Biomedical subjects

E Stephen Buescher

Publications and source records attributed to E Stephen Buescher.

13 recordsLinked to original sources

PubMed2005

Distinctive distribution of pathogens associated with peritonitis in neonates with focal intestinal perforation compared with necrotizing enterocolitis.

OBJECTIVE: Candida and coagulase-negative staphylococci are emerging pathogens associated with focal intestinal perforation (FIP) and necrotizing enterocolitis (NEC) in neonates. The objective of this study was to determine whether there are significant differences in the predominant pathogens in culture-positive cases of peritonitis associated with FIP compared with NEC in neonates. METHODS: A retrospective cross-sectional study was conducted of neonates with peritoneal culture-positive peritonitis associated with FIP or NEC over a 12-year study period (1989-2000). Cases with peritonitis were identified from a microbiology database. NEC was defined by radiologic evidence of pneumatosis intestinalis or portal venous gas or by pathology reports or surgical operative notes describing large areas of transmural bowel necrosis. FIP was defined as a <1-cm intestinal perforation surrounded by otherwise normal tissue in the absence of NEC. RESULTS: Thirty-six cases of FIP were compared with 80 cases of NEC. Birth weight and gestational age were significantly lower in infants with FIP compared with NEC. Age at intestinal perforation and case fatality rates were similar between FIP and NEC. There were striking differences in the distribution of predominant pathogens associated with peritonitis in NEC and FIP cases. Enterobacteriaceae were present in 60 (75%) of 80 NEC cases compared with 9 (25%) of 36 FIP cases. In contrast, Candida species were found in 16 (44%) of 36 FIP cases compared with 12 (15%) of 80 NEC cases, and coagulase-negative staphylococci were present in 18 (50%) of 36 FIP cases versus 11 (14%) of 80 NEC cases. There were no significant differences between FIP and NEC cases for the presence of Enterococcus species (28% vs 23%) or anaerobes (3% vs 6%). Stratified analysis for birth weight <1200 g found similar significant differences in the predominant pathogens for FIP (n = 29) and NEC (n = 38). Results from peritoneal fluid cultures resulted in changes in antimicrobial therapy in 46 (40%) of 116 cases. CONCLUSIONS: Candida species and coagulase-negative staphylococci were the predominant pathogens in FIP peritonitis in contrast to Enterobacteriaceae in NEC peritonitis. A peritoneal fluid culture should be obtained in all neonates with intestinal perforation, regardless of cause, because it may help to direct the choice of the most effective antimicrobial.

Bacteria, Anaerobic↗

PubMed2005

Serum complement factor I decreases Staphylococcus aureus phagocytosis.

Complement-mediated opsonization of Staphylococcus aureus is a critical host defense in animal models. Specifically, C3b and CD35 play important roles in effective opsonophagocytosis of S. aureus. We have shown that complement control protein factor I mediates cleavage of the complement opsonin C3b bound to the S. aureus surface. In this study, we examined the physiologic relevance of this observation by determining whether factor I-mediated cleavage of S. aureus-bound C3b decreased phagocytosis of S. aureus by neutrophils. Compared with controls, anti-factor I antibody inhibited C3b-cleavage on the S. aureus surface by >83% (as measured by iC3b generation) and increased phagocytosis of S. aureus by >100%. Treatment of C3b-coated S. aureus with factor I increased generation of iC3b (75%), decreased the total amount of C3-fragments bound to the S. aureus surface (58%), and decreased the number of bacteria phagocytosed (40%). Testing specifically for C3-fragments shed from the S. aureus surface, we found that factor I increased shedding (43%). Notably, these factor I-mediated effects were of the same magnitude regardless of whether factor H, a known cofactor for factor I, was present. These findings indicate that S. aureus benefits from, and possibly manipulates, the normally host-protective activity of factor I cleavage of C3b, which results in bacterial escape from complement-mediated opsonophagocytosis. Because escaping opsonophagocytosis-mediated destruction is a necessary mechanism for bacterial survival resulting in human disease, preventing cleavage of C3b on the S. aureus surface, and thereby enhancing opsonophagocytosis, is a promising potential target for therapeutic intervention.

Antibodies, Blocking↗

PubMed2005

Community-acquired methicillin-resistant Staphylococcus aureus in pediatrics.

PURPOSE OF REVIEW: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging problem in pediatrics, with clinical and microbiologic characteristics that differentiate it from hospital-acquired MRSA (HA-MRSA). RECENT FINDINGS: Relative to HA-MRSA, CA-MRSA tends to cause localized disease (although serious illness occurs), is susceptible to more antibiotics, and has the same risk factors for acquisition/disease as methicillin-susceptible S. aureus (MSSA). At the gene level, CA-MRSA is more similar to MSSA than HA-MRSA: its emergence is apparently due to acquisition by an MSSA of the Staphylococcal Cassette Chromosome that bears mecA: the gene that encodes the methicillin-resistant penicillin binding protein. Carriage of recognized staphylococcal virulence factors, particularly Panton-Valentine leukocidin, is common in CA-MRSA, emphasizing its potential for causing serious illness. CA-MRSA is usually susceptible to clindamycin, trimethoprim-sulfamethoxazole, and rifampin, but inducible macrolide-lincosamide-streptogramin resistance in a subset of CA-MRSA could be problematic when clindamycin is used. SUMMARY: The appearance and spread of CA-MRSA represents a new challenge in pediatric medicine. A high level of clinical suspicion and development of rapid methods for its identification are needs for the future.

Anti-Bacterial Agents↗

PubMed2005

West Nile virus infection in a teenage boy with acute lymphocytic leukemia in remission.

West Nile Virus (WNV) infection is an important cause of encephalitis. Although the medical literature contains examples of WNV encephalitis in susceptible, mainly elderly, immunocompromised hosts, few case reports have described pediatric cases. The authors describe an adolescent with acute lymphocytic leukemia and WNV encephalitis. Surveillance studies indicate an increase in WNV activity. Physicians need to be aware of WNV activity in their community and consider WNV as a potential source of infection.

Acyclovir↗

PubMed2004

Surfactant releases internal calcium stores in neutrophils by G protein-activated pathway.

Pulmonary surfactant with surfactant-associated proteins (PS+SAP) decreases pulmonary inflammation by suppressing neutrophil activation. We have observed that PS+SAP inserts channels into artificial membranes, depolarizes neutrophils, and depresses calcium influx and function in stimulated neutrophils. We hypothesize that PS+SAP suppresses neutrophil activation by depletion of internal Ca(++) stores and that PS+SAP induces depletion through release of Ca(++) stores and through inhibition of Ca(++) influx. Our model predicts that PS+SAP releases Ca(++) stores through insertion of channels, depolarization of neutrophils, and activation of a G protein-dependent pathway. If the model of channel insertion and membrane depolarization is accurate, then gramicidin-a channel protein with properties similar to those of PS+SAP-is expected to mimic these effects. Human neutrophils were monitored for [Ca(++)] responses after exposure to one of two different PS+SAP preparations, a PS-SAP preparation, gramicidin alone, and gramicidin reconstituted with phospholipid (PLG). [Ca(++)] responses were reexamined following preexposure to inhibitors of internal Ca(++) release or the G protein pathway. We observed that (i) 1% PS+SAP-but not PS-SAP-causes transient increase of neutrophil [Ca(++)] within seconds of exposure; (ii) 1% PLG-but not gramicidin alone-closely mimics the effect of PS+SAP on Ca(++) response; (iii) PS+SAP and PLG equally depolarize neutrophils; (iv) direct inhibition of internal Ca(++) stores releases or of G protein activation suppresses Ca(++) responses to PS+SAP and PLG; and (v) preexposure to either PS+SAP or PLG inhibits Ca(++) influx following fMLP stimulation. We conclude that PS+SAP independently depolarizes neutrophils, releases Ca(++) from internal stores by a G protein-mediated pathway, and alters subsequent neutrophil response to physiologic stimulants by depleting internal Ca(++) stores and by inhibiting Ca(++) influx during subsequent fMLP activation. The mimicking of these results by PLG supports the hypothesis that PS+SAP initiates depolarization via channel insertion into neutrophil plasma membrane.

Boron Compounds↗

PubMed2003

SHV-34: an extended-spectrum beta-lactamase encoded by an epidemic plasmid.

OBJECTIVES: To elucidate the causes for treatment failure in children given extended-spectrum cephalosporins. METHODS: During April 1998-March 2000, 18 isolates of members of the family Enterobacteriaceae, fulfilling microbiological criteria for carriage of extended-spectrum beta-lactamases (ESBLs) and carrying blaSHV, were isolated from paediatric inpatients. The collection was subjected to a retrospective molecular analysis. RESULTS: Three species were represented in the collection: Citrobacter koseri (one isolate), Escherichia coli (one isolate) and Klebsiella pneumoniae (16 isolates). A common plasmid was found in these bacteria, as judged by restriction endonuclease digestion. This was able to transfer an ESBL phenotype from donors to a laboratory strain of E. coli. Nucleotide sequence analysis revealed that this phenotype was associated with a new variant in blaSHV encoding SHV-34. CONCLUSIONS: Analysis reveals the presence of an epidemic plasmid in this collection of bacteria. This carries a gene encoding the SHV-34 ESBL, described for the first time in this report. Nucleotide sequence analysis shows that there is a mutation from A-->G affecting the codon at amino acid position 64 (GAA-->GGA), changing the glutamic acid typically seen in this position to glycine.

Amino Acid Substitution↗

PubMed2003

Clinical experience with linezolid for the treatment of nocardia infection.

Linezolid is an oxazolidinone that has activity against most gram-positive bacteria, including in vitro activity against all Nocardia species and strains. We describe 6 clinical cases of nocardiosis that were successfully treated with linezolid. Two patients had underlying X-linked chronic granulomatous disease, and 2 patients were receiving chronic corticosteroid therapy. Four of 6 patients had disseminated disease, and 2 of these 4 patients had multiple brain abscesses. Four patients primarily received monotherapy; for the fifth patient, linezolid was added to a failing multiple-drug regimen, and, for the sixth patient, it was used as part of combination therapy. All 6 patients were successfully treated, although 1 patient had a presumed relapse of central nervous system infection after premature discontinuation of the drug. Linezolid appears to be an effective alternative for the treatment of nocardiosis.

Acetamides↗

PubMed2003

Effects of nasal saline spray on human neutrophils.

BACKGROUND: Nasal saline spray (NSS) used in the treatment of rhinitis and sinusitis often contains the preservative benzalkonium chloride (BKC). Previous studies have shown that corticosteroid nasal sprays and topical decongestants containing BKC damage respiratory mucosa, decrease mucociliary activity, and inhibit neutrophil functions in vitro. OBJECTIVE: To evaluate the effects of NSS with BKC on human neutrophils. DESIGN: Prospective, basic science observations. METHODS: Human neutrophils were exposed to NSS with BKC or to phosphate-buffered saline (PBS) at varying times and concentrations. The cells were examined for morphologic changes by light microscopy and for viability as determined by trypan blue exclusion. Lactate dehydrogenase levels were measured to quantify neutrophil cell lysis. In vivo morphologic changes were studied in neutrophils obtained from the oral mucosa in human volunteers who rinsed their mouths with NSS or PBS. RESULTS: Neutrophils exposed to NSS concentrations as low as 15% showed near-total cell lysis, and neutrophils exposed to 20% NSS demonstrated no cell viability by trypan blue staining. Phosphate-buffered saline-exposed cells were unaffected. The release of lactate dehydrogenase from lysed neutrophils increased sharply at NSS concentrations higher than 10% but remained stable in PBS-exposed cells. All neutrophils isolated from NSS oral rinses were lysed, while a mean of 78% of neutrophils from PBS rinses showed normal morphologic structure. CONCLUSIONS: Nasal saline spray with BKC is toxic to human neutrophils even at concentrations far lower than those found in commercially available preparations. Saline solutions without BKC appear to be safer alternatives, and additional studies are needed to determine the clinical significance of these findings.

Administration, Intranasal↗

PubMed2003

The effects of intense submicrosecond electrical pulses on cells.

A simple electrical model for living cells predicts an increasing probability for electric field interactions with intracellular substructures of both prokaryotic and eukaryotic cells when the electric pulse duration is reduced into the sub-microsecond range. The validity of this hypothesis was verified experimentally by applying electrical pulses (durations 100 micros-60 ns, electric field intensities 3-150 kV/cm) to Jurkat cells suspended in physiologic buffer containing propidium iodide. Effects on Jurkat cells were assessed by means of temporally resolved fluorescence and light microscopy. For the longest applied pulses, immediate uptake of propidium iodide occurred consistent with electroporation as the cause of increased surface membrane permeability. For nanosecond pulses, more delayed propidium iodide uptake occurred with significantly later uptake of propidium iodide occurring after 60 ns pulses compared to 300 ns pulses. Cellular swelling occurred rapidly following 300 ns pulses, but was minimal following 60 ns pulses. These data indicate that submicrosecond pulses achieve temporally distinct effects on living cells compared to microsecond pulses. The longer pulses result in rapid permeability changes in the surface membrane that are relatively homogeneous across the cell population, consistent with electroporation, while shorter pulses cause surface membrane permeability changes that are temporally delayed and heterogeneous in their magnitude.

Cell Membrane↗

PubMed2003

Sub-microsecond, intense pulsed electric field applications to cells show specificity of effects.

Application of sub-microsecond duration (60-300 ns), intense (15-60 kV/cm) pulsed electric fields (sm/i-PEF) to six types of human cells was examined for its effects on individual cell surface membrane permeability and membrane potential. With short (60 ns) pulses, increasing percentages of Jurkat cells showed propidium iodide (PI) uptake at progressively shorter post-pulse times as the pulse train increased from 1 to 10 sequential pulses, while human blood polymorphonuclear leukocytes (PMN) were unresponsive to these short pulses regardless of train size. With 300 ns pulses, a similar pattern (increasing percentages of cells taking up PI, and progressively shorter times of onset after pulse applications as pulse train size increased) was seen with both Jurkat cells and PMN, but the patterns for both effects were different. Jurkat cell size did not appear to influence the responsiveness of this cell type. Comparisons of sm/i-PEF-induced PI uptake by human monocyte-derived macrophages vs. aged human mononuclear cells, human trunk skin (HTS) cells vs. fresh human mononuclear cells and human macrophages vs. HTS cells showed similar overall effects, but with differences between the patterns for each cell type compared (except the macrophages vs. HTS cells comparison). Application of sm/i-PEFs also caused different patterns of membrane potential loss in Jurkat cells vs. PMN. Jurkat cells developed significant decreases in t heir membrane potential only following the highest intensity pulse applications examined, i.e., 300 ns, 60 kV/cm x5, while PMN showed this effect over the entire range of pulse intensities (300 ns, 15-60 kV/cm, x5) applied. These data indicate that sm/i-PEF applications can have "specificity" (i.e., achieve different levels of effect in different cell types), that cell size does not appear to be the major factor determining sm/i-PEF effects in either Jurkat cells or PMN, that heterogeneous sm/i-PEF effects on cells tend to become homogeneous with increasing pulse train size, and that specificity of sm/i-PEF applications effects can occur at either end of the sm/i-PEF intensity spectrum examined.

Age Factors↗

PubMed2003

Central venous catheter removal versus in situ treatment in neonates with enterobacteriaceae bacteremia.

OBJECTIVE: To determine how often neonates with Enterobacteriaceae (ENTB) bacteremia can be treated successfully without removing central venous catheters (CVCs). METHODS: A retrospective cohort study was conducted of ENTB bacteremia and CVCs in infants in a neonatal intensive care unit during a 7-year period (1994-2000). Cases of ENTB bacteremia were identified from a microbiology database and limited to late-onset cases occurring after 3 days of age. RESULTS: There were 53 cases of ENTB bacteremia in infants with CVCs. Blood cultures were positive for ENTB within a median of 10 hours (range: 5-43). Timing of CVC removal was at the discretion of attending neonatologists. Fifteen cases had early-removal CVC (ER-CVC) within 2 days, and 38 cases had late-removal CVC (LR-CVC) >2 days after the first positive blood culture for ENTB. There were no significant differences between infants in the ER-CVC and LR-CVC groups for case fatality, recurrence, or duration of ENTB bacteremia. Although 16 (42%) of 38 (95% confidence interval [CI]: 26%-59%) LR-CVC cases required CVC removal to resolve ENTB bacteremia, 17 (45%) of 38 (95% CI: 29%-62%) LR-CVC cases were treated successfully without removal of CVCs. ENTB bacteremia was successfully treated without CVC removal in 85% of 13 LR-CVC cases with 1 day of bacteremia in contrast to 24% of 25 LR-CVC cases with >1 day of bacteremia (relative risk: 3.5; 95% CI: 1.7-7.4). CVC removal was required to resolve ENTB bacteremia in 9 (82%) of 11 LR-CVC cases with severe thrombocytopenia compared with 7 (32%) of 22 LR-CVC cases without severe thrombocytopenia (relative risk: 2.6; 95% CI: 1.3-5.0). CONCLUSIONS: Retention of CVCs was successful in 45% of cases of ENTB bacteremia in which it was attempted, but success was unlikely when bacteremia lasted >1 day. ENTB bacteremia cases associated with severe thrombocytopenia rarely resolved unless CVCs were removed.

Aminoglycosides↗

PubMed2002

Infections associated with pediatric sport participation.

Infections occur in childhood and adolescent athletes just as they do in all children and adolescents. Because of the sports environment, and in some instances the sport itself, athletes can be prone to infections that will alter their athletic performance or present risks to other athletes. Recognition of the infectious risks related to sports and the options for their treatment or, better yet, prevention, can help young athletes perform to their utmost potential.

Adolescent↗

PubMed2002

Central venous catheter removal versus in situ treatment in neonates with coagulase-negative staphylococcal bacteremia.

OBJECTIVE: To determine how often neonates with coagulase-negative staphylococcal (CONS) bacteremia can be treated successfully without removing the central venous catheter (CVC). METHODS: A cohort study of CONS bacteremia and CVCs was conducted in infants in a neonatal intensive care unit in a 5-year period (1994 through 1998). CONS bacteremia was defined as at least two positive blood cultures within 3 days of each other. RESULTS: Fifty-six infants had early removal CVC (ER-CVC) within 3 days, and 63 infants had late removal CVC (LR-CVC) >3 days after the first positive blood culture. All cases of CONS bacteremia were treated with vancomycin. There was no significant difference between infants in the ER-CVC and LR-CVC groups in terms of recurrence of bacteremia or case fatalities. CONS bacteremia of >3 days duration was more frequent in LR-CVC patients than ER-CVC patients: 43% vs. 13% (relative risk, 3.4; 95% confidence interval, 1.6 to 7.2). CONS bacteremia was successfully treated without CVC removal in 46% of LR-CVC cases. Seventy-nine percent of LR-CVC cases with CONS bacteremia lasting 1 or 2 days were treated successfully without CVC removal. The success rate decreased to 44% with a 3- to 4-day duration of bacteremia. None of 19 infants with CONS bacteremia lasting >4 days was treated successfully until CVCs were removed. CONCLUSIONS: Prolonged CONS bacteremia was avoided by early removal of CVCs. Retention of CVCs was successful in 46% of neonates with CONS bacteremia in whom it was attempted, but it was never successful if bacteremia lasted >4 days.

Bacteremia↗