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1.
Anaesthesia ; 77(2): 185-195, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34333761

ABSTRACT

We implemented the World Health Organization surgical safety checklist at Auckland City Hospital from November 2007. We hypothesised that the checklist would reduce postoperative mortality and increase days alive and out of hospital, both measured to 90 postoperative days. We compared outcomes for cohorts who had surgery during 18-month periods before vs. after checklist implementation. We also analysed outcomes during 9 years that included these periods (July 2004-December 2013). We analysed 9475 patients in the 18-month period before the checklist and 10,589 afterwards. We analysed 57,577 patients who had surgery from 2004 to 2013. Mean number of days alive and out of hospital (95%CI) in the cohort after checklist implementation was 1.0 (0.4-1.6) days longer than in the cohort preceding implementation, p < 0.001. Ninety-day mortality was 395/9475 (4%) and 362/10,589 (3%) in the cohorts before and after checklist implementation, multivariable odds ratio (95%CI) 0.93 (0.80-1.09), p = 0.4. The cohort changes in these outcomes were indistinguishable from longer-term trends in mortality and days alive and out of hospital observed during 9 years, as determined by Bayesian changepoint analysis. Postoperative mortality to 90 days was 228/5686 (4.0%) for Maori and 2047/51,921 (3.9%) for non-Maori, multivariable odds ratio (95%CI) 0.85 (0.73-0.99), p = 0.04. Maori spent on average (95%CI) 1.1 (0.5-1.7) fewer days alive and out of hospital than non-Maori, p < 0.001. In conclusion, our patients experienced improving postoperative outcomes from 2004 to 2013, including the periods before and after implementation of the surgical checklist. Maori patients had worse outcomes than non-Maori.


Subject(s)
Checklist/trends , Medical Audit/trends , Patient Discharge/trends , Patient Safety , Postoperative Complications/epidemiology , World Health Organization , Adolescent , Adult , Aged , Aged, 80 and over , Checklist/methods , Female , Humans , Male , Medical Audit/methods , Middle Aged , Postoperative Complications/diagnosis , Retrospective Studies , Young Adult
2.
Anaesthesia ; 77(12): 1346-1355, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36110039

ABSTRACT

The Difficult Airway Society recommends that all patients should be pre-oxygenated before the induction of general anaesthesia, but this may not always be easy or comfortable and anaesthesia may often be induced without full pre-oxygenation. We tested the hypothesis that high-flow nasal oxygen cannulae would be easier and more comfortable than facemasks for pre-oxygenation. We randomly allocated 199 patients undergoing elective surgery aged ≥ 10 years to pre-oxygenation using either high-flow nasal oxygen or facemask. Ease and comfort were assessed by anaesthetists and patients on 10-cm visual analogue scale and six-point smiley face scale, respectively. Secondary endpoints included end-tidal oxygen fraction after securing a definitive airway and time to secure an airway. A mean difference (95%CI) between groups in ratings of -0.76 (-1.25 to -0.27) cm for ease of use (p = 0.003) and -0.45 (-0.75 to -0.13) points for comfort (p = 0.006), both favoured high-flow nasal oxygen. A mean difference (95%CI) between groups in end-tidal oxygen fraction of 3.89% (2.41-5.37%) after securing a definitive airway also favoured high-flow nasal oxygen (p < 0.001). There was no significant difference between groups in the number of patients with hypoxaemia (Sp O2 < 90%) or severe hypoxaemia (Sp O2 < 85%) lasting ≥ 1 min or ≥ 2 min; in the proportion of patients with an end-tidal oxygen fraction < 87% in the first 5 min after tracheal intubation (52.2% vs. 58.9% in facemask and high-flow nasal oxygen groups, respectively; p = 0.31); or in time taken to secure an airway (11.6 vs. 12.2 min in facemask and high-flow nasal oxygen groups, respectively; p = 0.65). In conclusion, we found pre-oxygenation with high-flow nasal oxygen to be easier for anaesthetists and more comfortable for patients than pre-oxygenation with a facemask, with no clinically relevant differences in end-tidal oxygen fraction after securing a definitive airway or time to secure an airway. The differences in ease and comfort were modest.


Subject(s)
Masks , Oxygen , Humans , Cannula , Administration, Intranasal , Hypoxia , Oxygen Inhalation Therapy
3.
Br J Anaesth ; 122(2): 198-205, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30686305

ABSTRACT

BACKGROUND: Etomidate is frequently selected over propofol for induction of anaesthesia because of a putatively favourable haemodynamic profile, but data confirming this perception are limited. METHODS: Patients undergoing cardiac surgery were randomised to induction of anaesthesia with propofol or etomidate. Phase I (n=75) was conducted as open-label, whereas Phase II (n=75) was double blind. Mean arterial blood pressure (MAP) and boluses of vasopressor administered after induction were recorded. The primary endpoint was the area under the curve below baseline MAP (MAP-time integral) during the 10 min after induction. Secondary endpoints were the use of vasopressors over the same period, and the effect of blinding on the aforementioned endpoints. Groups were compared using regression models with phase and anaesthetist as factors. RESULTS: The mean difference between etomidate and propofol in the MAP-time integral below baseline was 2244 mm Hg s (95% confidence interval, 581-3906; P=0.009), representing a 34% greater reduction with propofol. Overall, vasopressors were used in 10/75 patients in the etomidate group vs 21/75 in the propofol group (P=0.38), and in 20/74 patients during the blinded phase vs 11/76 during the open-label phase (P=0.31). The interaction between randomisation and phase (open-labelled or blinded) was not significant for either primary (P=0.73) or secondary endpoints (P=0.90). CONCLUSIONS: Propofol caused a 34% greater reduction in MAP-time integral from baseline after induction of anaesthesia than etomidate, despite more frequent use of vasopressors with propofol, confirming the superior haemodynamic profile of etomidate in this context. The proportion of patients receiving vasopressors increased slightly, albeit not significantly, in both groups in the blinded phase. CLINICAL TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12614000717651.


Subject(s)
Anesthesia, General/methods , Cardiac Surgical Procedures/methods , Etomidate , Hemodynamics/drug effects , Hypnotics and Sedatives , Propofol , Adult , Aged , Aged, 80 and over , Arterial Pressure , Coronary Artery Bypass , Double-Blind Method , Female , Humans , Male , Middle Aged , Treatment Outcome , Vasoconstrictor Agents/therapeutic use
4.
J R Army Med Corps ; 164(3): 191-196, 2018 Jul.
Article in English | MEDLINE | ID: mdl-28495952

ABSTRACT

INTRODUCTION: Survival in exsanguinating cardiac arrest patients is poor, as is neurological outcome in survivors. Hypothermia has traditionally been seen as harmful to trauma patients and associated with increased mortality; however, there has been speculation that cooling to very low temperatures (≤20°C) could be used to treat haemorrhagic trauma patients by the induction of a suspended animation period through extreme cooling, which improves survival and preserves neurological function. This has been termed emergency preservation and resuscitation (EPR). METHODS: A systematic review of the literature was used to examine the evidence base behind the use of deep and profound hypothermia in haemorrhagic shock (HS). It included original research articles (human or animal) with cooling to ≤20°C after HS or an experimental model replicating it. Normovolaemic cardiac arrest, central nervous system injury and non-HS models were excluded. RESULTS: Twenty articles using 456 animal subjects were included, in which 327 were cooled to ≤20°C. All studies describing good survival rates were possible using EPR and 19/20 demonstrated that EPR can preserve neurological function after prolonged periods of circulatory arrest or minimal circulatory flow. This additional period can be used for surgical intervention to arrest haemorrhage in HS that would otherwise be lethal. CONCLUSIONS: The outcomes of this review have significant implications for application to human patients and the ongoing human clinical trial (EPR for Cardiac Arrest from Trauma). Current evidence suggests that hypothermia ≤20°C used in the form of EPR could be beneficial to the HS patient.


Subject(s)
Hypothermia, Induced , Shock, Hemorrhagic/therapy , Biomedical Research , Evidence-Based Medicine , Humans , Hypothermia, Induced/classification
5.
Br J Anaesth ; 119(suppl_1): i167-i175, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-29161398

ABSTRACT

Since the introduction of general anaesthetics into clinical practice, researchers have been mystified as to how these chemically disparate drugs act to produce their dramatic effects on central nervous system function and behaviour. Scientific advances, particularly during the last 25 years, have now begun to reveal the molecular mechanisms underpinning their behavioural effects. For certain i.v. general anaesthetics, such as etomidate and propofol, a persuasive case can now be made that the GABAA receptor, a major inhibitory receptor in the mammalian central nervous system, is an important target. Advances in molecular pharmacology and in genetic manipulation of rodent genes reveal that different subtypes of the GABAA receptor are responsible for mediating particular aspects of the anaesthetic behavioural repertoire. Such studies provide a better understanding of the neuronal circuitry involved in the various anaesthetic-induced behaviours and, in the future, may result in the development of novel therapeutics with a reduced propensity for side-effects.


Subject(s)
Anesthetics, General , Anesthetics, Intravenous/pharmacology , Central Nervous System/drug effects , Receptors, GABA-A/drug effects , Humans
6.
Acta Anaesthesiol Scand ; 59(8): 1015-21, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26040646

ABSTRACT

BACKGROUND: Bispectral index (BIS) monitoring is commonly used to decrease the risk of awareness during anaesthesia. We aimed to determine the relationship between blood alcohol concentration and brain function (as measured by BIS) in healthy adults. METHODS: In this prospective observational study, 21 anaesthetic registrars self-regulated alcohol consumption over a 3-h period. Expired alcohol concentration (breathalyser) and BIS measurements were performed hourly for 4 h. A venous blood alcohol sample was taken at the conclusion of the study period. RESULTS: The main outcome measures were the correlation between blood alcohol and brain function as measured by BIS and the change in BIS from baseline (∆BIS) at 4 h. The median number of standard drinks consumed was 9.1 (IQR 7.7-12.3), range 5.4-17. At 4 h, there was a moderate inverse correlation between BIS and blood alcohol (r = -0.49, P = 0.029) and between ∆BIS and blood alcohol (r = -0.46, P =0.043). CONCLUSION: In healthy young adults, we found a moderate correlation between venous blood alcohol concentration and BIS. This suggests that acute alcohol consumption can decrease BIS. This information may be relevant when providing anaesthesia to intoxicated patients who require urgent or time-critical surgery, although certain limitations of this study should be kept in mind.


Subject(s)
Alcoholic Intoxication/physiopathology , Brain/physiopathology , Consciousness Monitors/statistics & numerical data , Electroencephalography/statistics & numerical data , Acute Disease , Adult , Alcoholic Intoxication/blood , Blood Alcohol Content , Female , Humans , Male , Prospective Studies
7.
Perfusion ; 29(3): 219-25, 2014 May.
Article in English | MEDLINE | ID: mdl-24009263

ABSTRACT

OBJECTIVE: To compare the efficiency of 20 and 40 µm arterial line filters during cardiopulmonary bypass for the removal of emboli from the extracorporeal circuit. METHODS: Twenty-four adult patients undergoing surgery were perfused using a cardiopulmonary bypass circuit containing either a 20 µm or 40 µm arterial filter (n = 12 in both groups). The Emboli Detection and Classification system was used to count emboli upstream and downstream of the filter throughout cardiopulmonary bypass. The mean proportion of emboli removed by the filter was compared between the groups. RESULTS: The 20 µm filter removed a significantly greater proportion of incoming emboli (0.621) than the 40 µm filter (0.334) (p=0.029). The superiority of the 20 µm filter persisted across all size groups of emboli larger than the pore size of the 40 µm filter. CONCLUSION: The 20 µm filter removed substantially more emboli than the 40 µm filter during cardiopulmonary bypass in this comparison.


Subject(s)
Cardiopulmonary Bypass/instrumentation , Cardiopulmonary Bypass/methods , Embolic Protection Devices , Embolism, Air/prevention & control , Adult , Female , Humans , Male
9.
Undersea Hyperb Med ; 39(6): 1099-108, 2012.
Article in English | MEDLINE | ID: mdl-23342767

ABSTRACT

The Diving Committee of the Undersea and Hyperbaric Medical Society has reviewed available evidence in relation to the medical aspects of rescuing a submerged unresponsive compressed-gas diver. The rescue process has been subdivided into three phases, and relevant questions have been addressed as follows. Phase 1, preparation for ascent: If the regulator is out of the mouth, should it be replaced? If the diver is in the tonic or clonic phase of a seizure, should the ascent be delayed until the clonic phase has subsided? Are there any special considerations for rescuing rebreather divers? Phase 2, retrieval to the surface: What is a "safe" ascent rate? If the rescuer has a decompression obligation, should they take the victim to the surface? If the regulator is in the mouth and the victim is breathing, does this change the ascent procedures? If the regulator is in the mouth, the victim is breathing, and the victim has a decompression obligation, does this change the ascent procedures? Is it necessary to hold the victim's head in a particular position? Is it necessary to press on the victim's chest to ensure exhalation? Are there any special considerations for rescuing rebreather divers? Phase 3, procedure at the surface: Is it possible to make an assessment of breathing in the water? Can effective rescue breaths be delivered in the water? What is the likelihood of persistent circulation after respiratory arrest? Does the recent advocacy for "compression-only resuscitation" suggest that rescue breaths should not be administered to a non-breathing diver? What rules should guide the relative priority of in-water rescue breaths over accessing surface support where definitive CPR can be started? A "best practice" decision tree for submerged diver rescue has been proposed.


Subject(s)
Cardiopulmonary Resuscitation/standards , Diving/adverse effects , Diving/standards , Near Drowning/prevention & control , Rescue Work/standards , Unconsciousness , Algorithms , Cardiopulmonary Resuscitation/methods , Decision Trees , Epilepsy, Tonic-Clonic/physiopathology , Head , Humans , Out-of-Hospital Cardiac Arrest/prevention & control , Patient Positioning/methods , Patient Positioning/standards , Rescue Work/methods , Respiratory Insufficiency/prevention & control
10.
J Med Virol ; 83(9): 1650-6, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21739458

ABSTRACT

There is a need to provide rapid, sensitive, and often high throughput detection of pathogens in diagnostic virology. Viral gastroenteritis is a serious health issue often leading to hospitalization in the young, the immunocompromised and the elderly. The common causes of viral gastroenteritis include rotavirus, norovirus (genogroups I and II), astrovirus, and group F adenoviruses (serotypes 40 and 41). This article describes the work-up of two internally controlled multiplex, probe-based PCR assays and reports on the clinical validation over a 3-year period, March 2007 to February 2010. Multiplex assays were developed using a combination of TaqMan™ and minor groove binder (MGB™) hydrolysis probes. The assays were validated using a panel of 137 specimens, previously positive via a nested gel-based assay. The assays had improved sensitivity for adenovirus, rotavirus, and norovirus (97.3% vs. 86.1%, 100% vs. 87.8%, and 95.1% vs. 79.5%, respectively) and also more specific for targets adenovirus, rotavirus, and norovirus (99% vs. 95.2%, 100% vs. 93.6%, and 97.9% vs. 92.3%, respectively). For the specimens tested, both assays had equal sensitivity and specificity for astrovirus (100%). Overall the probe-based assays detected 16 more positive specimens than the nested gel-based assay. Post-introduction to the routine diagnostic service, a total of 9,846 specimens were processed with multiplex 1 and 2 (7,053 pediatric, 2,793 adult) over the 3-year study period. This clinically validated, probe-based multiplex testing algorithm allows highly sensitive and timely diagnosis of the four most prominent causes of viral gastroenteritis.


Subject(s)
Adenovirus Infections, Human/diagnosis , Astroviridae Infections/diagnosis , Caliciviridae Infections/diagnosis , Gastroenteritis/diagnosis , Molecular Diagnostic Techniques/methods , Multiplex Polymerase Chain Reaction , Rotavirus Infections/diagnosis , Adult , Child , DNA Primers , Feces/virology , Gastroenteritis/virology , Humans , Norovirus , Sensitivity and Specificity
11.
J Clin Pharm Ther ; 36(3): 327-35, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21545612

ABSTRACT

BACKGROUND: Paracetamol, a commonly used simple analgesic, can be fatal in overdose. Case reports suggest liver damage may occur at therapeutic doses. In older and particularly frail patients, dose reduction of therapeutic paracetamol is recommended due to concerns of an increased risk of hepatotoxicity. AIMS: This study aimed to investigate the effects of ageing and frailty on the safety of paracetamol in hospital inpatients commenced on short courses of the drug. METHODS: An observational cohort study of young (18-55 years, n = 19), older (≥ 70 years) fit (n = 24) and older frail (n = 28) hospital inpatients. Treatment group participants commenced regular paracetamol (3-4 g/day) during their hospital admission, whereas the control group was not exposed to paracetamol. In both groups, plasma alanine aminotransferase (ALT) was measured at baseline and day 5, and risk factors for raised ALT were recorded. A random serum paracetamol concentration was measured at day 5 in the treatment group. RESULTS: No older frail treatment participants had an abnormal day 5 ALT. Odds ratios for having a day 5 ALT above the upper limit of normal (ULN) with paracetamol use, compared with unexposed controls, were 3·7 [95% confidence intervals (CI): 0·32, 41·59] for older not frail participants and 2·5 (95% CI: 0·34, 18·3) for younger participants. Decreasing frailty score independently predicted a day 5 ALT above the ULN (P < 0·05). Day 5 serum paracetamol concentrations were highest in older frail participants (P < 0·005). CONCLUSION: Higher paracetamol concentrations observed in frail older patients after 5 days of therapeutic paracetamol do not necessarily indicate an increased risk of hepatotoxicity.


Subject(s)
Acetaminophen/adverse effects , Aging , Analgesics, Non-Narcotic/adverse effects , Chemical and Drug Induced Liver Injury/epidemiology , Acetaminophen/administration & dosage , Acetaminophen/blood , Acetaminophen/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Alanine Transaminase/blood , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Non-Narcotic/blood , Analgesics, Non-Narcotic/therapeutic use , Australia/epidemiology , Chemical and Drug Induced Liver Injury/blood , Chemical and Drug Induced Liver Injury/physiopathology , Cohort Studies , Female , Frail Elderly , Hospitalization , Humans , Incidence , Male , Middle Aged , Risk Factors , Time Factors , Young Adult
12.
Nat Protoc ; 15(2): 540-574, 2020 02.
Article in English | MEDLINE | ID: mdl-31915391

ABSTRACT

The number of people aged over 65 is expected to double in the next 30 years. For many, living longer will mean spending more years with the burdens of chronic diseases such as Alzheimer's disease, cardiovascular disease, and diabetes. Although researchers have made rapid progress in developing geroprotective interventions that target mechanisms of aging and delay or prevent the onset of multiple concurrent age-related diseases, a lack of standardized techniques to assess healthspan in preclinical murine studies has resulted in reduced reproducibility and slow progress. To overcome this, major centers in Europe and the United States skilled in healthspan analysis came together to agree on a toolbox of techniques that can be used to consistently assess the healthspan of mice. Here, we describe the agreed toolbox, which contains protocols for echocardiography, novel object recognition, grip strength, rotarod, glucose tolerance test (GTT) and insulin tolerance test (ITT), body composition, and energy expenditure. The protocols can be performed longitudinally in the same mouse over a period of 4-6 weeks to test how candidate geroprotectors affect cardiac, cognitive, neuromuscular, and metabolic health.


Subject(s)
Aging/physiology , Health , Aging/metabolism , Animals , Body Composition , Electrocardiography , Energy Metabolism , Glucose Tolerance Test , Hand Strength , Insulin Resistance , Longitudinal Studies , Mice , Mice, Inbred C57BL , Recognition, Psychology
13.
Intern Med J ; 39(11): 763-6, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19912402

ABSTRACT

The utility of regular medical fitness-for-diving examinations of occupational divers is unknown. The aim of this audit was to investigate the impact on the employment of occupational divers of a 5-yearly medical examination and an annual health surveillance questionnaire administered in intervening years. The medical records of all New Zealand occupational divers registered with the Department of Labour for at least 5 years were audited (n= 336). Each record included at least two full medical examinations (mean spacing of 5.6 years). An impact on career was defined as the diver being issued with either a conditional certificate of fitness or being graded as temporarily or permanently unfit for diving. The means by which the relevant medical issue was identified was recorded. Ten (3%) of 336 divers had an assessment outcome, which had a career impact. One was considered permanently unfit, four were temporarily unfit, and five were issued with conditional certification. Two were identified by respiratory function testing and eight by way of their responses to the questionnaire; none was found by the medical interview and examination process. The questionnaire system did not 'miss' any divers who developed a critically important health problem, and detected most of those with less important problems. Five yearly medical examinations have a low detection rate for important health problems, but remain useful for discussion of risk understanding, acceptance and mitigation.


Subject(s)
Diving , Occupational Health , Patient Acceptance of Health Care , Physical Examination/statistics & numerical data , Adolescent , Adult , Aged , Cohort Studies , Diving/adverse effects , Diving/physiology , Female , Humans , Male , Middle Aged , New Zealand , Occupational Diseases/diagnosis , Occupational Diseases/prevention & control , Occupational Diseases/therapy , Physical Fitness/physiology , Young Adult
14.
Anaesth Intensive Care ; 46(4): 368-373, 2018 07.
Article in English | MEDLINE | ID: mdl-29966109

ABSTRACT

There is evidence that even mild hyperthermia may exacerbate brain injury. There seem reasonable grounds for considering patients undergoing craniotomy as at risk for brain injury. A retrospective observational study was undertaken to measure the incidence of mild hyperthermia in craniotomy cases in which the patient was initially normothermic. Auckland City Hospital's database of electronic anaesthetic records was searched for adult patients who were normothermic (≤37°C) prior to undergoing craniotomy procedures. For each case, demographic data, intraoperative naso- or oropharyngeal temperature measurements, and paracetamol use were extracted. We identified the proportion of patients whose temperature rose to exceed normal (>37°C) and subdivided that group into the proportion in whom the temperature rose to ≥38°C. Two thousand, nine hundred and thirty-five craniotomy cases began their operations while normothermic and had adequate temperature data collected. There were 984 (33.5%) cases that had at least one temperature reading >37°C, for a mean (standard deviation [SD]) time of 66.0 (64.6) minutes, and 49 (1.7%) cases that had at least one reading ≥38°C for a mean (SD) time of 40.4 (38.1) minutes. The majority (77.8%) who became mildly hyperthermic remained so at the end of the procedure. New mild hyperthermia occurs commonly during craniotomy. In view of the compelling evidence of potential harm arising from mild hyperthermia in brain injury, these findings suggest an opportunity for practice improvement in the anaesthetic management of craniotomy patients. Reasonable steps should be taken by anaesthetists to avoid intraoperative hyperthermia of any degree.


Subject(s)
Craniotomy/adverse effects , Fever/epidemiology , Adult , Aged , Anesthesia , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies
15.
J Neuroendocrinol ; 30(2)2018 02.
Article in English | MEDLINE | ID: mdl-28905487

ABSTRACT

GABA plays a key role in both embryonic and neonatal brain development. For example, during early neonatal nervous system maturation, synaptic transmission, mediated by GABAA receptors (GABAA Rs), undergoes a temporally specific form of synaptic plasticity to accommodate the changing requirements of maturing neural networks. Specifically, the duration of miniature inhibitory postsynaptic currents (mIPSCs), resulting from vesicular GABA activating synaptic GABAA Rs, is reduced, permitting neurones to appropriately influence the window for postsynaptic excitation. Conventionally, programmed expression changes to the subtype of synaptic GABAA R are primarily implicated in this plasticity. However, it is now evident that, in developing thalamic and cortical principal- and inter-neurones, an endogenous neurosteroid tone (eg, allopregnanolone) enhances synaptic GABAA R function. Furthermore, a cessation of steroidogenesis, as a result of a lack of substrate, or a co-factor, appears to be primarily responsible for early neonatal changes to GABAergic synaptic transmission, followed by further refinement, which results from subsequent alterations of the GABAA R subtype. The timing of this cessation of neurosteroid influence is neurone-specific, occurring by postnatal day (P)10 in the thalamus but approximately 1 week later in the cortex. Neurosteroid levels are not static and change dynamically in a variety of physiological and pathophysiological scenarios. Given that GABA plays an important role in brain development, abnormal perturbations of neonatal GABAA R-active neurosteroids may have not only a considerable immediate, but also a longer-term impact upon neural network activity. Here, we review recent evidence indicating that changes in neurosteroidogenesis substantially influence neonatal GABAergic synaptic transmission. We discuss the physiological relevance of these findings and how the interference of neurosteroid-GABAA R interaction early in life may contribute to psychiatric conditions later in life.


Subject(s)
Brain/metabolism , Neurotransmitter Agents/physiology , Receptors, GABA-A/physiology , Synapses/metabolism , Animals , Brain/growth & development , Neurons/metabolism , Synaptic Transmission/physiology , gamma-Aminobutyric Acid/metabolism
16.
Cochrane Database Syst Rev ; (2): CD005277, 2007 Apr 18.
Article in English | MEDLINE | ID: mdl-17443579

ABSTRACT

BACKGROUND: Decompression illness (DCI) is due to bubble formation in the blood or tissues following the breathing of compressed gas. Clinically, DCI may range from a trivial illness to loss of consciousness, death or paralysis. Recompression is the universally accepted standard for the treatment of DCI. When recompression is delayed, a number of strategies have been suggested in order to improve the outcome. OBJECTIVES: To examine the effectiveness and safety of both recompression and adjunctive therapies in the treatment of DCI. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library 2005, Issue 2); MEDLINE (1966 to August 2005); CINAHL (1982 to August 2005); EMBASE (1980 to August 2005); the Database of Randomised Controlled Trials in Hyperbaric Medicine (August 2005), and hand-searched journals and texts. SELECTION CRITERIA: We included randomized controlled trials that compared the effect of any recompression schedule or adjunctive therapy with a standard recompression schedule. We applied no language restrictions. DATA COLLECTION AND ANALYSIS: Three authors extracted the data independently. We assessed each trial for internal validity and resolved differences by discussion. Data was entered into RevMan 4.2. MAIN RESULTS: Two randomized controlled trials satisfied the inclusion criteria. Pooling of data was not possible. In one study there was no evidence of improved effectiveness with the addition of a non-steroidal anti-inflammatory drug (tenoxicam) to routine recompression therapy (at six weeks: relative risk (RR) 1.04, 95% confidence interval (CI) 0.90 to 1.20, P = 0.58) but there was a reduction in the number of compressions required when tenoxicam was added (P = 0.01, 95% CI 0 to 1). In the other study, the odds of multiple recompressions was lower with a helium and oxygen (heliox) table compared to an oxygen treatment table (RR 0.56, 95% CI 0.31 to 1.00, P = 0.05). AUTHORS' CONCLUSIONS: Recompression therapy is standard for the treatment of DCI, but there is no randomized controlled trial evidence. Both the addition of an NSAID or the use of heliox may reduce the number of recompressions required, but neither improves the odds of recovery. The application of either of these strategies may be justified. The modest number of patients studied demands a cautious interpretation. Benefits may be largely economic and an economic analysis should be undertaken. There is a case for large randomized trials of high methodological rigour in order to define any benefit from the use of different breathing gases and pressure profiles during recompression therapy.


Subject(s)
Decompression Sickness/therapy , Hyperbaric Oxygenation/methods , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Humans , Piroxicam/analogs & derivatives , Piroxicam/therapeutic use , Randomized Controlled Trials as Topic
17.
J Neurosci ; 20(23): 8651-8, 2000 Dec 01.
Article in English | MEDLINE | ID: mdl-11102470

ABSTRACT

GABA type B receptors (GABA(B)-Rs) are present on excitatory terminals throughout the CNS, but surprisingly little is known about their role in modulating neurotransmission under physiological conditions. We have investigated activation of GABA(B)-Rs on excitatory terminals within the cerebellar glomerulus, a structure where glutamatergic excitatory and GABAergic inhibitory terminals are in close apposition and make axodendritic synapses onto granule cells. Application of the GABA(B)-R agonist baclofen depressed evoked mossy fiber EPSCs by 54% at 1 Hz. The amplitude of miniature EPSCs recorded in tetrodotoxin was unchanged in the presence of baclofen, but the frequency was significantly reduced, indicating a purely presynaptic action of baclofen under our recording conditions. At physiological temperature (37 degrees C) presynaptic GABA(B)-Rs were not tonically activated by spontaneous GABA release from Golgi cells, which fire at approximately 8 Hz in slices at this temperature. However, tonic activation could be induced by blocking GABA uptake or by lowering temperature. GABA(B)-Rs were activated at physiological temperature when Golgi cell firing was increased above the basal level by stimulating a single inhibitory Golgi cell input at 50 Hz, suppressing the mossy fiber-evoked EPSC by 24% at 1 Hz. Furthermore, glutamate release was selectively inhibited at low-frequency mossy fiber inputs (<10 Hz) during Golgi cell stimulation. Our findings suggest that GABA spillover in the glomerulus modulates sensory input to the cerebellar cortex.


Subject(s)
Axons/metabolism , Cerebellum/metabolism , Neural Inhibition/physiology , Synaptic Transmission/physiology , gamma-Aminobutyric Acid/metabolism , Animals , Baclofen/pharmacology , Cerebellum/cytology , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , GABA Agonists/pharmacology , GABA Antagonists/pharmacology , GABA-B Receptor Agonists , In Vitro Techniques , Nerve Fibers/drug effects , Nerve Fibers/metabolism , Presynaptic Terminals/metabolism , Rats , Rats, Sprague-Dawley , Receptors, GABA-B/metabolism , Synaptic Transmission/drug effects , Temperature , Tetrodotoxin/pharmacology , gamma-Aminobutyric Acid/pharmacology
18.
Trends Microbiol ; 4(9): 343-7, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8885168

ABSTRACT

Erythrocyte parasitism, or hemotrophy, is not a common strategy for bacteria. However, Bartonella species are elegantly adapted to parasitize a variety of cell types including red blood cells. Bartonella bacilliformis, a useful model organism for the genus, has been used to study virulence determinants involved in colonization, attachment and invasion of host cells.


Subject(s)
Bartonella Infections/etiology , Bartonella/pathogenicity , Erythrocytes/microbiology , Bacterial Adhesion , Bartonella/growth & development , Bartonella/ultrastructure , Models, Biological , Virulence/genetics
19.
Genetics ; 132(4): 1039-45, 1992 Dec.
Article in English | MEDLINE | ID: mdl-1360932

ABSTRACT

We have estimated DNA sequence variation within and between two populations of Drosophila ananassae, using six-cutter restriction site variation at vermilion (v) and furrowed (fw). These two gene regions are located close to the centromere on the left and right X chromosome arms, respectively. In the fw region, no DNA polymorphism was detected within each population. In the v region, average heterozygosity per nucleotide was very low in both populations (pi = 0.0005 in the Burma population, and 0.0009 in the India population). These estimates are significantly lower than those from loci in more distal gene regions. The distribution of DNA polymorphisms between both populations was also striking. At fw, three fixed differences between the Burma and India populations were detected (two restriction site differences and one insertion/deletion of approximately 2 kb). At v, each DNA polymorphism in high frequency in the total sample was nearly fixed in one or the other population, although none of them reached complete fixation. The observed pattern of reduced variation within populations and fixed differences between populations appears to correlate with recombination rate. We conclude that recent hitchhiking associated with directional selection is the best explanation for this pattern. The data indicate that different selective sweeps have occurred in the two populations. The possible role of genetic hitchhiking in rapid population differentiation in gene regions of restricted recombination is discussed.


Subject(s)
Centromere/ultrastructure , Drosophila/genetics , Genetics, Population , Animals , Genes, Insect , Heterozygote , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Recombination, Genetic , Restriction Mapping , X Chromosome
20.
Phys Rev E Stat Nonlin Soft Matter Phys ; 72(6 Pt 2): 065103, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16485997

ABSTRACT

Many systems of both theoretical and applied interest display multiaffine scaling at small length or time scales. We demonstrate analytically and numerically that when vertical discontinuities are introduced into a self-affine function, the function becomes multiaffine. The discontinuities may correspond to surface overhangs or some source of discontinuous noise. Two functions are numerically examined with different distributions of discontinuities. The multiaffinity is shown to arise simply from the function of discontinuities, and the analytic scaling form at small scales for the function of discontinuities is derived and compared to numerical results.

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