bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early treatment during a primary malaria infection modifies the development of cross immunity
Authors: Legorreta‐Herrera M. , Ventura‐Ayala M. L. , Licona‐Chávez R. N. , Soto‐Cruz I. , Hernández‐Clemente F. F. 
Published: June 2004

SUMMARY We have used a murine model to study the kinetics of cross‐protection when a primary infection is halted at different times. We analysed how parasitaemia is modified during a second infection with the homologous parasite, a heterologous parasite, or a mixture of the two. In addition, possible mechanisms involved in cross‐protection were analysed. Results show that treatment with pyrimethamine on day 5 during a primary infection with P. chabaudi AS (non‐lethal), prevents the generation of cross‐protection to a new challenge with lethal P. yoelii 17XL. In contrast, when treatment is on day 7, mice survive a P. yoelii infection. Differences between both groups suggest that in order for ‘preimmune’ mice to survive a lethal challenge, a predominantly TH2‐type response is required, with a higher mRNA expression level of IL‐4 and IL‐10, and a lower mRNA expression of IFN‐γ. This work shows that an early treatment of a malaria infection produced by a non‐lethal parasite drives the immune response towards a loss of cross‐protection to further infections, in particular with more virulent parasites. This finding should be taken into account for the development of effective malaria vaccines.
CTLA‐4 regulates the murine immune response to Trypanosoma cruzi infection
Authors: Graefe S. E. B. , Jacobs T. , Wächter U. , Bröker B. M. , Fleischer B. 
Published: June 2004

SUMMARY Infection with Trypanosoma cruzi causes a profound suppression of T cell responsiveness to polyclonal or antigenic stimuli. In this study, we quantified expression of the negative T cell regulatory molecule CTLA‐4 in T. cruzi infected mice and analysed its influence on the immune suppression. Levels of splenic CTLA‐4 expression were highest around day 10 after infection, reaching 5% in resistant B6D2F1 mice, but exceeding 10% of CD4+ T cells in C57BL/6 mice that were susceptible to mortal disease. The proliferative response of explanted splenocytes to CD3‐mediated stimulation was strongly suppressed in both the susceptible and the resistant strains. Blockade of CTLA‐4 in vitro with a monoclonal antibody affected neither proliferative response nor cytokine production (IFN‐γ, IL‐4 and IL‐2) by splenic T cells from infected C57BL/6 mice. Treatment of mice with anti‐CTLA‐4 antibody on the day of infection decreased IFN‐γ production and reduced mortality by about 50%. We conclude that high CTLA‐4 expression is a hallmark of severe disease in murine T. cruzi infection, and that CTLA‐4 has a regulative influence at the early stages during priming of the immune reaction to the parasite, augmenting a strong Th1‐biased response.
Are the cellular immune responses of children and adults with Schistosoma mansoni infection intrinsically different? Cytokines produced ex vivo in response to antigens and mitogens
Authors: Scott J. T. , Vereecken K. , Diakhaté M. M. , Vanagt T. , Sambou V. , Diop M. , Ly A. , Vercruysse J. , Gryseels B. , Kestens L. 
Published: June 2004

SUMMARY In recently exposed communities, intensity of schistosomiasis infection increases as children age and then drops again in adulthood, indicating that host maturity is an important aspect of resistance to schistosomiasis. We investigated whether the cellular immune response to the parasite was correlated with age in subjects with similar daily patterns of exposure, current intensities of infection and number of years of exposure. The cellular immune response of subjects with either ‘low’ (under 200 eggs per gram (EPG)) or ‘high’ (over 400 EPG) intensities of infection was investigated, in a recently established focus where subjects had similar histories of exposure and number of years of experience with Schistosoma mansoni. Subject's whole blood was cultured with adult worm antigen (AWA), a mixture of phytohaemagglutinin (PHA) and lipopolysaccharide (LPS), or left unstimulated, and culture supernatants were tested for IL‐4, IL‐5, IL‐10 and IFN‐γ. Children and adults tended to respond differently to schistosome antigen. The most statistically significant illustration of this was the negative correlation between age and IL‐5 produced by samples from people with low intensities of infection cultured with AWA (P < 0·003, P < 0·05 after Bonferroni correction). IL‐10 produced by samples cultured with PHA and LPS was also notably lower in children than in adults, although not formally significant after Bonferoni correction. This indicates that it is possible for age, independently of intensity of infection or experience with the parasite, to influence the immune response to schistosomiasis.
Validation of the protective Ostertagia ostertagi ES‐thiol antigens with different adjuvantia
Authors: Geldhof P. , Vercauteren I. , Vercruysse J. , Knox D. P. , Van Den Broeck W. , Claerebout E. 
Published: June 2004

SUMMARY Intramuscular immunization of calves with an excretory–secretory antigen fraction enriched for cysteine proteinase activity (ES‐thiol) and QuilA as adjuvant induces a protective immune response against the abomasal nematode Ostertagia ostertagi. The objectives of the present study were to confirm the protective capacity of ES‐thiol in combination with QuilA, to test Al(OH)3 as adjuvant for vaccination against O. ostertagi and to look for correlations between protection and immunological effector responses. Calves(seven animals/group) were vaccinated three times intramuscularly with 100 µg antigen and/or adjuvant (ES‐thiol with QuilA, ES‐thiol with Al(OH)3, QuilA alone and Al(OH)3 alone) and subsequently challenged with a trickled oral infection of 25 000 infective larvae in total over 25 days. Faecal egg counts in the ES‐thiol QuilA group were reduced by 56% during the two‐month period of the trial compared to the QuilA control group (P < 0·002). Calves immunized with ES‐thiol QuilA had significantly smaller adult worms (P < 0·002) and less eggs/female worm (P < 0·05) compared to the QuilA control group. No differences in egg output, worm counts or parameters of worm fitness were observed in the ES‐thiol Al(OH)3 group compared to the Al(OH)3 control group. Although the protective immune mechanism against O. ostertagi remains unknown, protection in the ES‐thiol QuilA group was associated with high levels of parasite‐specific antibodies in the abomasal mucosa.
Echinococcus granulosus‐specific T‐cell lines derived from patients at various clinical stages of cystic echinococcosis
Authors: Riganò R. , Buttari B. , De Falco E. , Profumo E. , Ortona E. , Margutti P. , Scottà C. , Teggi A. , Siracusano A. 
Published: June 2004

SUMMARY To investigate the role of T lymphocytes in the immune response to Echinococcus granulosus, using sheep hydatid fluid (SHF) and antigen B (AgB), we generated T‐cell lines from patients with active, transitional and inactive hydatid cysts. We established 16 T‐cell lines, eight specific to SHF and eight specific to AgB. At surface phenotyping 88–98% of cells displayed the helper/inducer CD4 antigen. In all patients, at all clinical stages of hydatid cyst disease, T‐cell stimulation with SHF and AgB invariably amplified a large number of almost identical Vβ subfamily fragments. Irrespective of antigen‐specificity, the two cell lines from the patient with an inactive cyst had a Th1 profile, because they exclusively expressed and produced IFN‐γ. Conversely, the T‐cell lines derived from the seven patients with active and transitional hydatid cysts had mixed Th1/Th2 and Th0 clones. The functional characteristics of the 16 T‐cell lines differed markedly in the various clinical stages of cystic echinococcosis, thus providing new in vitro evidence that Th1 lymphocytes contribute decisively to the inactive stage of hydatid disease, Th2 lymphocytes in the active and transitional stages. The parasite‐specific T‐cell lines, especially the two Th1 lines from the patient with an inactive cyst, may help identify Th1 protective epitopes on SHF and AgB.
Ov‐ASP‐1, the Onchocerca volvulus homologue of the activation associated secreted protein family is immunostimulatory and can induce protective anti‐larval immunity
Authors: MacDonald A. J. , Tawe W. , Leon O. , Cao L. , Liu J. , Oksov Y. , Abraham D. , Lustigman S. 
Published: June 2004

Summary Vaccination of mice with a recombinant protein, Ov‐ASP‐1, the Onchocerca volvulus homologue of the activation associated secreted gene family stimulated very high titres of both IgG1 and IgG2a without adjuvant. rOv‐ASP‐1 was also immuno‐reactive with IgG isotypes from both O. volvulus‐infected (INF) and putatively immune (PI) humans, with higher IgG4 in the former group. The protein also stimulated IFN‐γ secretion by PBMC from INF and PI and IL‐5 only in INF. Using a mouse diffusion chamber model, vaccination with rOv‐ASP‐1 resulted in partial but significant protection against challenge with infective third‐stage larvae (L3) but only when formulated with Freund's complete adjuvant (FCA) or alum. Protection was Th1‐dependent (highly elevated IgG2a) with FCA and contingent on a strongly Th2‐skewed (IgG1) response with alum. IgE responses to rOv‐ASP‐1 with or without adjuvant were weak or absent. When immunization using rOv‐ASP‐1 in adjuvant failed to induce adequate Th1 (FCA) or Th2 (alum) responses, protection efficacy was compromised. The recombinant protein appears to stimulate a mixed Th1/Th2 response but the outcome in terms of protective immunity is the result of a subtle interplay of its intrinsic and adjuvant‐augmented properties. Ov‐ASP‐1 is potentially secreted based on its localization in the secretory granules of L3.
The role of the senior health care worker in critical care
Authors: Ormandy Paula , Long Andrew F , Hulme Claire T , Johnson Martin 
Published: June 2004

Summary• This article identifies that the introduction of the support worker role in the critical care team facilitates flexibility when organizing and managing patient care• Qualified nurses' time can be used more effectively, enhancing the quality of the patient care delivered• Aspects of the qualified nurses' workload in critical care can be shared and delegated successfully to unqualified staff• It is our view that staffing levels in critical care environments need to be reviewed with more flexible working practices to meet the current and future demands of critical care• There is a need for national consensus amongst qualified nurses to clarify and define the role of the support worker and develop a critical care competency framework to standardize training• To ensure proficiency, adequate training and appropriate accountability, support workers require regulation by a nationally recognized body
Ultrasound guidance for infraclavicular brachial plexus anaesthesia in children
Authors: Marhofer P. , Sitzwohl C. , Greher M. , Kapral S. 
Published: June 2004

SummaryUltrasonography may offer significant advantages in regional anaesthesia of the upper and lower limbs. It is not known if the same advantages demonstrated in adults also apply to children. We therefore performed a prospective, randomised study comparing ultrasound visualisation to conventional nerve stimulation for infraclavicular brachial plexus anasesthesia in children. Forty children scheduled for arm and forearm surgery underwent infraclavicular brachial plexus blocks with ropivacaine 0.5 ml.kg−1 guided by either nerve stimulation or ultrasound visualisation. Evaluated parameters included sensory block quality, sensory block distribution and motor block. All surgical procedures were performed under brachial plexus anaesthesia alone. Direct ultrasound visualisation was successful in all cases and was associated with significant improvements when compared with the use of nerve stimulation: lower visual analogue scores during puncture (p = 0.03), shorter mean (median) sensory onset times (9 (5–15) min vs. 15 (5–25) min, p < 0.001), longer sensory block durations (384 (280–480) min vs. 310 (210–420) min, p < 0.001), and better sensory and motor block scores 10 min afrter block insertion. Ultrasound visualisation offers faster sensory and motor responses and a longer duration of sensory blockade than nerve stimulation in children undergoing infraclavicular brachial plexus blocks. In addition, the pain associated with nerve stimulation due to muscle contractions at the time of insertion is eliminated.
Abdominal muscle action during expiration can impair pressure controlled ventilation
Authors: Prasad C. V. , Drummond G. B. 
Published: June 2004

SummaryPressure controlled ventilation, and pressure support for spontaneous breathing are often used in intensive care because coordination of the ventilator with patient efforts can improve comfort and possibly reduce sedation. However we report a series of 10 patients whose efforts did not synchronise with pressure controlled ventilation. This was incorrectly diagnosed as inadequate sedation, and treated with increased sedation or muscle paralysis. Better recognition of this condition showed that slow respiratory rates and increased abdominal muscle action during expiration can affect pressure‐controlled ventilation and pressure assisted breathing. If the condition is not recognised, treatment for poor synchronisation may delay weaning or be inappropriate.
Propofol sedation using DiprifusorTM target‐controlled infusion in adult intensive care unit patients*
Authors: McMurray T. J. , Johnston J. R. , Milligan K. R. , Grant I. S. , Mackenzie S. J. , Servin F. , Janvier G. , Glen J. B. 
Published: June 2004

SummaryThis multicentre, non‐comparative study investigated the range of target blood propofol concentrations required to sedate 122 adult intensive care patients when propofol was administered using DiprifusorTM target‐controlled infusion systems together with opioid analgesia. Depth of sedation was assessed with a modified Ramsay score and the target blood propofol setting was adjusted to achieve the sedation desired for each patient. A desired level of sedation was achieved for 84% of the sedation period. In postcardiac surgery patients the median time‐weighted average propofol target setting was 1.34 μg.ml−1 (10th – 90th percentiles: 0.79–1.93 μg.ml−1). Values in brain injured and general ICU patients were 0.98 (10th – 90th percentiles: 0.60–2.55) μg.ml−1 and 0.42 (10th – 90th percentiles: 0.16–1.19) μg.ml−1, respectively. Measured propofol concentrations were generally close to values predicted by the DiprifusorTM system. Target settings in the range of 0.2–2.0 μg.ml−1 are proposed for propofol sedation in this setting with titration as required in individual patients.
The ‘fixed performance’ venturi: effect of downstream pressure on outflow and FIo2
Authors: Jones J. G. 
Published: June 2004

SummaryFixed performance venturi devices should provide a predetermined oxygen concentration at an outflow which exceeds an adult's peak resting inspiratory flow rate (approximately 30 l.min−1). Campbell's original description mentioned the sensitivity of the venturi device to downstream resistance but gave no further details. This study examined outflow and oxygen concentration from the five standard venturi devices (24–60% O2) when downstream pressure increased. Outflow was exquisitely sensitive to small increases in pressure. The outflow at zero downstream pressure for the 24–40% O2 venturi devices ranged from 40 to 50 l.min−1 but only 2–3 mmH2O was needed to halve this flow and increase oxygen concentration. The 60% O2 venturi delivered a maximum of only 30 l.min−1 at zero downstream pressure and flow was reduced further by increasing this pressure. An increase in downstream pressure of only a few mmH2O increased oxygen concentration and decreased outflow of all the venturi devices tested, in most to less than normal peak tidal flow in adults.
The effects of tracheostomy cuff deflation during continuous positive airway pressure*
Authors: Conway D. H. , Mackie C. 
Published: June 2004

SummaryContinuous flow positive pressure devices bridge the gap between mechanical and unsupported ventilation in patients recovering from critical illness. At this point, patients are often fully awake, yet the inflated tracheostomy cuff prevents them from speaking or swallowing. The aim of this study was to investigate the effects of cuff deflation. After ethics committee approval and informed consent, we recorded airway pressures with catheters placed 3 cm beyond the distal tracheostomy tip, respiratory rate, heart rate and peripheral oxygen saturation with continuous positive airway pressures set at 5, 7.5 and 10 cmH2O with the cuff inflated and deflated. Sixteen patients completed the study. There were small falls in end expiratory pressure on cuff deflation. The median (interquartile range) pressure drop with set airway pressure of 5 cmH2O was 0.25 (0–1.4) mmHg, which increased to 1 (0–3) mmHg at 7.5 cmH2O and 1.5 (0–4) mmHg at 10 cmH2O. These changes were not clinically significant and cardiopulmonary parameters remained stable. All patients were able to vocalise following cuff deflation. Twelve patients passed a blue dye swallow screen within a day of tolerating cuff deflation. These results suggest that pressures fall slightly following cuff deflation but this is associated with respiratory stability and may allow patients to talk and swallow.
Handover of responsibility for the anaesthetised patient – opinion and practice
Authors: Horn J. , Bell M. D. D. , Moss E. 
Published: June 2004

SummaryAnaesthesia is a critical and complex process that extends from the pre‐operative assessment through to the postoperative management of patients. Handover of responsibility for logistical as opposed to patient‐orientated reasons may compromise that process of care. If such handover becomes inevitable with shift‐based patterns of working, the implications need to be considered and procedures developed in order to minimise adverse consequences. This survey of national practice reveals little formalisation of procedure and a spectrum of opinion on the relevance of the key considerations. There is, however, a majority view amongst respondents that national guidelines would be of value and that professional defensibility would be aided by standardisation and documentation of any handover.
Performance of an oxygen delivery device for weaning potentially infectious critically ill patients*
Authors: So C. Y. , Gomersall C. D. , Chui P. T. , Chan M. T. V. 
Published: June 2004

SummaryOxygen delivery via a heat and moisture exchange filter with an attached T‐shaped reservoir satisfies infection control requirements of high efficiency bacterial and viral filtration and low gas flows. In order to assess the performance of such a device in critically ill patients being weaned from mechanical ventilation, we simulated 16 patients using a human patient simulator, measuring fractional inspired oxygen and carbon dioxide concentrations and work of breathing at three oxygen flow rates. Oxygen concentration was dependent on peak inspiratory flow rate, tidal volume and oxygen flow rate. Rebreathing, as indicated by inspired carbon dioxide concentration, was greatest at high respiratory rates and low tidal volumes. Imposed inspiratory work of breathing was relatively high (mean 0.88 J.l−1[SD 0.30]). We conclude that this method of oxygen delivery is only suitable for patients in whom rapid extubation is anticipated.
Difficult Airway Society guidelines for management of the unanticipated difficult intubation
Authors: Henderson J. J. , Popat M. T. , Latto I. P. , Pearce A. C. 
Published: June 2004

SummaryProblems with tracheal intubation are infrequent but are the most common cause of anaesthetic death or brain damage. The clinical situation is not always managed well. The Difficult Airway Society (DAS) has developed guidelines for management of the unanticipated difficult tracheal intubation in the non‐obstetric adult patient without upper airway obstruction. These guidelines have been developed by consensus and are based on evidence and experience. We have produced flow‐charts for three scenarios: routine induction; rapid sequence induction; and failed intubation, increasing hypoxaemia and difficult ventilation in the paralysed, anaesthetised patient. The flow‐charts are simple, clear and definitive. They can be fully implemented only when the necessary equipment and training are available. The guidelines received overwhelming support from the membership of the DAS. Disclaimer: It is not intended that these guidelines should constitute a minimum standard of practice, nor are they to be regarded as a substitute for good clinical judgement.
Pharmacokinetics and pharmacodynamics of terbogrel, a combined thromboxane A2 receptor and synthase inhibitor, in healthy subjects
Authors: Guth Brian D. , Narjes Hans , Schubert Hans‐Dieter , Tanswell Paul , Riedel Axel , Nehmiz Gerhard 
Published: June 2004

AimsTo characterize the pharmacokinetics of terbogrel, a new combined thromboxane A2 (TxA2) receptor and synthase inhibitor, in healthy human subjects after single or multiple oral administration.MethodsForty‐eight healthy male subjects received a single oral dose (10, 25, 50, 100, 150 or 200 mg) of terbogrel or placebo and 32 different subjects received one of the following treatments twice daily for 7 days: 50, 100 or 150 mg terbogrel, placebo, or once‐a‐day 330 mg acetylsalicylic acid.ResultsTerbogrel was well tolerated without obvious adverse effects following either a single oral dose or administration over 7 days. Plasma drug concentrations were dose‐linear and there was no accumulation over 7 days. There was a dose‐dependent blockade of TxA2 receptors and of inhibition of thromboxane synthase activity with values for IC50 of 12 ng ml−1 and 6.7 ng ml−1, respectively. At the highest dose tested (150 mg) there was almost complete inhibition of thomboxane synthase and thromboxane receptor occupancy. Even at trough concentrations, receptor occupancy remained above 80% and thromboxane synthase was still completely inhibited. These two activities were associated with a dose‐dependent inhibition of platelet aggregation (>80% at the 150 mg dose of terbogrel) and enhanced prostacyclin production.ConclusionsTerbogrel is a potent agent having two distinct, complimentary pharmacodynamic actions, namely inhibition of thromboxane synthase and antagonism of the TxA2 receptor. The antithrombotic effect of terbogrel was dose‐dependent and was associated with enhanced prostacyclin production. Terbogrel is an attractive candidate for long‐term antithrombotic therapy.
Iohexol contrast medium induces QT prolongation in amiodarone patients
Authors: Goernig Matthias , Kirmeier Thomas , Krack Andreas , Hartog Christiane S. , Figulla Hans R. , Leder Uwe 
Published: June 2004

AimsAmiodarone is widely used in ventricular tachyarrhythmias and atrial fibrillation, known to prolong QT‐intervals. Concurrent administration of drugs prolonging QT‐ time can induce life‐threatening ventricular tachyarrhythmia.MethodsQT‐interval changes following use of Iohexol contrast‐medium for coronarangiography were observed comparing 21 patients taking long‐term amiodarone therapy with 21 controls not taking amiodarone or QT‐prolonging drugs retrospectively.ResultsConcurrent use of Iohexol and amiodarone was associated with significant prolongation of QTc‐interval (433, 95%CI: 419–448 ms vs. 480, 95%CI: 422–483 ms, P < 0.001) the day after coronarangiograpgy. 6/21 patients showed severe prolonged QTc‐interval of >500 ms.ConclusionCaution is advised until more is known about pro‐arrhythmic effects of Iohexol.