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Biomedical subjects

S Morris

Publications and source records attributed to S Morris.

At least 19 recordsLinked to original sources

Cost effectiveness of recombinant activated factor VII for the control of bleeding in patients with severe blunt trauma injuries in the United Kingdom.

The aim of this study was to assess the lifetime cost effectiveness of recombinant activated factor VII vs placebo as adjunctive therapy for control of bleeding in patients with severe blunt trauma in the UK. We developed a cost-effectiveness model based on patient level data from a 30-day international, randomised, placebo-controlled Phase II trial. The data were supplemented with secondary data from UK sources to estimate lifetime costs and benefits. The model produced a baseline estimate of the incremental cost per life year gained with recombinant activated factor VII relative to placebo of 12 613 UK pounds. The incremental cost per quality adjusted life year gained was 18 825 UK pounds. These estimates are sensitive to the choice of discount rate and health state utility values used. Preliminary results suggest that relative to placebo, recombinant activated factor VII may be a cost-effective therapy to the UK National Health Service.

Adult↗

Enhancing cell survival of atrazine degrading Rhodococcus erythropolis NI86/21 cells encapsulated in alginate beads.

AIMS: To develop a method to produce beads with encapsulated Rhodococcus erythropolis NI86/21 with high cell density, extended shelf life, ease of handling and good atrazine degradation capabilities in both liquid and in agricultural soil. METHODS AND RESULTS: Our findings show that the supplementary recovery step in nutrient broth media shortly after cell encapsulation facilitates cell survival in both wet and dry beads upon extended storage at 4 degrees C. Air drying has little or no impact on encapsulated R. erythropolis cell's ability to degrade atrazine in liquid or soil. Bead storage for periods extending up to 12 months at 4 degrees C did not affect the capacity of R. erythropolis encapsulated cells to degrade atrazine in either BMN or nonsterile soil extracts. Bentonite-amended beads formulated with 1% skim milk and exposed to the supplementary growth step, outperformed all other bead formats. These beads provided adequate numbers of vigorous R. erythropolis cells in either liquid or soil media to degrade atrazine. CONCLUSIONS: Supplementary growth in nutrient broth media immediately following cell encapsulation greatly enhances R. erythropolis cells survival in both wet and dry beads upon extended storage at 4 degrees C. Wet and dried beads have similar capacity for atrazine degradation, and their usefulness and appeal in agronomic practise will only be known after bioassay evaluation and successful demonstration at field scale using incurred residues. SIGNIFICANCE AND IMPACT OF THE STUDY: R. erythropolis NI86/21 encapsulated cells have the potential to reduce residual atrazine in soil, thereby minimizing the likelihood of off-site transport to ground or river water and reduce the loss of crops because of phytotoxicity of residual herbicide. Owing to their ease of handling, storage and possible compatibilities with pre-existing mechanical equipment, dried bead formats are ideally suited for agricultural and remediational applications.

Alginates↗

Relationships between the density of different indicator organisms on sheep and beef carcasses and in frozen beef and sheep meat.

AIM: To describe the relationship between the concentration of different indicator bacteria in red meat. METHODS AND RESULTS: Enumeration data for aerobic plate count (APC), Enterobacteriaceae, coliforms and Escherichia coli biotype I were analysed from an Australia-wide survey of beef carcasses, sheep carcasses, frozen beef and frozen sheep meat. In all commodities, there was only low-to-moderate rank correlation (0.16-0.47) between concentration of APC and concentration of each Gram-negative indicator. Rank correlations between counts of Gram-negative indicators were much higher (0.47-0.92) especially when nondetections were excluded from analysis (0.78-0.94). Receiver-operator characteristics analysis showed that detection of coliforms can predict the presence of E. coli biotype I with almost 100% sensitivity but fails to predict absence in 2.7-8.5% of samples not containing E. coli biotype I. CONCLUSIONS: Enumeration of coliforms is a useful adjunct to enumeration of E. coli biotype I or Enterobacteriaceae in red meat. The density of coliforms or Enterobacteriaceae can be used to predict the presence or absence of E. coli biotype I, although when the latter is at low prevalence errors in positive test prediction can be large. SIGNIFICANCE AND IMPACT OF THE STUDY: A quantitative basis is provided for comparing the concentration of different indicator bacteria measured in the production, regulation and trade of red meat.

Animals↗

Assessment of fitness for purpose of an insect bioassay using the desert locust (Schistocerca gregaria L.) for the detection of paralytic shellfish toxins in shellfish flesh.

We have developed a bioassay using 5th instar desert locusts (Schistocerca gregaria L.) for the detection of saxitoxin-the paralytic shellfish poison in shellfish flesh. The bioassay procedure is to inject 10 locusts with a shellfish extract, and assess their conditions at time points up to 2h post injection, looking for an endpoint of paralysis. From the proportion responding, the equivalent dose of pure saxitoxin could be estimated. Performance characteristics of the bioassay were assessed using shellfish samples spiked with saxitoxin, and we found the bioassay could detect and quantify toxin levels in the range of regulatory relevance. Relative toxicities of selected saxitoxin analogues differed from those reported in mammalian systems. Variation for repeatability conditions was acceptable but variation was higher under reproducibility conditions. This was related to (a) batches of insects from different suppliers, (b) different operators, and (c) different observers assessing the endpoint. We also noted adverse reactions with some shellfish species. These problems may be resolved by further refinement of the method and operator training, before formal validation. Nevertheless, we suggest the method potentially offers a simple, ethically acceptable, broad-specificity functional bioassay, which is desirable in any toxin-monitoring programme.

Animals↗

Outcome following deep wound contamination in cemented arthroplasty.

Infection remains a devastating complication of joint replacement surgery causing a significant burden to both patient and surgeon. However, despite exhaustive prophylactic measures, intraoperative contamination still occurs during cemented arthroplasty with current infection rates of 1-2%. A study was undertaken to determine the incidence of perioperative contamination in cemented arthroplasty patients, to identify contaminating organisms, to identify contaminated regions within the operative wound, to identify factors associated with increased contamination, and finally to assess the medium-term clinical outcome in patients with confirmed intraoperative wound contamination. Eighty consecutive patients undergoing hip and knee cemented arthroplasty were prospectively enrolled over a 6-month period. All scrubbed personnel wore total body exhaust isolation suits and procedures were carried out in ultra-clean air theatres. Of 441 samples, contamination was identified at 21 sites (4.8%) representing a cohort of 18 patients (22.5%). Longer duration of surgery predisposed to higher contamination rates while lower contamination rates were significantly related to fewer gowned personnel within the ultra-clean system, and fewer total personnel in theatre during the procedure. None of the patients developed clinical evidence of deep prosthetic infection at follow-up. We noted a high incidence of intraoperative contamination despite standard prophylaxis. However, this was not reflected by a similar rate of postoperative infection. This may be due to a small bacterial inoculum in each case or may be due to the therapeutic effect of perioperative intravenous antibiotic prophylaxis.

Anti-Bacterial Agents↗

Distinct recognition of antibodies to centromere proteins in primary Sjogren's syndrome compared with limited scleroderma.

BACKGROUND: Anticentromere antibodies are characteristically observed in scleroderma but have recently been reported in other autoimmune rheumatic disorders, including Sjögren's syndrome. It is not known whether distinct centromere proteins (CENP) are targeted in primary Sjögren's syndrome (pSS) and scleroderma. OBJECTIVE: To determine whether antibodies to CENP-B and CENP-C are present in these two disorders. METHODS: Sera from 45 patients with pSS and 33 with limited scleroderma were studied. All patients met classification criteria for pSS and scleroderma, respectively. Sera were used to immunoprecipitate in vitro translated CENP-B and CENP-C. The proportions recognising CENP-B or CENP-C were compared. RESULTS: 10 of 45 patients (22%) with pSS and 18 of 33 (55%) with scleroderma had antibodies recognising CENPs (p = 0.004). Seven of 10 (70%) CENP positive patients with pSS recognised CENP-C alone, compared with one of 18 (6%) CENP positive patients with scleroderma (odds ratio (OR) = 40 (95% confidence interval (CI), 3.5 to 450) (p = 0.003). In contrast, the majority (15 of 18 (83%)) of CENP positive scleroderma sera recognised both CENP-B and CENP-C, compared with none of 10 pSS sera (OR = 93 (95% CI, 4.4 to 1979) (p = 0.0001). CONCLUSIONS: The pattern of CENP recognition differs markedly in pSS and limited scleroderma. While patients with pSS predominantly recognise CENP-C alone, dual recognition of CENP-B and CENP-C is most frequent in scleroderma. These findings suggest that obtaining antibodies to specific centromere antigens is useful diagnostically, and imply that distinct mechanisms underlie the unique patterns of centromere autoreactivity in pSS and scleroderma.

Adult↗

Which radiological investigations should be performed to identify fractures in suspected child abuse?

AIMS: To determine which radiological investigations should be performed and which children should be investigated. MATERIALS AND METHODS: An all language literature search of original articles; from 1950-October 2005. Two reviewers independently reviewed each article. A third was carried out on disagreement. Each study was assessed using standardised data extraction, critical appraisal and evidence forms. RESULTS: Thirty-four studies were included. Fifteen addressed the question: which investigation has a higher yield, skeletal surveys (SS) or bone scintigraphy (BS)? Studies gave conflicting results. Overall neither investigation is as good as the two combined. BS predominately missed skull, metaphyseal and epiphyseal fractures, whereas SS commonly missed rib fractures. Two studies showed that a repeat SS 2 weeks after the initial study provided significant additional information about tentative findings, the number and age of fractures. A comparative study evaluated additional oblique views of ribs in 73 children and showed improved diagnostic sensitivity, specificity and accuracy. Four studies addressed the diagnostic yield for occult fractures with respect to age. This was significant for children under 2-years old. CONCLUSIONS: In children under 2-years old, where physical abuse is suspected, diagnostic imaging of the skeleton should be mandatory. SS or BS alone is inadequate to identify all fractures. It is recommended that all SS should include oblique views of the ribs. This review suggests that the following options would optimize the diagnostic yield. However, each needs to be evaluated prospectively: SS that includes oblique views, SS and BS, a SS with repeat SS or selected images 2 weeks later or a BS plus skull radiography and coned views of metaphyses and epiphyses.

Adolescent↗

A comparison of the Seeing Optical Stylet and the gum elastic bougie in simulated difficult tracheal intubation: a manikin study.

Management of the difficult airway is one of the major challenges that anaesthetists face. The flexible fibreoptic scope is widely available but its use requires a level of skill, training and continued practice that is not universally found in all anaesthetists, particularly trainees. The Seeing Optical Stylet is a new, semirigid fibreoptic stylet 'scope. We compared the Seeing Optical Stylet with a gum elastic bougie in a simulated Cormack and Lehane Grade 3 laryngoscopy in a manikin. Forty-four anaesthetists were timed while intubating the manikin's trachea with both devices. The mean (SD) time taken with the Seeing Optical Stylet was 20.8 (9.3) s and with the bougie 30 (19.8) s (p = 0.001). Oesophageal intubation occurred six times with the bougie but did not occur with the Seeing Optical Stylet (p = 0.011). We conclude that the Seeing Optical Stylet may be superior to the bougie in difficult tracheal intubation. We feel that the results of this manikin trial are sufficiently encouraging to proceed to a clinical trial in patients.

Clinical Competence↗

Novel conjugate of moxifloxacin and carboxymethylated glucan with enhanced activity against Mycobacterium tuberculosis.

Mycobacterium tuberculosis is an intracellular pathogen that persists within macrophages of the human host. One approach to improving the treatment of tuberculosis (TB) is the targeted delivery of antibiotics to macrophages using ligands to macrophage receptors. The moxifloxacin-conjugated dansylated carboxymethylglucan (M-DCMG) conjugate was prepared by chemically linking dansylcadaverine (D) and moxifloxacin (M) to carboxymethylglucan (CMG), a known ligand of macrophage scavenger receptors. The targeted delivery to macrophages and the antituberculosis activity of the conjugate M-DCMG were studied in vitro and in vivo. Using fluorescence microscopy, fluorimetry, and the J774 macrophage cell line, M-DCMG was shown to accumulate in macrophages through scavenger receptors in a dose-dependent (1 to 50 microg/ml) manner. After intravenous administration of M-DCMG into C57BL/6 mice, the fluorescent conjugate was concentrated in the macrophages of the lungs and spleen. Analyses of the pharmacokinetics of the conjugate demonstrated that M-DCMG was more rapidly accumulated and more persistent in tissues than free moxifloxacin. Importantly, therapeutic studies of mycobacterial growth in C57BL/6 mice showed that the M-DCMG conjugate was significantly more potent than free moxifloxacin.

Animals↗

The effect of lead on the metabolic and energetic status of the Yabby, Cherax destructor, during environmental hypoxia.

The concomitant effects of Pb and hypoxia on respiration and muscle energy status were examined in the freshwater crayfish Cherax destructor to determine if Pb intoxication exacerbated the effects of hypoxia. C. destructor, either intoxicated for 14 days with 0.5 mgL(-1)Pb, or from Pb-free control conditions, were subjected to progressive hypoxia at -2.7 kPah(-1) to a O2 partial pressure in the water (PwO2) of 1.33 kPa. This hypoxia was then sustained for 3 h. Pb-exposure reduced O2-uptake (MO2) at all PwO2 above 1.33 kPa but without any saving in ventilation, implying that Pb either unlinked ventilation from actual O2 requirements or rendered O2 transfer across the gill less efficient. Hypoxia alone induced no change in the adenylate energy charge (AEC), total adenylate (TAN), ATP/ADP ratio or in the equilibrium constant for adenylate kinase K'(ADEN), apparently due to protection of ATP levels by arginine phosphate. Under maximal hypoxia (PwO2=1.33 kPa) the Pb-exposed crayfish increased muscle ADP by 73% (tail) and 158% (chelae) but without any change in AMP, ATP or TAN. Thus, AEC declined (chelae AEC=0.71; tail AEC=0.85), as did the ATP/ADP ratio and K'(ADEN). L-Lactate increased in the muscle tissues of control but not Pb-exposed crayfish, consistent with a lowered O2 requirement in the Pb-exposed animals. The Pb intoxication slowed respiration and probably glycolysis, possibly altering the [ATP]:[ADP] equilibrium concentrations for adenylate kinase K'(AK). Lowered MO2 during severe hypoxia slows oxidative phosphorylation and ADP accumulation could occur as non-utilised substrate and may reflect a transient disequilibrium. During this time ATP levels were protected by arginine phosphate. AEC is sensitive to Pb in hypoxic crayfish but the changes have low importance for the energetic competence of the crayfish. During sustained hypoxia the crayfish recovered their energy status regardless of the Pb-exposure and this was, therefore, not a feature of Pb intoxication. Consequently, the ADP was recovered into the ATP pool of the hypoxic crayfish, and demand on arginine phosphate relieved. The Pb exposure did not otherwise exacerbate the effect of sustained hypoxia and C. destructor appeared to cope well with Pb intoxication, apparently by a specific Pb-induced hypometabolism separate from hypoxic response. Lowered metabolism as a survival response has limitations in the longer term and the implications for crustaceans generally warrant further study.

Adenosine Diphosphate↗

Economic evaluation of voriconazole compared with conventional amphotericin B for the primary treatment of aspergillosis in immunocompromised patients.

OBJECTIVE: The objective of this study was to conduct an economic evaluation of voriconazole compared with conventional amphotericin B deoxycholate (CAB) using data from a recently reported randomized comparative trial in patients with various underlying immunosuppressive conditions. This trial demonstrated the superiority of voriconazole in terms of clinical response, survival and safety when used as primary therapy for invasive aspergillosis. METHODS: A decision analytic model was designed using an expert panel and populated primarily with efficacy and resource utilization data collected prospectively during the clinical trial. The analysis was carried out from the perspective of the health care system and all costs are reported in 2002 US dollars. RESULTS: Average total treatment costs per patient were 10% lower in the voriconazole arm ($30 664) than in the CAB arm ($34 144), resulting from reduced consumption of hospital resources and fewer changes in antifungal therapy. In the base case analysis, voriconazole provided an average saving of $3481 per treated patient, resulted in a lower cost per survivor ($43 310 versus $58 971) and a lower cost per successfully treated patient ($58 100 versus $108 124) compared with CAB. Sensitivity analyses demonstrated that the cost savings observed were maintained over a wide range of alternative values for both unit costs and resource utilization, including length of hospital stay, time spent in intensive care units, bed day costs and the cost of lipid formulations of amphotericin B. CONCLUSION: Incremental cost-effectiveness analysis indicated the dominance of voriconazole because of both lower costs and greater efficacy.

Amphotericin B↗

Modulation of the mouse testis transcriptome during postnatal development and in selected models of male infertility.

The aim of this study is to develop an overview of genetic events during spermatogenesis using a novel, specifically targeted gonadal gene set. Two subtracted cDNA libraries enriched for testis specific and germ cell specific genes were constructed, characterized and sequenced. The combined libraries contain >1905 different genes, the vast majority previously uncharacterized in testis. cDNA microarray analysis of the first wave of murine spermatogenesis and of selected germ cell-deficient models was used to correlate the expression of groups of genes with the appearance of defined germ cell types, suggesting their cellular expression patterns within the testis. Real-time RT-PCR and comparison to previously known expression patterns confirmed the array-derived transcription profiles of 65 different genes, thus establishing high confidence in the profiles of the uncharacterized genes investigated in this study. A total of 1748 out of 1905 genes showed significant change during the first spermatogenic wave, demonstrating the successful targeting of the libraries to this process. These findings highlight unknown genes likely to be important in germ cell production, and demonstrate the utility of these libraries in further studies. Transcriptional analysis of well-characterized mouse models of infertility will allow us to address the causes and progression of the pathology in related human infertility phenotypes.

Animals↗

Recurrent transverse myelitis associates with anti-Ro (SSA) autoantibodies.

Transverse myelitis (TM) is an idiopathic inflammatory disorder of the spinal cord. The authors observed cases of recurrent TM in patients where anti-Ro (SSA) antibodies were present and therefore performed a case-control study to examine the frequency of anti-Ro autoantibodies in patients with recurrent TM and control subjects. Antibodies to 52-kd Ro were demonstrated in 77% of cases (10/13) compared with only 33% of control subjects (4/12).

Adolescent↗

Haemoglobin function and respiratory status of the Port Jackson shark, Heterodontus portusjacksoni, in response to lowered salinity.

Haemoglobin function and respiratory status of sub-adult sharks, Heterodontus portusjacksoni was investigated for up to 1 week following transfer from 100% to either 75% or 50% seawater. Metabolic rates were unusually low and arterial-venous differences in blood O2 small. Haemodilution from osmotic inflow lowered haematocrit and reduced blood O2 content by up to 50%. There was no change in O2 consumption rate, blood O2 partial pressure, cardiac output, or the arterial-venous O2 content difference, and thus O2 delivery was maintained. Ventilation was acutely elevated but returned to normal within 24 h. The O2 delivery to the tissues was facilitated by decreased blood O2-affinity that could not be simply ascribed to changes in the osmolyte concentration. The Hb was unaffected by changes in intra-erythrocyte fluid urea or trimethylamine-N-oxide (TMAO) but was sensitive to changes in NaCl. The Bohr shifts in whole blood were low and there was little role for pH in modulating O2 transport. Venous Hb saturation remained close to 65%, at the steepest part of the in vivo O2 equilibrium curve, such that O2 unloading could be facilitated by small reductions in pressure without increasing cardiac or ventilatory work. H. portusjacksoni tolerated 50% seawater for at least 1 month, but there was little evidence of respiratory responses being adaptive which instead appeared to be consequential on changes in osmotic and ionic status.

Acclimatization↗

Hormonally impregnated intrauterine systems (IUSs) versus other forms of reversible contraceptives as effective methods of preventing pregnancy.

BACKGROUND: In the 1970s a new approach to the delivery of hormonal contraception was researched and developed. It was suggested that the addition of a progestogen to a non-medicated contraceptive device improved its contraceptive action. An advantage of these hormonally impregnated intrauterine systems (IUS) is that they are relatively maintenance free, with users having to consciously discontinue using them to become pregnant rather than taking a proactive daily decision to avoid conception. OBJECTIVES: To assess the contraceptive efficacy, tolerability and acceptability of hormonally impregnated intrauterine systems (IUSs) in comparison to other reversible contraceptive methods. SEARCH STRATEGY: Literature was identified through database searches, reference lists and individuals/organisations working in the field. Searches covered the period from 1972 to November 2003. SELECTION CRITERIA: All randomised controlled trials comparing IUSs with other forms of reversible contraceptives and reporting on pre-determined outcomes in women of reproductive years. The primary outcomes were pregnancy due to method/user failure and continuation rate. DATA COLLECTION AND ANALYSIS: The quality assessment of studies and data extraction were completed independently by two blinded reviewers. A quality checklist was designed to identify general methodological and contraceptive specific factors which could bias results. Events per women months and single decrement life table rates were extracted where possible for pregnancy, continuation, adverse events and reasons for discontinuation. Events per total number of women at follow up were collected for hormonal side effects and menstrual disturbance. When appropriate, data were pooled at the same points of follow up to calculate rate ratios in order to determine the relative effectiveness of one method compared to another. For the single decrement life table rates, the rate differences were pooled to determine the absolute difference in effectiveness of one method compared to another. Interventions were only combined if the contraceptive methods were similar. Non-hormonal IUDs were divided into three categories for the purpose of comparison with IUSs: IUDs >250mm2 (i.e. CuT 380A IUD and CuT 380 Ag IUD), IUDs <=250mm2 (i.e. Nova-T, Multiload, CuT 200 and CuT 220 IUDs) and non-medicated IUDs. MAIN RESULTS: Twenty-one RCTs comparing hormonally impregnated IUSs to a reversible contraceptive method met the inclusion criteria and it was possible to include eight of these in the meta-analyses, four comparing LNG-20 IUSs with non-hormonal IUDs, one comparing the LNG-20 IUS with Norplant-2 and three comparing Progestasert with non-hormonal IUDs. No significant difference was observed between the pregnancy rates for the LNG-20 users and those for the IUD >250mm2 users. However, women using the LNG-20 IUS were significantly less likely to become pregnant than those using the IUD <=250mm2. Women using the LNG-20 IUS were more likely to experience amenorrhoea and device expulsion than women using IUDs >250mm2. LNG-20 users were significantly more likely than all the IUD users to discontinue because of hormonal side effects and menstrual disturbance, which on further breakdown of the data was due to amenorrhoea. When the LNG-20 IUS was compared to Norplant-2, the LNG-20 users were significantly more likely to experience amenorrhoea and oligomenorrhoea, but significantly less likely to experience prolonged bleeding and spotting. No other significant differences were observed. Progestasert users were significantly less likely to become pregnant and less likely to continue on the method than non-medicated IUD users after one year, but no significant difference was noted for these two outcomes when Progestasert users were compared to IUD<=250mm2 users. The only other significant differences found in the meta-analyses were that Progestasert users were less likely to expel the device and more likely to discontinue the method because of menstrual bleeding and pain than users of IUDs <=250mm2. REVIEWERS' CONCLUSIONl the device and more likely to discontinue the method because of menstrual bleeding and pain than users of IUDs <=250mm2. REVIEWERS' CONCLUSIONS: Current evidence suggests LNG-20 IUS users are no more or less likely to have unwanted pregnancies than IUD >250mm2 and Norplant-2 users. The LNG-20 IUS was more effective in preventing either intrauterine or extrauterine pregnancies than IUDs <=250mm2. The contraceptive effectiveness of Progestasert was significantly better than non-medicated IUDs, but no difference was observed when compared to IUDs<=250mm2. Continuation of LNG-20 IUS use was similar to continuation of the non-hormonal IUDs and Norplant-2. Amenorrhoea was the main reason for the discontinuation for the LNG-20 IUS and women should be informed of this prior to starting this method.

Contraceptive Agents, Female↗