Difficult airway equipment: a survey of standards across metropolitan Perth.

The importance of appropriate equipment to manage the difficult airway has been highlighted by the publication of the Australian and New Zealand College of Anaesthetists (ANZCA) guidelines in 2012. We set out to audit compliance with these guidelines in all public and private sites providing general anaesthesia in metropolitan Perth. Public and private health care websites identified 39 sites of which 37 were studied. Institutional and ethics approval was obtained. A tick-box design audit tool, based on the ANZCA guidelines, was used to collect information regarding the dedicated difficult airway container (DDAC) at each site. As recommended in the guidelines, only equipment within the DDAC was considered. Further data about each site, including the number of theatre suites, satellite anaesthetic areas, use of capnography and categories of patients treated (adult, obstetric and paediatric) were collected. An adult DDAC was found at 92% of all sites, but none of the sites had all the essential equipment listed in the ANZCA guidelines. There was limited provision of adult difficult airway equipment within private sites compared to public, and less provision of paediatric difficult airway equipment across all sites treating paediatric patients in metropolitan Perth. Capnography was available in 76% of post anaesthesia care units and used regularly in 27%. Adherence to the ANZCA guidelines regarding the DDAC could be improved. Standardised equipment across a metropolitan region would be of value in the management of the difficult airway.

Audit of cardiac pathology detection using a criteria-based perioperative echocardiography service.

Transthoracic echocardiography is often used to screen patients prior to non-cardiac surgery to detect conditions associated with perioperative haemodynamic compromise and to stratify risk. However, anaesthetists' use of echocardiography is quite variable. A consortium led by the American College of Cardiology Foundation has developed appropriate use criteria for echocardiography. At Joondalup Hospital in Western Australia, we have used these criteria to order echocardiographic studies in patients attending our anaesthetic pre-admission clinic. We undertook this audit to determine the incidence of significant echocardiographic findings using this approach. In a 22-month period, 606 transthoracic echocardiographic studies were performed. This represented 8.7% of clinic attendees and 1.7% of all surgical patients. In about two-thirds of the patients, the indication for echocardiography was identified on the basis of a telephone screening questionnaire. The most common indications were poor exercise tolerance (27.4%), ischaemic heart disease (20.9%) and cardiac murmurs (16.3%). Over 26% of patients studied had significant cardiac pathology (i.e. moderate or severe echocardiographic findings), most importantly moderate or severe aortic stenosis (8.6%), poor left ventricular function (7.1%), a regional wall motion abnormality (4.3%) or moderate or severe mitral regurgitation (4.1%). Using appropriate use criteria to guide ordering transthoracic echocardiography studies led to a high detection rate of clinically important cardiac pathology in our perioperative service.

Controlling sludge settleability in the oxidation ditch process.

This paper describes an investigation aimed at developing an operating technique for controlling sludge settleability in the oxidation ditch form of the nitrification denitrification activated sludge process. It was hypothesized that specific sludge volume index (SSVI) is lowest at an optimum process anoxic fraction and increases at higher and lower fractions. Using effluent ammonia:nitrate ratio as a surrogate for anoxic fraction, it was found that a simple empirical model based on a three solids retention time moving average nitrogen ratio was able to replicate the long-term SSVI variations in two independent oxidation ditches at a full-scale plant. Operating data from a second oxidation ditch plant during periods when a prefermenter was on- or off-line showed that SSVI also varies with RBCOD, greater RBCOD giving lower SSVI. It was concluded that best settleability occurs at about the same anoxic fraction as lowest effluent total nitrogen concentration, with an ammonia:nitrate ratio of about 1. An operating rule of thumb is to use dissolved oxygen control to maintain effluent ammonia and nitrate nitrogen concentrations about equal. A third oxidation ditch plant deliberately operated in this manner achieved 15-month median operating values for SSVI of 60mL/g and for effluent ammonia, nitrate and total N, respectively, of 0.2, 0.3 and 2.0mgN/L.

Greenhouse gas production in wastewater treatment: process selection is the major factor.

Many practical design and operating decisions on wastewater treatment plants can have significant impacts on the overall environmental performance, in particular the greenhouse gas (GHG) emissions. The main factor in this regard is the use of aerobic or anaerobic treatment technology. This paper compares the GHG production of a number of case studies with aerobic or anaerobic main and sludge treatment of domestic wastewater and also looks at the energy balances and economics. This comparison demonstrates that major advantages can be gained by using primarily anaerobic processes as it is possible to largely eliminate any net energy input to the process, and therefore the production of GHG from fossil fuels. This is achieved by converting the energy of the incoming wastewater pollutants to methane which is then used to generate electricity. This is sufficient to power the aerobic processes as well as the mixing etc. of the anaerobic stages. In terms of GHG production, the total output (in CO2 equivalents) can be reduced from 2.4 kg CO2/kg COD(removed) for fully aerobic treatment to 1.0 kg CO2/kg COD(removed) for primarily anaerobic processes. All of the CO2 produced in the anaerobic processes comes from the wastewater pollutants and is therefore greenhouse gas neutral, whereas up to 1.4 kg CO2/kg COD(removed) originates from power generation for the fully aerobic process. This means that considerably more CO2 is produced in power generation than in the actual treatment process, and all of this is typically from fossil fuels, whereas the energy from the wastewater pollutants comes primarily from renewable energy sources, namely agricultural products. Even a change from anaerobic to aerobic sludge treatment processes (for the same aerobic main process) has a massive impact on the CO2 production from fossil fuels. An additional 0.8 kg CO2/kg COD(removed) is produced by changing to aerobic sludge digestion, which equates for a typical 100,000 EP plant to an additional production of over 10 t CO2 per day. Preliminary cost estimates confirm that the largely anaerobic process option is a fully competitive alternative to the mainly aerobic processes used, while achieving the same effluent quality.

Comparison of morpholino based translational inhibition during the development of Xenopus laevis and Xenopus tropicalis.

Morpholino (MO) based inhibition of translational initiation represents an attractive methodology to eliminate gene function during Xenopus development (Heasman et al., 2000). However, the degree to which a given target protein can be eliminated and the longevity of this effect during embryogenesis has not been documented. To examine the efficacy of MOs, we have used transgenic Xenopus lines that harbour known numbers of integrations of a GFP reporter under the control of the ubiquitous and highly expressed CMV promoter (Fig. 1a). In addition we have investigated the longevity of the inhibitory effect by using transgenic lines expressing GFP specifically in the lens of tadpoles. These transgenic lines represent the ideal control for the technique as the promoters are highly expressed and GFP can be easily detected by fluorescence and immunoblotting. Moreover, as GFP has no function in development, the levels of inhibition can be tested in an otherwise normal individual. Here we report that MOs are able to efficiently and specifically inhibit the translation of GFP in transgenic lines from Xenopus laevis and Xenopus tropicalis and the inhibitory effect is long-lived, lasting into the tadpole stages. genesis 30:110--113, 2001.

Transgenic Xenopus embryos reveal that anterior neural development requires continued suppression of BMP signaling after gastrulation.

In vertebrates, BMP signaling before gastrulation suppresses neural development. Later in development, BMP signaling specifies a dorsal and ventral fate in the forebrain and dorsal fate in the spinal cord. It is therefore possible that a change in the competence of the ectoderm to respond to BMP signaling occurs at some point in development. We report that exposure of the anterior neural plate to BMP4 before gastrulation causes suppression of all neural markers tested. To determine the effects of BMP4 after gastrulation, we misexpressed BMP4 using a Pax-6 promoter fragment in transgenic frog embryos and implanted beads soaked in BMP4 in the anterior neural plate. Suppression of most anterior neural markers was observed. We conclude that most neural genes continue to require suppression of BMP signaling into the neurula stages. Additionally, we report that BMP4 and BMP7 are abundantly expressed in the prechordal mesoderm of the neurula stage embryo. This poses the paradox of how the expression of most neural genes is maintained if they can be inhibited by BMP signaling. We show that at least one gene in the anterior neural plate suppresses the response of the ectoderm to BMP signaling. We propose that the suppressive effect of BMP signaling on the expression of neural genes coupled with localized suppressors of BMP signaling result in the fine-tuning of gene expression in the anterior neural plate.

A gene trap approach in Xenopus.

The frog transgenesis technique ultimately promises to make mutagenesis possible through random insertion of plasmid DNA into the genome. This study was undertaken to evaluate whether a gene trap approach combined with transgenesis would be appropriate for performing insertional mutagenesis in Xenopus embryos. Firstly, we confirmed that the transgenic technique results in stable integration into the genome and that transmission through the germline occurs in the expected Mendelian fashion. Secondly, we developed several gene trap vectors, using the green fluorescent protein (GFP) as a marker. Using these vectors, we trapped several genes in Xenopus laevis that are expressed in a spatially restricted manner, including expression in the epiphysis, the olfactory bulb and placodes, the eyes, ear, brain, muscles, tail and intestine. Finally, we cloned one of the trapped genes using 5' rapid amplification of cDNA ends polymerase chain reaction (RACE PCR). These results suggest that the transgenic technique combined with a gene trap approach might provide a powerful method for generating mutations in endogenous genes in Xenopus.

Quality of life in treated hypertension: a case-control community based study.

The aim of this case-control community study was to determine whether there was a difference in quality of life between hypertensive subjects and matched normotensive controls. Cases aged 40-79 years were randomly selected from a hypertensive register and matched with controls for age, sex, ethnicity and health centre. Cases had phase V diastolic blood pressure (DBP) > or = 100 mm Hg or systolic blood pressure (SBP) > or = 180 mm Hg, or were on anti-hypertensive medication. Controls had DBP < or = 90 mm Hg and no record of raised BP or anti-hypertensive treatment within the past year. Quality of life was measured by self-administered questionnaire. Data from 90 matched pairs, average age 62 years, with 47% men, were analysed; 80 hypertensive subjects were on anti-hypertensive medication. Hypertensive subjects showed an impairment in well-being compared with controls. They had a lower Health Status Index, had more sickness absence from work, greater symptomatic complaint and impaired psychological well-being. Relatives also reported a poorer quality of life in the hypertensive subjects. This impairment could be a result of the disease, adverse effects of drug treatment or to the effects of labelling.

The preclinical toxicological evaluation of sumatriptan.

1 Sumatriptan is a potent and selective 5-HT1 receptor agonist marketed for the treatment of migraine by both oral and subcutaneous routes. An extensive toxicological programme employing high doses of sumatriptan was carried out in a range of animal species. The studies evaluated both the local and systemic tolerance to single and repeated dosing, effects on all stages of reproduction, as well as the genotoxic and oncogenic potential of sumatriptan. 2 The administration of relatively high single and repeated doses of sumatriptan was well tolerated by both rodents and dogs by the oral, subcutaneous and intravenous routes. Behavioural effects, suggestive of involvement of the central nervous system, were the most obvious result of such doses and were generally more pronounced in dogs than rodents. The reason for this may be related to the higher plasma concentrations of the drug achievable in dogs. Additional observations restricted to dogs, were transient, and included tachycardia, facial oedema and breaks in the continuity of secretion films on the corneal surface. A tendency for an increase in weight gain was seen for rats, while a slight decrease was usually seen for dogs. The only pathological changes related to treatment with high concentrations of sumatriptan consisted of local reactions at the site of subcutaneous administration. 3 Sumatriptan is an indole; the structures of this chemical class show varying propensities for nitrosation. However, appropriate testing with sumatriptan failed to identify any mutagenic nitroso compounds. 4 Sumatriptan was neither genotoxic nor oncogenic. 5 Reproductive studies demonstrated that sumatriptan was not teratogenic and had no effect on peri- and postnatal development. Some embryotoxicity was observed, but only at maternally toxic doses. A slight decrease in the success of insemination was also noted at high oral doses in rats. 6 Results of the toxicological programme performed in support of migraine therapy with sumatriptan provide good assurance of safety for subcutaneous and oral use.

DNA-dependent protein kinase catalytic subunit: a relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene product.

DNA-dependent protein kinase (DNA-PK), which is involved in DNA double-stranded break repair and V(D)J recombination, comprises a DNA-targeting component called Ku and an approximately 460 kDa catalytic subunit, DNA-PKcs. Here, we describe the cloning of the DNA-PKcs cDNA and show that DNA-PKcs falls into the phosphatidylinositol (PI) 3-kinase family. Biochemical assays, however, indicate that DNA-PK phosphorylates proteins but has no detectable activity toward lipids. Strikingly, DNA-PKcs is most similar to PI kinase family members involved in cell cycle control, DNA repair, and DNA damage responses. These include the FKBP12-rapamycin-binding proteins Tor1p, Tor2p, and FRAP, S. pombe rad3, and the product of the ataxia telangiectasia gene, mutations in which lead to genomic instability and predisposition to cancer. The relationship of these proteins to DNA-PKcs provides important clues to their mechanisms of action.

Gene for the catalytic subunit of the human DNA-activated protein kinase maps to the site of the XRCC7 gene on chromosome 8.

The DNA-activated serine/threonine protein kinase (DNA-PK) is composed of a large (approximately 460 kDa) catalytic polypeptide (DNA-PKcs) and Ku, a heterodimeric DNA-binding component (p70/p80) that targets DNA-PKcs to DNA. A 41-kbp segment of the DNA-PKcs gene was isolated, and a 7902-bp segment was sequenced. The sequence contains a polymorphic Pvu II restriction enzyme site, and comparing the sequence with that of the cDNA revealed the positions of nine exons. The DNA-PKcs gene was mapped to band q11 of chromosome 8 by in situ hybridization. This location is coincident with that of XRCC7, the gene that complements the DNA double-strand break repair and V(D)J recombination defects (where V is variable, D is diversity, and J is joining) of hamster V3 and murine severe combined immunodeficient (scid) cells.

Decreasing the complications of renal osteodystrophy secondary to high phosphorus levels by using an innovative self-monitoring educational program.

We wanted continuous ambulatory peritoneal dialysis (CAPD) and continuous cycling peritoneal dialysis (CCPD) patients to become more cognitive of the complications of high-serum phosphorus levels (> 6.0 mg/dL). The phosphorus self-monitoring program was designed to encourage patients to be more responsible for preventing the complications of renal osteodystrophy. Patients' phosphorus levels were graphed monthly on a poster in the exam room. Additional posters discussed their responsibilities to control phosphorus and the complications associated with hyperphosphatemia. All patients received an informative letter regarding the inception of the program in March 1994 and also were assured total anonymity of their laboratory results. At monthly clinic appointments, they received additional written information on phosphorus and discussed their phosphorus levels. Our teaching method proved effective in our CAPD/CCPD population. In March 1994, 31% of our patients had a phosphorus level greater than 6.0 mg/dL versus 10% in September 1994. The ability of patients to see their monthly progress and the comparison with other patients encouraged much interest and questions regarding phosphorus control.

Cognitive function in hypertension: a community based study.

Cognitive function was investigated in a random sample of subjects on the general practitioners' registry of hypertensive patients in an inner city area and matched with normotensive controls. The response rate was 66% giving 90 matched pairs, average age 63 yrs, with 47% men. There was no difference in educational background or measures of reading ability between the two groups. Cognitive function tests showed a consistent trend of poorer performance in hypertensives, with significant differences in Verbal Learning (immediate recall and retention). Age was inversely related to cognitive function, but no additional deterioration with increasing age was shown in hypertensives.

Myocardial infarction and stroke during treatment of hypertensive patients with different diuretic regimes.

A retrospective analysis of mortality and cardiovascular morbidity in patients being treated with a potassium losing diuretic alone or the combination of a potassium losing and sparing diuretic was performed in 1,935 patients attending a hypertension clinic between 1971 and 1981. In all, 713 patients were treated with a potassium losing diuretic and 472 patients were on a potassium sparing diuretic, usually in combination with a potassium loser. Presenting data on risk factors were similar between the two groups and age-adjusted cardiovascular morbidity and mortality was similar between the two groups. The relative risk (RR) for a myocardial infarction event on a potassium losing drug was 1.1 (95% CI 0.5-2.3) in men and 1.0 (0.4-2.5) in women. The corresponding risks for stroke were 0.8 and 0.7 respectively and total mortality was 1.3 and 1.1. However, following exclusion of patients with previous history of cardiovascular disease the risk of myocardial infarction in the potassium losing group was over three times that on a sparing diuretic, though the confidence intervals were wide. Total male mortality tended to be higher (RR = 2.4) but again failed to achieve statistical significance. An excess risk from potassium losing diuretics was found only in patients without cardiovascular disease and cannot be readily explained. This may be the result of treatment selection in different 'at risk' groups or chance in the performance of subgroup analyses.

Risk of serious morbidity associated with hydralazine versus methyldopa treatment in hypertensive patients.

The medical records of patients presenting to the Hammersmith Hospital hypertension clinic between 1971 and 1981 were examined to determine presenting clinical data, treatment regimes, and both cardiovascular and non cardiovascular mortality and morbidity. When compared with 1004 patients receiving treatment other than hydralazine 310 patients on hydralazine had a significantly higher risk of developing renal disease (RR = 2.71) in men, and severe weight loss in women (RR = 3.06). Renal disease risk also tended to be high in women on hydralazine (RR = 1.95) compared with all other treatments, but this was not statistically significant and could be explained by poorer renal function and significantly higher untreated blood pressure in the hydralazine treated group at presentation. The 422 patients who were treated with methyldopa but not hydralazine had similar risk factors for cardiovascular disease compared with a group of 167 who received hydralazine but not methyldopa. Comparisons of event rates failed to find significant differences in morbidity or mortality between these two groups. The age adjusted male mortality was 14/1000 patient years on hydralazine and 12/1000 on methyldopa and 13/1000 and 6/1000 years for women respectively. There was no evidence of an increased risk of either renal disease (RR = 0.3 in men, RR = 0.3 in women) on hydralazine or weight loss (RR = 0.7 in men, RR = 1.6 in women), with similar presenting data. Systemic lupus erythematosus was a rare complication (2 of 314) of treatment with hydralazine.

Detection of novel splicing patterns in a HPV16-containing keratinocyte cell line.

The W12 cell line was derived from a low grade cervical lesion, and is unique among HPV16-containing cell lines in carrying its HPV16 genome as a multicopy episome. As such it is thought to be more representative of a premalignant HPV16-induced tumor than the cervical cancers from which other cell lines have been derived. Using the polymerase chain reaction (PCR), we report here the identification and cloning of a number of novel cDNA species, which appear to be characteristic of the W12 cell line. Two species were identified with E6* coding capacity (E6*I and E6*III). The smaller of these (1009 bp) was predicted to encode a novel E6*III polypeptide containing C-terminal amino acids derived from an out of frame region of the E2/E4 ORFs. The larger species (1480 bp) contained, in addition to the E6*I ORF, an intact E7 ORF and probably represents the transcript for E7 expression, as the E7 protein was readily detectable in the W12 cell line. Both species appeared to be transcribed from the p97 promoter which has been shown to be active in other cell lines. A putative E2 repressor cDNA (891 bp), an E1/E4 message (883 bp), and two novel late cDNA species (1757 and 2031 bp) were also detected, allowing the identification of a splice acceptor immediately in front of the L1 open reading frame (nt 5637) and a splice donor at nt 3631. Although the 1757-base species has the capacity to encode a full-length L1 protein, both messages use a splice donor at nt 1301, and are thus not analogous to late species previously identified in HPV11. Of the six cDNAs cloned, only the 1480-bp E7 message has been observed in other HPV16-containing cell lines. The presence of L1 transcripts, and an E2 repressor mRNA, although unexpected, may reflect the different origins of the W12 cell line.

m-BACOD treatment for intermediate- and high-grade malignant lymphomas: a Southwest Oncology Group phase II trial.

One hundred six eligible patients with advanced intermediate- or high-grade malignant lymphoma were treated with methotrexate with leucovorin rescue, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) in a Southwest Oncology Group phase II trial. Patients were stratified by estimated bone marrow reserve, and impaired marrow reserve patients received reduced doses of cyclophosphamide and doxorubicin. The complete remission rate for normal marrow reserve patients was 65%, while the complete remission rate for impaired marrow reserve patients was 29%. With a median follow-up period of 41 months, 64% of complete responders in the normal marrow group are disease-free 3 years after their response. Three-year survival is 61% in the normal marrow reserve group and is 29% in the impaired marrow reserve group. Eighty-seven percent of treatment courses were given in accordance with protocol dosing and schedule. For doxorubicin, relative dose intensities were 0.75 and 0.61 (normal and impaired marrow reserve arms, respectively), for cyclophosphamide, 0.76 and 0.61, and for methotrexate, 0.55 and 0.45. Serum lactic dehydrogenase (LDH) level was the only pretreatment characteristic found to have a significant effect on overall survival. Severe or greater toxicity occurred in 97% and 89% of the normal and impaired marrow reserve groups, respectively, with granulocytopenia the principal toxicity. Treatment-related fatalities occurred in 8% of patients. m-BACOD is an effective but toxic treatment program for intermediate- and high-grade malignant lymphomas.

Alcohol, tobacco and public policy: the contribution of economics.

This article shows the contribution of economics to debates about prevention policy. The arguments used by various pressure groups favouring or opposing more effective prevention policies need to be subject to critical scrutiny and empirical testing. The market failure case for state intervention in alcohol and tobacco markets is assessed and an alternative public choice approach is outlined. The supply side of the market in the form of the alcohol and tobacco industries is analysed using a structure-performance framework. Consideration is given to how firms might respond to prevention policies through, say, lobbying or shifting higher taxes to suppliers or by diversifying into new markets.