bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosis of fungal infections: current status
Authors: Stevens David A. 
Published: January 2012

Abstract
Diagnosing infections remains a problem in the management of fungal diseases, particularly in the immunocompromised host. Signs and symptoms are non-specific, colonization is difficult to distinguish from invasive disease, blood cultures are commonly negative and patients are often unable to undergo invasive diagnostic procedures. This situation has led to the strategy of initiating empirical therapy in the high-risk patient. A variety of tests has been applied to several body fluids. At the simplest level, the clinician must be familiar with the appearance of various fungi in tissue. Non-culture methods include antibody- and antigen-based assays, metabolite detection and molecular identification. The latter includes PCR identification of fungal DNA from body fluid samples using conserved or specific genome sequences. Detection of glucan in blood has been achieved using crab amoebocyte lysate. With aspergillosis, predictive clinical correlates have been defined, respiratory tract cultures are highly predictive of invasive disease in the appropriate setting and certain CT scan findings enable early diagnosis. Bronchoalveolar lavage is also very useful. Galactomannan antigen testing of blood is routine in some European centres, with EIA methodology supplanting agglutination because of apparently greater sensitivity. PCR has been made specific by genus-specific probes, with 100% sensitivity and reasonable specificity. In candidosis, the number of sites of colonization correlates with invasion. Tests for mannan antibodies and antigenaemia are currently of interest. Metabolite assays appeared promising but have not been pursued commercially. In cryptococcosis, pronase treatment of serum has reduced false positives and false negatives, and improved reproducibility of titres. Birdseed agar improves culture specificity. In coccidioidomycosis, serology is the exemplar for all mycology. Gene probes have accelerated diagnosis by culture. In histoplasmosis, the antigenuria test's high sensitivity and specificity has dispelled the chronic confusion in interpreting antibody test results.
AmBisome: liposomal formulation, structure, mechanism of action and pre-clinical experience
Authors: Adler-Moore Jill , Proffitt Richard T. 
Published: January 2012

Abstract
Amphotericin B is the treatment of choice for life-threatening systemic fungal infections such as candidosis and aspergillosis. To improve this drug's efficacy and reduce its acute and chronic toxicities, several lipid formulations of the drug have been developed, including AmBisome, a liposomal formulation of amphotericin B. The liposome is composed of high transition temperature phospholipids and cholesterol, designed to incorporate amphotericin B securely into the liposomal bilayer. AmBisome can bind to fungal cell walls, where the liposome is disrupted. The amphotericin B, after being released from the liposomes, is thought to transfer through the cell wall and bind to ergosterol in the fungal cell membrane. This mechanism of action of AmBisome results in its potent in vitro fungicidal activity while the integrity of the liposome is maintained in the presence of mammalian cells, for which it has minimal toxicity. In animal models, AmBisome is effective in treating both intracellular (leishmaniasis and histoplasmosis) and extracellular (candidosis and aspergillosis) systemic infections. Because of its low toxicity at the organ level, intravenous AmBisome can be safely delivered at markedly high doses of amphotericin B (1–30 mg/kg) for the treatment of systemic fungal infections. AmBisome has a circulating half-life of 5–24 h in animals, and in animal models appears to localize at sites of infection in the brain (cryptococcosis, aspergillosis, coccidioidomycosis), lungs (blastomycosis, paracoccidioidomycosis, aspergillosis) and kidneys (candidosis), delivering amphotericin B that remains bioavailable in tissues for several weeks following treatment.
Overview of the lipid formulations of amphotericin B
Authors: Dupont Bertrand 
Published: January 2012

Abstract
Invasive fungal infections have been increasingly recognized as a major cause of morbidity and mortality in the immunocompromised host. Amphotericin B has a broad spectrum and has remained the drug of choice for life-threatening invasive fungal infections. However, adverse events, particularly renal insufficiency, are limiting factors in achieving an effective dose: the prescription of amphotericin B is a compromise between toxicity and efficacy. Lipid formulations offer a better therapeutic index by circumscribing amphotericin B toxicity. Three lipid formulations are available in most countries: AmBisome, the only true liposome; Abelcet, with a ribbon-like structure; and Amphocil/Amphotec, composed of disc-like structures. All these formulations contain amphotericin B, but they differ in shape, size, reticuloendothelial clearance, Cmax, AUC and visceral diffusion. The impact of these differences in pharmacokinetics and pharmacodynamics on clinical efficacy is still unclear. Efficacy has been shown in neutropenic patients with fever of unknown origin, systemic candidosis, invasive aspergillosis, cryptococcal meningitis and a variety of other difficult-to-treat mycoses, such as Fusarium or Zygomycetes infections. The effective dose may vary from one formulation to the other and is c. 3–5 mg/kg/day. All formulations are less nephrotoxic than amphotericin B. In one randomized double-blind study, AmBisome 3 or 5 mg/kg/day was less nephrotoxic and gave fewer infusion-related events than Abelcet 5 mg/kg/day. Abelcet induces fewer infusion-related side effects than Amphocil. All formulations seem at least as effective as amphotericin B. In some patients with life-threatening mycosis who failed treatment with, or were intolerant to, amphotericin B, the lipid formulations were effective. Further studies with comparable selected high-risk patients are warranted to clarify the usefulness and the indications of each of the formulations. Cost is a factor limiting prescription in many institutions, where use is often restricted to patients intolerant of, or refractory to, amphotericin B.
Amphotericin B nephrotoxicity
Authors: Deray Gilbert 
Published: January 2012

Abstract
The use of amphotericin B limited by dose-dependent nephrotoxicity. Elevated creatinine associated with amphotericin B is not only a marker for renal dysfunction, but is also linked to an increase in hospital costs and a substantial risk for the use of haemodialysis and a higher mortality rate. Therefore, amphotericin B nephrotoxicity is not a benign complication and its prevention is essential. Several manipulations have been proposed to minimize amphotericin B-induced nephrotoxicity. Mannitol and frusemide administration are reported to be protective based on anecdotal observational reports. Small prospective and randomized trials do not suggest a protective effect. Three new formulations have been developed in attempts to improve both efficacy and tolerability: amphotericin B in a lipid complex (ABLC; Abelcet); amphotericin B colloidal dispersion; and liposomal amphotericin B (AmBisome). Three prospective randomized studies have clearly shown that AmBisome is less nephrotoxic than amphotericin B. In a double-blind randomized trial significantly fewer patients receiving AmBisome had nephrotoxic effects. This significant reduction in azotaemia was also observed among subgroups of patients receiving concomitant therapy with nephrotoxic agents. Moreover, there were fewer patients with hypokalaemia in the group receiving AmBisome. A recent multicentre double-blind study has shown that AmBisome (3 or 5 mg/kg/day) has a better safety profile than Abelcet (5 mg/kg). Patients in both AmBisome treatment groups experienced less chills/rigors, less nephrotoxicity based on a doubling of serum creatinine, and fewer toxic reactions resulting in discontinuation of therapy. In conclusion, amphotericin B nephrotoxicity is observed frequently. It clearly increases patient mortality. Nephrotoxicity must be recognized early, based on tubular abnormalities and a mild increase in serum creatinine. Its prevention relies on the detection and suppression of risk factors and the use of AmBisome.
AmBisome in the treatment of fungal infections: the UK experience
Authors: Chopra Rajesh 
Published: January 2012

Abstract
Despite a number of recent advances in diagnosis and treatment strategies, fungal infections remain an important cause of morbidity and mortality in neutropenic and immunosuppressed patients. The main fungal infections are candidosis and aspergillosis, although an increased incidence of rarer fungal infections including Fusarium spp., Aurebasidium pullulans and Mucor spp. has been noted. Mortality may be decreased with earlier diagnosis and aggressive treatment with lipid-associated amphotericin B. Invasive pulmonary aspergillosis (IPA) in the neutropenic host presents particular challenges in terms of diagnosis and therapy. We undertook a prospective study over a 36 month period to link the status of early diagnosis and early aggressive therapy with lipid-associated amphotericin B. Early investigation comprised the use of bronchoscopy and bronchoalveolar lavage together with real-time PCR to detect Aspergillus spp. This combined approach revealed the incidence of proven or probable IPA to be 19%. Early therapy resulted in no mortality from IPA. In treating the rarer fungal species, AmBisome was found to be the most effective agent, and could be used at doses of up to 12 mg/kg with few side effects.
Liposomal amphotericin B (AmBisome): efficacy and safety of low-dose therapy in pulmonary fungal infections
Authors: Lequaglie Cosimo 
Published: January 2012

Abstract
A prospective study of the treatment of fungal infections with low-dose AmBisome enrolled 36 of 52 patients with thoracic malignancies who developed pulmonary fungal infections in the National Cancer Centre, Milan, over a 3.5 year period. Thirty-three high-risk patients had received standard prophylaxis with iv fluconazole. In these patients, symptoms indicating deep mycosis were detected after 7–9 days of primary prophylactic therapy. Another three patients, not treated with fluconazole, showed similar symptoms. Bronchoalveolar lavage, blood culture and/or CT scan of chest diagnosed invasive aspergillosis in 29 patients and deep invasive Candida infection in seven. AmBisome was given at 1–2.2 mg/kg/day iv for 10 days to avoid or decrease toxicity normally induced by amphotericin B. The fungal infection was eradicated in all 36 patients. Negative cultures were obtained after 5 or 6 days of antifungal treatment. No adverse reactions attributed to AmBisome were detected. After a follow up of 5–48 months, 30 patients were still alive. Six patients had died, two due to adult respiratory distress syndrome and four due to progression of cancer. No mycotic relapses or reinfections were detected during follow up. In a subset of critically ill patients with thoracic malignancies, the administration of low-dose liposomal amphotericin B (AmBisome) resulted in complete eradication of pulmonary Aspergillus and Candida infections, and was remarkably well tolerated.
Ten years' experience with liposomal amphotericin B in transplant recipients at Huddinge University Hospital
Authors: Ringdén Olle 
Published: January 2012

Abstract
Our substantial experience in several trials with AmBisome in adult and paediatric patients undergoing transplantation has shown this formulation of amphotericin B to be safe and effective in therapeutic and prophylactic use. AmBisome has shown a significant reduction in fungal colonization and invasive Candida infections compared with placebo in a prospec-tive, double-blind study in bone marrow transplantation, and eradication of invasive fungal infections in 86% of 14 children undergoing bone marrow transplantation. The main side effects of AmBisome use are elevations in serum potassium and creatinine, but these lead to very few withdrawals from treatment. Compared with conventional amphotericin B, AmBisome is very expensive, but its much improved safety profile and proven efficacy make it an excellent agent for management of invasive fungal disease in transplant recipients.
Cryptococcosis in Australasia and the treatment of cryptococcal and other fungal infections with liposomal amphotericin B
Authors:   the Australasian Society for Infectious Diseases (ASID) Mycoses Interest Group, Chen Sharon C. A. 
Published: January 2012

Abstract
Cryptococcus neoformans is an important fungal pathogen in both immunocompromised and immunocompetent hosts. The mean annual incidence during 1994–1997 was 6.6 cases per million people per year in Australia, and 2.2 cases per million people per year in New Zealand. C. neoformans var. neoformans caused 85% of 312 episodes (98% of episodes in immunocompromised hosts) and C. neoformans var. gattii caused 15% (44% in immunocompetent hosts). The AIDS-specific incidence declined significantly over the 3 years. Mortality from cryptococcosis remains substantial. In trials involving small numbers of AIDS patients, liposomal amphotericin B (AmBisome) was found to be active against C. neoformans, with mycological response rates of 67–85%; however, maintenance therapy with an oral antifungal agent is required indefinitely. In a randomized study of patients with cryptococcal meningitis, AmBisome (4 mg/kg/day) produced mycological eradication in 73% of patients compared with 38% with conventional amphotericin. AmBisome resulted in significantly earlier sterilization of cerebrospinal fluid than conventional amphotericin (7–14 days versus 21 days) and was less nephrotoxic. The benefit of this reduced toxicity is denied to many patients because of an enormous cost barrier. In a survey of the practices of clinical mycologists in Australia, 11 experts responded to a questionnaire survey regarding the use of available lipid preparations. Their indications for use as initial therapy were mucormycosis (7/10), renal failure (7/10), Fusarium infection (2/10) and aspergillosis (2/10). Cryptococcosis, candidosis and febrile neutropenia were rarely regarded as an indication; failed therapy with conventional amphotericin was an indication to use AmBisome for 8/11 respondents. The majority believed that AmBisome was equivalent to conventional amphotericin, with amphotericin B lipid complex and AmBisome equivalent to each other in terms of efficacy. The main barrier to replacement of conventional amphotericin with lipid preparations was seen as an issue of cost.
Suspected infection in children with cancer
Authors: Shaw Peter J. 
Published: January 2012

Abstract
A common complication of the intensive therapy that children with cancer receive is infection. The Oncology Unit of The Children's Hospital at Westmead maintains a comprehensive database of all admissions for suspected sepsis. From July 1994 to June 1999 broad-spectrum antibiotics were commenced in 2331 episodes. With early and aggressive use of empirical amphotericin B, 545 courses were given. Bacteraemia was documented in 701 episodes and invasive fungal disease in 73. Trends seen during the study included: (i) the proportion of febrile neutropenic patients receiving granulocyte colony stimulating factor increased from 40% to 60%; (ii) the mean neutrophil count at cessation of antibiotics fell from 0.97 to 0.63 × 109 cells/L for patients not receiving growth factors; (iii) the proportion of non-albicans Candida species infections increased. In addition, an outbreak of infection caused by Scedosporium sp. was documented; (iv) first-line empirical antibiotic combinations containing vancomycin fell from 20% to 7%; and (v) the ability to maintain or escalate anti-fungal therapy with reduced nephrotoxicity through use of lipid formulations of amphotericin was increasingly apparent in high-risk patients. During the study, infection was the primary cause of death in 11 non-bone marrow transplant (BMT) patients (five fungal, four viral, one bacterial infection and one sepsis syndrome) and five BMT patients (two bacterial and three viral). A prospective randomized study of toxicity due to amphotericin B given in either lipid emulsion or dextrose showed no significant difference, but both groups showed a lower incidence of amphotericin B intolerance in comparison with the adult series. The inability to reduce toxicity of amphotericin B by simple mixing with lipid emulsion has led to increasing use of commercially available lipid formulations of amphotericin B.
The unfolded protein response at the crossroads of cellular life and death during endoplasmic reticulum stress
Authors: Jäger Richard , Bertrand Mathieu J.M. , Gorman Adrienne M. , Vandenabeele Peter , Samali Afshin 
Published: January 2012

AbstractOne of the early cellular responses to endoplasmic reticulum (ER) stress is the activation of the unfolded protein response (UPR). ER stress and the UPR are both implicated in numerous human diseases and pathologies. In spite of this, our knowledge of the molecular mechanisms that regulate cell fate following ER stress is limited. The UPR is initiated by three ER transmembrane receptors: PKR‐like ER kinase (PERK), activating transcription factor (ATF) 6 and inositol‐requiring enzyme 1 (IRE1). These proteins sense the accumulation of unfolded proteins and their activation triggers specific adaptive responses to resolve the stress. Intriguingly, the very same receptors can initiate signalling pathways that lead to apoptosis when the attempts to resolve the ER stress fail. In this review, we describe the known pro‐apoptotic signalling pathways emanating from activated PERK, ATF6 and IRE1 and discuss how their signalling switches from an adaptive to a pro‐apoptotic response.
Addiction research centres and the nurturing of creativity. The Korean Institute on Alcohol Problems (KIAP)
Authors: Chun Sungsoo , Reid Easton A. , Sohn Aeree , Welch Michael E. , Yun‐Welch Sunmee , Yun Mieun 
Published: January 2012

ABSTRACTThe aim of this paper is to provide an account of the history, current status and vision of the Korean Institute on Alcohol Problems (KIAP). In the context of increasing alcohol consumption, rising second‐hand effects and industry‐friendly government policy, the Korean College Alcohol Study (KCAS) was established in the Republic of Korea in 1999, and changed its name to the Korean Institute on Alcohol Problems (KIAP) in 2005. KIAP's mission is to decrease alcohol consumption and its related harms by promoting research, advocating policy, developing intervention programmes and preparing media communications. Since 1999, KIAP has published scientific papers and books in alcohol research and used the internet and other media for dissemination of specialized information to the general population. In the last decade, KIAP has trained front‐line alcohol researchers, and advanced domestic and international networks to promote evidence‐based alcohol control policy in Korea. The light of hope shines brightly as KIAP grows and establishes critical linkages to move forward in its mission.
Respiratory arrest in an obstetric patient using remifentanil patient‐controlled analgesia*
Authors: Bonner J. C. , McClymont W. 
Published: January 2012

SummaryRemifentanil patient‐controlled analgesia is well established in many centres and provides satisfactory pain relief for many women in labour. We describe a patient using remifentanil patient‐controlled analgesia who suffered a respiratory arrest requiring a brief period of ventilation. In our institution, remifentanil patient‐controlled analgesia has been offered to women in labour since 2009. Up to this point, we had not observed any critical incidents in over 130 patients using this mode of analgesia in our labour suite.
Does anthropogenic nitrogen deposition induce phosphorus limitation in herbivorous insects?
Authors: Tao Leiling , Hunter Mark D. 
Published: January 2012

AbstractAnthropogenic nitrogen deposition has shifted many ecosystems from nitrogen (N) limitation to phosphorus (P) limitation. Although well documented in plants, no study to date has explored whether N deposition exacerbates P limitation at higher trophic levels, or focused on the effects of induced plant P limitation on trophic interactions. Insect herbivores exhibit strict N : P homeostasis, and should therefore be very sensitive to variations in plant N : P stoichiometry and prone to experiencing deposition‐induced P limitation. In the current study, we investigated the effects of N deposition and P availability on a plant‐herbivorous insect system. Using common milkweed (Asclepias syriaca) and two of its specialist herbivores, the monarch caterpillar (Danaus plexippus) and milkweed aphid (Aphis asclepiadis) as our study system, we found that experimental N deposition caused P limitation in milkweed plants, but not in either insect species. However, the mechanisms for the lack of P limitation were different for each insect species. The body tissues of A. asclepiadis always exhibited higher N : P ratios than that of the host plant, suggesting that the N demand of this species exceeds P demand, even under high N deposition levels. For D. plexippus, P addition increased the production of latex, which is an important defense negatively affecting D. plexippus growth rate. As a result, we illustrate that P limitation of herbivores is not an inevitable consequence of anthropogenic N deposition in terrestrial systems. Rather, species‐specific demands for nutrients and the defensive responses of plants combine to determine the responses of herbivores to P availability under N deposition.
Land‐atmosphere exchange of methane from soil thawing to soil freezing in a high‐Arctic wet tundra ecosystem
Authors: Tagesson Torbern , Mölder Meelis , Mastepanov Mikhail , Sigsgaard Charlotte , Tamstorf Mikkel P. , Lund Magnus , Falk Julie M. , Lindroth Anders , Christensen Torben R. , Ström Lena 
Published: January 2012

AbstractThe land‐atmosphere exchange of methane (CH4) and carbon dioxide (CO2) in a high‐Arctic wet tundra ecosystem (Rylekærene) in Zackenberg, north‐eastern Greenland, was studied over the full growing season and until early winter in 2008 and from before snow melt until early winter in 2009. The eddy covariance technique was used to estimate CO2 fluxes and a combination of the gradient and eddy covariance methods was used to estimate CH4 fluxes. Small CH4 bursts were observed during spring thawing 2009, but these existed during short periods and would not have any significant effect on the annual budget. Growing season CH4 fluxes were well correlated with soil temperature, gross primary production, and active layer thickness. The CH4 fluxes remained low during the entire autumn, and until early winter. No increase in CH4 fluxes were seen as the soil started to freeze. However, in autumn 2008 there were two CH4 burst events that were highly correlated with atmospheric turbulence. They were likely associated with the release of stored CH4 from soil and vegetation cavities. Over the measurement period, 7.6 and 6.5 g C m−2 was emitted as CH4 in 2008 and in 2009, respectively. Rylekærene acted as a C source during the warmer and wetter measurement period 2008, whereas it was a C sink for the colder and drier period of 2009. Wet tundra ecosystems, such as Rylekærene may thus play a more significant role for the climate in the future, as temperature and precipitation are predicted to increase in the high‐Arctic.