 mm Hg, pulmonary arterial occlusion pressure was 15 mm Hg or greater, urine output was 20 ml or less for 2 consecutive hours, and there was clinical evidence of poor peripheral perfusion, underwent a comparative therapeutic trial with dopamine at 200 μg · min-1 and 400 μg · min-1 (2.5–5.5 μg · kg-1 · min-1), dobutamine 250 μg · min-1 and 500 μg · min-1 (3.5–7 μg · kg-1 · min-1) and isoproterenol 2 μg · min-1 and 4 μg · min-1 (0.025–0.055 μg · kg-1 · min-1). Isoproterenol at 2 μg · min-1, produced a significant increase in pulse rate, cardiac output, left ventricular stroke work index and decrease in mean pulmonary blood pressure and pulmonary arterial occlusion pressure and at 4 μg · min-1 a significant increase in stroke volume, mixed venous oxygen tension and decrease in right atrial pressure and systemic vascular resistance was also observed. Dopamine at 200 μg · min-1 produced a significant increase in cardiac output, pulmonary arterial occlusion pressure and mixed venous oxygen tension and at 400 μg · min-1 a significant increase in pulse rate, mean arterial blood pressure mean pulmonary blood pressure, right ventricular stroke work index, right atrial pressure and pulmonary arterial occlusion pressure and decrease in arterial oxygen tension was also observed. Dobutamine at 250 μg · min-1 produced a significant increase in cardiac output, and at 500 μg · min-1 a significant increase in pulse rate, mixed venous oxgen tension and decrease in pulmonary arterial occlusion pressure. All agents increased pulse rate and cardiac output, although in the dosages chosen dopamine was the only agent do so with an increase in pulmonary arterial occlusion pressure and decrease in arterial oxygen tension. In patients in shock if an inotropic agent is considered necessary its pulmonary effect should be considered along with its effect on coronary and peripheral perfusion since dopamine may reduce arterial oxygenation.

Electronic Resource