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Funding Acknowledgements None Background Patients undergoing angiography and percutaneous coronary intervention (PCI) were historically reviewed post procedure by a member of the medical team who assesses the patient’s suitability for discharge and completes the discharge letter. Over the past 10 years, the number of patients admitted for these procedures as day cases has increased significantly. In addition, there has been an expansion in nursing roles in the UK with the development of a variety of clinical nurse specialist (CNS) posts which have taken over many of the traditional medical roles. The majority of patients undergoing elective angiography and PCI are admitted to a day case unit at this tertiary cardiac centre. There is no designated medical cover for the unit and medical staff from the acute cardiac unit are called to review patients and complete their discharge paperwork in addition to their other duties. This frequently results in delayed discharge and patients going home without a discharge summary. It was therefore proposed that suitably qualified CNSs could be trained to discharge these patients and others undergoing day case cardiology procedures. From June 2017, the CNS team took over the role of reviewing patients post procedure and completing the discharge letter. Purpose The aim of the study was to evaluate if CNSs were able to discharge patients and provide a timely and effective service following elective cardiology procedures and to obtain patient feedback. Method Data on the number of patients reviewed by the CNSs from June 2017 to the end of December 2019, were prospectively collected in a dedicated database. A pilot study of patient experience was carried out in January 2020. Patients were given a questionnaire which asked about the explanation they received from the CNS regarding the procedure they had undergone, if their medication was reviewed and discussed with them, and if they received a discharge summary to take home. Results 1287 patients were reviewed by the CNS team during the above period. 811 (63.0%) patients had undergone angiography and 423 (32.9%) PCI. Informal feedback from the staff working on the day case unit included that patients were discharged earlier, had improved knowledge about their procedure and that the discharge letter was more detailed when completed by the CNS team. Eight patients completed the pilot questionnaire. Six were discharged by one of the CNS team, one by a doctor and one patient was not sure who did their discharge. All patients were very satisfied with the process and the information they were given. Conclusion Experienced CNSs can deliver high-quality, timely discharge of patients following cardiology procedures. This process is being used as a template to expand nurse-led discharge to other areas in cardiology. Patient experience will continue to be audited with a larger sample size in 2020.

Funding Acknowledgements None Background Rapid Access Chest Pain clinics (RACPCs) were established in the UK in 2000 following the publication of the National Service Framework for Coronary Heart Disease. Patients underwent an exercise test (ETT) in the clinic as part of a ‘one-stop’ protocol with follow-up only if further investigation was required. In 2010, the National Institute for Health and Care Excellence (NICE) produced guidelines for the assessment and diagnosis of chest pain of recent onset (CG95), replacing the recommendation for ETT with non-invasive functional testing for patients with an intermediate pre-test probability of coronary artery disease (CAD), necessitating multiple appointments to evaluate the patient’s symptoms. The guidelines were updated in 2016, with a new recommendation that patients with atypical or typical chest pain should undergo CT coronary angiography (CTCA) as the first diagnostic test. Purpose The aim of this study was to investigate the feasibility and potential benefit of performing same -day CTCA in the RACPC. Method From November 2016 all patients with atypical or typical chest pain attending the RACPC at this tertiary cardiac centre were referred for CTCA unless alternative investigation was clinically indicated. From February 2018, same day CTCA was offered to some patients. Up to two scans could be performed in each clinic, which was increased to up to three in June 2018. Results A total of 985 patients were seen in the nurse-led clinic between 12/02/2018 and 30/11/2019. 473 patients were referred for CTCA (48.0%) and 314 scans were carried out in the clinic (66.4%). Of those scans carried out in clinic, 128 patients had a CTCA which showed no evidence of CAD (40.8%) and 34.4% of scans showed non-obstructive CAD. In 18.2% of patients, the CTCA showed significant CAD and in 21 patients (6.7%) the scan was inconclusive. Patient with inconclusive scans underwent further testing which was negative in all cases. The outcome for patients with significant CAD (57 patients) is shown in the table. Conclusion CTCA on the same day as the RACPC appointment is feasible and facilitates rapid further investigation and treatment of patients with potentially significant CAD. It also enables patients with non-significant or no CAD to be reassured that their symptoms are unlikely to be cardiac which will reduce anxiety and allow timely investigation of other causes of the chest pain. Nurses need training in the risks of radiation in order to be able to request the scans and enable the clinic to be nurse-led.

Predator–prey interactions are a key part of ecosystem function, and non-consumptive effects fall under the landscape of fear theory. Under the landscape of fear, the antipredator responses of prey are based on the spatial and temporal distribution of predatory cues in the environment. However, the aversive stimuli (fear) are not the only stimuli prey can utilize when making behavioral decisions. Prey might also be using attractive stimuli that represent safety to guide decision making. Using a novel, orthogonal design, we were able to spatially separate aversive and attractive stimuli to determine whether prey are utilizing safety cues to navigate their environment. Crayfish Faxonius rusticus were placed in the center of a behavioral arena. Aversive stimuli of either predatory bass Micropterus salmoides cues or conspecific alarm cues increased along the x-axis of the behavioral arena. Safety cues (shelters) increased along the y-axis by decreasing the number of shelter openings in this direction. Crayfish were allowed two phases to explore the arena: one without the fearful stimuli and one with the stimuli. Linear mixed models were conducted to determine whether movement behaviors and habitat utilization were affected by the phase of the trial and the type of aversive stimuli. Crayfish responded more strongly to alarm cues than to fear cues, with only alarm cues significantly impacting habitat utilization. When responding to alarm cues, crayfish used safety cues as well as fear cues to relocate themselves within the arena. Based on these results, we argue that crayfish utilize a landscape of safety in conjunction with a landscape of fear when navigating their environment.

The dual-representation model of posttraumatic stress disorder (PTSD; Brewin, Gregory, Lipton, & Burgess, Psychological Review, 117, 210-232 2010) argues that intrusions occur when people fail to construct context-based representations during adverse experiences. The present study tested a specific prediction flowing from this model. In particular, we investigated whether the efficiency of temporal-lobe-based spatial configuration learning would account for individual differences in intrusive experiences and physiological reactivity in the laboratory. Participants (N = 82) completed the contextual cuing paradigm, which assesses spatial configuration learning that is believed to depend on associative encoding in the parahippocampus. They were then shown a trauma film. Afterward, startle responses were quantified during presentation of trauma reminder pictures versus unrelated neutral and emotional pictures. PTSD symptoms were recorded in the week following participation. Better configuration learning performance was associated with fewer perceptual intrusions, r = -.33, p < .01, but was unrelated to physiological responses to trauma reminder images (ps > .46) and had no direct effect on intrusion-related distress and overall PTSD symptoms, rs > -.12, ps > .29. However, configuration learning performance tended to be associated with reduced physiological responses to unrelated negative images, r = -.20, p = .07. Thus, while spatial configuration learning appears to be unrelated to affective responding to trauma reminders, our overall findings support the idea that the context-based memory system helps to reduce intrusions.

SUMMARY Punishment is clearly defined and re-examined as a treatment technique in a positive and not negative light. A treatment setting involving handicapped children is described and a system of punishment is outlined as an essential part of the regime. The objections to punishment are considered and, in conclusion, a philosophical basis is provided on which it is contended that punishment is a dignified alternative.

Objective: The aim of this study is to report and emphasize unusual presentations of pyruvate dehydrogenase (PDH) deficiency (OMIM 312170). Methods: PDH activity and PDHA1 gene were studied in two siblings presenting with intermittent ataxia in childhood. Similar presentations in reported PDH-deficient patients were searched for using the Medline database. Results: Both patients had PDH deficiency caused by a new mutation (G585C) in the PDHA1 gene, which is predicted to replace a highly conserved glycine at codon 195 by alanine. Although this mutation lies within the thiamine pyrophosphate binding domain, there was no thiamine responsiveness in vivo. The patients presented recurrent episodes of acute isolated ataxia in infancy. Both had normal blood and CSF lactate levels. Although symptoms initially resolved between episodes during the first decade, both patients subsequently worsened and developed progressive and severe encephalopathy, leading to death in their twenties. The spectrum of intermittent presentations in PDH deficiency includes episodic ataxia, intermittent peripheral weakness, recurrent dystonia and extrapyramidal movement disorders. Conclusions: PDH deficiency should be considered in patients with unexplained intermittent and recurrent acute neurological symptoms. Long-term prognosis and outcome remain uncertain. PDH deficiency can occur even with normal CSF lactate concentration.

We investigate the $g_2$-invariant bulk (1+1D, factorized) $S$-matrix constructed by Ogievetsky, using the bootstrap on the three-point coupling of the vector multiplet to constrain its CDD ambiguity. We then construct the corresponding boundary $S$-matrix, demonstrating it to be consistent with $Y(g_2,a_1\times a_1)$ symmetry., Comment: 7 pages

Collings, L. V., Blair, A. M., Gay, A. P., Dyer, C. J., MacKay, W. (2003). The effect of weather factors on the performance of herbicides to control Alopecurus myosuroides in winter wheat. Weed Research, 43 (2), 146-153. Sponsorship: Ministry of Agriculture Fisheries and Food (now DEFRA)

OBJECTIVE: To determine whether antibiotic and bronchodilator treatment of acute bronchitis in patients without lung disease is efficacious. DESIGN: A MEDLINE search of the literature from 1966 to 1995 was done, using “Bronchitis” as the key word. Papers addressing acute bronchitis in adults were used as well as several citations emphasizing pediatric infections. A manual search of papers addressing the microorganisms causing acute bronchitis was also done. Data were extracted manually from relevant publications. SETTING: All published reports were reviewed. Papers dealing with exacerbations of chronic bronchitis were excluded in this review. RESULTS: Although acute bronchitis has multiple causes, the large majority of cases are of viral etiology.Mycoplasma pneumoniae, Chlamydia pneumoniae, andBordetella pertussis are the only bacteria identified as contributing to the cause of acute bronchitis in otherwise healthy adults. Nine double-blind, placebo-controlled trials were reviewed. Four studies showed no advantage for doxycycline and one study showed no advantage for erythromycin. One study using erythromycin and one study using trimethoprim and sulfamethoxazole showed that these antibiotics were slightly better than placebo. Two other studies showed an impressive superiority for liquid or inhaled albuterol when compared with erythromycin. CONCLUSIONS: Most studies showed no significant difference between drug and placebo, and the two studies that did showed only small clinical differences. Albuterol had an impressive advantage over erythromycin. Antibiotics should not be used in the treatment of acute bronchitis in healthy persons unless convincing evidence of a bacterial infection is present.

The most common defect associated with deficiency of the pyruvate dehydrogenase (PDH) complex occurs in the E1 component, specifically due to mutations in the X-linked E1 alpha gene. Clinical sequelae of these mutations, which range from severe neonatal lactic acidosis to carbohydrate-sensitive ataxia, can be different in males and females depending on the nature of the mutation and, in the case of females, on the X-inactivation pattern in different tissues. Males have a high representation of missense mutations among the patient cohort, while females are much more likely to have DNA rearrangements, particularly toward the 3' end of the coding sequence of the gene. Missplicing mutations involving exon 6 deletion have been reported, as has a missense mutation conferring true thiamin-responsiveness of the enzyme and the patient's clinical symptoms. Pyruvate carboxylase deficiency, on the other hand, is a true autosomal recessive disease, though it has high occurrences in particular ethnic groups, especially in Algonkian-speaking Amerindians and in Arabs. In the former group the defect is a simple type in which material cross-reactive to pyruvate carboxylase antibody is present in cultured cells (CRM+ve). In the latter group, cross-reacting material is rarely present (CRM-ve). The CRM+ve patients can survive into teenage years with careful supervision, while the CRM-ve patients have complications due to hyperammonaemia and dysfunction of the urea cycle and rarely survive beyond 3 months of life.

Objectives: Three dimensional (3D) printing technology has many current and future applications in orthopaedics. The objectives of this article are to review published literature regarding applications of 3D technology in orthopaedic surgery with a focus on knee surgery. Methods: A narrative review of the applications of 3D printing technology in orthopaedic practice was achieved by a search of computerised databases, internet and reviewing references of identified publications. Results: There is current widespread use of 3D printing technology in orthopaedics. 3D technology can be used in education, preoperative planning and custom manufacturing. Custom manufacturing applications include surgical guides, prosthetics and implants. Many future applications exist including biological applications. 3D printed models of anatomy have assisted in the education of patients, students, trainees and surgeons. 3D printed models also assist with surgical planning of complex injuries or unusual anatomy. 3D printed surgical guides may simplify surgery, make surgery precise and reduce operative time. Computer models based on MRI or CT scans are utilised to plan surgery and placement of implants. Complex osteotomies can be performed using 3D printed surgical guides. This can be particularly useful around the knee. A 3D printed guide allows pre osteotomy drill holes for the plate fixation and provides an osteotomy guide to allow precise osteotomy. 3D printed surgical guides for knee replacement are widely available. 3D printing has allowed the emergence of custom implants. Custom implants that are patient specific have been particularly used for complex revision arthroplasty or for very difficult cases with altered anatomy. Future applications are likely to include biological 3D printing of cartilage and bone scaffolds. Conclusion: 3D printing in orthopaedic surgery has and will continue to change orthopaedic practice. Its role is to provide safe, reproducible, reliable models with reduced operative time and improves patient outcomes compared to traditional surgical techniques. Long term follow up of the techniques is still required.

Summary A questionnaire survey was conducted in all primary schools in the Dunbarton division of Strathclyde region (N=117) to obtain the views of headteachers regarding the involvement of local authority educational psychologists in the area of learning difficulties. This was a follow‐up to a previously published study of the views of learning support coordinators in secondary schools throughout the division. The results of the primary survey are presented and comparisons made with the secondary schools. The findings suggest that schools perceive psychologists as having a central role to play in the area of learning difficulties but indicate a considerable shortfall between present and desired levels of service. It was also noted that after more than a decade of reconstruction of psychological services in which a major theme has been a reduced emphasis on direct work with individual children, the traditional role of individual assessment and counselling is the one which continues to be strongly endorsed ...

Cytochrome c oxidase (COX) is the terminal enzyme of the respiratory chain, with subunits originating both from the mitochondrial and nuclear genome. An eleven-year-old female presented initially with a seizure followed two months later with tonic-clonic seizures, weakness and aphasia. MRI of the cerebral hemispheres showed multiple infarcts. Previous history suggested gross and fine motor control deficits with learning difficulties. A muscle biopsy showed a specific decrease of COX staining in all fibres and pleomorphic mitochondria. Respiratory chain studies confirmed an isolated complex IV defect in muscle, whilst fibroblasts showed an initial COX activity below normal which rapidly came up to the normal range on culture. Sequencing of mtDNA revealed an heteroplasmic m.7023G>A mutation in the COX1 gene, with levels of 96% in muscle, 70% in blood and 50% in the initial skin fibroblast culture dropping to 10% in later passages. The mutation was present in a critical region of the COX1 gene, the V374M change being close to the two histidine residues His376 and His378 co-ordinating with the heme a and a (3), and His367 which co-ordinates a magnesium ion. This case highlights that a MELAS-like syndrome can occur with isolated COX deficiency.

Pyruvate dehydrogenase phosphatase deficiency has previously only been confirmed at the molecular level in two brothers and two breeds of dog with exercise intolerance. A female patient, who died at 6 months, presented with lactic acidemia in the neonatal period with serum lactate levels ranging from 2.5 to 17 mM. Failure of dichloroacetate to activate the PDH complex in skin fibroblasts was evident, but not in early passages. A homozygous c.277G > T (p.E93X) nonsense mutation in the PDP1 gene was identified in genomic DNA and immunoblotting showed a complete absence of PDP1 protein in mitochondria. Native PDHC activity could be restored by the addition of either recombinant PDP1 or PDP2. This highlights the role of PDP2, the second phosphatase isoform, in PDP1-deficient patients for the first time. We conclude that the severity of the clinical course associated with PDP1 deficiency can be quite variable depending on the exact nature of the molecular defect.

Three patients with chronic lacticacidemia and deficiency of the pyruvate dehydrogenase complex demonstrated in cultured skin fibroblasts showed abnormalities on Western blotting with anti-pyruvate dehydrogenase complex antiserum which were not located in the E1 (alpha and beta) component of the complex. One of these patients had an enzymatically demonstrable deficiency in the E2 dihydrolipoyl transacetylase segment of the complex and very low observable E2 protein component on Western blotting of fibroblast proteins. The other two patients had abnormalities observable in the X component but no observable reduction in either E1, E2, or E3 enzymatic activities. One patient appeared to have a missing X component while the other had two distinct bands where X should be on Western blotting of fibroblast proteins. All three patients appeared to have severe clinical sequelae resulting from these defects. This is the first time that defects in either the E2 or the X component of the pyruvate dehydrogenase complex have been observed in the human population.

A prospective, randomised, controlled clinical study was performed to compare the incidence and severity of postoperative peripheral venous thrombophlebitis associated with a single intravenous cannula used for both intra-operative and postoperative purposes, and two cannulae, one used intra-operatively and the other postoperatively. Sixty American Society of Anaesthesiologists (ASA) physical status I or II patients aged 18-65 years undergoing elective surgery were studied. The technique of cannula insertion was standardised. After surgery, the cannulation sites were examined daily by a blinded investigator for the presence and severity of thrombophlebitis using the Baxter Scale. The two groups were similar in terms of age, gender, weight, type and duration of surgical procedures, and drugs and fluids administered both intra-operatively and postoperatively. The proportion of patients that developed phlebitis was significantly less in the two cannulae group (26.1%) than in the single cannula group (63.3%) (p < 0.0001). The severity of phlebitis was greater in the single cannula group than in the two cannulae group. These results indicate that the use of a dedicated cannula for postoperative use decreases the incidence and severity of postoperative, peripheral, cannula-related phlebitis.

The objective of the MATTUS intercollegiate exercise was to set up and audit a training initiative list scheme (TILS) by which funds are awarded to Trust hospitals for operative sessions used specifically for the training of staff in minimal access therapy (MAT). A prospective centralized audit of TILS involving nine Trust hospitals in Scotland over a 12-month period (1 March 1995-end of February 1996) was carried out. These hospitals had contracted for 510 4-h training sessions (389 for minimal access surgery, 121 for allied interventional techniques) by MATTUS accredited consultant tutors. The scheme covered training in technical competence for Minimal Access Surgery (MAS), interventional flexible endoscopy and interventional radiology within Scottish Hospitals. The main outcome measures used in the audit were trainee completion rates, conversion rates, morbidity and mortality, assessment of training received by trainees and assessment of aptitude by the trainers. The results were as follows. Of 510 sessions, 482 (95%) were completed within the deadline. Of these, 463 sessions were audited (367 for MAS, 69 for flexible endoscopy and 27 for interventional radiology). During these sessions, 817 operations/procedures were performed (781 training and 36 developmental). A total of 544 operations were performed during 339 MAS training sessions and 237 radiological/flexible endoscopy procedures in 96 MAT training sessions. The trainee was the principal operator in 643 (82%) procedures and completed the task in 581 (74%) cases. Four per cent of the MAS operations (22/544) required conversion. Post-operative complications occurred in 42 out of 817 patients (5%). Four patients, all with advanced malignancy, died within 30 days of the procedure. Trainees graded 355 sessions as excellent, 109 good, two as average and one as unsatisfactory. The tutors graded their trainees' aptitude to perform the operation as excellent in 34%, good in 53%, average in 11% and poor in1%. The training initiative list scheme which allows unhurried training in MAT by consultant tutors using operating sessions that are extra to the service lists is operationally and educationally viable. Furthermore, it can be implemented within a pre-determined budget. The audit of TILS has also demonstrated that the immediate clinical outcome of patients is not compromised by this type of training.

We present an update on mutations and polymorphisms in the human X chromosome located pyruvate dehydrogenase E1 alpha gene. A total of 20 different mutations are tabulated. The mutations include deletions, insertions, and point mutations. Certain sequences seem particularly prone to mutation. Most of the mutations are found in exons 10 and 11. Furthermore, four of the mutations are seen in unrelated patients. Little is known about how the mutations affect the structure or function of the pyruvate dehydrogenase complex.

The enteric adenovirus type 40 cannot be passaged in HeLa cells, but will grow productively in cells that express the E1B region of adenovirus types 2 or 5. Even in such permissive cells, the lytic cycle is prolonged, there is an abnormal pattern of E1B early gene expression and a failure to switch off host cell functions, suggesting that other gene functions might be impaired in Ad40. For Ad2, E4 ORF 6 and ORF 3 proteins are known to have an essential role in progressing from the early to the late phase of lytic infection and the shutoff of host functions requires an interaction between the E4 ORF 6 34K protein and the E1B 55K protein. To test whether E4 functions of Ad40 are impaired, complementation tests have been made between Ad40 and the E4 deletion mutant Ad2 dl808, which lacks all but ORF 1 of the E4 region. In HeLa and Vero cells, Ad40 complements dl808 to levels equivalent to an Ad2 wild-type infection, as demonstrated by measuring virion packaged DNA, virus titration, and viral protein synthesis. Surprisingly, Ad2 dl808 fails to reciprocally complement Ad40. The results show that Ad40 produces functional E4 ORF 6 and/or ORF 3 activity, and that their expression precedes DNA replication.

There are four administrative areas (Health and Social Services Boards) in Northern Ireland. Two prevalence surveys, carried out several years apart, show that there is a significant geographical gradient in the rates of severe mental handicap (IQ less than 50). The rates in the 20-29-year-old groups in the Eastern and Northern Boards range between 4.07 and 4.82 per thousand; comparable rates in the Southern and Western Boards range between 5.17 and 6.37. A similar gradient was discernible in the distribution of Down's syndrome.

The introduction of organic chemicals to the environment can cause a variety of ecological problems. One of the most serious of these is the accumulation of chemical agents in an ecosystem. Routes for their introduction are diverse and include direct dumping, accidental spillage, run-off, leaching from containment sites or vessels, and intentional application (e. g. agriculture). The types of chemicals are equally varied and range from industrial and household solvents to crude and refined oils (Calabrese and Kostecki 1989) and pesticides (Biggar and Seiber 1987; Grover 1989).

This short article has been written to ensure that the origin and history of the Badge of the Scottish Society of Physicians is well documented, lest this knowledge be lost.

The group C adenoviruses type 2 (Ad2) and type 5 (Ad5) are distinguished serologically by the antigenic determinants of the hexon and fiber capsomers . The hexon-coding region of the viral genome (map units 51.6-59.7) can be divided into three major zones with regard to DNA sequence homology between Ad2 and Ad5 on the basis of fine structure disclosed by restriction endonuclease site mapping ( Boursnell , M.E.G., and Mautner , V. (1981) Virology 112, 198-209). At the NH2-terminal end, there is almost complete restriction enzyme site homology between Ad2 and Ad5, the COOH terminus displays partial homology, and a central zone (map units 52.7-56.0) is heterologous and has no common restriction sites. We report here the DNA sequence of the Ad5 hexon gene (map units 51.6-59.7). This sequence is compared to that established for Ad2 (G. Akusj arvi , P. Alestr om, M. Pettersson , H. Jornvall , and U. Pettersson , manuscript submitted for publication), and the heterologous zone is shown to encode an amino acid sequence that differs from that of Ad2 at many different loci within the zone (map units 52.7-56.0), interspersed with short stretches of highly conserved sequence.

Superoxide dismutase activity (SOD), plasma and lysate thiol concentrations (PSH and LSH), and caeruloplasmin oxidase activity (CP) reflect the underlying reduction-oxidation imbalance associated with rheumatoid arthritis (RA), and are believed to be involved in the protection of the cell against free radical activity. The early and late changes in these parameters have been observed and compared with standard clinical and biochemical assessments of disease activity in 90 patients with active RA, randomly assigned to receive either sodium aurothiomalate, auranofin, or auranofin placebo. An index based on clinical criteria was used to identify patients as responders or non-responders after 24 weeks of therapy. In the first six weeks of treatment a change in SOD activity and LSH concentration in a direction away from controls was followed by a return towards control levels in responders only. This suggests that in RA evidence of clinical improvement induced by gold drugs is preceded by an initial biochemical response in an inflammatory direction. The extracellular parameters PSH and CP did not show the same early response, but PSH levels in responders showed a slower change towards normal values, though at no time were values obtained that might suggest a complete remission. Thus the intracellular parameters appear to reflect an early effect of the drugs on cells which may possibly be of use in predicting the outcome of therapy, whereas the extracellular parameters provide confirmatory evidence for an eventual improvement.

Presentation de la theorie de l'organisation neurologique decrite par les membres des «Institutes for the Achievement of Human Potential» (principalement Doman et Delacato) ainsi que de leurs methodes de traitement pour les enfants soufrant de troubles cerebraux organiques

A 1.5-kilobase cDNA clone for human pyruvate dehydrogenase E1 was isolated from a lambda gt11 expression library by screening with polyclonal antiserum to the E1 alpha subunit of the porcine pyruvate dehydrogenase complex, a polyclonal antibody against bovine pyruvate dehydrogenase complex and a synthetic oligonucleotide based on the known amino acid sequence of the amino-terminal of the bovine pyruvate dehydrogenase-E1 alpha subunit. Nucleotide sequence analysis of the cDNA revealed a 5'-untranslated sequence of 72 nucleotides, a translated sequence of 1170 nucleotides, and a 3'-untranslated sequence of 223 nucleotides with a poly(A) tail. The cDNA structure predicts a leader sequence of 29 amino acids and a mature protein of 362 amino acids comprising an amino-terminal peptide identical to that of the bovine E1 alpha subunit and three serine phosphorylation sites whose sequence was also identical to those in the bovine E1 alpha subunit. The translated sequence for the mature protein differs substantially from that described by Dahl et al. (Dahl, H. H., Hunt, S. M., Hutchison, W. M., and Brown, G. K. (1987) J. Biol. Chem. 262, 7398-7403) by virtue of a frameslip between bases 390 and 594. This amended sequence is confirmed by the presence of additional restriction sites for the enzymes NaeI and HaeII at the beginning and end, respectively, of this section. The leader sequence is typical for mitochondrial enzymes being composed of a combination of neutral and basic residues. The amino acid composition is strikingly similar to that of the bovine protein. This cDNA clone hybridizes with a 1.8-kilobase mRNA on a Northern blot analysis of human fibroblasts, and a second minor band of 4.4 kilobases is also detected.

The authors evaluated the financial and health implications of treatment choices for three serious classes of infection: hospital-acquired pneumonia, intra-abdominal infection, and sepsis of unknown origin. Data were obtained from a systematic review of clinical literature and published data bases, by written questionnaire from a panel of infectious disease authorities, and from actual costs at a tertiary-care hospital. For pneumonia and sepsis, the third-generation cephalosporin evaluated (ceftizoxime) was found to be less expensive than other regimens, when costs of dose preparation and administration, monitoring, and toxicity were added to drug acquisition costs. The lowest-cost regimen for intra-abdominal infection was metronidazole plus gentamicin. Modest differences in efficacy would easily outweigh differences in toxicity, however, and could justify the use of more expensive regimens (e.g., mezlocillin plus gentamicin for hospital-acquired pneumonia, and cefoxitin plus gentamicin for intra-abdominal infection). If all regimens are assumed to be equally efficacious, then the third-generation cephalosporin was both lowest in cost and, owing to its low toxicity, greatest in net health benefit.

The venoms of three mambas (Dendroaspis angusticeps, Dendroaspis polylepis and Dendroaspis jamesoni) were shown to be anticoagulant, an effect due largely to interference with the blood thromboplastin mechanism. The venoms were also capable of inhibiting platelet aggregation and reactivity to ADP. All three venoms possessed proteolytic properties but paradoxically reduced euglobulin clot lysis activity. When studied in purified systems this effect was shown to be due to uncompetitive inhibition of plasmin.