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Biomedical subjects

Charles R Woods

Publications and source records attributed to Charles R Woods.

At least 19 recordsLinked to original sources

Advances in diagnosis and therapy of childhood tuberculosis.

Tuberculosis remains a major health problem worldwide. Recently developed diagnostic blood tests may supplant or supplement TB skin test in some settings. Emergence of drug-resistant strains remains a global concern. New anti-tuberculous agents are being developed and are greatly needed. There is mounting evidence that BCG has significant effectiveness in prevention, but development of improved vaccines for tuberculosis should remain a priority.

Adjuvants, Immunologic↗

Antimicrobial resistance: mechanisms and strategies.

Antimicrobial resistance is a growing threat worldwide. S. aureus strains that combine resistance and virulence genes have become a major treatment problem in Europe and the U.S. Extended-spectrum beta-lactamases are an emerging problem in many settings. Resistance mechanisms have been found for every class of antibiotic agent. Development of new classes of antibiotics or more robust versions of old classes will be essential in the years to come. Judicious use of antimicrobial agents and improved infection control methods must become health care priorities.

Anti-Bacterial Agents↗

Catheter-related bacteremia due to Roseomonas species in pediatric hematology/oncology patients.

Roseomonas is a newly described genus of pink-pigmented, gram-negative bacteria. Human infections caused by Roseomonas species are very rare. We report two cases of central venous catheter-related bacteremia associated with Roseomonas species (one case with R. gilardii and one with R. fauriae), and review the clinical spectrum of previously reported cases in the literature. Clinicals should be aware that Roseomonas species may cause serious infections in children.

Bacteremia↗

Orbital cellulitis in children.

BACKGROUND: To review the epidemiology and management of orbital cellulitis in children. METHODS: The medical records of children < or = 18 years old and hospitalized from June 1, 1992, through May 31, 2002, at the Brenner Children's Hospital, with a discharge ICD-9 code indicating a diagnosis of orbital cellulitis and confirmed by computed tomography scan were reviewed. A literature search for additional studies for systematic review was also conducted. RESULTS: Forty-one children with orbital cellulitis were identified. The mean age was 7.5 years (range, 10 months to 16 years), and 30 (73%) were male (male:female ratio = 2.7). All cases of orbital cellulitis were associated with sinusitis; ethmoid sinusitis was present in 40 (98%) patients. Proptosis and/or ophthalmoplegia was documented in 30 (73%), and 34 (83%) had subperiosteal and/or orbital abscesses. Twenty-nine (71%) had surgical drainage and 12 (29%) received antibiotic therapy only. The mean duration of hospitalization was 5.8 days. The mean duration of antibiotic therapy was 21 days. CONCLUSIONS: Orbital cellulitis occurs throughout childhood and in similar frequency among younger and older children. It is twice as common among males as females. Selected cases of orbital cellulitis, including many with subperiosteal abscess, can be treated successfully without surgical drainage.

Abscess↗

Multicenter surveillance of invasive meningococcal infections in children.

OBJECTIVES: Meningococcal disease continues to result in substantial morbidity and mortality in children, but there is limited recent surveillance information regarding serogroup distribution and outcome in children in the United States. The objective of this study was to collect demographic, clinical, laboratory, and outcome information for infants and children who had Neisseria meningitidis infections of various serogroups and were cared for in 10 pediatric hospitals. METHODS: Investigators at each of the participating hospitals identified children with meningococcal infections and collected demographic and clinical information using a standard data form. Meningococcal isolates were sent to a central laboratory for serogrouping by slide agglutination and penicillin susceptibility. RESULTS: From January 1, 2001, through March 15, 2005, 159 episodes of systemic meningococcal infections were detected. The greatest numbers of children were younger than 12 months (n = 41) or were 12 to 24 months of age (n = 22). Meningitis was the most common clinical manifestation of disease accounting for 112 (70%) cases; 43 (27%) children had bacteremia only. Children who were younger than 5 years (17 of 102) were significantly less likely to require mechanical ventilation than children who were 5 to 10 years of age (12 of 24) or children who were older than 10 years (13 of 33). Overall, 55 (44%) isolates were serogroup B, 32 (26%) were serogroup C, and 27 (22%) were serogroup Y. All but 1 isolate (intermediate) were susceptible to penicillin. The overall mortality rate was 8% (13 of 159) but was greater for children who were > or = 11 years of age (7 [21.2%] of 33) than for children who were younger than 11 years (6 [4.8%] of 126). Unilateral or bilateral hearing loss occurred in 14 (12.5%) of 112 children with meningitis. CONCLUSIONS: The morbidity and the mortality of meningococcal infections are substantial. With the recent licensure of meningococcal conjugate vaccines, our baseline trends in meningococcal disease can be compared with those seen after widespread vaccination to assess the success of routine immunization.

Adolescent↗

Bone marrow-derived mesenchymal stem cells in repair of the injured lung.

We sought to determine whether an intact bone marrow is essential to lung repair following bleomycin-induced lung injury in mice, and the mechanisms of any protective effects conferred by bone marrow-derived mesenchymal stem cell (BMDMSC) transfer. We found that myelosupression increased susceptibility to bleomycin injury and that BMDMSC transfer was protective. Protection was associated with the differentiation of engrafted BMDMSC into specific and distinct lung cell phenotypes, with an increase in circulating levels of G-CSF and GM-CSF (known for their ability to promote the mobilization of endogenous stem cells) and with a decrease in inflammatory cytokines. In vitro, cells from injured, but not from normal, mouse lung produced soluble factors that caused BMDMSC to proliferate and migrate toward the injured lung. We conclude that bone marrow stem cells are important in the repair of bleomycin-injured lung and that transfer of mesenchymal stem cells protects against the injury. BMDMSC localize to the injured lung and assume lung cell phenotypes, but protection from injury and fibrosis also involves suppression of inflammation and triggering production of reparative growth factors.

Animals↗

Lung infection with gamma-herpesvirus induces progressive pulmonary fibrosis in Th2-biased mice.

Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrotic lung disease of unknown etiology. A viral pathogenesis in IPF has been suggested since >95% of IPF patients have evidence of chronic pulmonary infection with one or more herpesviruses. To determine whether pulmonary infection with herpesvirus can cause lung fibrosis, we infected mice with the murine gamma-herpesvirus 68 (MHV68). Because IPF patients have a T helper type 2 (Th2) pulmonary phenotype, we used IFN-gammaR-/-, a strain of mice biased to develop Th2 responses. Chronic MHV68 infection of IFN-gammaR-/- mice resulted in progressive deposition of interstitial collagen as shown by light and electron microscopy. A significant decrease in tidal volume paralleled the collagen deposition. Five features typically seen in IPF, increased transforming growth factor-beta expression, myofibroblast transformation, production of Th2 cytokines, hyperplasia of type II cells, and increased expression of matrix metalloproteinase-7, were also present in chronically infected IFN-gammaR-/- mice. There also was altered synthesis of surfactant proteins, which is seen in some patients with familial IPF. MHV68 viral protein was found in type II alveolar epithelial cells, especially in lung areas with extensive alveolar remodeling. In summary, chronic herpesvirus pulmonary infection in IFN-gammaR-/- mice causes progressive pulmonary fibrosis and many of the pathological features seen in IPF.

Animals↗

Children's health and workers' productivity: an examination of family interference with work in rural America.

This article examines the association of children's health with their parents' performance in the workplace using data from a random survey sample of adults living in rural western North Carolina (N=206). Guided by the effort-recovery model, the authors hypothesized that parents whose children are more ill have poorer performance in the workplace because their parenting requires greater effort and they have less opportunity for physical and psychological recovery. Child health was unassociated with parents cutting back at work because of physical health. Poorer child health was associated with parents cutting back at work because of emotional health, and a portion of this association, as hypothesized, was explained by more limited opportunities for parental recovery. There was no evidence suggesting that associations differed by parental gender.

Adult↗

Syphilis in children: congenital and acquired.

Syphilis rates in women and congenital syphilis rates have declined steadily in the United States in recent years. However, syphilis remains a worldwide public health problem, with more than 12 million cases in adults and more than half a million pregnancies affected yearly. Prenatal screening and treatment programs are limited or nonexistent in many developing countries. The genome of Treponema pallidum, one of the smallest among prokaryotes, has been sequenced, but methods for continuous in vitro cultivation of the microbe remain elusive. There are no promising candidates for future vaccines at this time. Serologic testing, for both specific treponemal and nontreponemal antibodies, continues to be a primary means of diagnosis. Penicillin remains the drug of choice for congenital and acquired syphilis in childhood. The diagnosis of syphilis beyond early infancy raises concerns for possible child sexual abuse, although progression of congenital syphilis may account for some cases. Syphilis is a potentially eradicable disease, but this can be achieved only with sustained international will and cooperation to fund the necessary screening and treatment programs.

Adult↗

Gonococcal infections in neonates and young children.

Gonorrhea has been recognized since antiquity, and more than 60 million new cases occur yearly worldwide. Much has been learned about the molecular pathogenesis of infection by Neisseria gonorrhoeae, but immunity from natural infection does not protect against reinfection with the same strain, and the goal of a protective vaccine remains elusive. Gonococcal ophthalmia neonatorum is the most common manifestation in infants born to mothers with gonococcal genital tract infections. Genital and pharyngeal gonococcal infections in young children almost always are acquired from sexual abuse by an infected adult. Invasive disease can occur at any age but is uncommon. Nonculture diagnostic tests are widely used in adults, but culture is required in children for medicolegal purposes. N. gonorrhoeae strains have developed resistance to many antibiotic classes, and resistance profiles vary among geographic regions and within regions over time. Current guidelines for treatment of gonococcal infections in children in the United States are reviewed.

Adolescent↗

Human papillomavirus infections of the genital and respiratory tracts in young children.

Human papillomavirus (HPV) causes papillomas (warts) on the skin and respiratory mucosal surfaces (laryngeal and oral papillomas) in addition to condyloma acuminata (anogenital warts). HPV has become one of the most common sexually transmitted diseases in adults. Vertical transmission from mother to infant during birth is well recognized. Laryngeal papillomas are the most common tumors of the larynx in children worldwide, and recurrent lesions are common occurrences. Anogenital warts in children are problematic in that child sexual abuse is a potential means of acquisition, but many cases are acquired perinatally. Postnatal acquisition by nonsexual means also can occur. The likelihood of sexual abuse as the mode of acquisition increases with increasing age in childhood. The virus infects primarily epithelial cells, where it can exist as a long-term latent infection that can reactivate or persist actively (even subclinically), with resultant accumulation of host chromosomal mutations. The latter accounts for the oncogenic potential of a number of HPV types, and childhood infections may lead to neoplasia later in life. Regression of papillomas over the course of months to years is the usual natural course. Numerous treatments are available, but most do not prevent persistent infection or problematic recurrences. Multivalent HPV vaccines have been developed, and early results of clinical trials appear to be very promising.

Adult↗

Lactobacillus sepsis associated with probiotic therapy.

Probiotic strains of lactobacilli are increasingly being used in clinical practice because of their many health benefits. Infections associated with probiotic strains of lactobacilli are extremely rare. We describe 2 patients who received probiotic lactobacilli and subsequently developed bacteremia and sepsis attributable to Lactobacillus species. Molecular DNA fingerprinting analysis showed that the Lactobacillus strain isolated from blood samples was indistinguishable from the probiotic strain ingested by the patients. This report indicates, for the first time, that invasive disease can be associated with probiotic lactobacilli. This report should not discourage the appropriate use of Lactobacillus or other probiotic agents but should serve as a reminder that these agents can cause invasive disease in certain populations.

Anti-Bacterial Agents↗

Anogenital and respiratory tract human papillomavirus infections among children: age, gender, and potential transmission through sexual abuse.

OBJECTIVES: To evaluate human papillomavirus (HPV) presentation among children <13 years of age and its association with suspected child sexual abuse (CSA), and to assess sexual abuse consideration among different clinical services treating these children. METHODS: Records of children <13 years of age from 1985 to 2003 were selected for review if the children had a HPV-related International Classification of Diseases, Ninth Revision, code or had been examined in the CSA clinic. Abstracted data included demographic features, clinical findings, clinical services involved, age at diagnosis, age when care was first sought, and age when symptoms were first noted. RESULTS: HPV was identified by clinical examination and/or biopsy for 124 children, 40 with laryngeal lesions, 67 with anogenital lesions, 10 with oral lesions, and 7 with both anogenital and oral lesions. The mean age at HPV diagnosis was 4.0 +/- 2.9 years, compared with 6.4 +/- 3.0 years for 1565 HPV-negative children. Among 108 HPV cases with data for age when symptoms were first noted, the mean age was 3.3 +/- 2.9 years (median: 2.2 years) for children with anogenital and oral HPV and 2.4 +/- 2.3 years (median: 1.9 years) for children with laryngeal HPV. Among HPV-positive patients, 56% were female, compared with 82% of HPV-negative children. Fifty-five (73%) of 75 children with anogenital HPV infections were referred to the CSA clinic for evaluation, compared with none of 49 children with laryngeal or oral HPV infections treated by the otolaryngology service. Laryngeal cases presented earlier than anogenital and oral lesions. Abuse was considered at least possible for 17 of 55 children with any CSA evaluation. The mean age of likely abused, HPV-positive children was 6.5 +/- 3.8 years (median: 5.3 years), compared with 3.6 +/- 2.3 years (median: 2.6 years) for likely not abused, HPV-positive children. The likelihood of possible abuse as a source of HPV infection increased with age. The positive predictive value of HPV for possible sexual abuse was 36% (95% confidence interval: 13-65%) for children 4 to 8 years of age and 70% (95% confidence interval: 35-93%) for children >8 years of age. CONCLUSIONS: The data from this epidemiologic study of HPV suggest that many anogenital and laryngeal HPV infections among preadolescent children are a result of nonsexual horizontal transmission, acquired either perinatally or postnatally. It seems that many children >2 years of age acquire HPV infection from nonsexual contact. Different subspecialties vary greatly in their suspicion and evaluation of CSA. At this time, there remains no clear age below which sexual abuse is never a concern for children with anogenital HPV infections. Every case needs a medical evaluation to determine whether enough concern for abuse exists to pursue additional investigations.

Child↗

Endotoxin-induced lung injury in mice: structural, functional, and biochemical responses.

Acute lung injury is usually a complication of sepsis, and endotoxin treatment of mice is a frequently used experimental model. To define this model and to clarify pathogenesis of the lung injury, we injected with 1 mg/kg endotoxin ip and measured pulmonary function, pulmonary edema, serum concentrations of cytokines and growth factors, and lung histology over 48 h. During the first 6 h, tidal volume and minute volume increased and respiratory frequency decreased. Serum concentrations of cytokines showed three patterns: 10 cytokines peaked at 2 h and declined rapidly, two peaked at 6 h and declined, and two had biphasic peaks at 2 and 24 h. Growth factors increased later and remained elevated longer. Both collagen and fibronectin were deposited in the lungs beginning within hours of endotoxin and resolving over 48 h. Histologically, lungs showed increased cellularity at 6 h with minimal persistent inflammation at 48 h. Lung water peaked at 6 h and gradually decreased over 48 h. We conclude that intraperitoneal administration of endotoxin to mice causes a transient systemic inflammatory response and transient lung injury and dysfunction. The response is characterized by successive waves of cytokine release into the circulation, early evidence of lung fibrogenesis, and prolonged increases in growth factors that may participate in lung repair.

Animals↗

Clinical practice guideline: Otitis media with effusion.

The clinical practice guideline on otitis media with effusion (OME) provides evidence-based recommendations on diagnosing and managing OME in children. This is an update of the 1994 clinical practice guideline "Otitis Media With Effusion in Young Children," which was developed by the Agency for Healthcare Policy and Research (now the Agency for Healthcare Research and Quality). In contrast to the earlier guideline, which was limited to children aged 1 to 3 years with no craniofacial or neurologic abnormalities or sensory deficits, the updated guideline applies to children aged 2 months through 12 years with or without developmental disabilities or underlying conditions that predispose to OME and its sequelae. The American Academy of Pediatrics, American Academy of Family Physicians, and American Academy of Otolaryngology-Head and Neck Surgery selected a subcommittee composed of experts in the fields of primary care, otolaryngology, infectious diseases, epidemiology, hearing, speech and language, and advanced practice nursing to revise the OME guideline. The subcommittee made a strong recommendation that clinicians use pneumatic otoscopy as the primary diagnostic method and distinguish OME from acute otitis media (AOM). The subcommittee made recommendations that clinicians should (1) document the laterality, duration of effusion, and presence and severity of associated symptoms at each assessment of the child with OME; (2) distinguish the child with OME who is at risk for speech, language, or learning problems from other children with OME and more promptly evaluate hearing, speech, language, and need for intervention in children at risk; and (3) manage the child with OME who is not at risk with watchful waiting for 3 months from the date of effusion onset (if known), or from the date of diagnosis (if onset is unknown). The subcommittee also made recommendations that (4) hearing testing be conducted when OME persists for 3 months or longer, or at any time that language delay, learning problems, or a significant hearing loss is suspected in a child with OME; (5) children with persistent OME who are not at risk should be reexamined at 3- to 6-month intervals until the effusion is no longer present, significant hearing loss is identified, or structural abnormalities of the eardrum or middle ear are suspected; and (6) when a child becomes a surgical candidate, tympanostomy tube insertion is the preferred initial procedure. Adenoidectomy should not be performed unless a distinct indication exists (nasal obstruction, chronic adenoiditis); repeat surgery consists of adenoidectomy plus myringotomy, with or without tube insertion. Tonsillectomy alone or myringotomy alone should not be used to treat OME. The subcommittee made negative recommendations that (1) population-based screening programs for OME not be performed in healthy, asymptomatic children and (2) antihistamines and decongestants are ineffective for OME and should not be used for treatment; antimicrobials and corticosteroids do not have long-term efficacy and should not be used for routine management. The subcommittee gave as options that (1) tympanometry can be used to confirm the diagnosis of OME and (2) when children with OME are referred by the primary clinician for evaluation by an otolaryngologist, audiologist, or speech-language pathologist, the referring clinician should document the effusion duration and specific reason for referral (evaluation, surgery), and provide additional relevant information such as history of AOM and developmental status of the child. The subcommittee made no recommendations for (1) complementary and alternative medicine as a treatment for OME based on a lack of scientific evidence documenting efficacy and (2) allergy management as a treatment for OME based on insufficient evidence of therapeutic efficacy or a causal relationship between allergy and OME. Last, the panel compiled a list of research needs based on limitations of the evidence reviewed. The purpose of this guideline is to inform clinicians of evidence-based methods to identify methods to identify, monitor, and manage OME in children aged 2 months through 12 years. The guideline may not apply to children older than 12 years because OME is uncommon and the natural history is likely to differ from younger children who experience rapid developmental change. The target population includes children with or without developmental disabilities or underlying conditions that predispose to OME and its sequelae. The guideline is intended for use by providers of health care to children, including primary care and specialist physicians, nurses and nurse practitioners, physician assistants, audiologists, speech-language pathologists, and child development specialists. The guideline is applicable to any setting in which children with OME would be identified, monitored, or managed. This guideline is not intended as a sole source of guidance in evaluating children with OME. Rather, it is designed to assist primary care and other clinicians by providing an evidence-based framework for decision-making strategies. It is not intended to replace clinical judgment or establish a protocol for all children with this condition, and may not provide the only appropriate approach to diagnosing and managing this problem.

Acoustic Impedance Tests↗