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Biomedical subjects

M C Harris

Publications and source records attributed to M C Harris.

At least 37 records · Page 2Linked to original sources
PubMed1994

Prospective analysis of coagulase-negative staphylococcal infection in hospitalized infants.

Coagulase-negative staphylococci are the major cause of late-onset nosocomial neonatal sepsis. We prospectively examined all infants less than 6 months of age hospitalized at Children's Hospital of Philadelphia from whom at least one of two or more blood cultures grew coagulase-negative staphylococci. We considered as infections only those episodes in which multiple blood cultures grew identical isolates. Among 59 episodes that yielded specimens meeting study criteria, 25 were considered infection and 34 contamination. Cultures from infected infants yielded significantly higher numbers of coagulase-negative staphylococci than cultures representing contamination (p = 0.001). Infected infants were more likely to have central venous lines (p = 0.009), and to have received any parenteral nutrition (p = 0.002) or lipids (0.017). Hematologic values were not helpful in distinguishing between infected and uninfected infants. Isolates representing true infection were not different from contaminants in the frequency of positivity for putative virulence phenotypes. Our data corroborate previous studies indicating risk factors and predictors of coagulase-negative staphylococcal infection.

Bacteremia↗
PubMed1994

Cytokine elevations in critically ill infants with sepsis and necrotizing enterocolitis.

We hypothesized that plasma levels of cytokines such as interleukin-6 and tumor necrosis factor (TNF) are elevated in critically ill infants with sepsis and necrotizing enterocolitis (NEC) and that the magnitude of their elevation is correlated with mortality rate. We measured plasma levels of interleukin-6 and TNF in 62 newborn infants with suspected sepsis or NEC. Eighteen infants had bacterial sepsis, 9 had bacterial sepsis plus NEC, and 15 had NEC but negative culture results. Twenty comparably ill infants with negative results on culture of systemic specimens served as study control subjects. Interleukin-6 levels were five- to tenfold higher in infants with bacterial sepsis plus NEC at the onset of disease than in infants with bacterial sepsis alone, in infants with NEC but negative culture results, and in control infants (p < 0.01). These differences persisted throughout the 48-hour study period. Interleukin-6 levels were also significantly higher in nonsurvivors than in survivors (p < 0.001). In contrast, plasma TNF values were not consistently increased in any of the groups. We conclude that plasma interleukin-6 is a more reliable indicator of bacterial sepsis and NEC than plasma TNF and may identify infants who might benefit from immunotherapeutic strategies.

Analysis of Variance↗
PubMed1994

Misalignment of pulmonary veins with alveolar capillary dysplasia: affected siblings and variable phenotypic expression.

Misalignment of pulmonary veins with alveolar capillary dysplasia is recognized as a rare cause of persistent pulmonary hypertension of the neonate. Until now, misalignment of pulmonary veins was thought to be a random occurrence, but its appearance in siblings at our institution suggests that there may be a familial predisposition. There have been reports of variable expression and variable severity in this disease; our report describes this variability in family members.

Abnormalities, Multiple↗
PubMed1993

Diminished actin polymerization by neutrophils from newborn infants.

During the newborn period, abnormalities of neutrophil (PMN) function predispose infants to serious bacterial disease. Actin is a major contributor to PMN shape change and motile behavior. To determine the mechanism underlying defects in newborn granulocyte polarity and chemotaxis, we investigated actin polymerization by cord blood PMN from healthy term infants and adult controls. F-actin (filamentous) content was quantified in the resting state and after stimulation by fluorescence-activated cell-sorter analysis of nitrobenzoxadiazole-phallacidin-stained cells. PMN from newborn infants demonstrated similar basal F-actin levels when compared with adults. N-formyl methionyl leucyl phenylalanine induced a marked increase in actin polymerization that was maximal at 30 s in both neonates and adults and that then declined slowly (depolymerization) over the following 10 min. However, the F-actin content of PMN from newborn infants was significantly diminished when compared with adults at 30 and 60 s after N-formyl methionyl leucyl phenylalanine stimulation (p < 0.05). Both the rate and dose response of N-formyl methionyl leucyl phenylalanine-induced actin polymerization were similar for adult and neonatal PMN. PMN from newborn infants also demonstrated significantly diminished actin polymerization when compared with adults 60 s after stimulation with platelet-activating factor (p < 0.05). Decreased concentrations of F-actin may help explain the observed abnormalities of PMN polarity and chemotaxis in healthy newborn infants.

Actins↗
PubMed1992

Idiopathic arterial calcification of infancy: prenatal and postnatal effects of therapy in an infant.

In an infant with idiopathic arterial calcification of infancy, prenatal diagnosis of arterial calcification was made by ultrasonography and allowed initiation of therapy in utero. Etidronate therapy produced apparent radiographic and ultrasonographic improvement in the degree of vascular calcification but did not prevent the lethal progression of intimal vascular occlusive disease.

Arterial Occlusive Diseases↗
PubMed1992

Correlation of plasma cytokine elevations with mortality rate in children with sepsis.

Cytokines are thought to be important endogenous mediators of the host immune response to bacterial infection. We hypothesized that plasma levels of cytokines are elevated in children with sepsis and that the magnitude of elevation of these cytokines is correlated with severity of illness and mortality rate. We determined plasma levels of tumor necrosis factor, interleukin-6, and interleukin-1 in 21 children with sepsis. Plasma samples were collected at presentation and at 12, 24, and 48 hours thereafter. Cytokine levels were elevated in pediatric patients with bacterial sepsis during the first 48 hours after presentation; levels were undetectable in study control subjects. The tumor necrosis factor and interleukin-6 levels (p less than 0.001), as well as levels of interleukin-1 (p = 0.05), were significantly higher in nonsurvivors than in survivors and were independent of severity of illness (pediatric risk of mortality (PRISM) score) at presentation. Elevations of tumor necrosis factor and interleukin-6 were sustained for longer than 24 to 48 hours in nonsurvivors: II-1 concentrations were significantly increased only at time zero. Of 11 children with an interleukin-6 value greater than 2 ng/ml during the first 48 hours, 10 died; only one of 10 not reaching that level died (p less than 0.001). Cytokines were elevated as frequently with gram-positive as with gram-negative infections. We speculate that cytokine determinations may identify children who might benefit from immunotherapeutic interventions.

Adolescent↗
PubMed1991

Coagulase-negative staphylococcal infection in the neonate.

During the last decade, improved neonatal care has permitted the survival of extremely low birthweight infants who are at increased risk for the development of nosocomial infection. The coagulase-negative staphylococci currently represent the most frequent nosocomial pathogen isolated from infants in the newborn intensive care unit. This article details pathogenesis, clinical manifestations, diagnosis, treatment, and prevention of neonatal infection with this organism.

Humans↗
PubMed1990

Expression of the complement receptors CR1 and CR3 and the type III Fc gamma receptor on neutrophils from newborn infants and from fetuses with Rh disease.

Developmental defects in neutrophil function, including diminished expression of plasma membrane receptors, may play an important role in the susceptibility of the newborn infant to infection. We used monoclonal antibodies and flow cytometry to study the expression of complement receptor type one (CR1), complement receptor type three (CR3), and Fc gamma receptor type three (FcRIII) on neutrophils from six fetuses with Rh disease, 10 preterm infants, nine term infants, and nine adults. Expression of the complement receptors on unstimulated cells was similar for all groups, but significant differences in complement receptor expression were observed after stimulation with N-formyl-methionyl-leucyl-phenylalanine (FMLP). Fetal, preterm, and term infant neutrophils expressed less CR3 than FMLP-stimulated neutrophils of adults [61 +/- 2, 48 +/- 4, and 66 +/- 4% (mean +/- SEM) of the mean for adults, p less than 0.05]. FMLP-stimulated CR1 expression for these groups was 61 +/- 6, 73 +/- 6, and 91 +/- 9% of the adult mean (p less than 0.05, fetal versus term infant and adult). Expression of both CR3 and CR1 increased with postconceptional age in the infants (r2 = 0.49, p less than 0.001 for CR3; r2 = 0.23, p less than 0.05 for CR1). Neutrophils of the preterm and term infants expressed less FcRIII than adult neutrophils (68 +/- 10 and 77 +/- 7% of the adult mean, p less than 0.05, for FMLP-stimulated cells), whereas fetal neutrophil FcRIII expression did not differ from that of the adult.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Differentiation↗
PubMed1990

Distinguishing sepsis from blood culture contamination in young infants with blood cultures growing coagulase-negative staphylococci.

In the ideal situation, the evaluation for sepsis in the young infant should include collection of multiple blood cultures before the institution of antibiotics. Unfortunately, in some infants, it may not be possible to obtain more than a single blood culture at the time of initial evaluation. If this single culture ultimately grows coagulase-negative staphylococci and the infant has been treated with antimicrobial therapy in the interim, it is often difficult to determine whether the positive culture represents true infection or contamination. Our data suggest that peripheral blood cultures yielding high colony counts most likely represent infection. Furthermore, in this high-risk patient population, low colony-count growth should not be ignored as contamination, particularly if there are significant clinical findings or if the infant has a central catheter or hematologic abnormality. Future studies should examine these important issues.

Blood Specimen Collection↗
PubMed1989

Neonatal Staphylococcus epidermidis meningitis with unremarkable CSF examination results.

We identified 10 infants (mean +/- SD birth weight, 1000 +/- 500 g; gestation, 29 +/- 3 weeks; postnatal age, 24 +/- 19 days) who had Staphylococcus epidermidis meningitis despite unremarkable cerebrospinal fluid (CSF) blood cell counts and glucose and protein levels. Staphylococcus epidermidis meningitis was diagnosed if all the following criteria were satisfied: (1) a CSF culture positive for S epidermidis within 48 hours, (2) a blood culture positive for S epidermidis with antibiotic sensitivities identical to those of the CSF isolate, and (3) clinical symptomatology. Lumbar puncture yielded white blood cell counts lower than 10 x 10(6)/L in 8 infants. Two subjects had CSF white blood cell counts of 11 x 10(6)/L and 14 x 10(6)/L. Cerebrospinal fluid glucose (2.8 +/- 0.9 mmol/L) and protein (1.15 +/- 0.32 g/L) concentrations were also unremarkable. Infants were treated with parenteral antibiotics for 19 +/- 5 days. There was no mortality or short-term morbidity. Staphylococcus epidermidis is a recognized cause of nosocomial meningitis in low-birth-weight infants and frequently occurs without CSF abnormalities.

Cerebrospinal Fluid Proteins↗
PubMed1989

Stimulation of carotid body chemoreceptors does not influence the discharge of A1 neurons projecting to the forebrain.

Stimulation of carotid body chemoreceptors activates putative vasopressin neurons in the supraoptic nucleus, an effect which has been abolished by lesions in the caudal ventrolateral medulla. Stimulation within the A1 catecholamine cell group in the ventrolateral medulla also activates supraoptic neurons and releases vasopressin. Therefore the A1 catecholamine neurons may be the means by which carotid body chemoreceptors influence the supraoptic nucleus and other parts of the forebrain. To test this possibility the influence of carotid body chemoreceptors on the discharge of rostrally-projecting neurons in the A1 region of the caudal ventrolateral medulla has been assessed in rats anaesthetized with a mixture of urethane and sodium pentobarbitone. Tests were performed on 131 neurons, 23 of which were antidromically invaded following electrical stimulation within the supraoptic nucleus, the medial forebrain bundle or the ventral noradrenergic bundle. The positions of all antidromically invaded neurons were marked with dye and in six animals subsequent fluorescence histochemistry showed that the blue spots were in the proximity of one or more catecholamine-containing cell bodies in the ventrolateral medulla. The recorded neurons were therefore presumed to be part of the A1 group of catecholamine-containing neurons. All neurons located were tested for their responses to specific stimulation of ipsilateral carotid body chemoreceptors and also to general baroreflex activation. Not one of the antidromically invaded neurons was affected by chemoreceptor stimulation and only one was activated by baroreflex activation. Of the non-antidromically invaded neurons, seven were activated and 13 were depressed following chemoreceptor stimulation but in many cases the latency to onset was very long.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1989

Surface colonization with coagulase-negative staphylococci in premature neonates.

To follow the emergence of surface colonization with coagulase-negative staphylococci in neonates, we sampled four surface sites (axilla, ear, nasopharynx, and rectum) in 18 premature infants during the first 4 weeks of life. Swabs were obtained on the first day of life, twice weekly for 2 weeks, and weekly thereafter. Isolates were characterized by species, biotype, antibiotic susceptibility patterns, and slime production. Over 4 weeks the percentage of infants with Staphylococcus epidermidis as the only surface coagulase-negative staphylococci rose from 11% to 100%. Predominance of a single S. epidermidis biotype increased from none to 89%. Multiple antibiotic resistance rose from 32% to 82% of isolates, and the prevalence of slime production increased from 68% to 95%. This microbiologic pattern was established by the end of the first week of life and persisted throughout the month of study. In three infants, S. epidermidis sepsis developed with organisms identical to their predominant surface isolate. We conclude that species, multiple antibiotic resistance, and slime production appear to confer a selective advantage for the surface colonization of premature newborn infants in the intensive care nursery environment. Infants so colonized may be at greater risk for subsequent infection with these strains of coagulase-negative staphylococci.

Age Factors↗
PubMed1989

Investigation of apparent false-positive urine latex particle agglutination tests for the detection of group B streptococcus antigen.

In our nursery, we identified neonates with positive urine latex particle agglutination (LPA) tests for group B streptococcus (GBS) antigen who did not have corroborating cultural evidence of infection. To investigate the mechanisms underlying these apparent false-positive reactions, we examined the urine LPA test in an unselected population of neonates suspected of sepsis. Urine specimens for LPA testing and culture and simultaneous perirectal cultures were obtained from 134 neonates with suspected sepsis. Six infants had positive blood cultures for GBS; four of the six were positive by LPA testing. An additional 20 infants had positive LPA tests but negative blood cultures; of these, 13 had mothers who received antibiotic treatment prior to delivery. Two infants with positive LPA results and negative blood cultures had bacteria isolated from urine cultures obtained in a nonsterile fashion (GBS, Escherichia coli). GBS was not isolated from perirectal swabs of infants with positive LPA tests and negative blood cultures. In conclusion, (i) a high proportion of neonates evaluated for sepsis gave positive LPA tests and negative blood cultures, (ii) local contamination of the perirectal skin or urinary tract with GBS was an unlikely source of false-positive LPA reactions, and (iii) maternal antibiotic pretreatment during labor may represent an important cause of apparent false-positive LPA reactions.

Anti-Bacterial Agents↗
PubMed1989

Ontogeny of the antibody response to cow milk proteins.

Twenty-nine infants were followed prospectively for the development of immunoglobulin G (IgG) and IgE antibodies to the cow milk proteins (CMPs) alpha-lactalbumin, alpha-casein, and beta-lactoglobulin. Thirteen infants were fed formula, eight were exclusively breast fed, and eight were breast fed with formula supplementation. By 4 months of life, infants fed formula or breast milk with formula supplementation had elevated IgE and IgG antibody levels to CMPs, when compared with values before 1 month of age. Further, breast-fed infants demonstrated significantly lower levels of IgE and IgG antibodies to CMPs than infants who received formula or breast milk with formula supplementation. Clinical symptoms of cow milk allergy were more common in infants fed formula or breast fed with supplementation, but were not significantly related to the presence of specific antibody. Our data suggest that the formation of CMP antibodies may reflect a normal humoral response following exposure to CMP antigens in this age group.

Animals↗
PubMed1988

Long-latency baroreceptor inhibition of supraoptic neurones in the cat.

Experiments were done to determine the central delay to inhibition of supraoptic neurosecretory neurones by carotid baroreceptors in chloralose-anaesthetised, paralysed cats. Fourteen out of 18 neurosecretory cells (identified by antidromic activation from the pituitary neural lobe) were tested for their response to inflation of the ipsilateral carotid sinus (prepared as a blind sac). This stimulus inhibited the spontaneous activity of 10 neurones, which were thus identified as putative vasopressin cells. Repetitive, precisely timed pressure pulses were delivered to the carotid sinus and used to construct post-stimulus histograms of this inhibition. The latency measured from the baroreceptor afferent barrage (recorded from the sinus nerve) to the onset of inhibition in supraoptic neurones was 251 +/- 58 ms (range 152-328, n = 10). The significance of this long latency for the neural pathways involved is discussed.

Afferent Pathways↗