What About the Little Ones? Systematic Review of Cognitive and Behavioral Outcomes Following Early TBI.

There is increasing empirical focus on the effects of early traumatic brain injuries (TBI; i.e., before the age of six years) on child development, but this literature has never been synthetized comprehensively. This systematic review aimed to document the cognitive, academic, behavioral, socio-affective, and adaptive consequences of early TBI. Four databases (Medline, PsycNET, CINAHL, PubMed) were systematically searched from 1990 to 2019 using key terms pertaining to TBI and early childhood. Of 12, 153 articles identified in the initial search, 43 were included. Children who sustain early TBI are at-risk for a range of difficulties, which are generally worse when injury is sustained at a younger age, injury severity is moderate to severe, and injury mechanisms are non-accidental. Early childhood is a sensitive period for the emergence and development of new skills and behaviors, and brain disruption during this time is not benign. Research, clinical management, intervention, and prevention efforts should be further developed with consideration of the unique characteristics of the early childhood period.

Anaesthesia-related morbidity in Victoria: a report from 1990 to 2005.

This report involves a review of 736 cases of anaesthesia-related morbidity reported from 1990 to 2005 by the Victorian Consultative Council on Anaesthetic Mortality and Morbidity. Using a combination of an established classification system, emerging categorisation definitions and appropriate keywords, an analysis of the clinical issues and contributory factors was undertaken. Airway-related morbidity, respiratory complications and drug-related adverse events are the most commonly reported. Organisational issues are increasingly implicated in adverse anaesthesia outcomes.

Unplanned admission to the intensive care unit in postoperative patients--an indicator of quality of anaesthetic care?

As a clinical indicator, unplanned admission to the Intensive Care Unit from the operating room has been thought to reflect the quality of anaesthesia care intraoperatively. To explore this concept, we examined all such admissions at three hospitals over a three-month period. Cases were classified according to the Victorian Consultative Council on Anaesthetic Mortality and Morbidity (VCCAMM) classification system and an assessment was made as to whether the admission was inevitable or not. Demographic data were collected as well as co-morbidities, severity of illness, length of stay, discharge functional status and destination. There were 165 admissions identified: 55.8% were male, the median age was 63.5 years (range 15-90). There were 24 in-hospital deaths: 151 patients suffered serious morbidity or mortality. In 32 patients (19.4%), the morbidity or mortality was considered at least partially anaesthetic-related, and in 20 (12.1%), under the control of the anaesthetist. There were 28 admissions (17.0%) with a further 9 anaesthetic-related admissions (5.5%) which were considered potentially avoidable. Avoidable anaesthetic-related admissions were due to drug overdosage (5 cases), drug error (1 case), problems relating to preoperative assessment (1 case), aspiration (1 case) and pulmonary oedema (1 case). These findings suggest that unplanned admission to the Intensive Care Unit from the operating room is not a satisfactory indicator of quality of care by the anaesthesia team. This indicator appears to represent mainly the surgical and medical conditions of the patients, and their complications. Only one in twenty unplanned admissions in this series were potentially avoidable due to complications of the anaesthetic or the postoperative analgesia.

Crisis management during anaesthesia: embolism.

BACKGROUND: Embolism with gas, thrombus, fat, amniotic fluid, or particulate matter may occur suddenly and unexpectedly during anaesthesia, posing a diagnostic and management problem for the anaesthetist. OBJECTIVES: To examine the role of a previously described core algorithm "COVER ABCD-A SWIFT CHECK" supplemented by a specific sub-algorithm for embolism, in the management of embolism occurring in association with anaesthesia. METHODS: The potential performance of this structured approach for each of the relevant incidents among the first 4000 reported to the Australian Incident Monitoring Study (AIMS) was compared with the actual management as reported by the anaesthetists involved. RESULTS: Among the first 4000 incidents reported to AIMS, 38 reports of embolism were found. A sudden fall in end-tidal carbon dioxide and oxygen saturation were the cardinal signs of embolism, each occurring in about two thirds of cases, with hypotension and electrocardiographic changes each occurring in about one third of cases. CONCLUSION: The potential value of an explicit structured approach to the diagnosis and management of embolism was assessed in the light of AIMS reports. It was considered that, correctly applied, it potentially would have led to earlier recognition of the problem and/or better management in over 40% of cases.

Multiple antimicrobial resistant Salmonella enterica serovar Paratyphi B variant Java in cattle: a case report.

An epidemiological investigation of a calf rearing premises and a closely associated dairy herd was carried out after the isolation of Salmonella enterica serovar Paratyphi B variant Java phage type 3b variant 2 from clinically diseased calves on the premises. The isolate was resistant to ampicillin, chloramphenicol, streptomycin, sulphonamides, tetracyclines, trimethoprim and cefoperazone. The organism was widespread on the calf unit and was also recovered from the dairy premises, mainly from groups of weaned calves. The investigation was extended to 10 epidemiologically linked farms but no S Java was isolated from any of the 40 to 60 samples collected from each premises. Molecular studies showed that the S Java isolates were genetically most similar to isolates from cases of human disease associated with ornamental fish tanks or feed. Long PCR and resistance gene profiling identified a resistance island which was indistinguishable from the human 'fish tank' strain of S Java and animal and human epidemic strains of S Typhimurium DT104. The isolates were clearly distinguished from multi-resistant S Java strains commonly associated with continental poultry. This is the first report of S Java with this resistance pattern in Great Britain.

Pharmacokinetics and anti-hyperglycaemic efficacy of a novel inhibitor of glycogen phosphorylase, 1,4-dideoxy-1,4-imino-d- arabinitol, in glucagon-challenged rats and dogs and in diabetic ob/ob mice.

AIM: To further characterize the properties of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB), a recently described novel and potent inhibitor of glycogen phosphorylase and potential anti-diabetic agent, we have determined its pharmacokinetic properties in rats, dogs and mice and compared these to its pharmacodynamic anti-hyperglycaemic efficacy. METHODS: Male Sprague Dawley rats, beagle dogs and diabetic Umeå ob/ob mice were administered DAB or 14C-DAB at various doses and by different routes and in either the conscious or the unconscious state and with or without glucagon, as appropriate. At different time points thereafter, blood, tissue and urine samples were withdrawn for analyses of DAB or 14C-DAB, and blood samples were taken for glucose concentration. RESULTS: DAB suppressed the blood glucose excursion in glucagon-challenged rats with an ID100 of 1-2 mg/kg per orally and intravenously and had a pharmacodynamic t50 for 1.6 mg/kg intravenously and for 1.2 mg/kg per orally of 50 and 60 min respectively. The pharmacokinetics of c. 2 mg/kg DAB in rats revealed elimination half-lives of 25 min after intravenous (i.v.) and 49 min after per oral (p.o.) administration; the oral bioavailability was 89%. In rats, DAB was distributed preferentially in liver vs. skeletal muscle and was eliminated predominantly through urine as parent compound. The pharmacokinetics of 4 mg/kg DAB in dogs showed elimination half-lives of 107 min after i.v. and 129 min after p.o. administration with an estimated oral availability of 78%. At 4 mg/kg DAB p.o., glucagon-induced hyperglycaemia in dogs was reduced in a time-dependent manner with an estimated t50 of 4 h. DAB was very rapidly cleared in mice; nevertheless, a dose-dependent reduction of blood glucose of up to 9 mmol/l was seen in diabetic ob/ob mice dosed subcutaneously, with statistically significant effects evident from 30 to 120 min. CONCLUSIONS: These data show that DAB is nearly completely orally available in rats and dogs and that it can reduce glucagon-induced and spontaneous hyperglycaemia. Inhibition of hepatic glycogen phosphorylase may benefit glycaemic control in patients with type 2 diabetes.

Mapping of obesity QTLs in a cross between mouse lines divergently selected on fat content.

A genome-wide quantitative trait locus (QTL) analysis was performed in a polygenic obesity mouse model resulting from a long-term selection experiment. The parental lines were outbred lines divergently selected for 53 generations for high-fat (fat, F line) or low-fat (lean, L line) percentage (fat%) that differed fivefold in fat% at 14 weeks of age. An F2 population of 436 mice was used for the QTL analysis with 71 markers distributed across the genome. The analysis revealed significant QTLs Fob1 (for F-line obesity QTL 1), Fob2, Fob3, and Fob4, on Chromosomes (Chrs) 2, 12, 15, and X, respectively. None of these QTLs map to regions of known single gene obesity mutations (Lepob, Leprdb, Cpefat, Ay, tub), though they map to regions of previously described obesity QTLs and candidate genes. The effects of Fob1, Fob3, Fob4 were additive, and that of Fob2 was dominant. Fob2 also showed a significant female-specific effect. Fob1, Fob2, Fob3, and Fob4 explained 4.9%, 19.5%, 14.4%, and 7.3% of the F2 phenotypic variance for fat%, respectively. This study identified four loci that contributed to the response to divergent selection and control a significant proportion of the difference in obesity between the F and L lines.

Changes in auxin response from mutations in an AUX/IAA gene.

Transcription of the AUX/IAA family of genes is rapidly induced by the plant hormone auxin, but evidence that AUX/IAA genes mediate further responses to auxin has been elusive. Changes in diverse auxin responses result from mutations in the Arabidopsis AXR3 gene. AXR3 was shown to be a member of the AUX/IAA family, providing direct evidence that AUX/IAA genes are central in auxin signaling. Molecular characterization of axr3 gain-of-function and loss-of-function mutations established the functional importance of domains conserved among AUX/IAA proteins.

Stimulation of insulin release by repaglinide and glibenclamide involves both common and distinct processes.

The action of repaglinide, a novel insulin secretagogue, was compared with the sulfonylurea glibenclamide with regard to the hypoglycemic action in vivo, binding to betaTC-3 cells, insulin secretion from perifused mouse islets, and capacity to stimulate exocytosis by direct interaction with the secretory machinery in single voltage-clamped mouse beta-cells. Two binding sites were identified: a high-affinity repaglinide (KD = 3.6 nmol/l) site having lower affinity for glibenclamide (14.4 nmol/l) and one high-affinity glibenclamide (25 nmol/l) site having lower affinity for repaglinide (550 nmol/l). In contrast to glibenclamide, repaglinide (in concentrations as high as 5 micromol/l) lacked the ability to enhance exocytosis in voltage-clamped beta-cells. Repaglinide was more potent than glibenclamide in stimulating insulin release from perifused mouse islets (EC50 29 vs. 80 nmol/l). The greater potency of repaglinide in vitro was paralleled by similar actions in vivo. The ED50 values for the hypoglycemic action were determined to be 10.4 and 15.6 microg/kg after intravenous and oral administration, respectively. The corresponding values for glibenclamide were 70.3 microg/kg (intravenous) and 203.2 microg/kg (oral). Further, repaglinide (1 mg/kg p.o.) was effective (P < 0.001) as an insulin-releasing agent in a rat model (low-dose streptozotocin) of type 2 diabetes. These observations suggest that the insulinotropic actions of repaglinide and glibenclamide in vitro and in vivo are secondary to their binding to the high-affinity repaglinide site and that the insulinotropic action of repaglinide involves both distinct and common cellular mechanisms.

Randomised controlled double blind study of role of recombinant erythropoietin in the prevention of chronic lung disease.

AIM: To evaluate the role of recombinant human erythropoietin (R-HuEpo) in reducing iron infusion, which may exacerbate free radical damage, leading to chronic lung disease. METHODS: A multicentre, randomised, placebo controlled, double blind study was carried out in four neonatal intensive care units in Yorkshire. Infants were randomly allocated and received either R-HuEpo (480 U/kg/wk) or placebo by twice weekly subcutaneous injection. The primary outcome measure was the number of days on respiratory support and a secondary outcome the number of blood transfusions required. RESULTS: Forty two very low birthweight (VLBW) infants were randomly allocated. There was little difference in the need for respiratory support one month after randomisation, but subsequently there was a trend towards a reduction in the proportion requiring respiratory support in the R-HuEpo group (difference at three months -0.50, 95% confidence interval -1.00, 0.17). During stay in hospital, the median number of blood transfusions was lower for infants in the R-HuEpo group (difference in medians -2, 95% CI -4, 0). The study was stopped early because of failure to recruit babies at the expected rate. CONCLUSIONS: R-HuEpo seems to reduce the number of days in oxygen for ill VLBW infants. These data could be used to construct a larger multicentre study to evaluate this effect further.

Treatment with GAD65 or BSA does not protect against diabetes in BB rats.

The M(r) 65,000 isoform of glutamic acid decarboxylase (GAD65) has been implicated as the initiating islet cell antigen in the pathogenesis of diabetes, primarily based on studies in non-obese diabetic (NOD) mice. To test the role of this islet cell autoantigen in the pathogenesis of spontaneously occurring diabetes in another animal model, purified recombinant human islet GAD65 was injected i.v. at 200 micrograms/animal into 18-day-old diabetes-prone BB rats. For controls, bovine serum albumin (BSA), which has also been implicated in the pathogenesis of diabetes, or buffer alone was injected into age matched BB rats. At 210 days of age there were no differences in diabetes incidence in the 3 groups, i.e. 73% (11 of 15) in the GAD65-treated, 81% (13 of 16) in the BSA-treated and 65% (11 of 17) in the buffer-treated animals, or in the median age at onset of disease, i.e. 79 days (range 65-111), 87 days (range 60-107) and 86 days (range 74-109), respectively. The lack of protection against diabetes following GAD65 treatment could hypothetically be explained by no or by an aberrant expression of GAD in BB-rat islet cells. However, immunohistochemistry of pancreata and immunoblotting analysis of isolated islets showed that the expression of GAD65 and GAD67 was similar in BB and Lewis rats. In conclusion, these data indicate that neither GAD65 nor BSA autoimmunity is important for the development of diabetes in BB rats, in contrast to the situation in NOD mice, and further emphasizes that extrapolation from only one animal model to autoimmune diabetes in general may not be appropriate.

Adoptive transfer of diabetes to and from old normoglycaemic BB rats.

Approximately 4% of diabetes-prone BB/Mol rats escape overt diabetes which occurs in other rats between 56 and 130 days of age. The ability of preactivated spleen cells from older non-diabetic and from acutely diabetic rats to adoptively transfer diabetes into young diabetes-prone rats was compared, and it was found that they transferred disease with similar incidence and with overlapping onset times in the recipients. Old non-diabetic rats were themselves susceptible to diabetes adoptively transferred from acutely diabetic or from old nondiabetic donors. Lymphocytic insulitis and pancreatic insulin content in unmanipulated old non-diabetic rats were both intermediate between those seen in acutely diabetic and in diabetes-resistant rats. In vivo treatment with polyinosinic-polycytidylic acid induced diabetes with faster onset in old non-diabetic rats than in young diabetes-prone rats. Adoptive transfer of fresh, whole spleen cells from old nondiabetic rats did not protect young BB rats against spontaneous diabetes, while cells from diabetes-resistant rats did. Spleens from old non-diabetic rats contained significantly lower percentages of T cells than spleens from acutely diabetic rats but not lower than spleens from age-matched diabetic rats, suggesting that this reduction was age-related. Finally, spleens from both old non-diabetic and from acutely diabetic rats were negative for the regulatory RT6+ T-cell subset. It is concluded that quiescent beta-cell autoimmunity seen in a fraction of BB/Mol rats can be reactivated upon non-antigen-specific immune stimulation.

Predilatation of the cervix before suction curettage for therapeutic abortion in early pregnancy.

The oral use of a synthetic methyl ester analogue of prostaglandin E1 (misoprostol) prior to suction curettage for therapeutic abortion in early pregnancy is reported. Misoprostol was found to be an effective, inexpensive and safe agent for preoperative cervical treatment.

Pancreatic exocrine function and necrotising enterocolitis.

Pancreatic protease deficiency may be an aetiological factor in enteritis necroticans, a disease sharing some features of necrotising enterocolitis (NEC). Using faecal chymotrypsin measurement we have prospectively studied pancreatic exocrine function in infants at risk of NEC. No significant difference was found comparing those infants who subsequently developed NEC and those who did not.

The Australian Incident Monitoring Study: an analysis of 2000 incident reports.

The Australian Patient Safety Foundation was formed in 1987; it was decided to set up and co-ordinate the Australian Incident Monitoring Study as a function of this Foundation; 90 hospitals and practices joined the study. Participating anaesthetists were invited to report, on an anonymous and voluntary basis, any unintended incident which reduced, or could have reduced, the safety margin for a patient. Any incident could be reported, not only those which were deemed "preventable" or were thought to involve human error. The Mark I AIMS form was developed which incorporated features and concepts from several other studies. All the incidents in this symposium were reported using this form, which contains general instructions to the reporter, key words and space for a narrative of the incident, structured sections for what happened (with subsections for circuitry incidents, circuitry involved, equipment involved, pharmacological incidents and airway incidents), why it happened (with subsections for factors contributing to the incident, factors minimising the incident and suggested corrective strategies), the type of anaesthesia and procedure, monitors in use, when and where the incident happened, the experience of the personnel involved, patient age and a classification of patient outcome. Enrollment, reporting and data-handling procedures are described. Data on patient outcome are presented; this is correlated with the stages at which the incident occurred and with the ASA status of the patients. The locations at which the incidents occurred and the types of procedures, the sets of incidents analysed in detail and a breakdown of the incidents due to drugs are also presented.(ABSTRACT TRUNCATED AT 250 WORDS)