Racism and Older Black Americans' Health: a Systematic Review.

We reviewed research that examines racism as an independent variable and one or more health outcomes as dependent variables in Black American adults aged 50 years and older in the USA. Of the 43 studies we reviewed, most measured perceived interpersonal racism, perceived institutional racism, or residential segregation. The only two measures of structural racism were birth and residence in a "Jim Crow state." Fourteen studies found associations between racism and mental health outcomes, five with cardiovascular outcomes, seven with cognition, two with physical function, two with telomere length, and five with general health/other health outcomes. Ten studies found no significant associations in older Black adults. All but six of the studies were cross-sectional. Research to understand the extent of structural and multilevel racism as a social determinant of health and the impact on older adults specifically is needed. Improved measurement tools could help address this gap in science.

Exploring genetic diversity, population structure, and phylogeography in Paracoccidioides species using AFLP markers.

Paracoccidioidomycosis (PCM) is a life-threatening systemic fungal infection acquired after inhalation of Paracoccidioides propagules from the environment. The main agents include members of the P. brasiliensis complex (phylogenetically-defined species S1, PS2, PS3, and PS4) and P. lutzii. DNA-sequencing of protein-coding loci (e.g., GP43, ARF, and TUB1) is the reference method for recognizing Paracoccidioides species due to a lack of robust phenotypic markers. Thus, developing new molecular markers that are informative and cost-effective is key to providing quality information to explore genetic diversity within Paracoccidioides. We report using new amplified fragment length polymorphism (AFLP) markers and mating-type analysis for genotyping Paracoccidioides species. The bioinformatic analysis generated 144 in silico AFLP profiles, highlighting two discriminatory primer pairs combinations (#1 EcoRI-AC/MseI-CT and #2 EcoRI-AT/MseI-CT). The combinations #1 and #2 were used in vitro to genotype 165 Paracoccidioides isolates recovered from across a vast area of South America. Considering the overall scored AFLP markers in vitro (67-87 fragments), the values of polymorphism information content (PIC = 0.3345-0.3456), marker index (MI = 0.0018), effective multiplex ratio (E = 44.6788-60.3818), resolving power (Rp = 22.3152-34.3152), discriminating power (D = 0.5183-0.5553), expected heterozygosity (H = 0.4247-0.4443), and mean heterozygosity (H avp  = 0.00002-0.00004), demonstrated the utility of AFLP markers to speciate Paracoccidioides and to dissect both deep and fine-scale genetic structures. Analysis of molecular variance (AMOVA) revealed that the total genetic variance (65-66 %) was due to variability among P. brasiliensis complex and P. lutzii (PhiPT = 0.651-0.658, P < 0.0001), supporting a highly structured population. Heterothallism was the exclusive mating strategy, and the distributions of MAT1-1 or MAT1-2 idiomorphs were not significantly skewed (1:1 ratio) for P. brasiliensis s. str. (χ2 = 1.025; P = 0.3113), P. venezuelensis (χ2 = 0.692; P = 0.4054), and P. lutzii (χ2 = 0.027; P = 0.8694), supporting random mating within each species. In contrast, skewed distributions were found for P. americana (χ2 = 8.909; P = 0.0028) and P. restrepiensis (χ2 = 4.571; P = 0.0325) with a preponderance of MAT1-1. Geographical distributions confirmed that P. americana, P. restrepiensis, and P. lutzii are more widespread than previously thought. P. brasiliensis s. str. is by far the most widely occurring lineage in Latin America countries, occurring in all regions of Brazil. Our new DNA fingerprint assay proved to be rapid, reproducible, and highly discriminatory, to give insights into the taxonomy, ecology, and epidemiology of Paracoccidioides species, guiding disease-control strategies to mitigate PCM.

Trends in the molecular epidemiology and population genetics of emerging Sporothrix species.

Sporothrix (Ophiostomatales) comprises species that are pathogenic to humans and other mammals as well as environmental fungi. Developments in molecular phylogeny have changed our perceptions about the epidemiology, host-association, and virulence of Sporothrix. The classical agent of sporotrichosis, Sporothrix schenckii, now comprises several species nested in a clinical clade with S. brasiliensis, S. globosa, and S. luriei. To gain a more precise view of outbreaks dynamics, structure, and origin of genetic variation within and among populations of Sporothrix, we applied three sets of discriminatory AFLP markers (#3 EcoRI-GA/MseI-TT, #5 EcoRI-GA/MseI-AG, and #6 EcoRI-TA/MseI-AA) and mating-type analysis to a large collection of human, animal and environmental isolates spanning the major endemic areas. A total of 451 polymorphic loci were amplified in vitro from 188 samples, and revealed high polymorphism information content (PIC = 0.1765-0.2253), marker index (MI = 0.0001-0.0002), effective multiplex ratio (E = 15.1720-23.5591), resolving power (Rp = 26.1075-40.2795), discriminating power (D = 0.9766-0.9879), expected heterozygosity (H = 0.1957-0.2588), and mean heterozygosity (Havp  = 0.000007-0.000009), demonstrating the effectiveness of AFLP markers to speciate Sporothrix. Analysis using the program structure indicated three genetic clusters matching S. brasiliensis (population 1), S. schenckii (population 2), and S. globosa (population 3), with the presence of patterns of admixture amongst all populations. AMOVA revealed highly structured clusters (PhiPT = 0.458-0.484, P < 0.0001), with roughly equivalent genetic variability within (46-48 %) and between (52-54 %) populations. Heterothallism was the exclusive mating strategy, and the distributions of MAT1-1 or MAT1-2 idiomorphs were not significantly skewed (1:1 ratio) for S. schenckii (χ2 = 2.522; P = 0.1122), supporting random mating. In contrast, skewed distributions were found for S. globosa (χ2 = 9.529; P = 0.0020) with a predominance of MAT1-1 isolates, and regional differences were highlighted for S. brasiliensis with the overwhelming occurrence of MAT1-2 in Rio de Janeiro (χ2 = 14.222; P = 0.0002) and Pernambuco (χ2 = 7.364; P = 0.0067), in comparison to a higher prevalence of MAT1-1 in the Rio Grande do Sul (χ2 = 7.364; P = 0.0067). Epidemiological trends reveal the geographic expansion of cat-transmitted sporotrichosis due to S. brasiliensis via founder effect. These data support Rio de Janeiro as the centre of origin that has led to the spread of this disease to other regions in Brazil. Our ability to reconstruct the source, spread, and evolution of the ongoing outbreaks from molecular data provides high-quality information for decision-making aimed at mitigating the progression of the disease. Other uses include surveillance, rapid diagnosis, case connectivity, and guiding access to appropriate antifungal treatment.

The global epidemiology of emerging Histoplasma species in recent years.

Histoplasmosis is a serious infectious disease in humans caused by Histoplasma spp. (Onygenales), whose natural reservoirs are thought to be soil enriched with bird and bat guano. The true global burden of histoplasmosis is underestimated and frequently the pulmonary manifestations are misdiagnosed as tuberculosis. Molecular data on epidemiology of Histoplasma are still scarce, even though there is increasing recognition of histoplasmosis in recent years in areas distant from the traditional endemic regions in the Americas. We used multi-locus sequence data from protein coding loci (ADP-ribosylation factor, H antigen precursor, and delta-9 fatty acid desaturase), DNA barcoding (ITS1/2+5.8s), AFLP markers and mating type analysis to determine the genetic diversity, population structure and recognise the existence of different phylogenetic species among 436 isolates of Histoplasma obtained globally. Our study describes new phylogenetic species and the molecular characteristics of Histoplasma lineages causing outbreaks with a high number of severe outcomes in Northeast Brazil between 2011 and 2015. Genetic diversity levels provide evidence for recombination, common ancestry and clustering of Brazilian isolates at different geographic scales with the emergence of LAm C, a new genotype assigned to a separate population cluster in Northeast Brazil that exhibited low diversity indicative of isolation. The global survey revealed that the high genetic variability among Brazilian isolates along with the presence of divergent cryptic species and/or genotypes may support the hypothesis of Brazil being the center of dispersion of Histoplasma in South America, possibly with the contribution of migratory hosts such as birds and bats. Outside Brazil, the predominant species depends on the region. We confirm that histoplasmosis has significantly broadened its area of occurrence, an important feature of emerging pathogens. From a practical point of view, our data point to the emergence of histoplasmosis caused by a plethora of genotypes, and will enable epidemiological analysis focused on understanding the processes that lead to histoplasmosis. Further, the description of this diversity opens avenues for comparative genomic studies, which will allow progress toward a consensus taxonomy, improve understanding of the presence of hybrids in natural populations of medically relevant fungi, test reproductive barriers and to explore the significance of this variation.

Speciation despite globally overlapping distributions in Penicillium chrysogenum: the population genetics of Alexander Fleming's lucky fungus.

Eighty years ago, Alexander Fleming described the antibiotic effects of a fungus that had contaminated his bacterial culture, kick starting the antimicrobial revolution. The fungus was later ascribed to a putatively globally distributed asexual species, Penicillium chrysogenum. Recently, the species has been shown to be genetically diverse, and possess mating-type genes. Here, phylogenetic and population genetic analyses show that this apparently ubiquitous fungus is actually composed of at least two genetically distinct species with only slight differences detected in physiology. We found each species in air and dust samples collected in and around St Mary's Hospital where Fleming worked. Genotyping of 30 markers across the genome showed that preserved fungal material from Fleming's laboratory was nearly identical to derived strains currently in culture collections and in the same distinct species as a wild progenitor strain of current penicillin producing industrial strains rather than the type species P. chrysogenum. Global samples of the two most common species were found to possess mating-type genes in a near 1:1 ratio, and show evidence of recombination with little geographic population subdivision evident. However, no hybridization was detected between the species despite an estimated time of divergence of less than 1MYA. Growth studies showed significant interspecific inhibition by P. chrysogenum of the other common species, suggesting that competition may facilitate species maintenance despite globally overlapping distributions. Results highlight under-recognized diversity even among the best-known fungal groups and the potential for speciation despite overlapping distribution.

A retrospective 'real-world' cohort study of azole therapeutic drug monitoring and evolution of antifungal resistance in cystic fibrosis.

BACKGROUND: Individuals with cystic fibrosis (CF) have an increased susceptibility to fungal infection/allergy, with triazoles often used as first-line therapy. Therapeutic drug monitoring (TDM) is essential due to significant pharmacokinetic variability and the recent emergence of triazole resistance worldwide. OBJECTIVES: In this retrospective study we analysed the 'real-world' TDM of azole therapy in a large CF cohort, risk factors for subtherapeutic dosing, and the emergence of azole resistance. METHODS: All adults with CF on azole therapy in a large single UK centre were included. Clinical demographics, TDM and microbiology were analysed over a 2 year study period (2015-17) with multivariate logistic regression used to identify risk factors for subtherapeutic dosing. RESULTS: 91 adults were treated with azole medication during the study period. A high prevalence of chronic subtherapeutic azole dosing was seen with voriconazole (60.8%) and itraconazole capsule (59.6%) use, representing significant risk factors for subtherapeutic levels. Rapid emergence of azole resistance was additionally seen over the follow-up period with a 21.4% probability of CF patients developing a resistant fungal isolate after 2 years. No significant relationship was found however between subtherapeutic azole dosing and azole resistance emergence. CONCLUSIONS: Our study demonstrates a high prevalence of subtherapeutic azole levels in CF adults with increased risk using itraconazole capsules and voriconazole therapy. We show rapid emergence of azole resistance highlighting the need for effective antifungal stewardship. Further large longitudinal studies are needed to understand the effects of antifungal resistance on outcome in CF and the implications of subtherapeutic dosing on resistance evolution.

Erratum to: A retrospective 'real-world' cohort study of azole therapeutic drug monitoring and evolution of antifungal resistance in cystic fibrosis.

[This corrects the article DOI: 10.1093/jacamr/dlab026.].

The COX-2 inhibitor market withdrawals and prescribing patterns by rheumatologists in patients with gastrointestinal and cardiovascular risk.

OBJECTIVE: To examine effects of the COX-2 inhibitor market withdrawals on NSAID utilization among patients at increased risk of gastrointestinal (GI) and cardiovascular (CV) toxicities. METHODS: A prospective cohort study was conducted using patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) Registry. The study population included rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients prescribed NSAIDs by rheumatologists from 1/1/2003 to 12/31/2005. Three cohorts were defined based on calendar year. The primary outcome assessed whether or not an NSAID gastroprotective strategy was prescribed. Secondary outcomes included rates of COX-2 inhibitor utilization and gastroprotective co-therapy utilization, stratified by the presence of cardiac and GI risk factors. RESULTS: NSAID gastroprotection utilization decreased from 65.1% in 2003 to 47.7% (p<0.001) in 2005. COX-2 inhibitor use decreased from 55.1% to 29.2% (p<0.001), whereas nonselective NSAIDs (nsNSAIDs) use increased from 50.2% to 73.9% (p=<0.01). Among patients with two or more risk factors for NSAID related GI bleeding, gastroprotection decreased from 74.4% in 2003 to 60.9% (p<0.01). For patients with two or more CV risk factors from 2003 to 2005, COX-2 inhibitor utilization decreased significantly, whereas nsNSAID utilization increased significantly. CONCLUSIONS: The COX-2 inhibitor withdrawals resulted in a rapid decline in NSAID gastroprotection prescribed by participating U.S. rheumatologists despite the availability of other gastroprotective options. Channeling toward nsNSAID use was widespread, including among patients at increased CV risk. Longer term follow-up is required to determine the clinical significance of these changes in NSAID prescribing, particularly for NSAID-related GI and CV-related toxicities.

Using itraconazole to clear Batrachochytrium dendrobatidis infection, and subsequent depigmentation of Alytes muletensis tadpoles.

Batrachochytrium dendrobatidis (Bd) is a global threat to amphibian biodiversity. Current calls for conservation through captive breeding require that efficient and reliable antifungal treatments be developed for target species. Here we confirm that the antifungal itraconazole is an effective treatment for infection in larval Alytes muletensis. Exceptionally low doses applied as few as 7 times were effective at clearing infection from tadpoles for up to 28 d after treatment. However, we cannot recommend itraconazole as a treatment for this species as depigmentation of tadpoles was observed. Further research is required to determine the putative hepatotoxicity of this treatment.

Non-invasive sampling methods for the detection of Batrachochytrium dendrobatidis in archived amphibians.

Chytridiomycosis, an emerging infectious disease of amphibians caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd), is associated with amphibian population declines worldwide. Investigation of the origin and spread of the pathogen requires examination of archived museum specimens of amphibians. Examination for Bd infection is usually done using histological techniques, which are often too destructive for valuable museum material. Three alternative methods for Bd detection (skin swabbing, brushing and scraping) were evaluated for ability to yield Bd DNA and destructiveness to specimens. Archived amphibians known to be Bd positive and which had been preserved in either formalin or ethanol for many years were used. Samples were analysed using a Bd-specific quantitative real-time Taqman PCR (qPCR) assay. There was no difference in the ability of each of the techniques to detect Bd infection, with the pathogen being detected in 75 to 81% of the 16 ethanol-fixed frogs examined. Visible evidence of sampling was left by scraping, but not by swabbing or brushing. The brush-qPCR technique detected higher counts of genomic equivalents than the other 2 sampling methods, although differences were not statistically significant. The qPCR assay did not detect Bd from any of the 6 formalin-fixed frogs examined, regardless of the sampling method. Nondestructive sampling techniques enable qPCR analysis of ethanol-preserved museum specimens for Bd. Recently, the incorporation of DNA cleanup steps allowed the detection of Bd in destructively sampled tissues from formalin preserved specimens. Further studies using nondestructive sampling incorporating DNA cleanup steps for the detection of Bd in formalin preserved specimens are warranted.

Genomic epidemiology of the emerging pathogen Batrachochytrium dendrobatidis from native and invasive amphibian species in Chile.

Emerging fungal diseases represent a threat to food security, animal and human health worldwide. Amphibian chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), has been associated with catastrophic and well-documented amphibian population declines and extinctions. For the first time, Bd was cultured from native and non-native wild amphibians in Chile. Phylogenomic analyses revealed that Chilean isolates AVS2, AVS4 and AVS7 group within the global panzootic lineage of Bd (BdGPL) in a single highly supported clade that includes a genotype previously isolated from the United Kingdom. Our results extend the known distribution of BdGPL in South America and suggest a single and relatively recent introduction of BdGPL into the country, providing additional support to the role of anthropogenic activity in the global spread of this panzootic lineage.

Levamisole effects on major histocompatibility complex and adhesion molecule expression and on myeloid cell adhesion to human colon tumor cell lines.

BACKGROUND: The drug levamisole has been successfully used in combination with fluorouracil to increase the disease-free interval and survival of patients who have undergone surgical resection of Dukes' stage C colon cancer. Levamisole is thought to affect the host immune response. Several recent studies have examined its effect on the expression of major histocompatibility complex (MHC) class I molecules, but the results have been inconsistent. An equally important requirement for a host cellular immune response is the adhesion of leukocytes to tumor cells. The latter may be required for cell-mediated antitumor cytotoxic responses. PURPOSE: We evaluated the ability of levamisole to affect the expression of MHC class I molecules and cell-adhesion molecules and determined whether levamisole could affect leukocyte adhesion to tumor cells that had been treated with the drug. METHODS: A panel of four human colon tumor cell lines (HT-29, SW-620, HCT-15, and LoVo), A-375 human melanoma cells, and human umbilical vein endothelial cells (HUVEC) were cultured in the presence of levamisole and examined by solid-phase enzyme immunoassay to determine the level of expression of MHC class I, intercellular adhesion molecule 1 (ICAM-1), vascular cell-adhesion molecule-1 (VCAM-1), leukocyte integrin VLA-4, and lymphocyte-functional antigen (LFA-1) molecules. Adhesion of HL-60 and THP-1 myeloid cells to tumor cells was also evaluated. Tumor necrosis factor (TNF) at 10 ng/mL was used as a positive control for increasing adhesion molecule expression and cell-cell adhesion. The statistical significance of differences in cell surface molecule expression and functional adhesion between treated and control cells were tested by use of analysis of variance and the two-tailed Dunnett's test. RESULTS: Treatment with levamisole (0.1 and 1 micrograms/mL) caused the levels of MHC class I expression to increase approximately threefold above control levels on HCT-15 and LoVo colon tumor cells (P < .05 in each case) compared with untreated cells, caused minimal increases on HT-29 cells (to 1.5 times control levels), but caused no significant increases on SW-620 colon tumor or A-375 melanoma cells. The HCT-15 and LoVo colon tumor cells had very low basal MHC expression Levamisole (1 micrograms/mL) increased VCAM-1 expression on HT-29 and SW-620 colon tumor cells to 4.3 and 2.4 times (P < .05 in each case) control levels, respectively, doubled ICAM-1 expression on HT-29 cells (P < .05), and increased LFA-1 expression on HT-29, LoVo, and A-375 cells to 2.1, 3.2, and 1.8 (P < .05 in each case) times control levels, respectively. TNF (10 ng/mL) was used as a positive control and yielded increased expression of MHC class I molecules on the HT-29, LoVo, SW-620, and HCT-15 cells (2.5, 7.8, 1.9, and 4.8 times control levels, respectively; P < .05 in each case). TNF increased VCAM-1 expression to 4.2 times the vehicle-treated control levels (P < .05) on HT-29 cells and increased ICAM-1 expression on HT-29, LoVo, and SW-620 cells (8.4, 1.8, and 1.9 times vehicle control levels, respectively; P < .05 in each case). THP-1 and HL-60 cells demonstrated increased adhesion to levamisole-treated HT-29 colon tumor cells. HL-60 cells also exhibited increased levamisole-mediated adherence to LoVo and HCT-15 cells. Adherence by THP-1 was significantly improved after levamisole treatment of the HUVEC, SW-620, and A-375 cells (P < .05 in each case). CONCLUSIONS: Levamisole can directly affect the expression and function of molecules that are engaged in cell-cell recognition and signaling on the surfaces of some tumor cell lines. However, no consistent pattern between cell-adhesion molecule expression, cell-cell adhesion, or levamisole concentration could be discerned.

Levamisole causes differential cytokine expression by elicited mouse peritoneal macrophages.

Thioglycolate-elicited peritoneal macrophages from normal C57B1/6J mice were examined in vitro for bacterial lipopolysaccharide (LPS)-stimulated interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF) production. Macrophages from mice administered a single oral dose of levamisole (3 mg/kg) 1 to 4 days prior to macrophage harvest demonstrated a twofold enhancement of IL-1 production compared to vehicle-treated mice. In contrast, IL-6 production and TNF production by the same macrophages were inhibited up to 36 and 62%, respectively, compared to production by macrophages harvested from vehicle-treated mice. Similar results were observed when IL-1 production and TNF production were followed in peritoneal exidate cells directly stimulated with levamisole in vitro. The ex vivo LPS-stimulated IL-1 production was enhanced 4 days after macrophage elicitation, whereas TNF and IL-6 production returned to baseline by 72 h after macrophage recruitment and augmentation. No evidence could be found for the presence of inhibitors of TNF or IL-6. The specificity of the IL-1, IL-6, and TNF bioactivities was demonstrated by neutralization with specific antisera. Immunoprecipitation studies of supernatants from biosynthetically labeled macrophages also revealed augmented IL-1 production and decreased IL-6 and TNF, indicating that levamisole may have affected cytokine production at the translational level. Kinetics studies revealed that ex vivo release of IL-6 and TNF by macrophages from levamisole-dosed mice was delayed compared to production of these cytokines by macrophages harvested from mice given vehicle only. The results may explain, in part, the reported ability of levamisole to ameliorate cases of rheumatoid arthritis or other autoimmune and inflammatory diseases by affecting the relative levels of cytokines produced by macrophages recruited to sites of injury, which are associated with inflammation and acute-phase protein synthesis.

Cerebrospinal fluid analysis in systemically ill children without central nervous system disease.

OBJECTIVE: Experience led us to question the applicability of standards for normal cerebrospinal fluid (CSF), originally developed in healthy children, to children with systemic illness but without central nervous system (CNS) infection. The purpose of this study was to test our hypothesis that systemically ill children, in the absence of CNS infection, have an elevated CSF white blood cell count and a greater percentage of neutrophils than accepted norms. METHODS: We enrolled 345 patients in the following diagnostic categories: infants 1 month of age or younger with possible sepsis (n = 95), patients older than 1 month of age with possible sepsis (n = 155), patients with a focus of infection in close proximity to the CNS (n = 51), and patients presenting with seizures and fevers (n = 45). Sociodemographic data and results of CSF examination were abstracted from the medical records. Statistical analysis systems were used for data processing. RESULTS: The CSF white blood cell count did not significantly differ from standards except for a lower mean count in the group presenting with seizures. The percent of CSF neutrophils was significantly greater than standards, however, for those patients older than 1 month of age with possible sepsis, those with a focus of infection in close proximity to the CNS, and those presenting with seizures. Data analysis by quantiles shows only 25% to 50% of patients, in each of the diagnostic categories, meeting the current definition of normal CSF neutrophil count. CONCLUSIONS: Our results show that a mean of at least 5% neutrophils may be present in the CSF with a diagnosis of fever without a source, a focus of infection in close proximity to the CNS, or a seizure with fever in the absence of CNS infection. These data support tailoring treatment based on clinical assessment rather than what is considered an abnormal CSF neutrophil count by current standards.

The population genetic structure of the facultatively sexual parasitic nematode Strongyloides ratti in wild rats.

We have investigated the population genetic structure of the parasitic nematode Strongyloides ratti in wild rats. In the UK, S. ratti reproduces predominantly by mitotic parthenogenesis, with sexual forms present at a rate of less than 1%. S. ratti was found to be a prevalent parasite and substantial genetic diversity was detected. Most rats were infected with a genotypic mixture of parasites. A hierarchical analysis of the genetic variation found in S. ratti sampled across Britain and Germany showed that 73.3% was explained by variation between parasites within individual hosts and 25.3% by variation between rats within sample sites. Only a small proportion (1.4%) of the total genetic variation was attributable to genetic subdivision between sample sites, suggesting that there is substantial gene flow between these sites. Most parasites sampled were found to exist in Hardy-Weinberg equilibrium and this population genetic structure is discussed in view of the virtual absence of sexual reproduction.

Predictors of infectious complications after burn injuries in children.

BACKGROUND: Infections are the major life-threatening complication of burn injury and occur with the greatest frequency in children. Knowledge of their occurrence and management, however, is extrapolated from studies in adults. We performed a prospective study of infectious complications in burned children. OBJECTIVE: To delineate epidemiology, risk factors and microbiology of infections in burned children where burn care and surgical interventions are optimal. METHODS: Children hospitalized for burns were entered into prospective study. Characteristics of the burn injury were assessed, and active surveillance for infections was performed. RESULTS: Seventy patients were entered [mean age, 42 months; mean total body surface area (TBSA), burn 15%]. Twenty-seven percent of patients developed 39 infections: 13 involved the burn wound (burn wound sepsis, 6; graft loss, 5; and cellulitis, 2); 13 were catheter-associated septicemia; 13 involved other sites (i.e. pneumonia, 4; urinary tract infection, 3; bacteremia, 2; endocarditis, 1; myocardial abscess, 1; toxin-mediated syndrome, 1; and otitis media, 1). Twenty-three infections were caused by a single organism, 9 infections by more than 1 organism and in 7 infections defined by CDC criteria no organism was recovered. Organisms causing infection were: Staphylococcus aureus, 19; Candida albicans, 4; Pseudomonas aeruginosa, 4; coagulase-negative Staphylococcus, 4; Enterococcus sp., 3; Escherichia coli, 1; Klebsiella oxytoca, 1; Serratia marcescens, 1; Streptococcus pneumoniae, 1; Streptococcus pyogenes, 1; Aspergillus fumigatus, 1; and Candida parapsilosis, 1. Burn mechanism (flame and inhalation), extent (TBSA >30%) and depth (full thickness) were risk factors for infection; young age and site of burn were not. CONCLUSION: The most common infections occurring in burn children are burn wound infections and catheter-associated septicemia. Characteristics of burn injury predict risk of infection. Children with flame and inhalation injury, TBSA burned >30% and full thickness burns are at high risk of infectious complications.

Quantitative skin cultures at potential catheter sites in neonates.

OBJECTIVE: To identify and quantify the bacterial and fungal flora present at body sites used for vascular catheterization of infants in a neonatal intensive care unit. DESIGN: Quantitative skin cultures were obtained from a group of neonatal patients to determine the bacterial flora found on the skin at four sites. Quantitative cultures of the jugular, subclavian, umbilical, and femoral sites were obtained on 50 infants, ranging in age from 2 days to 3 months old. SETTING: The neonatal intensive care unit of St. Christopher's Hospital for Children, a university-affiliated tertiary care children's hospital. RESULTS: Colony counts ranged from 0 to 10(6) colony-forming units/10 cm2. Types of organisms found were consistent with other published studies and included coagulase-negative staphylococci, Staphylococcus aureus, yeast, aerobic gram-negative rods, Enterococcus species, Corynebacterium species, and alpha-hemolytic streptococci. There was a significantly higher mean colony count at the combined jugular/femoral sites versus the subclavian site (P < 0.01) and umbilical site (P < 0.05). Mean colony counts did not differ significantly between the jugular and femoral site, or between the subclavian and umbilical site. The umbilical site was more likely to be colonized with aerobic gram-negative rods, Enterococcus species, and yeast, while the subclavian had coagulase-negative staphylococci as the predominant organism. The jugular and femoral sites demonstrated a higher colony count of aerobic gram-negative rods, Enterococcus species and yeast than the other sites. If central venous catheters need to be in place for extended periods of time, placement at a site with lower bacterial densities on the skin may help minimize catheter-associated infections. This study supports the subclavian as the preferred site.

Recovery of Pseudomonas cepacia and other Pseudomonas species from the environment.

Nine hundred sixteen cultures were obtained from homes of patients with cystic fibrosis, control homes, salad bars, and food markets, and analyzed for the presence of Pseudomonas cepacia and related bacteria. P cepacia was recovered from 5 (18%) of 27 homes, and from 20 (4%) of 509 cultures collected outside of homes. Relative to other pseudomonads, P cepacia is found infrequently in the environment. It is not clear how frequently these sources contribute to acquisition of this bacteria by persons with cystic fibrosis.

Nutrition evaluation of published weight-reducing diets.

The objective of this study was to determine the nutritional adequacy of some of the popular published diet plans. Diet analyses were made using the University of Massachusetts Nutrient Data Bank. Not one of the 11 diets evaluated provided 100% of the U.S. Recommended Daily Allowances for the 13 vitamins and minerals studied. The nutrients most often below recommended levels were thiamin, vitamin B-6, vitamin B-12, calcium, iron, zinc, and magnesium. Vitamin and mineral supplementation may be warranted for individuals following some diet plans.

2-Deoxy-D-glucose antinociception and serotonin receptor subtype antagonists: test-specific effects in rats.

The antinociceptive actions of 2-deoxy-D-glucose (2-DG) are mediated in part by endogenous opioid, dopaminergic, cholinergic, histaminergic, and neurohormonal influences. Although 2-DG antinociception was not affected by tryptophan hydroxylase inhibition, a possible serotonergic role in 2-DG antinociception was investigated because of the existence of serotonin [5-hydroxytryptamine (5-HT)] receptor subtypes. The present study examined the effects of general (methysergide: 5 and 10 mg/kg), 5-HT2 (ritanserin: 2.5 mg/kg), and 5-HT3 (ICS-205,930: 0.25-5 mg/kg) receptor subtype antagonists upon 2-DG antinociception on the tail-flick and jump tests in rats. On the tail-flick test, 2-DG (450 mg/kg) antinociception was significantly reduced by all ICS-205,930 doses (48-58%) but unaffected by either methysergide (22-29% reduction) or ritanserin (6% reduction). In contrast, 2-DG antinociception on the jump test was significantly potentiated across the 120-min time course and across the 2-DG dose-response curve (100-650 mg/kg) by methysergide, ritanserin, and ICS-205,930 pretreatment. Each of the three antagonists produced significant leftward shifts in the peak and total 2-DG dose-response curve for the jump test. These data suggest different sites of action for 2-DG antinociception as a function of the pain test employed and a differential modulation by serotonin receptor subtypes at those sites.