Documentation of 50% water conservation in a single process at a beef abattoir.

Beef slaughter is water intensive due to stringent food safety requirements. We conducted a study at a commercial beef processor to demonstrate water conservation by modifying the mechanical head wash. We documented the initial nozzle configuration (112 nozzles), water pressure (275kPa), and flowrate (152L/head washed), then developed a 3-D CAD model to identify regions of water use redundancy. The mechanical head wash was modified by reducing nozzle count (72), decreasing pressure (138kPa) and flowrate (78.4L/head). To objectively document visual cleansing, heads were photographed at three locations post decapitation: 1) prior to manual wash, 2) prior to entering, and 3) upon exit of the mechanical head wash. Changes in red saturation between stations 1 and 3 provided an objective measure of relative cleanliness. Prior to altering operating parameters, the post-wash red saturation was 5%; after modification this increased slightly to 7.5%. Water use was reduced by 48.4% without altering head cleanliness acceptance.

Creating the optimal workspace for hospital staff using human centred design.

We were tasked with creating best possible non-clinical workspace solutions for approximately 450 hospital staff across 11 departments encompassing medical, nursing, allied health, administrative and other support staff. We used a Human-Centred Design process, involving 'Hear, Create and Deliver' stages. We used observations, contextual enquiry and role-specific workshops to understand needs, key interactions and drivers of behaviour. Co-design workshops were then used to explore and prototype-test concepts for the final design. With extensive employee engagement and design process expertise, an innovative solution was created that focussed on meeting the functional workspace needs of a diverse group of staff requiring a range of different spaces, incorporating space constraints and equity. This project demonstrated the strength of engaging employees in an expert-led Human-Centred Design process. We believe this is a successful blueprint process for other institutions to embrace when facing similar workspace design challenges.

Substantial energetic improvement with minimal structural perturbation in a high affinity mutant antibody.

Here, we compare an antibody with the highest known engineered affinity (K(d)=270 fM) to its high affinity wild-type (K(d)=700 pM) through thermodynamic, kinetic, structural, and theoretical analyses. The 4M5.3 anti-fluorescein single chain antibody fragment (scFv) contains 14 mutations from the wild-type 4-4-20 scFv and has a 1800-fold increase in fluorescein-binding affinity. The dissociation rate is approximately 16,000 times slower in the mutant; however, this substantial improvement is offset somewhat by the association rate, which is ninefold slower in the mutant. Enthalpic contributions to binding were found by calorimetry to predominate in the differential binding free energy. The crystal structure of the 4M5.3 mutant complexed with antigen was solved to 1.5A resolution and compared with a previously solved structure of an antigen-bound 4-4-20 Fab fragment. Strikingly, the structural comparison shows little difference between the two scFv molecules (backbone RMSD of 0.6A), despite the large difference in affinity. Shape complementarity exhibits a small improvement between the variable light chain and variable heavy chain domains within the antibody, but no significant improvement in shape complementarity of the antibody with the antigen is observed in the mutant over the wild-type. Theoretical modeling calculations show electrostatic contributions to binding account for -1.2 kcal/mol to -3.5 kcal/mol of the binding free energy change, of which -1.1 kcal/mol is directly associated with the mutated residue side-chains. The electrostatic analysis reveals several mechanistic explanations for a portion of the improvement. Collectively, these data provide an example where very high binding affinity is achieved through the cumulative effect of many small structural alterations.

The use of the Hospital Anxiety and Depression Scale (HADS) in patients with chronic obstructive pulmonary disease: a pilot study.

AIMS: To investigate the use of the Hospital Anxiety and Depression Scale (HADS) with recuperating chronic obstructive pulmonary disease (COPD) patients. To study prevalence rates and changes in clinically relevant anxiety and depression during rehabilitation. METHODS: Consecutive patients admitted to a non acute respiratory ward over a twelve week period were asked to complete a HADS questionnaire on three occasions. Nurses recorded basic demographic information on admission. Additional demographic, medical and psychiatric data were obtained by retrospective review of medical records. RESULTS: Of 93 consecutive inpatients, 79 (85%) completed the admission HADS. 72 patients were eligible to complete the day three HADS and 60 the discharge HADS. Clinically relevant anxiety (HADS score of > or =8) was indicated in 39 patients (50%) and depression in 22 (28%). HADS anxiety (p=0.05) and total scores (anxiety+depression) (p=0.03) decreased between admission and discharge. A larger proportion of patients scored within the normal or mild psychopathology range by discharge. More severe COPD (FEV1% predicted) correlated with higher HADS anxiety scores (r=-0.39, p<0.001) and HADS depression scores (r=-0.34, p<0.005). Patients with a recorded history of anxiety (p<0.0001) and depression (p<0.02) had higher WADS scores. Females (n=37) when compared to males (n=42), recorded significantly higher HADS anxiety scores throughout (p<0.005). CONCLUSIONS: Clinically relevant anxiety, indicated by higher HADS scores, was more common in patients with severe COPD, a past history of anxiety or depression and females. Anxiety and total mood improved during inpatient rehabilitation. The use of this instrument with New Zealand COPD patients may improve identification and treatment of anxious and depressed patients.

Life on carbon monoxide: X-ray structure of Rhodospirillum rubrum Ni-Fe-S carbon monoxide dehydrogenase.

A crystal structure of the anaerobic Ni-Fe-S carbon monoxide dehydrogenase (CODH) from Rhodospirillum rubrum has been determined to 2.8-A resolution. The CODH family, for which the R. rubrum enzyme is the prototype, catalyzes the biological oxidation of CO at an unusual Ni-Fe-S cluster called the C-cluster. The Ni-Fe-S C-cluster contains a mononuclear site and a four-metal cubane. Surprisingly, anomalous dispersion data suggest that the mononuclear site contains Fe and not Ni, and the four-metal cubane has the form [NiFe(3)S(4)] and not [Fe(4)S(4)]. The mononuclear site and the four-metal cluster are bridged by means of Cys(531) and one of the sulfides of the cube. CODH is organized as a dimer with a previously unidentified [Fe(4)S(4)] cluster bridging the two subunits. Each monomer is comprised of three domains: a helical domain at the N terminus, an alpha/beta (Rossmann-like) domain in the middle, and an alpha/beta (Rossmann-like) domain at the C terminus. The helical domain contributes ligands to the bridging [Fe(4)S(4)] cluster and another [Fe(4)S(4)] cluster, the B-cluster, which is involved in electron transfer. The two Rossmann domains contribute ligands to the active site C-cluster. This x-ray structure provides insight into the mechanism of biological CO oxidation and has broader significance for the roles of Ni and Fe in biological systems.

Adenosylcobalamin-dependent isomerases: new insights into structure and mechanism.

Adenosylcobalamin-dependent isomerases catalyze a variety of chemically difficult 1,2-rearrangements that proceed through a mechanism involving free radical intermediates. These radicals are initially generated by homolysis of the cobalt-carbon bond of the coenzyme. Recently, the crystal structures of several of these enzymes have been solved, revealing two modes of coenzyme binding and highlighting the role of the protein in controlling the rearrangement of reactive substrate radical intermediates. Complementary data from kinetic, spectroscopic and theoretical studies have produced insights into the mechanism by which substrate radicals are generated at the active site, and the pathways by which they rearrange.

Refined structures of oxidized flavodoxin from Anacystis nidulans.

Flavodoxin from Anacystis nidulans (Synechococcus PCC 7942) was the first member of the flavodoxin family to be characterized, and is the structural prototype for the "long-chain" flavodoxins that have molecular masses of approximately 20 kDa. Crystal structure analyses and refinements of three orthorhombic forms of oxidized A. nidulans flavodoxin are reported, and salient features of the fold and the FMN binding site are compared with other flavodoxins. The structure of form I (wild-type: P212121, a=57.08 A, b=69.24 A, c=45.55 A), determined initially by multiple isomorphous replacement, has been refined to R=0.183 and R(free)=0.211 for data from 10.0 to 1.7 A resolution. Structures of form II (wild-type: P212121, a=60.05 A, b=65.85 A, c=51.36 A) and form III (Asn58Gly: P212121, a=51.30 A, b=59.15 A, c=94.44 A) have been determined by molecular replacement and refined versus data to 2.0 A and 1.85 A, respectively; the R values for forms II and III are 0.147 and 0.150. Changes in the molecular contacts that produce the alternative packings in these crystalline forms are analyzed. Deletion of the Asn side-chain in the mutant Asn58Gly removes an intermolecular stacking interaction and allows the alternative packing found in form III crystals. The functionally important 50's loop of the FMN binding site is less restrained by intermolecular contacts in these crystals but maintains the same conformation as in oxidized wild type protein. The structures reported here provide the starting point for structure-function studies of the reduced states and of mutants, described in the accompanying paper.

Comparisons of wild-type and mutant flavodoxins from Anacystis nidulans. Structural determinants of the redox potentials.

The long-chain flavodoxins, with 169-176 residues, display oxidation-reduction potentials at pH 7 that vary from -50 to -260 mV for the oxidized/semiquinone (ox/sq) equilibrium and are -400 mV or lower for the semiquinone/hydroquinone (sq/hq) equilibrium. To examine the effects of protein interactions and conformation changes on FMN potentials in the long-chain flavodoxin from Anacystis nidulans (Synechococcus PCC 7942), we have determined crystal structures for the semiquinone and hydroquinone forms of the wild-type protein and for the mutant Asn58Gly, and have measured redox potentials and FMN association constants. A peptide near the flavin ring, Asn58-Val59, reorients when the FMN is reduced to the semiquinone form and adopts a conformation ("O-up") in which O 58 hydrogen bonds to the flavin N(5)H; this rearrangement is analogous to changes observed in the flavodoxins from Clostridium beijerinckii and Desulfovibrio vulgaris. On further reduction to the hydroquinone state, the Asn58-Val59 peptide in crystalline wild-type A. nidulans flavodoxin rotates away from the flavin to the "O-down" position characteristic of the oxidized structure. This reversion to the conformation found in the oxidized state is unusual and has not been observed in other flavodoxins. The Asn58Gly mutation, at the site which undergoes conformation changes when FMN is reduced, was expected to stabilize the O-up conformation found in the semiquinone oxidation state. This mutation raises the ox/sq potential by 46 mV to -175 mV and lowers the sq/hq potential by 26 mV to -468 mV. In the hydroquinone form of the Asn58Gly mutant the C-O 58 remains up and hydrogen bonded to N(5)H, as in the fully reduced flavodoxins from C. beijerinckii and D. vulgaris. The redox and structural properties of A. nidulans flavodoxin and the Asn58Gly mutant confirm the importance of interactions made by N(5) or N(5)H in determining potentials, and are consistent with earlier conclusions that conformational energies contribute to the observed potentials.The mutations Asp90Asn and Asp100Asn were designed to probe the effects of electrostatic interactions on the potentials of protein-bound flavin. Replacement of acidic by neutral residues at positions 90 and 100 does not perturb the structure, but has a substantial effect on the sq/hq equilibrium. This potential is increased by 25-41 mV, showing that electrostatic interaction between acidic residues and the flavin decreases the potential for conversion of the neutral semiquinone to the anionic hydroquinone. The potentials and the effects of mutations in A. nidulans flavodoxin are rationalized using a thermodynamic scheme developed for C. beijerinckii flavodoxin.

Evaluation of a self-management plan for chronic obstructive pulmonary disease.

We hypothesized that the use of an Action Plan might assist self-management for patients with chronic obstructive pulmonary disease (COPD). A pilot process and randomized, controlled study were undertaken to evaluate an Action Plan that provided advice on management of usual care and exacerbations, together with a booklet on self-management. Fifty six subjects with COPD recruited through general practitioners (GPs) completed the 6 month study, 27 in the control group and 29 in the intervention group. The control group received usual care from their GP, and the intervention group received a booklet and Action Plan from their practice nurse plus a supply of prednisone and antibiotic from their GP. The two groups were demographically similar with a mean age of 68 yrs. The resources were well received by GPs, practice nurses and intervention group subjects. After 6 months, there were no differences in quality of life scores or pulmonary function. There were significant changes in self-management behaviour in the intervention group compared to controls. In response to deteriorating symptoms, 34 versus 7% (p=0.014) initiated prednisone treatment and 44 versus 7% (p=0.002) initiated antibiotics. Subjects in the intervention group readily adopted self-management skills but did not show any difference in quality of life or lung function parameters. A larger, prospective, controlled, clinical trial of this approach is warranted.

A protein radical cage slows photolysis of methylcobalamin in methionine synthase from Escherichia coli.

Methionine synthase from Escherichia coli is a B12-dependent enzyme that utilizes a methylcobalamin prosthetic group. In the catalytic cycle, the methyl group of methylcobalamin is transferred to homocysteine, generating methionine and cob(I)-alamin, and cob(I)alamin is then remethylated by a methyl group from methyltetrahydrofolate. Methionine synthase occasionally undergoes side reactions that produce the inactive cob(II)alamin form of the enzyme. One such reaction is photolytic homolysis of the methylcobalamin C-Co bond. Binding to the methionine synthase apoenzyme protects the methylcobalamin cofactor against photolysis, decreasing the rate of this reaction by approximately 50-fold. The X-ray structure of the cobalamin-binding region of methionine synthase suggests how the protein might protect the methylcobalamin cofactor in the resting enzyme. In particular, the upper face (methyl or beta face) of the cobalamin cofactor is in contact with several hydrophobic residues provided by an alpha-helical domain, and these residues could slow photolysis by caging the methyl radical and favoring recombination of the CH3./cob(II)alamin radical pair. We have introduced mutations at three positions in the cap domain; phenylalanine 708, phenylalanine 714, and leucine 715 have each been replaced by alanine. Calculations based on the wild-type structure predict that two of these three mutations (Phe708Ala and Leu715Ala) will increase solvent accessibility to the methylcobalamin cofactor, and in fact these mutations result in dramatic increases in the rate of photolysis. The third mutation, Phe714Ala, is not predicted to increase the accessibility of the cofactor and has only a modest effect on the photolysis rate of the enzyme. These results confirm that the alpha-helical domain covers the cofactor in the resting methylcobalamin enzyme and that residues from this domain can protect the enzyme against photolysis. Further, we show that binding the substrate methyltetrahydrofolate to the wild-type enzyme results in a saturable increase in the rate of photolysis, suggesting that substrate binding induces a conformational change in the protein that increases the accessibility of the methylcobalamin cofactor.

The reactivity of B12 cofactors: the proteins make a difference.

Determination of the structure of intact methylmalonyl-CoA mutase from Propionibacterium shermanii, and comparisons with the structure of the cobalamin-binding fragment of methionine synthase from Escherichia coli, afford a first glimpse at the similarities and distinctions between the two principal classes of B12-dependent enzymes: the mutases and the methyltransferases.

Molecular basis for dysfunction of some mutant forms of methylmalonyl-CoA mutase: deductions from the structure of methionine synthase.

Inherited defects in the gene for methylmalonyl-CoA mutase (EC 5.4.99.2) result in the mut forms of methylmalonic aciduria. mut- mutations lead to the absence of detectable mutase activity and are not corrected by excess cobalamin, whereas mut- mutations exhibit residual activity when exposed to excess cobalamin. Many of the mutations that cause methylmalonic aciduria in humans affect residues in the C-terminal region of the methylmalonyl-CoA mutase. This portion of the methylmalonyl-CoA mutase sequence can be aligned with regions in other B12 (cobalamin)-dependent enzymes, including the C-terminal portion of the cobalamin-binding region of methionine synthase. The alignments allow the mutations of human methylmalonyl-CoA mutase to be mapped onto the structure of the cobalamin-binding fragment of methionine synthase from Escherichia coli (EC 2.1.1.13), which has recently been determined by x-ray crystallography. In this structure, the dimethylbenzimidazole ligand to the cobalt in free cobalamin has been displaced by a histidine ligand, and the dimethylbenzimidazole nucleotide "tail" is thrust into a deep hydrophobic pocket in the protein. Previously identified mut0 and mut- mutations (Gly-623 --> Arg, Gly-626 --> Cys, and Gly-648 --> Asp) of the mutase are predicted to interfere with the structure and/or stability of the loop that carries His-627, the presumed lower axial ligand to the cobalt of adenosylcobalamin. Two mutants that lead to severe impairment (mut0) are Gly-630 --> Glu and Gly-703 --> Arg, which map to the binding site for the dimethylbenzimidazole nucleotide substituent of adenosylcobalamin. The substitution of larger residues for glycine is predicted to block the binding of adenosylcobalamin.

Asthma management at Christchurch Hospital: compliance with guidelines.

AIM: To audit compliance with guidelines for the assessment and management of adult patients admitted to Christchurch Hospital with acute asthma. METHODS: An asthma admission form and management guidelines, based on international consensus statements, were designed for use by resident staff at Christchurch Hospital. Compliance with these guidelines was audited during the winter of 1994 by means of retrospective case record review. RESULTS: One hundred and forty three admissions were screened. The form was used in 99 patients (69%), of which 97 had records available for audit. Sixty two patients were admitted under general medical services and 35 under respiratory specialist services. The median age was 34 years (range 14-84) and 77% were female. The history including interval status was adequately documented in over 95% of cases. Peak flow rate was recorded on admission in 93 patients (96%) and spirometry in 62 (64%). During the acute phase of treatment 528 items were prescribed, of which 382 (72%) were appropriate according to the guidelines. The major area (55%) of nonguideline prescribing was the use of nebulised ipratropium in addition to salbutamol for mild or moderate asthma. Written evidence of asthma education was present in 42 (43%). In 34 patients (35%) there was specific reference to the introduction of an asthma action plan. Of the 33 smokers only 17 appeared to have been given smoking cessation advice. Discharge prescribing complied with the guidelines in 71%. The most common variation from the guidelines for discharge therapy related to the manner of prednisone dose reduction. The readmission rate at 1 month was 11%. CONCLUSIONS: The introduction of an asthma admission form enhanced the quality of clinical data gathering by junior staff. Compliance with management guidelines was adequate. Specific sections pertaining to the use of chest radiographs, arterial blood gases and the prescribing of ipratropium and prednisone will be reviewed in updated guidelines.

A synthetic module for the metH gene permits facile mutagenesis of the cobalamin-binding region of Escherichia coli methionine synthase: initial characterization of seven mutant proteins.

Cobalamin-dependent methionine synthase from Escherichia coli is a monomeric 136 kDa protein composed of multiple functional regions. The X-ray structure of the cobalamin-binding region of methionine synthase reveals that the cofactor is sandwiched between an alpha-helical domain that contacts the upper face of the cobalamin and an alpha/beta (Rossmann) domain that interacts with the lower face. An unexpected conformational change accompanies binding of the methylcobalamin cofactor. The dimethylbenzimidazole ligand to the lower axial position of the cobalt in the free cofactor is displaced by histidine 759 from the Rossmann domain [Drennan, C. L., Huang, S., Drummond, J. T., Matthews, R. G., & Ludwig, M. L. (1994) Science 266, 1669]. In order to facilitate studies of the roles of amino acid residues in the cobalamin-binding region of methionine synthase, we have constructed a synthetic module corresponding to nucleotides (nt) 1741-2668 in the metH gene and incorporated it into the wild-type metH gene. This module contains unique restriction sites at approximately 80 base pair intervals and was synthesized by overlap extension of 22 synthetic oligonucleotides ranging in length from 70 to 105 nt and subsequent amplification using two sets of primers. Expression of methionine synthase from a plasmid containing the modified gene was shown to be unaffected by the introduction of the synthetic module. E. coli does not synthesize cobalamin, and overexpression of MetH holoenzyme requires accelerated cobalamin transport. Growth conditions are described that enable the production of holoenzyme rather than apoenzyme. We describe the construction and initial characterization of seven mutants. Four mutations (His759Gly, Asp757Glu, Asp757Asn, and Ser810Ala) alter residues in the hydrogen-bonded network His-Asp-Ser that connects the histidine ligand of the cobalt to solvent. Three mutations (Phe708Ala, Phe714Ala, and Leu715Ala) alter residues in the cap region that covers the upper face of the cobalamin. The His759Gly mutation has profound effects, essentially abolishing steady-state activity, while the Asp757, Ser810, Phe708, and Leu715 mutations lead to decreases in activity. These mutations asses the importance of individual residues in modulating cobalamin reactivity.

Mutations in the B12-binding region of methionine synthase: how the protein controls methylcobalamin reactivity.

Vitamin B12-dependent methionine synthase catalyzes the transfer of a methyl group from methyltetrahydrofolate to homocysteine via the enzyme-bound cofactor methylcobalamin. To carry out this reaction, the enzyme must alternately stabilize six-coordinate methylcobalamin and four-coordinate cob(I)alamin oxidation states. The lower axial ligand to the cobalt in free methylcobalamin is the dimethylbenzimidazole nucleotide substituent of the corrin ring; when methylcobalamin binds to methionine synthase, the ligand is replaced by histidine 759, which in turn is linked by hydrogen bonds to aspartate 757 and thence to serine 810. We have proposed that these residues control the reactivity of the enzyme-bound cofactor both by increasing the coordination strength of the imidazole ligand and by allowing stabilization of cob(I)alamin via protonation of the His-Asp-Ser triad. In this paper we report results of mutation studies focusing on these catalytic residues. We have used visible absorbance spectroscopy and electron paramagnetic resonance spectroscopy to probe the coordination state of the cofactor and have used stopped-flow kinetic measurements to explore the reactivity of each mutant. We show that mutation of histidine 759 blocks turnover, while mutations of aspartate 757 or serine 810 decrease the reactivity of the methylcobalamin cofactor. In contrast, we show that mutations of these same residues increase the rate of AdoMet-dependent reactivation of cob(II)alamin enzyme. We propose that the reaction with AdoMet proceeds via a different transition state than the reactions with homocysteine and methyltetrahydrofolate. These results provide a glimpse at how a protein can control the reactivity of methylcobalamin.

A community-wide promotion of asthma self-management in New Zealand.

Asthma affects approximately 9% of young adults in New Zealand, with evidence of an increase in prevalence over recent years. Morbidity and mortality from this condition have caused widespread concern. In response to identified deficiencies in asthma management, initiatives to promote self-management using an asthma action plan were promoted throughout the Canterbury region in 1991 as part of a regional pilot study. A resource kit was prepared and self-management principles were promoted to general practitioners in discussion workshops. A community-wide promotion of the action plan was followed by a process and outcome evaluation. The plan and associated resources were well received by doctors and patients. Seventy-seven percent of doctors responding to a questionnaire had used the plan, and of these, 94% indicated that they would continue to use the plan in the future. Patients who obtained a completed plan experienced a greater reduction in nocturnal waking with asthma and improved self-management skills.

How a protein binds B12: A 3.0 A X-ray structure of B12-binding domains of methionine synthase.

The crystal structure of a 27-kilodalton methylcobalamin-containing fragment of methionine synthase from Escherichia coli was determined at 3.0 A resolution. This structure depicts cobalamin-protein interactions and reveals that the corrin macrocycle lies between a helical amino-terminal domain and an alpha/beta carboxyl-terminal domain that is a variant of the Rossmann fold. Methylcobalamin undergoes a conformational change on binding the protein; the dimethylbenzimidazole group, which is coordinated to the cobalt in the free cofactor, moves away from the corrin and is replaced by a histidine contributed by the protein. The sequence Asp-X-His-X-X-Gly, which contains this histidine ligand, is conserved in the adenosylcobalamin-dependent enzymes methylmalonyl-coenzyme A mutase and glutamate mutase, suggesting that displacement of the dimethylbenzimidazole will be a feature common to many cobalamin-binding proteins. Thus the cobalt ligand, His759, and the neighboring residues Asp757 and Ser810, may form a catalytic quartet, Co-His-Asp-Ser, that modulates the reactivity of the B12 prosthetic group in methionine synthase.

Cobalamin-dependent methionine synthase: the structure of a methylcobalamin-binding fragment and implications for other B12-dependent enzymes.

Cobalamin-dependent methionine synthase is a large enzyme composed of structurally and functionally distinct regions. Recent studies have begun to define the roles of several regions of the protein. In particular, the structure of a 27 kDa cobalamin-binding fragment of the enzyme from Escherichia coli has been determined by X-ray crystallography, and has revealed the motifs and interactions responsible for recognition of the cofactor. The amino acid sequences of several adenosylcobalamin-dependent enzymes, the methylmalonyl coenzyme A mutases and glutamate mutases, show homology with the cobalamin-binding region of methionine synthase and retain conserved residues that are determinants for the binding of the prosthetic group, suggesting that these mutases and methionine synthase share common three-dimensional structures.

An audit of the assessment and management of patients admitted to Christchurch Hospital with chronic obstructive pulmonary disease.

AIM: To audit the assessment and management of patients admitted to hospital with chronic obstructive pulmonary disease (COPD) during three months of the winter of 1992. METHODS: Consensus management guidelines were developed as the basis for the audit. Consecutive cases were audited by review of the case notes. Half were admitted initially under a respiratory physician and half under a general physician. Ninety-five cases were audited. RESULTS: The overall standard of medical assessment was adequate but a number of deficiencies were identified. The mean duration of stay in hospital was nine days. In the emergency department the use of pulse oximetry in preference to arterial blood gas analysis led to failure to diagnose significant ventilatory failure in five cases. Initial assessment by junior medical staff failed to include comment about level of consciousness in 50% of cases and chest hyperinflation in 40%. Oxygen therapy was given in 87% of cases, but was not prescribed in one third and was often not adequately monitored. Peak flow monitoring was performed on admission in 74% of cases and arterial blood gas measurement in 81%. Over 90% of patients were given nebulised bronchodilator therapy with both nebulised ipratropium bromide and salbutamol. Antibiotics were given in 77% of cases. Corticosteroids were given in 95% of cases, usually orally. Sedatives were prescribed inappropriately in six cases where there was acute ventilatory failure. Four patients died in hospital, none unexpectedly. Three patients were mechanically ventilated and all survived to leave hospital. There was no discharge summary in the case records in 29% of cases. CONCLUSIONS: Standards of assessment and treatment were adequate. Several areas were identified where improvements are required, particularly in the prescribing and monitoring of oxygen therapy. Hospital-wide guidelines for the management of COPD are to be developed.