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Sass L.,Childrens Specialty Group | Sass L.,Eastern Virginia Medical School
Pediatrics in Review | Year: 2012

• GBS remains an important neonatal pathogen despite a dramatic decline in the incidence of invasive disease. • Strong evidence exists demonstrating the importance of obtaining maternal cultures to determine who requires intrapartum prophylaxis in an attempt to prevent early onset sepsis. • Unfortunately, this approach has not changed the incidence of LOD, so it is important to keep GBS as part of the differential diagnosis when evaluating infants who show late signs consistent with infection. • Prevention measures as outlined in the 2010 CDC guidelines (9) and the 2011 American Academy of Pediatrics Policy Statement (10) should be followed in clinical practice.

Sharp J.A.,Eastern Virginia Medical School | Cunnion K.M.,Eastern Virginia Medical School | Cunnion K.M.,Childrens Specialty Group
Molecular Immunology | Year: 2011

Staphylococcus aureus is a significant human pathogen that causes skin-structure, invasive, and hospital-associated infections worldwide. The complement system is vital to innate defense against many bacterial infections. As shown with other pathogens, mechanisms for circumventing complement attack may include recruitment of the complement regulatory protein factor H (fH). In the present study, we show that S. aureus binds fH in a dose-dependent and time-dependent manner. Interestingly, this interaction does not require complement activation nor C3-fragment presence and occurs efficiently in the absence of other serum components suggesting a mechanism other than bridging between intermediary molecules. However, fH binding is greater when incubated with normal human serum compared to heat-inactivated serum, which suggests that complement activation may enhance fH binding. S. aureus-bound fH was found to inhibit the alternative pathway through disruption of the alternative pathway C3 convertase as shown by an increase in Bb release and a decrease in total C3-fragment deposition. Furthermore, S. aureus-bound fH retains cofactor activity for factor-I mediated cleavage of C3b. These studies show that the acquisition of fH to the S. aureus surface inhibits complement-mediated opsonization via disruption of the alternative pathway convertase; thus, we report an immune-evasion mechanism not previously described for S. aureus. © 2010 Elsevier Ltd.

Hair P.S.,Eastern Virginia Medical School | Gronemus J.Q.,Eastern Virginia Medical School | Crawford K.B.,Eastern Virginia Medical School | Salvi V.P.,University of Texas Health Science Center at Tyler | And 6 more authors.
Molecular Immunology | Year: 2010

Human astroviruses (HAstVs) constitute a family of non-enveloped, RNA viruses which cause infantile gastroenteritis. We have previously demonstrated that purified HAstV coat protein (CP), multiple copies of which compose the viral capsid, bind C1q resulting in inhibition of classical complement pathway activity. The objective of this study was to further analyze the mechanism by which CP inhibits C1 activation. CP inhibited C1 activation, preventing cleavage of C1s to its active form in the presence of heat-aggregated IgG, a potent classical pathway activator. CP also inhibited generation of the potent anaphylatoxin C5a. CP dose-dependently bound to C1q, the isolated globular heads and the collagen-like regions of the C1q molecule. When CP was added to C1, C1s dissociated from C1q suggesting that CP functionally displaces the protease tetramer (C1s-C1r-C1r-C1s). Given the structural and functional relatedness of C1q and MBL, we subsequently investigated the interactions between CP and MBL. CP bound to purified MBL and was able to inhibit mannan-mediated activation of the lectin pathway. Interestingly, CP did not bind to a variant of MBL that replaces a lysine residue (Lys55) critical for binding to MASP-2, a functional homolog of C1s. Finally, CP was shown to cross the species barrier to inhibit C3 activation and MAC formation in rat serum. These findings suggest CP inhibits C1 and MBL activation via a novel mechanism of interference with the normal interaction of the recognition molecule with its cognate serine proteases. © 2010 Elsevier Ltd. All rights reserved.

Krishna N.K.,Eastern Virginia Medical School | Cunnion K.M.,Eastern Virginia Medical School | Cunnion K.M.,Childrens Specialty Group
Medical Clinics of North America | Year: 2012

Clinical laboratories have traditionally relied on time-consuming phenotypic methods such as culture, serology, and biochemical tests for detection, identification, and characterization of microbial pathogens. Real-time polymerase chain reaction technology can now identify many pathogenic organisms that constitute infectious disease emergencies in normal and immune-compromised hosts. Use of this molecular technology for the accurate diagnosis of infectious disease agents by clinical laboratories reduces the time to diagnosis for many pathogens. This article is designed such that the clinician evaluating a patient with severe acute illness can reference the most relevant molecular diagnostics available pertinent to the predominant organ system involved. © 2012 Elsevier Inc.

Jamshidi R.,Pediatric Surgeons of Phoenix | Sato T.T.,Childrens Specialty Group
Pediatrics in Review | Year: 2013

• Burn injuries include skin or tissue injury due to sun exposure, radioactivity, electricity, chemical exposure, friction, heat, or cold. The mechanism of burn injury remains important because there may be other medical and surgical issues associated with the type of injury. • On the basis of strong research evidence and consensus (8,12), burn severity should be described by estimated depth (superficial, partial thickness, or full thickness), total body surface area (TBSA) involved with partial- or full-thickness burn (size), and identification of associated problems, for example, airway control, breathing, circulation, eye involvement, and/or inhalational injury. • Primarily on the basis of consensus due to lack of relevant clinical studies, pediatric burns appropriate for outpatient management may include partialthickness burns that involve less than 5% TBSA or full-thickness burns that involve less than 2%TBSA. A clinician must use discretion and judgment and have planned follow-up for all outpatient burns. • On the basis of strong research evidence (9) and consensus, severe burn injury requires significant intravenous (IV) fluid volume resuscitation because the burn injury creates a systemic inflammatory response that affects both injured and noninjured tissues. Fluid resuscitation is used to restore intravascular volume and maintain perfusion. Estimation of initial fluid resuscitation requirements in the first 24 hours after burn injury can be calculated by the following equation: IV Fluid Volume (in Milliliters) = Body Weight (in Kilograms) × Percentage of TBSA Burn × 3 to 4 mL of Lactated Ringer Solution Half of the estimated IV fluid volume is given in the first 8 hours and the remaining half during 16 hours. • On the basis of some research evidence (7)(8) and consensus, contemporary wound care management for a 5% TBSA partial-thickness burn includes antimicrobial ointments, such as silver sulfadiazine, biocomposite temporary skin substitutes, and silver ion-impregnated, flexible, self-adhesive dressings. • On the basis of some research evidence (5)(8)(9) and consensus, indications for referral to a regional burn center include full-thickness burns; partial-thickness burns greater than 10% TBSA; electrical or chemical burns; inhalational injury; associated traumatic injuries or comorbid conditions; burns to the face, hands, feet, genitalia, or joints; suspected intentional injury; and burns that exceed local specialist or institutional capacity.

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