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Lowell S. Young

Bio: Lowell S. Young is an academic researcher from California Pacific Medical Center. The author has contributed to research in topics: Antibacterial agent & Mycobacterium avium-intracellulare infection. The author has an hindex of 39, co-authored 87 publications receiving 7744 citations.


Papers
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Journal ArticleDOI
TL;DR: This work presents a meta-analyses of the immune system’s response to chemotherapy, which shows clear patterns of decline in the immune systems of patients diagnosed with central giant cell cancer.
Abstract: Walter T. Hughes, Donald Armstrong, Gerald P. Bodey, Eric J. Bow, Arthur E. Brown, Thierry Calandra, Ronald Feld, Philip A. Pizzo, Kenneth V. I. Rolston, Jerry L. Shenep, and Lowell S. Young St. Jude Children’s Research Hospital, Memphis, Tennessee; Memorial Sloan-Kettering Cancer Center, New York, New York; University of Texas M. D. Anderson Cancer Center, Houston; Harvard Medical School, Boston, Massachusetts; Stanford University School of Medicine, Palo Alto, and Kuzell Institute for Arthritis, San Francisco, California; University of Manitoba, Winnipeg, and Princess Margaret Hospital, Toronto, Canada; and Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

1,881 citations

Journal ArticleDOI
TL;DR: This is the first in a series of practice guidelines commissioned by the Infectious Diseases Society of America through its Practice Guidelines Committee to provide assistance to clinicians when making decisions on treating the conditions specified in each guideline.
Abstract: This is the first in a series of practice guidelines commissioned by the Infectious Diseases Society of America through its Practice Guidelines Committee. The purpose of these guidelines is to provide assistance to clinicians when making decisions on treating the conditions specified in each guideline. The targeted providers are internists, pediatricians, and family practitioners. The targeted patients and setting for the fever and neutropenia guideline are hospitalized individuals with neutropenia secondary to cancer chemotherapy. Panel members represented experts in adult and pediatric infectious diseases and oncology. The guidelines are evidence-based. A standard ranking system was used for the strength of the recommendations and the quality of the evidence cited in the literature reviewed. The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council. An executive summary, algorithms, and tables highlight the major recommendations. The guideline will be listed on the IDSA home page at http://www.idsociety.org.

636 citations

Journal ArticleDOI
TL;DR: The incidence of aspergillosis is increasing and should be considered in the setting of progressive pulmonary infiltrates in leukemic and other heavily immunosuppressed patients who respond poorly to antibacterial therapy.

504 citations

Journal ArticleDOI
TL;DR: Research in patients with chronic mucocutaneous candidiasis and in-vitro manipulations have begun to elucidate normal immune defense mechanisms against Candida, including serum factors, phagocytosis, intracellular killing mechanisms, and lymphocyte function (particularly T cell).
Abstract: Disseminated candidiasis has become an important infection, particularly in immunocompromised and postoperative patients. Although serologic tests may, in some settings, facilitate a premortem diagnosis, the disease is usually diagnosed by comprehensive clinical evaluation. Detection of the relatively newly recognized peripheral manifestations of candidemia may be vital to early diagnosis: endophthalmitis, osteomyelitis, arthritis, myocarditis, meningitis, and macronodular skin lesions. Studies in patients with chronic mucocutaneous candidiasis and in-vitro manipulations have begun to elucidate normal immune defense mechanisms against Candida, including serum factors, phagocytosis, intracellular killing mechanisms, and lymphocyte function (particularly T cell). The primary drugs for the treatment of disseminated candidiasis are still amphotericin B or amphotericin B plus 5-fluorocytosine; the mainstay of therapy for chronic mucocutaneous candidiasis is amphotericin B. Other antifungals and immune system-stimulating modalities (transfer factor, thymosin, thymus epithelial cell transplantation, and levamisol) may be useful for chronic mucocutaneous candidiasis in some settings and deserve further evaluation.

341 citations

Journal ArticleDOI
TL;DR: The findings, based on both in vitro and animal-model studies, have identified drugs which, when used in combination, are potentially of therapeutic utility.
Abstract: Serious infections caused by the Mycobacterium avium complex (MAC) have been increasingly recognized over the last three decades. However, the epidemic of the acquired immunodeficiency syndrome (AIDS) has increased interest in these infections. Disseminated mycobacterial disease is common in patients with AIDS, and MAC is the predominant bacterial isolate. Indeed, at UCLA Medical Center, MAC organisms are now the predominant isolates in both AIDS- and non-AIDS-associated mycobacterial disease. MAC lung infections have been difficult to treat. Complex regimens employing four to six drugs are not clearly effective and are usually associated with considerable toxicity. Treatment of MAC infections in patients with AIDS has been particularly frustrating, and evidence that treatment can either eradicate disease or prolong life is limited. MAC organisms are invariably resistant to traditional antituberculosis medications. We have examined a variety of other compounds, and our findings, based on both in vitro and animal-model studies, have identified drugs which, when used in combination, are potentially of therapeutic utility.

276 citations


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Journal ArticleDOI
TL;DR: In this paper, the authors provide an update to the original Surviving Sepsis Campaign clinical management guidelines for management of severe sepsis and septic shock, published in 2004.
Abstract: Objective To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004.

3,928 citations

01 Jan 2008
TL;DR: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, the GRADE system was used to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations.
Abstract: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004. Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [1] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [2] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥ 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

3,824 citations

Journal ArticleDOI
TL;DR: These updated guidelines replace the previous guidelines published in the 15 January 2004 issue of Clinical Infectious Diseases and are intended for use by health care providers who care for patients who either have or are at risk of these infections.
Abstract: Guidelines for the management of patients with invasive candidiasis and mucosal candidiasis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous guidelines published in the 15 January 2004 issue of Clinical Infectious Diseases and are intended for use by health care providers who care for patients who either have or are at risk of these infections. Since 2004, several new antifungal agents have become available, and several new studies have been published relating to the treatment of candidemia, other forms of invasive candidiasis, and mucosal disease, including oropharyngeal and esophageal candidiasis. There are also recent prospective data on the prevention of invasive candidiasis in high-risk neonates and adults and on the empiric treatment of suspected invasive candidiasis in adults. This new information is incorporated into this revised document.

3,016 citations

Journal ArticleDOI
TL;DR: This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002 and developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis.
Abstract: This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002. It is intended as a guide for the use of antimicrobial agents in managing patients with cancer who experience chemotherapy-induced fever and neutropenia. Recent advances in antimicrobial drug development and technology, clinical trial results, and extensive clinical experience have informed the approaches and recommendations herein. Because the previous iteration of this guideline in 2002, we have a developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis. Furthermore, categorizing neutropenic patients as being at high risk or low risk for infection according to presenting signs and symptoms, underlying cancer, type of therapy, and medical comorbidities has become essential to the treatment algorithm. Risk stratification is a recommended starting point for managing patients with fever and neutropenia. In addition, earlier detection of invasive fungal infections has led to debate regarding optimal use of empirical or preemptive antifungal therapy, although algorithms are still evolving. What has not changed is the indication for immediate empirical antibiotic therapy. It remains true that all patients who present with fever and neutropenia should be treated swiftly and broadly with antibiotics to treat both gram-positive and gram-negative pathogens. Finally, we note that all Panel members are from institutions in the United States or Canada; thus, these guidelines were developed in the context of North American practices. Some recommendations may not be as applicable outside of North America, in areas where differences in available antibiotics, in the predominant pathogens, and/or in health care-associated economic conditions exist. Regardless of venue, clinical vigilance and immediate treatment are the universal keys to managing neutropenic patients with fever and/or infection.

2,664 citations

Journal ArticleDOI
TL;DR: This research presents a novel, scalable, scalable and scalable approach that allows for real-time evaluation of the impact of Epstein-Barr virus on the development and management of childhood cancer in rats.
Abstract: Aspergillus species have emerged as an important cause of life-threatening infections in immunocompromised patients. This expanding population is composed of patients with prolonged neutropenia, advanced HIV infection, and inherited immunodeficiency and patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT) and/or lung transplantation. This document constitutes the guidelines of the Infectious Diseases Society of America for treatment of aspergillosis and replaces the practice guidelines for Aspergillus published in 2000 [1]. The objective of these guidelines is to summarize the current evidence for treatment of different forms of aspergillosis. The quality of evidence for treatment is scored according to a standard system used in other Infectious Diseases Society of America guidelines. This document reviews guidelines for management of the 3 major forms of aspergillosis: invasive aspergillosis, chronic (and saprophytic) forms of aspergillosis, and allergic forms of aspergillosis. Given the public health importance of invasive aspergillosis, emphasis is placed on the diagnosis, treatment, and prevention of the different forms of invasive aspergillosis, including invasive pulmonary aspergillosis, sinus aspergillosis, disseminated aspergillosis, and several types of single-organ invasive aspergillosis. There are few randomized trials on the treatment of invasive aspergillosis. The largest randomized controlled trial demonstrates that voriconazole is superior to deoxycholate amphotericin B (D-AMB) as primary treatment for invasive aspergillosis. Voriconazole is recommended for the primary treatment of invasive aspergillosis in most patients (A-I). Although invasive pulmonary aspergillosis accounts for the preponderance of cases treated with voriconazole, voriconazole has been used in enough cases of extrapulmonary and disseminated infection to allow one to infer that voriconazole is effective in these cases. A randomized trial comparing 2 doses of liposomal amphotericin B (L-AMB) showed similar efficacy in both arms, suggesting that liposomal therapy could be considered as alternative primary therapy in some patients (A-I). For salvage therapy, agents include lipid formulations of amphotericin (LFAB; A-II), posaconazole (B-II), itraconazole (B-II), caspofungin (B-II), or micafungin (B-II). Salvage therapy for invasive aspergillosis poses important challenges with significant gaps in knowledge. In patients whose aspergillosis is refractory to voriconazole, a paucity of data exist to guide management. Therapeutic options include a change of class using an amphotericin B (AMB) formulation or an echinocandin, such as caspofungin (B-II); further use of azoles should take into account host factors and pharmacokinetic considerations. Refractory infection may respond to a change to another drug class (B-II) or to a combination of agents (B-II). The role of combination therapy in the treatment of invasive aspergillosis as primary or salvage therapy is uncertain and warrants a prospective, controlled clinical trial. Assessment of patients with refractory aspergillosis may be difficult. In evaluating such patients, the diagnosis of invasive aspergillosis should be established if it was previously uncertain and should be confirmed if it was previously known. The drug dosage should be considered. Management options include a change to intravenous (IV) therapy, therapeutic monitoring of drug levels, change of drug class, and/or combination therapy. Antifungal prophylaxis with posaconazole can be recommended in the subgroup of HSCT recipients with graft-versus-host disease (GVHD) who are at high risk for invasive aspergillosis and in neutropenic patients with acute myelogenous leukemia or myelodysplastic syndrome who are at high risk for invasive aspergillosis (A-I). Management of breakthrough invasive aspergillosis in the context of mould-active azole prophylaxis is not defined by clinical trial data. The approach to such patients should be individualized on the basis of clinical criteria, including host immunosuppression, underlying disease, and site of infection, as well as consideration of antifungal dosing, therapeutic monitoring of drug levels, a switch to IV therapy, and/or a switch to another drug class (B-III). Certain conditions of invasive aspergillosis warrant consideration for surgical resection of the infected focus. These include but are not limited to pulmonary lesions contiguous with the heart or great vessels, invasion of the chest wall, osteomyelitis, pericardial infection, and endocarditis (B-III). Restoration of impaired host defenses is critical for improved outcome of invasive aspergillosis (A-III). Recovery from neutropenia in a persistently neutropenic host or reduction of corticosteroids in a patient receiving high-dose glucocorticosteroids is paramount for improved outcome in invasive aspergillosis. A special consideration is made concerning recommendations for therapy of aspergillosis in uncommon sites, such as osteomyelitis and endocarditis. There are very limited data on these infections, and most involve D-AMB as primary therapy simply because of its long-standing availability. Based on the strength of the randomized study, the panel recommends voriconazole for primary treatment of these very uncommon manifestations of invasive aspergillosis (B-III). Management of the chronic or saprophytic forms of aspergillosis varies depending on the condition. Single pulmonary aspergillomas may be best managed by surgical resection (B-III), whereas chronic cavitary and chronic necrotizing pulmonary aspergillosis require long-term medical therapy (B-III). The management of allergic forms of aspergillosis involves a combination of medical and anti-inflammatory therapy. For example, management of allergic bronchopulmonary aspergillosis (ABPA) involves the administration of itraconazole and corticosteroids (A-I). © 2008 by the Infectious Diseases Society of America. All rights reserved.

2,463 citations