bluuebunny/crossref_metadata_2025 huggingface dataset:
miR-147, a microRNA that is induced upon Toll-like receptor stimulation, regulates murine macrophage inflammatory responses
Authors: Liu Gang , Friggeri Arnaud , Yang Yanping , Park Young-Jun , Tsuruta Yuko , Abraham Edward
Published: September 2009

Toll-like receptors (TLRs) are major receptors that enable inflammatory cells to recognize invading microbial pathogens. MicroRNAs are small non-coding RNAs that play important regulatory roles in a variety of biological processes. In this study, we found that a microRNA, miR-147, was induced upon stimulation of multiple TLRs and functioned as a negative regulator of TLR-associated signaling events in murine macrophages. We first demonstrated that the NMES1 transcript was a functional primary miR-147. miR-147 was induced in LPS-stimulated mouse macrophages and under in vivo conditions in the lungs of LPS-treated mice. Expression of miR-147 was greater after cellular activation by TLR4 than after engagement of either TLR2 or TLR3, suggesting that maximal induction of miR-147 required activation of both NF-κB and IRF3. TLR4-induced miR-147 expression was both MyD88- and TRIF-dependent. The miR-147 promoter was responsive to TLR4 stimulation and both NF-κB and STAT1α bound to the miR-147 promoter. miR-147 mimics or induced expression of miR-147 decreased, whereas miR-147 knockdown increased inflammatory cytokine expression in macrophages stimulated with ligands to TLR2, TLR3, and TLR4. These data demonstrate a negative-feedback loop in which TLR stimulation induces miR-147 to prevent excessive inflammatory responses.
Netrin-1 up-regulation in inflammatory bowel diseases is required for colorectal cancer progression
Authors: Paradisi Andrea , Maisse Carine , Coissieux Marie-May , Gadot Nicolas , Lépinasse Florian , Delloye-Bourgeois Céline , Delcros Jean-Guy , Svrcek Magali , Neufert Clemens , Fléjou Jean-François , Scoazec Jean-Yves , Mehlen Patrick
Published: September 2009

Chronic inflammation and cancer are intimately associated. This is particularly true for inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, which show a major increased risk for colorectal cancer. While the understanding of the molecular pathogenesis of IBD has recently improved, the mechanisms that link these chronic inflammatory states to colorectal cancer development are in large part unknown. One of these mechanisms is NF-κB pathway activation which in turn may contribute to tumor formation by providing anti-apoptotic survival signals to the epithelial cells. Based on the observation that netrin-1, the anti-apoptotic ligand for the dependence receptors DCC and UNC5H is up-regulated in colonic crypts in response to NF-κB, we show here that colorectal cancers from inflammatory bowel diseases patients have selected up-regulation of netrin-1. Moreover, we demonstrate that this inflammation-driven netrin-1 up-regulation is causal for colorectal cancer development as interference with netrin-1 autocrine loop in a mouse model for ulcerative colitis-associated colorectal cancer, while showing no effect on inflammation, inhibits colorectal cancer progression.
Conformational differences between the Pfr and Pr states in
Pseudomonas aeruginosa
bacteriophytochrome
Authors: Yang Xiaojing , Kuk Jane , Moffat Keith
Published: September 2009

Phytochromes are red-light photoreceptors that regulate light responses in plants, fungi, and bacteria by means of reversible photoconversion between red (Pr) and far-red (Pfr) light-absorbing states. Here, we report the crystal structure of the Q188L mutant of
Pseudomonas aeruginosa
bacteriophytochrome (PaBphP) photosensory core module, which exhibits altered photoconversion behavior and different crystal packing from wild type. We observe two distinct chromophore conformations in the Q188L crystal structure that we identify with the Pfr and Pr states. The Pr/Pfr compositions, varying from crystal to crystal, seem to correlate with light conditions under which the Q188L crystals are cryoprotected. We also compare all known Pr and Pfr structures. Using site-directed mutagenesis, we identify residues that are involved in stabilizing the 15
E
a (Pfr) and 15
Z
a (Pr) configurations of the biliverdin chromophore. Specifically, Ser-261 appears to be essential to form a stable Pr state in PaBphP, possibly by means of its interaction with the propionate group of ring C. We propose a “flip-and-rotate” model that summarizes the major conformational differences between the Pr and Pfr states of the chromophore and its binding pocket.
Generation of pluripotent stem cells from patients with type 1 diabetes
Authors: Maehr René , Chen Shuibing , Snitow Melinda , Ludwig Thomas , Yagasaki Lisa , Goland Robin , Leibel Rudolph L. , Melton Douglas A.
Published: September 2009

Type 1 diabetes (T1D) is the result of an autoimmune destruction of pancreatic β cells. The cellular and molecular defects that cause the disease remain unknown. Pluripotent cells generated from patients with T1D would be useful for disease modeling. We show here that induced pluripotent stem (iPS) cells can be generated from patients with T1D by reprogramming their adult fibroblasts with three transcription factors (OCT4, SOX2, KLF4). T1D-specific iPS cells, termed DiPS cells, have the hallmarks of pluripotency and can be differentiated into insulin-producing cells. These results are a step toward using DiPS cells in T1D disease modeling, as well as for cell replacement therapy.
Blockage of A2Aand A3adenosine receptors decreases the desensitization of human GABAAreceptors microtransplanted toXenopusoocytes
Authors: Roseti Cristina , Palma Eleonora , Martinello Katiuscia , Fucile Sergio , Morace Roberta , Esposito Vincenzo , Cantore Gianpaolo , Arcella Antonietta , Giangaspero Felice , Aronica Eleonora , Mascia Addolorata , Di Gennaro Giancarlo , Quarato Pier Paolo , Manfredi Mario , Cristalli Gloria , Lambertucci Catia , Marucci Gabriella , Volpini Rosaria , Limatola Cristina , Eusebi Fabrizio
Published: September 2009

We previously found that the endogenous anticonvulsant adenosine, acting through A2Aand A3adenosine receptors (ARs), alters the stability of currents (IGABA) generated by GABAAreceptors expressed in the epileptic human mesial temporal lobe (MTLE). Here we examined whether ARs alter the stability (desensitization) of IGABAexpressed in focal cortical dysplasia (FCD) and in periglioma epileptic tissues. The experiments were performed with tissues from 23 patients, using voltage-clamp recordings inXenopusoocytes microinjected with membranes isolated from human MTLE and FCD tissues or using patch-clamp recordings of pyramidal neurons in epileptic tissue slices. On repetitive activation, the epileptic GABAAreceptors revealed instability, manifested by a large IGABArundown, which in most of the oocytes (≈70%) was obviously impaired by the new A2Aantagonists ANR82, ANR94, and ANR152. In most MTLE tissue-microtransplanted oocytes, a new A3receptor antagonist (ANR235) significantly improved IGABAstability. Moreover, patch-clamped pyramidal neurons from human neocortical slices of periglioma epileptic tissues exhibited altered IGABArundown on ANR94 treatment. Our findings indicate that antagonizing A2Aand A3receptors increases the IGABAstability in different epileptic tissues and suggest that adenosine derivatives may offer therapeutic opportunities in various forms of human epilepsy.
Comparative genomics reveals mechanism for short-term and long-term clonal transitions in pandemic
Vibrio cholerae
Authors: Chun Jongsik , Grim Christopher J. , Hasan Nur A. , Lee Je Hee , Choi Seon Young , Haley Bradd J. , Taviani Elisa , Jeon Yoon-Seong , Kim Dong Wook , Lee Jae-Hak , Brettin Thomas S. , Bruce David C. , Challacombe Jean F. , Detter J. Chris , Han Cliff S. , Munk A. Christine , Chertkov Olga , Meincke Linda , Saunders Elizabeth , Walters Ronald A. , Huq Anwar , Nair G. Balakrish , Colwell Rita R.
Published: September 2009

Vibrio cholerae
, the causative agent of cholera, is a bacterium autochthonous to the aquatic environment, and a serious public health threat.
V. cholerae
serogroup O1 is responsible for the previous two cholera pandemics, in which classical and El Tor biotypes were dominant in the sixth and the current seventh pandemics, respectively. Cholera researchers continually face newly emerging and reemerging pathogenic clones carrying diverse combinations of phenotypic and genotypic properties, which significantly hampered control of the disease. To elucidate evolutionary mechanisms governing genetic diversity of pandemic
V. cholerae
, we compared the genome sequences of 23
V. cholerae
strains isolated from a variety of sources over the past 98 years. The genome-based phylogeny revealed 12 distinct
V. cholerae
lineages, of which one comprises both O1 classical and El Tor biotypes. All seventh pandemic clones share nearly identical gene content. Using analogy to influenza virology, we define the transition from sixth to seventh pandemic strains as a “shift” between pathogenic clones belonging to the same O1 serogroup, but from significantly different phyletic lineages. In contrast, transition among clones during the present pandemic period is characterized as a “drift” between clones, differentiated mainly by varying composition of laterally transferred genomic islands, resulting in emergence of variants, exemplified by
V. cholerae
O139 and
V. cholerae
O1 El Tor hybrid clones. Based on the comparative genomics it is concluded that
V. cholerae
undergoes extensive genetic recombination via lateral gene transfer, and, therefore, genome assortment, not serogroup, should be used to define pathogenic
V. cholerae
clones.
Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung
Authors: Lee Jae W. , Fang Xiaohui , Gupta Naveen , Serikov Vladimir , Matthay Michael A.
Published: September 2009

Recent studies have suggested that bone marrow-derived multipotent mesenchymal stem cells (MSCs) may have therapeutic applications in multiple clinical disorders including myocardial infarction, diabetes, sepsis, and hepatic and acute renal failure. Here, we tested the therapeutic capacity of human MSCs to restore alveolar epithelial fluid transport and lung fluid balance from acute lung injury (ALI) in an ex vivo perfused human lung preparation injured by
E. coli
endotoxin. Intra-bronchial instillation of endotoxin into the distal airspaces resulted in pulmonary edema with the loss of alveolar epithelial fluid transport measured as alveolar fluid clearance. Treatment with allogeneic human MSCs or its conditioned medium given 1 h following endotoxin-induced lung injury reduced extravascular lung water, improved lung endothelial barrier permeability and restored alveolar fluid clearance. Using siRNA knockdown of potential paracrine soluble factors, secretion of keratinocyte growth factor was essential for the beneficial effect of MSCs on alveolar epithelial fluid transport, in part by restoring amiloride-dependent sodium transport. In summary, treatment with allogeneic human MSCs or the conditioned medium restores normal fluid balance in an ex vivo perfused human lung injured by
E. coli
endotoxin.
Single-molecule imaging reveals transforming growth factor-β-induced type II receptor dimerization
Authors: Zhang Wei , Jiang Yaxin , Wang Qiang , Ma Xinyong , Xiao Zeyu , Zuo Wei , Fang Xiaohong , Chen Ye-Guang
Published: September 2009

Transforming growth factor-β (TGF-β) elicits its signals through two transmembrane serine/threonine kinase receptors, type II (TβRII) and type I receptors. It is generally believed that the initial receptor dimerization is an essential event for receptor activation. However, previous studies suggested that TGF-β signals by binding to the preexisting TβRII homodimer. Here, using single molecule microscopy to image green fluorescent protein (GFP)-labeled TβRII on the living cell surface, we demonstrated that the receptor could exist as monomers at the low expression level in resting cells and dimerize upon TGF-β stimulation. This work reveals a model in which the activation of serine-threonine kinase receptors is also accomplished via dimerization of monomers, suggesting that receptor dimerization is a general mechanism for ligand-induced receptor activation.
Posttranslational interference of Ty1 retrotransposition by antisense RNAs
Authors: Matsuda Emiko , Garfinkel David J.
Published: September 2009

Transposable elements impact genome function by altering gene expression and causing chromosome rearrangements. As a result, organisms have evolved mechanisms, such as RNA-interference, to minimize the level of transposition. However, organisms without the conserved RNAi pathways, like
Saccharomyces cerevisiae
, must use other mechanisms to prevent transposon movement. Here, we provide evidence that antisense (AS) RNAs from the retrovirus-like element Ty1 inhibit retrotransposition posttranslationally in
Saccharomyces
. Multiple Ty1AS transcripts overlap Ty1 sequences necessary for copy number control (CNC) and inhibit transposition
in trans
. Altering Ty1 copy number or deleting sequences in the CNC region that are required for reverse transcription affect Ty1AS RNA level and Ty1 movement. Ty1AS RNAs are enriched in virus-like particles, and are associated with a dramatic decrease in the level of integrase, less reverse transcriptase, and an inability to synthesize Ty1 cDNA. Thus, Ty1AS RNAs are part of an intrinsic mechanism that limits retrotransposition by reducing the level of proteins required for replication and integration.
Dynamics of myosin, microtubules, and Kinesin-6 at the cortex during cytokinesis in Drosophila S2 cells
Authors: Vale Ronald D. , Spudich James A. , Griffis Eric R.
Published: September 2009

Signals from the mitotic spindle during anaphase specify the location of the actomyosin contractile ring during cytokinesis, but the detailed mechanism remains unresolved. Here, we have imaged the dynamics of green fluorescent protein–tagged myosin filaments, microtubules, and Kinesin-6 (which carries activators of Rho guanosine triphosphatase) at the cell cortex using total internal reflection fluorescence microscopy in flattened Drosophila S2 cells. At anaphase onset, Kinesin-6 relocalizes to microtubule plus ends that grow toward the cortex, but refines its localization over time so that it concentrates on a subset of stable microtubules and along a diffuse cortical band at the equator. The pattern of Kinesin-6 localization closely resembles where new myosin filaments appear at the cortex by de novo assembly. While accumulating at the equator, myosin filaments disappear from the poles of the cell, a process that also requires Kinesin-6 as well as possibly other signals that emanate from the elongating spindle. These results suggest models for how Kinesin-6 might define the position of cortical myosin during cytokinesis.
P115 RhoGEF and microtubules decide the direction apoptotic cells extrude from an epithelium
Authors: Slattum Gloria , McGee Karen M. , Rosenblatt Jody
Published: September 2009

To preserve epithelial barrier function, dying cells are squeezed out of an epithelium by “apoptotic cell extrusion.” Specifically, a cell destined for apoptosis signals its live neighboring epithelial cells to form and contract a ring of actin and myosin II that squeezes the dying cell out of the epithelial sheet. Although most apoptotic cells extrude apically, we find that some exit basally. Localization of actin and myosin IIA contraction dictates the extrusion direction: basal extrusion requires circumferential contraction of neighboring cells at their apices, whereas apical extrusion also requires downward contraction along the basolateral surfaces. To activate actin/myosin basolaterally, microtubules in neighboring cells reorient and target p115 RhoGEF to this site. Preventing microtubule reorientation restricts contraction to the apex, driving extrusion basally. Extrusion polarity has important implications for tumors where apoptosis is blocked but extrusion is not, as basal extrusion could enable these cells to initiate metastasis.
TOR-mediated autophagy regulates cell death in Drosophila neurodegenerative disease
Authors: Wang Tao , Lao Uyen , Edgar Bruce A.
Published: September 2009

Target of rapamycin (TOR) signaling is a regulator of cell growth. TOR activity can also enhance cell death, and the TOR inhibitor rapamycin protects cells against proapoptotic stimuli. Autophagy, which can protect against cell death, is negatively regulated by TOR, and disruption of autophagy by mutation of Atg5 or Atg7 can lead to neurodegeneration. However, the implied functional connection between TOR signaling, autophagy, and cell death or degeneration has not been rigorously tested. Using the Drosophila melanogaster visual system, we show in this study that hyperactivation of TOR leads to photoreceptor cell death in an age- and light-dependent manner and that this is because of TOR's ability to suppress autophagy. We also find that genetically inhibiting TOR or inducing autophagy suppresses cell death in Drosophila models of Huntington's disease and phospholipase C (norpA)–mediated retinal degeneration. Thus, our data indicate that TOR induces cell death by suppressing autophagy and provide direct genetic evidence that autophagy alleviates cell death in several common types of neurodegenerative disease.
Epstein-Barr virus (EBV)–encoded small RNA is released from EBV-infected cells and activates signaling from toll-like receptor 3
Authors: Iwakiri Dai , Zhou Li , Samanta Mrinal , Matsumoto Misako , Ebihara Takashi , Seya Tsukasa , Imai Shosuke , Fujieda Mikiya , Kawa Keisei , Takada Kenzo
Published: September 2009

Epstein-Barr virus–encoded small RNA (EBER) is nonpolyadenylated, noncoding RNA that forms stem-loop structure by intermolecular base-pairing, giving rise to double-stranded RNA (dsRNA)–like molecules, and exists abundantly in EBV-infected cells. Here, we report that EBER induces signaling from the Toll-like receptor 3 (TLR3), which is a sensor of viral double-stranded RNA (dsRNA) and induces type I IFN and proinflammatory cytokines. A substantial amount of EBER, which was sufficient to induce signaling from TLR3, was released from EBV-infected cells, and the majority of the released EBER existed as a complex with a cellular EBER-binding protein La, suggesting that EBER was released from the cells by active secretion of La. Sera from patients with infectious mononucleosis (IM), chronic active EBV infection (CAEBV), and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), whose general symptoms are caused by proinflammatory cytokines contained EBER, and addition of RNA purified from the sera into culture medium induced signaling from TLR3 in EBV-transformed lymphocytes and peripheral mononuclear cells. Furthermore, DCs treated with EBER showed mature phenotype and antigen presentation capacity. These findings suggest that EBER, which is released from EBV-infected cells, is responsible for immune activation by EBV, inducing type I IFN and proinflammatory cytokines. EBER-induced activation of innate immunity would account for immunopathologic diseases caused by active EBV infection.
Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease
Authors: Kovalenko Andrew , Kim Jin-Chul , Kang Tae-Bong , Rajput Akhil , Bogdanov Konstantin , Dittrich-Breiholz Oliver , Kracht Michael , Brenner Ori , Wallach David
Published: September 2009

Expression of enzymatically inactive caspase-8, or deletion of caspase-8 from basal epidermal keratinocytes, triggers chronic skin inflammation in mice. Unlike similar inflammation resulting from arrest of nuclear factor κB activation in the epidermal cells, the effect induced by caspase-8 deficiency did not depend on TNF, IL-1, dermal macrophage function, or expression of the toll-like receptor adapter proteins MyD88 or TRIF. Both interferon regulatory factor (IRF) 3 and TANK-binding kinase were constitutively phosphorylated in the caspase-8–deficient epidermis, and knockdown of IRF3 in the epidermis-derived cells from these mice abolished the expression of up-regulated genes. Temporal and spatial analyses of the alterations in gene expression that result from caspase-8 deficiency reveal that the changes are initiated before birth, around the time that cornification develops, and occur mainly in the suprabasal layer. Finally, we found that caspase-8–deficient keratinocytes display an enhanced response to gene activation by transfected DNA. Our findings suggest that an enhanced response to endogenous activators of IRF3 in the epidermis, presumably generated in association with keratinocyte differentiation, contributes to the skin inflammatory process triggered by caspase-8 deficiency.
Nosocomial Infection Rates at an Oncology Center
Authors: Rotstein Coleman , Cummings K. Michael , Nicolaou Andreas L. , Lucey Joyce , Fitzpatrick John
Published: September 2009

Nosocomial infection rates were computed for 5,031 patients at an oncology center during a 20-month period. Twelve percent of the patients developed nosocomial infections, accounting for a total of 802 infections. The overall incidence of nosocomial infections during this study period was 6.27 infections per 1,000 patient days. The highest incidence of nosocomial infections was found in patients having acute myelogenous leukemia (30.49 infections per 1,000 patient days); bone and joint cancer (27.27 infections per 1,000 patient days); and liver cancer (26.58 infections per 1,000 patient days). The respiratory tract was the most common site of infection, followed by blood-stream, surgical wound, and urinary tract infections. Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and coagulase-negative staphylococci were most frequently implicated as pathogens. The distribution of specific types of infection according to underlying malignancy was also tabulated. These data provide nosocomial infection rates, common pathogens, and sites of infection for cancer patients, thus assisting in directing appropriate therapy for these patients.
Product Commentary: Housekeeping Products: The Choice Is Yours
Authors: Crow Sue
Published: September 2009

For years, Infection Control Practitioners have been asked to identify the “ultimate” hospital::: disinfectant. Health care personnel seem to want a multipurpose product; one that can he used for handwashing for, instrument disinfection and for cleaning the commode. Simply stated, there is not one product that call successfully do all three. Antiseptic solutions, which are approved by the Food and Drug Administration are for use on skin (ie, handwashing and skirt preparation whereas disinfectants are for use in the inanimate environment and are approved by the Environmental Protection Agency.

There are two classifications of' disinfectants housekeeping disinfectants and instrument disinfectants. Housekeeping disinfectants are generally low-level disinfectants, and quartenary ammonium compounds or phenol-based solutions are the most common. Instrument disinfectants are high-level disinfectants such as glutaraldehydes and chlorine dioxide.
Topics in Clinical Epidemiology: Linking Hospital Epidemiology and Quality Assurance: Seasoned Concepts in a New Role
Authors: Crede William , Hierholzer Walter J.
Published: September 2009

As with all human endeavors, medical care in any setting has observable and occult benefits and risks. The methods of study of these facets of medical care have become known as “clinical epidmiology.”

This article is the introduction to a new series entitled “Topics in Clinical Epidemiology.” The authors are practicing clinicians, one as director of the Quality Assurance department and the other as director of the Hospital Epidemiology department, both at a large tertiary teaching hospital. The series will attempt, in the fashion of the old shoe leather epidemiologist, to reflect those problems and interactions which are the realities of our current practice milieu and experience. That this collection of manuscripts will be presented in an infection control periodical reflects the journal's and the authors' perspective that the same epidemiological techniques that have made infection control clinically successful and cost-effective can be used to reduce noninfectious hazards of medical care, and to enhance the diagnostic and therapeutic benefits of modern medical management.
Number of Comorbidities as a Predictor of Nosocomial Infection Acquisition
Authors: Gross Peter A. , DeMauro Peter J. , Antwerpen Carole Van , Wallenstein Sylvan , Chiang Stanley
Published: September 2009

Infection control programs are primarily oriented toward chronicling the incidence of nosocomial infections (NI). Intervention programs oriented toward preventing infection would be facilitated by identifying patients at greatest risk of NI acquisition. We studied the number of comorbidities as a risk predictor for NIs in patients admitted to the medical intensive care unit (ICU) for three or more days. In 148 patients, we found by regression analysis that the number of comorbidities varied directly with the development of nosocomial infections, as well as with the appearance of new complications and length of ICU stay. Diagnosis-related groups did not adequately account for the variance in comorbidities observed.
Factitious Meningitis: A Recurring Problem
Authors: Penn Robert L. , Normand Richard , Klotz Stephen A.
Published: September 2009

Although gram-negative meningitis is rare in our hospital, between July, 1982 and July, 1983 clusters of cerebrospinal fluid (CSF) smears were reported positive for gram-negative bacilli. Fourteen specimens were obtained by diagnostic lumbar punctures, and one was obtained during a myelogram. No CSF cultures were positive, and a diagnosis of factitious meningitis was eventually established for each patient. Nonviable gram-negative bacilli were found in 6.7% of manometers, and 23.3% to 90% of the specimen tubes tested from the same lots of commercial lumbar puncture trays. It was estimated that there were between 44 and 333 organisms per specimen tube. Two lots of the commercial myelogram trays yielded nonviable gram-negative bacilli from 50% of the specimen tubes and 33.3% of the manometers tested. Retrospective review of laboratory records for 1982 and 1983 revealed 23 total CSF smears positive for gram-negative bacilli. No CSF grew gram-negative bacilli, and chart reviews confirmed a diagnosis of factitious meningitis in each case. In addition to the clusters of false-positive smears, this had occurred sporadically in both years. The problem did not recur after separate sterile tubes were provided for CSF collection. Physicians and laboratories should be aware that nonviable contaminants in commercial products may be a source of false-positive CSF gram-stained smears.
Brief Report: Biological Indicators
Authors: McCormick Patrick J.
Published: September 2009

I read with great interest the article by Kotilainen and Gantz in Infection Control [now Infection Control and Hospital Epidemiology] regarding biological indicators (BIs) for use with flash sterilization processes. Although this study was conducted with greater care than previous investigations in this area, we believe that certain relevant factors regarding the effect of BI design on BI performance may have been overlooked. Because of differences in the design and construction of the BIs evaluated, a significant variation in response to flash sterilization or high temperature processing may result. Such an effect was first noted by Perkins et al and has been commented on by Reich and Fitzpartrick and Joslyn.
Evolution of the Infectious Diseases Practitioner
Authors: Ervin F. Richard
Published: September 2009

In 1986, I wrote of the imminent decline in professional opportunities for the infectious diseases clinician because of unique problems with clinical practice in this specialty.' Although others have disagreed with my prophecy, none were able to refute my basic contention that it soon will be almost impossible for most new physicians with specialty training in infectious diseases to become self-supporting from a purely clinical practice. If a clinician is “an expert clinical [pertaining to or founded on actual observation and treatment of patients] physician and teacher,” then many of us are no longer only clinicians in the strictest sense of the word. The bell does toll for the pure clinician in this field of medicine, and the time of the easy establishment of a clinical practice is coming to a close. Future viability depends on developing beyond the role of clinician and becoming an “infectious diseases practitioner.”
The Effectiveness of Medical Care
Authors: Nettleman Mary D.
Published: September 2009

Medical care has come a long way in the last century. People live longer; deadly diseases are prevented, cured, or ameliorated. In short, medical care is more effective than at any previous time. In this sense, effectiveness is a straightforward concept that measures changes in life expectancy, quality of life, and occurrence of disease. Effectiveness is sometimes difficult to quantitate; yet it is an important part of clinical decision making. For example, is the use of universal precautions effective in preventing the spread of the human immunodeficiency virus? Is antibiotic prophylaxis effective in preventing postoperative wound infections? Is chest percussion effective in the therapy of' pneumonia? Is a brain biopsy more effective than empiric therapy in treating encephalitis?
A Prospective Study of Infections in Hemodialysis Patients: Patient Hygiene and Other Risk Factors for Infection
Authors: Kaplowitz Lisa G. , Cornstock Jane A. , Landwehr Douglas M. , Dalton Harry P. , Mayhall C. Glen
Published: September 2009

We performed a prospective randomized study on 71 patients on chronic outpatient hemodialysis to determine whether a sterile technique was better than a clean technique for preparation of the skin over the vascular access site prior to cannulation. In addition, we wanted to determine overall and site-specific infection rates, microbial etiologies of infection, and risk factors for infection. The overall infection rate was 4.7 infections per 100 dialysis months; the vascular access-site infection rate was 1.3 infections per 100 dialysis months; and the rate for bacteremia was 0.7 cases per 100 dialysis months. Staphylococcus aureus was the most common pathogen, but infections were equally divided between gram-positive cocci and gram-negative bacilli. Advanced age (P = 0.02), a low Karnofsky activity score (P = 0.05), poor hygiene (P = 0.0004) and number of hospitalizations (P = 0.0002) were risk factors for infections in general while only poor hygiene (P = 0.002) was a risk factor for vascular access-site infection. Sterile preparation of the skin over the vascular access site was no more effective at preventing infection than was clean technique (P = 0.80). Maintenance of good personal hygiene may be one of the most important measures for prevention of infections in hemodialysis patients
Occult Endemic Tuberculosis in a Chronic Care Facility
Authors: Brennen Carole , Muder Robert R. , Muraca Paul W.
Published: September 2009

During the course of a tuberculosis skin testing program at a chronic care Veterans Administration Medical Center, we uncovered evidence of occult transmission of endemic tuberculosis. Skin test conversion of eight patients (one of whom had unsuspected progressive primary tuberculosis) and two employees was ultimately traced to a patient in whom tuberculosis was first diagnosed at autopsy three years earlier. Identification of employee skin test conversions was a key factor in recognizing and terminating disease transmission. Throughout the institution, 33% of patients were tuberculin-positive; 10.8% demonstrated the booster phenomenon after initial negative skin tests. Prevalence of tuberculin positivity among employees was 28%. Twelve percent of initially tuberculin-negative employees converted during employment. Our experience documents the value of tuberculin testing of both patients and staff in a chronic care environment, and the necessity of vigorous investigation of skin test conversions.
Nosocomial Infections on a Rehabilitation Unit in an Acute Care Hospital
Authors: Nicolle Lindsay E. , Buffet Lisa , Alfieri Nancy , Tate Robert
Published: September 2009

In a one-year retrospective review, 138 symptomatic infections were identified in 145 admissions to a rehabilitation unit. One hundred twenty-six (91%) infections were either urinary or skin and soft tissue infections. The daily incidence of infection increased with increasing numbers of infections for infected patients. Patient factors associated with infection included male sex, young age, spinal cord injury, admission for management of decubitus ulcers or urinary infection, history of urinary infection, urologic interventions or skin breakdown, and bladder and bowel incontinence. All patients with a history of chronic urinary infection or skin breakdown developed infection. In a logistic regression model, factors that were independently associated with risk of infection in the remaining patients included sex, incontinence, chronic neurologic disease, and prior urologic interventions. This review suggests rehabilitation patients are at high risk of acquiring nosocomial infection. The subgroup of patients with the highest risk of infection are identifiable by specific characteristics.
The Problem of Selecting Antimicrobial Agents Before (or Without) the Results of Susceptibility Testing
Authors: Stratton Charles W.
Published: September 2009

A recent article in this section reviewed some problem areas of susceptibility testing. In particular, the “myth” of susceptibility testing being predictive of clinical outcome was discussed. The realization of this myth often leaves clinicians less comfortable when selecting antimicrobial agents. The question they often ask is, “How does one select antibiotics?” This question has always been important for empiric therapy of the septic patient. It has become even more important in the cost containment era. The introduction of new antimicrobial agents that are very costly when compared with older agents has greatly complicated antimicrobial therapy. It is now possible to use antibiotics correctly in a therapeutic sense, but to misuse them in an economic sense. Nonetheless, recognition of new pathogens, increasing resistance of pathogens to older antimicrobial agents and more complicated clinical problems have increased the need for these new agents. The following discussion will focus on those factors upon which the selection of a specific antimicrobial agent (or combination of agents) is based, the least of which should be the results of susceptibility tests.
Sample Size for Prospective and Retrospective Studies: The 2 × 2 Table
Authors: McNutt Louise-Anne , Woolson Robert F.
Published: September 2009

Previous papers in this series have discussed the design of epidemiologic studies and analysis for data that can be presented in a 2 × 2 table. The purpose of this paper is to explain how sample sizes are determined for unmatched prospective and retrospective studies. One of the most common questions asked in planning a project is “What sample size do I need for my study?” Determining the correct sample size is an important consideration that is best resolved prior to data collection. In this paper we assume the goal of the study is to examine the association between a dichotomous risk factor and the presence or absence of disease; therefore, the analysis will be that of a 2 × 2 table. We also assume throughout that sample sizes are to be equal for the two comparison groups (ie, equal numbers of exposed and unexposed for a prospective study, and equal numbers of cases and controls for a retrospective study). Sample size curves used to determine sample sizes will be presented. The results here are based on a paper by Schlesselman that contains sample size formulae for these study designs, and to which the reader may refer for an excellent technical discussion of their derivation.
A Cost Comparison Analysis for Screening and Vaccination of Hospital Personnel with High- and Low-Prevalence Hepatitis B Virus Antibodies in California
Authors: Tong Myron J. , Co Ruth L. , Marci Robin D. , Michaelson Phyllis M. , Ortega George
Published: September 2009

We compared the cost of antibody screening and the projected cost for hepatitis B vaccination of antibody-negative individuals at hospitals with “high prevalence” and “low prevalence” rates for hepatitis B virus antibodies among their employees. The use of hepatitis B core antibody for screening and subsequent hepatitis B vaccination of antibody-negative personnel was most cost-effective for hospitals considered to have high prevalence for hepatitis B virus antibodies among its staff, although use of hepatitis B surface antibody in this setting only increased costs by 1.4%. In a hospital with low prevalence for hepatitis B virus antibodies among its staff, use of hepatitis B surface antibody and subsequent vaccination of antibody-negative individuals was the most cost-effective approach, while use of hepatitis B core antibody for the above purposes would have increased costs by 3.4%. The use of both hepatitis B surface antibody and core antibody in either setting followed by immunization was least economical, as costs were increased by 13% and 13.5% respectively.

We concluded that hepatitis B core antibody should be used for screening in hospitals with high prevalence for hepatitis B virus antibodies among employees while hepatitis B surface antibody be used for screening in hospitals with low prevalence for hepatitis B virus antibodies among employees. A prediction of high and low prevalence for hepatitis B virus antibodies in hospital personnel may be made by knowledge of the distribution in ethnicity of staff.
Evaluation of a Urinary Catheter with a Preconnected Closed Drainage Bag
Authors: DeGroot-Kosolcharoen Jane , Guse Rhonda , Jones Jeffrey M.
Published: September 2009

The incidence of hacteriuria, significant urinary tract infection, and cost associated with the use of two urinary catheter drainage systems were evaluated in a population of hospitalized adult males. A commercially available device comprised of a Foley catheter attached with a heat-shrunk plastic seal to the tubing of a closed drainage hag (preconnected system) was compared with a standard system that had the Foley catheter attached to the closed drainage hag after it had been inserted. Using a randomized prospective design, the performance of the preconnected system in 97 patients was compared with that of the standard system in 105 patients. Catheters were left in place a mean of 6.4 and 7.6 days in the respective groups. Bacteriuria occurred after catheter insertion in 11.3% of patients receiving the preconnected system and 13.3% of patients receiving the standard system (not statistically significant). When bacteriuria developed, it occurred within seven days of catheter insertion in 50% of instances, irrespective of drainage system employed, suggesting that manipulations related to catheter insertion were important in initiating bacteriuria. Significant urinary tract infections occurred in only 2% of all patients studied. The higher cost for purchasing the preconnected system was not warranted for the population of patients studied.
Nosocomial Pseudomonas aeruginosa Conjunctivitis in a Pediatric Hospital
Authors: King Susan , Devi Shashi P. , Mindorff Cathy , Patrick Mary Lou , Gold Ronald , Ford-Jones E. Lee
Published: September 2009

Conjunctivitis accounted for 5% of nosocomial infections occurring in a university-affiliated pediatric hospital between January 1984 and April 1986. Pseudomonas aeruginosa was recovered from the conjunctiva of 30 patients. The primary diseases of these patients were chronic and debilitating. Eighty percent of patients were under 18 months of age although only 30% of admissions are represented in this age group. Seventy percent of cases occurred in pediatric intensive care unit/neonatal intensive care unit patients. Seventy percent of patients who had antecedent nasopharyngeal/ endotracheal cultures obtained were colonized with P aeruginosa. All patients except one had one or more of the following interventions prior to the onset of conjunctivitis: tracheostomy, endotracheal tube, oxygen by hood, or suctioning. Two children (7.4%) have residual corneal scars. Improvements in eye care including protection of the eye during suctioning, other respiratory care, and nasogastric tube procedures are warranted.
Computers in Hospital Epidemiology Practice
Authors: Birnbaum David
Published: September 2009

Beyond a potential role in infection surveillance, computers offer epidemiologists several important and unique potentials. Epidemiologists deal with complex interrelationships when interpreting or contributing information in the biomedical literature. Annals of Internal Medicine recently published a series dealing with the general problem of information management. The commentary that follows examines one area in which computers can be applied to our advantage-electronic exchange of information-and presents a practical example of using database searches.
NosocomialAchromobacter xylosoxidansInfections
Authors: Schoch Paul E. , Cunha Burke A.
Published: September 2009

In 1971, Yabuuchi and Ohyama named and describedAchromobacter xylosoxidansas a distinctive gram-negative, nonfermentative bacillus. During the past 15 years,A xylosoxidanshas been infrequently reported in the literature as a nosocomial pathogen. The organism has usually been associated with aquatic surroundings and frequently colonizes aqueous fluids in the hospital environment, awaiting the opportunity to infect compromised patients. Several outbreaks have been reported to be caused byAchromobacter, and all have contaminated fluids as the epidemiologic “common denominator.”Achromobacteris an emerging pathogen that has been recognized and appreciated with increasing frequency during the past few years. It is a microorganism ideally suited to the hospital environment in that it is resistant to many disinfectants and most antibiotics.AchromobactermimicsPseudomonas aeruginosamicrobiologically and clinically, but may be differentiated from the latter on the basis of flagella arrangement and antibiotic suscep-tibilities.
Decision Analysis: A Tool for Infection Control
Authors: Nettleman Mary D.
Published: September 2009

Financial resources for health care have been restricted. Constraints demand that physicians and administrators get the most for their money, yet the myriad of diagnostic tests and antibiotics available today can easily boggle the minds of those who must choose among them. This situation is particularly true of infection control where active research continually produces new products. Each hospital must choose among disinfectants, detergents, antibiotics, protective clothing, immunizations, dressing supplies, respiratory therapies, and many other products. At every point, questions arise. Is a new product worth the extra money? Alternatively, is a less expensive product really more cost-effective? How many additional infections must be prevented before a product “pays” for itself?
The Impact of Preoperative Skin Disinfection on Preventing lntraoperative Wound Contamination
Authors: Garibaldi Richard A. , Skolnick Deborah , Lerer Trudy , Poirot Andrea , Graham Jeffrey , Krisuinas Edward , Lyons Robert
Published: September 2009

The efficacy of total body showering and incision site scrub with disinfectant agents was evaluated in a randomized, prospective study of 575 patients undergoing selected surgical procedures. Patients who showered twice with 4% chlorhexidine gluconate had lower mean colony counts of skin bacteria at the surgical incision site in the operating room prior to the final scrub than patients who showered twice with povidone-iodine solution or medicated bar soap. Patients in the chlor-hexidine group had no growth on 43% of the incision site skin cultures compared with 16% in the povidone-iodine group and 6% in the soap and water group. Patients who showered and who were scrubbed with chlorhexidine also had lower rates of intraoperative wound contamination. Bacteria were recovered from the wounds of 4% of patients using this regimen compared with 9% for patients who used povidone-iodine and 15% for patients who showered with medicated soap and water and were scrubbed with povidone-iodine. We noted no difference in surgery-specific infection rates among patients in the three treatment groups; however, our sample sizes were too small to evaluate this outcome parameter adequately.

These data suggest that preoperative showering and scrubbing with chlorhexidine is an effective regimen to reduce extrinsic intraoperative contamination of the surgical wound from skin bacteria. The efficacy of this regimen to prevent postoperative wound infection needs to be evaluated in a well-designed, carefully controlled prospective trial with adequate numbers of patients to achieve statistically valid conclusions.
Effect of Bedside Needle Disposal Units on Needle Recapping Frequency and Needlestick Injury
Authors: Edmond Michael , Khakoo Rashida , McTaggart Bonny , Solomon Rose
Published: September 2009

Needle recapping has been shown to be one of the leading causes of needlestick injuries. Frequency of recapping has not been reported. This study was designed to determine the frequency of needle recapping by nursing personnel and the effect of bedside needle disposal units on the frequency of recapping and needlesticks. Seventy-four nurses carrying out 312 activities involving use of needles were observed. The subjects were not aware of the nature of the study. The recapping frequency was 93.9%. The study was repeated after educational programs and following installation of a hospital-wide bedside needle disposal system. Fifty-three nurses performing 151 activities with needles were observed. Frequency of recapping was 94%. There was no significant difference in the rate of recapping or needlestick injuries after installation of the new needle disposal system. Educational programs regarding recapping, a very common practice, may be ineffective. Alternate methods for preventing nee-dlesticks may be necessary.
Brief Report: The Detection of Blood on Gloved Hands of Central Sterile Supply Personnel and Cleaned Instruments Used for Procedures on Patient Units
Authors: Kennedy Patricia B. , Gwaltney Jack M.
Published: September 2009

Patient blood is recognized as a dangerous substance because it may contain infectious agents. While the practice of gloving provides some protection to hospital personnel exposed to instruments contaminated with patient blood, frequent breaks in techniques occur in which personnel inadvertently touch surfaces and objects in the environment with the potentially contaminated gloves. Also, “cleaned” instruments are placed on environmental surfaces to which other personnel are exposed. The purpose of this study was to determine the frequency of blood contamination of “cleaned” instruments used for patient procedures in the hospital, and on the gloved hands of central sterile supply (CSS) personnel handling those instruments.