Therapeutic hypothermia in comatose patients after out-of-hospital cardiac arrest.

Our intensive care unit has been treating comatose patients, following an out-of-hospital cardiac arrest, with therapeutic hypothermia since 2002. In all, 139 out-of-hospital cardiac arrest patients were admitted in the 4-year period 2002-5. Of these, 27% had a favourable outcome (discharged home or to rehabilitation). Forty-one per cent of patients presenting with ventricular fibrillation (VF) and 7% of non-VF patients had a favourable outcome. No patient with an estimated time from collapse to first attempt at cardiopulmonary resuscitation over 12 min survived to hospital discharge. Twenty-two per cent of patients over 70 years were discharged home, suggesting age was not a barrier to surviving out-of-hospital cardiac arrest. The introduction of a therapeutic hypothermia clinical pathway, at the end of 2003 improved the efficiency of cooling. The percentage of patients cooled to below 34 degrees C within 4 h increased from 15 to 51% and those cooled for more than 12 h increased from 30 to 83%.

Effect of awake Carotid Endarterectomy under local anaesthesia on peri-operative blood pressure: blood pressure is normalised when carotid stenosis is treated under local anaesthesia.

BACKGROUND: Carotid Endarterectomy can be performed under local, regional or general anaesthesia. One of the most important effects of the type of anaesthetic used is on the systemic blood pressure. Although variations in blood pressure during and following carotid endarterectomy have been studied previously, the effects of awake carotid endarterectomy under local anaesthesia on blood pressure and its comparison with similar procedures under similar types of anaesthesia have not. METHODS: Peri-operative blood pressure measurements were collected from the records of 25 consecutive patients for each of the following five procedures; Carotid Endarterectomy under general anaesthesia (CEAGA), Anterior Cervical Discectomy and Fusion under general anaesthesia (ACDF), Cerebral Angiography under local anaesthesia (ANG), Carotid Endarterectomy patients under local anaesthesia who were symptomatic (CEALAS) and Carotid Endarterectomy patients under local anaesthesia who were asymptomatic (CEALAA). The recordings were then analysed to find out if there were any clinically significant variations in peri-operative blood pressure. FINDINGS: There is a significant and consistent difference when the pre-operative value was compared with the 4 hour and 24 hour post-operative recordings between the local and general anaesthetic groups for carotid endarterectomy. Carotid endarterectomy reduces the systolic and diastolic blood pressures post-operatively when performed under local anaesthesia and only the diastolic pressure was reduced when performed under general anaesthesia. CONCLUSION: The study provides evidence about the effect of carotid endarterectomy on the systemic blood pressure and its variations when performed under different types of anaesthesia. There is significant post-operative reduction in both the systolic and diastolic blood pressure values and the intraoperative fluctuation is minimal when local anaesthesia is used. Further studies are required to find out how this affects the long-term blood pressure and clinical outcome of the patient.

Novel quorum-sensing-controlled genes in Erwinia carotovora subsp. carotovora: identification of a fungal elicitor homologue in a soft-rotting bacterium.

Seven new genes controlled by the quorum-sensing signal molecule N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) have been identified in Erwinia carotovora subsp. carotovora. Using TnphoA as a mutagen, we enriched for mutants defective in proteins that could play a role in the interaction between E. carotovora subsp. carotovora and its plant hosts, and identified NipEcc and its counterpart in E. carotovora subsp. atroseptica. These are members of a growing family of proteins related to Nep1 from Fusarium oxysporum which can induce necrotic responses in a variety of dicotyledonous plants. NipEcc produced necrosis in tobacco, NipEca affected potato stem rot, and both affected virulence in potato tubers. In E. carotovora subsp. carotovora, nip was shown to be subject to weak repression by the LuxR family regulator, EccR, and may be regulated by the negative global regulator RsmA.

Genome sequence of the enterobacterial phytopathogen Erwinia carotovora subsp. atroseptica and characterization of virulence factors.

The bacterial family Enterobacteriaceae is notable for its well studied human pathogens, including Salmonella, Yersinia, Shigella, and Escherichia spp. However, it also contains several plant pathogens. We report the genome sequence of a plant pathogenic enterobacterium, Erwinia carotovora subsp. atroseptica (Eca) strain SCRI1043, the causative agent of soft rot and blackleg potato diseases. Approximately 33% of Eca genes are not shared with sequenced enterobacterial human pathogens, including some predicted to facilitate unexpected metabolic traits, such as nitrogen fixation and opine catabolism. This proportion of genes also contains an overrepresentation of pathogenicity determinants, including possible horizontally acquired gene clusters for putative type IV secretion and polyketide phytotoxin synthesis. To investigate whether these gene clusters play a role in the disease process, an arrayed set of insertional mutants was generated, and mutations were identified. Plant bioassays showed that these mutants were significantly reduced in virulence, demonstrating both the presence of novel pathogenicity determinants in Eca, and the impact of functional genomics in expanding our understanding of phytopathogenicity in the Enterobacteriaceae.

Insulin reduces serum glycosylphosphatidylinositol phospholipase D levels in human type I diabetic patients and streptozotocin diabetic rats.

The enzyme glycosylphosphatidylinositol phospholipase D has a postulated role in the insulin-mimetic signaling pathway of glycosylphosphatidylinositol compounds. We have investigated enzyme activity in the serum of human type I diabetic patients and plasma and tissues of streptozotocin-induced diabetic rats following insulin administration. In the human diabetic patients serum enzyme activity fell by an average of 10.6% (SEM = 2.7; P = 0.008; n = 20) following administration of insulin. In addition serum enzyme activity appeared to be depleted by 27% (SEM = 8.8; P = 0.011; n = 10) compared to nondiabetic controls. In untreated diabetic rats plasma enzyme activity gradually increased 0.3-fold over a 6-week period (P < 0.001; n = 8), this increase was reversed and activity normalized when these animals were treated with insulin. Cloning of the rat glycosylphosphatidylinositol phospholipase D cDNA enabled confirmation of the liver as the principal organ of synthesis. Analysis of mRNA levels in the livers of the diabetic rats showed that gene expression was reduced in the insulin-treated animals compared to the noninsulin-treated controls by 0.7-fold (P = 0.004; n = 4). Tissue enzyme activity was also reduced in the insulin-treated rats; in skeletal muscle enzyme activity was 0.3-fold lower (P = 0.001; n = 4). Insulin therefore decreases glycosylphosphatidylinositol phospholipase D synthesis in diabetic animals resulting in decreased serum enzyme levels, suggesting a relationship between this enzyme and the function of insulin.

Women and traumatic brain injury.

Women with TBI have been inadequately studied in relation to most aspects of pathophysiology, recovery, health and behavioral issues, and community integration. This is not entirely surprising in light of the preponderance of men with TBI but also reflects the traditional tendency of medical researchers to concentrate their efforts on men. Although most of the residual effects of TBI are gender-neutral, women may present some unique problems in relation to pain and endocrine issues, reproduction, and sexual functioning In addition, a woman's roles as wife, mother, and daughter are likely to result in a different constellation of family dynamics when TBI is introduced. Attention to enrollment of women in research studies and the increasing number of multi-institutional studies of TBI may provide enlightenment on these issues in the future.

Cloning and expression of a DAX1 homologue in the chicken embryo.

DAX1 is an unusual member of the orphan nuclear receptor family of transcription factors. Mutations in human DAX1 cause X-linked adrenal hypoplasia congenita, while abnormal duplication of the gene is responsible for male-to-female dosage-sensitive sex reversal. Based on these and other observations, DAX1 is thought to play a role in adrenal and gonadal development in mammals. As DAX1 has not previously been described in any other vertebrate, a putative avian DAX1 clone was isolated from an embryonic chicken (Gallus domesticus) urogenital ridge cDNA library. The expression profile of this cDNA was then examined during gonadogenesis. The clone included the conserved 3' ligand-binding motif identified in humans and mice but the 5' region lacked the repeat motif thought to specify a DNA-binding domain in mammals. Southern blot analysis and fluorescence in situ hybridisation mapping showed that the gene is autosomal, located on chromosome 1q. Sequence comparisons showed that the putative chicken DAX1 protein has 63 and 60% identity with the human and mouse proteins respectively over the region of the conserved ligand-binding domain. However, stronger identity (74%) exists with a putative alligator DAX1 sequence over the same region. Northern blotting detected a single 1.4 kb transcript in late embryonic chicken gonads, while RNase protection assays revealed expression in the embryonic gonads of both sexes during the period of sexual differentiation. Expression increased in both sexes during gonadogenesis, but was higher in females than in males. This is the first description of a DAX1 homologue in a non-mammalian vertebrate.

Spinal cord stimulation for chronic low back pain: a systematic literature synthesis.

A systematic literature synthesis was performed to analyze the long-term risks and benefits of spinal cord stimulation for patients with failed back surgery syndrome. Relevant articles were identified through a MEDLINE search (January 1966-June 1994), bibliography reviews, searches of personal files, and literature supplied by a stimulator manufacturer. Two investigators independently reviewed each article to determine whether it met the following study inclusion criteria: 1) original data on return to work, pain, medication use, reoperations, functional disability, or stimulator use after permanent implantation of spinal cord stimulators in patients with chronic low back or leg pain despite previous back surgery; and 2) follow-up > or = 30 days for all patients. Articles were excluded if data from patients with other diagnoses were mixed with (and could not be separated from) data from patients with chronic low back or leg pain, or if their data were redundant with those reported in an included article. Articles written in languages other than English or French were excluded. Thirty-nine studies, all case studies, were analyzed. At follow-up (mean, 16 mo; range, 1-45 mo), an average of 59% of patients had > or = 50% pain relief (range, 15-100% of patients). Complications occurred in 42% of patients but were generally minor. It seems that approximately 50 to 60% of patients with failed back surgery syndrome report > 50% pain relief with the use of spinal cord stimulation at follow-up; the lack of randomized trials precludes conclusions concerning the effectiveness of spinal cord stimulation relative to other treatments, placebo, or no treatment.

A controlled trial of intra-operative autologous transfusion in cardiothoracic surgery measuring effect on transfusion requirements and clinical outcome.

We carried out a prospective, controlled trial of intra-operative autologous transfusion (IOAT) in cardiac surgery using the Haemonetics Cellsaver 4, to determine the effects on transfusion requirements and early clinical outcome. Intra-operative autologous transfusion in unselected patients resulted in a reduction in the use of red cells in patients undergoing first-time operations (IOAT median 3 units, controls median 4 units, P = 0.0023), with no difference in the use of other blood products. Post-operative haemoglobin was higher in IOAT patients (IOAT 11.6 g/dl +/- 1.1 versus controls 11.2 g/dl +/- 0.98, P < 0.001). There is therefore the potential for a further reduction in homologous blood use in the IOAT group. There was no difference in early clinical outcome in the two groups; in particular the incidence of coagulopathies was not influenced by IOAT. The routine use of IOAT would add substantially to the cost of these operations. The decision to use it must therefore be based on an assessment of the value of the reduction in risk to the patient achieved by a small reduction in homologous donor exposures.

Studies on the procurement of blood coagulation factor VIII. In vivo studies on blood components prepared in half-strength citrate anticoagulant.

To determine the viability of blood cells collected in half-strength (0.5 CPD.A2) and full-strength citrate anticoagulants, paired crossover autologous survival studies were performed in normal volunteers using 51Cr-labelled red cells after 35 days storage and 111In-labelled platelets after 5 days storage. For both studies, viability was better maintained in 0.5 CPD.A2 anticoagulant. This was significant for red cells (24-hour survival: 80 +/- 6 vs. 52 +/- 21%) but not for platelets by either linear or multiple-hit models (recovery 51 +/- 13 vs. 38 +/- 14%, survival 5.1 +/- 1.4 vs. 3.7 +/- 1.5 days). The poor viability of red cells after storage in full-strength anticoagulant was associated with low cellular adenosine triphosphate levels and was confirmed in follow-up studies.

A comparative study of diagnostic tests for the assessment of herd magnesium status in cattle.

In nine of ten pre-calving dairy herds we found that herd magnesium (Mg) status could be determined with 95% confidence by measurements of serum Mg (S-Mg), urinary Mg fractional clearance ratio (FCR) or creatinine corrected urinary Mg concentration (CUM) from 10 representative cows. Our findings support clinical impressions that FCR and CUM are more sensitive than S-Mg as predictors of a positive production response to Mg supplementation of dairy cows. The available clinical data is not adequately controlled and there is a need for controlled production-response trials to refine interpretation and to confirm the predictive value of these tests. Pending such trials we suggest that mean FCR >10% or CUM >1.0 mmol/l indicate that a positive response is likely. In seven lactating herds the act of milking was not associated with depression of S-Mg and we conclude that sampling cows immediately after milking Gould not result in spurious elevations of FCR. FCR and CUM show close correlation with each other but not with S-Mg.