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Biomedical subjects

S L Kaplan

Publications and source records attributed to S L Kaplan.

At least 19 recordsLinked to original sources

Immunogenicity of Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in children with sickle hemoglobinopathy or malignancies, and after systemic Haemophilus influenzae type b infection.

To determine the immunogenicity of Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in specific populations at risk, we administered vaccine to children with sickle cell anemia (n = 19; mean age, 18.3 months, malignancies (n = 18; mean age, 43.1 months), or a recent history of systemic H. influenzae type b infection (n = 17; mean age, 11.9 months). After one dose of polyribosylribitol phosphate-tetanus toxoid conjugate vaccine the geometric mean titers for polyribosylribitol phosphate antibody were 4.8 micrograms/ml (14/19 greater than 1 microgram/ml), 1.4 micrograms/ml (9/18 greater than 1 microgram/ml), and 5.6 micrograms/ml (15/17 greater than 1 microgram/ml) in these three groups, respectively. Children with sickle cell anemia or a recent history of systemic H. influenzae type b infection had polyribosylribitol phosphate antibody levels comparable to those of normal children of similar age after one or two doses of polyribosylribitol phosphate-tetanus toxoid conjugate vaccine. We conclude that this vaccine is immunogenic in children with underlying conditions associated with an increased risk of H. influenzae type b infection.

Anemia, Sickle Cell

Interaction of Citrobacter diversus strains with HEp-2 epithelial and human umbilical vein endothelial cells.

More than 75% of neonates with Citrobacter diversus meningitis develop brain abscesses. Interaction of C. diversus strains with HEp-2 and human umbilical vein endothelial cells (HUVEC) was studied to examine mechanisms related to brain abscess formation. Two of 9 strains invaded HEp-2 cells and 0 of 6 invaded HUVEC better than the others. C. diversus survived at least 20 h within HEp-2 cells (in decreasing numbers). Adhesion to HEp-2 cells was increased in 3 of 4 strains expressing type 1 fimbriae, but this did not correlate with increased invasion. Inhibition of RNA or protein synthesis blocked invasion but not adhesion. Thus, invasion requires ongoing protein synthesis, and adhesion to and invasion of HEp-2 cells by type-1-fimbriated strains are independent steps. Invasion was inhibited by cytochalasin D. A 32-kDa protein found in cerebrospinal fluid isolates of C. diversus was not related to invasion of either cell line. Ability to invade HEp-2 cells was not increased among strains isolated from central nervous system sources.

Bacterial Adhesion

Increased rate of isolation of penicillin-resistant Streptococcus pneumoniae in a children's hospital and in vitro susceptibilities to antibiotics of potential therapeutic use.

The isolation of Streptococcus pneumoniae with both high and intermediate resistance to penicillin has increased in our institution since 1989 to an average of 12.1% of all isolates. We determined the susceptibilities of 95 isolates (34 susceptible to penicillin, 42 intermediate in resistance to penicillin, and 19 resistant to penicillin) to 16 antimicrobial agents of potential use in the treatment of disease caused by S. pneumoniae. Susceptibility to penicillin was determined by broth macrodilution with Mueller-Hinton broth supplemented with 5% lysed horse blood. Isolates were classified as highly resistant when the MIC was greater than or equal to 2.0 micrograms/ml, intermediate in resistance when the MIC was between 0.1 and 1.0 microgram/ml, and susceptible when the MIC was less than 0.1 microgram/ml. Fifteen of 19 isolates found to be highly resistant to penicillin were recovered from the middle ear of children. None of the isolates recovered from cerebrospinal fluid was highly resistant to penicillin. Fifteen of these isolates highly resistant to penicillin were found to be serogroup 6. Susceptibilities to other antibiotics were determined by the agar dilution method with Mueller-Hinton agar containing 5% lysed horse blood and an inoculum of 10(4) CFU per spot delivered by a replicator device. The MIC for 90% of isolates increased with increasing penicillin resistance for all antibiotics tested, except chloramphenicol, ciprofloxacin, rifampin, and vancomycin. Regardless of the classification of penicillin resistance, all isolates were classified as susceptible to cefotaxime, cefpirome, cefpodoxime, clarithromycin, imipenem, rifampin, and vancomycin on the basis of National Committee for Clinical Laboratory Standards interpretive guidelines. Interpretation of susceptibilities on the basis of currently available guidelines is difficult in that susceptibility guidelines applicable specifically to S. pneumoniae are not available.

Anti-Bacterial Agents

A note on racial bias in the admission of children and adolescents to state mental health facilities versus correctional facilities in New York.

OBJECTIVE: In response to several studies suggesting that there is racial bias in the admission of proportionately more white children and adolescents to the child and adolescent mental health system than to the juvenile justice system, the authors tested whether white children and adolescents would be overrepresented compared with black children and adolescents in mental health facilities and underrepresented compared with black children and adolescents in juvenile correctional facilities when ethnic distribution in the general population was controlled. METHOD: Ethnicity, age, and sex of all white, black, and Hispanic 10-18-year-olds admitted in a 1-year period to facilities of the Office of Mental Health and facilities of the correctional system (the Division for Youth) of New York State were converted into rates per 100,000 population by using U.S. census data for the state. Admission rates per 100,000 population for ethnicity, age, sex, and source of referral were then compared in the two types of facilities. RESULTS: There were no meaningful differences in population-corrected admission rates among black, white, and Hispanic children and adolescents in the state mental health system. In contrast, there was a vast preponderance of black children and adolescents admitted to the state juvenile correctional system. The systems have different points of entry: 100% of the juvenile justice admissions versus 17% of the mental health admissions were referred by the courts. CONCLUSIONS: Analysis of demographic variables failed to support an allegation of racial bias in admission to the child and adolescent public mental health system in New York State.

Adolescent

Systemic infections due to Streptococcus pneumoniae relatively resistant to penicillin in a children's hospital: clinical management and outcome.

Streptococcus pneumoniae isolates relatively (0.1 microgram/mL < minimum inhibitory concentration < or = 1.0 microgram/mL) resistant to penicillin (RRP) have been recovered worldwide, but reports of therapy and outcome of systemic infections due to these strains are limited. This retrospective study of prospectively identified patients reviews the clinical features, management, and outcome of 19 children with systemic infections due to S pneumoniae. From January 1, 1989 to December 31, 1991, 13 of 244 blood (5.3%) and 4 of 32 cerebrospinal fluid (12.5%) pneumococcal isolates were relatively resistant to penicillin. The serotypes were as follows: 14 (12 isolates), 6 (4 isolates), 19 (2 isolates), 23 (1 isolates). One peritoneal fluid isolate and one joint fluid isolate were also relatively resistant to penicillin. The mean age of the 19 patients was 30 months (range 5 to 104 months), and five children had underlying disorders. Eleven children (nine inpatients) were treated initially with a parenteral cephalosporin. Six patients were treated as outpatients, and all had (occult) bacteremia. Three of these patients received ceftriaxone intramuscularly in the emergency department; five were treated with amoxicillin/clavulanic acid, and one received amoxicillin. Seven of 13 children treated in the hospital became afebrile in 48 hours. Three others were afebrile from the time of admission. Repeat blood cultures obtained within 24 to 48 hours after therapy was initiated were sterile in 10 children. All but one child responded to initial therapy. The recovery of S pneumoniae isolates relatively resistant to penicillin has increased in our hospital during the last 3 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents

New aspects of prevention and therapy of meningitis.

Cefotaxime and ceftriaxone are currently the agents of first choice for empiric treatment of bacterial meningitis in children. Further studies are necessary to determine the optimal antibiotic therapy for meningitis caused by Streptococcus pneumoniae isolates relatively or fully resistant to penicillin. The Haemophilus influenzae type b capsular polysaccharide-protein conjugate vaccines undoubtedly will alter the relative importance of the three common meningeal pathogens in pediatrics and make additional studies of the adjunctive use of dexamethasone in the treatment of bacterial meningitis even more critical.

Anti-Bacterial Agents

Immunogenicity of four Haemophilus influenzae type b conjugate vaccines in 17- to 19-month-old children.

OBJECTIVE: To compare the immunogenicity of four Haemophilus influenzae type b (Hib) conjugate vaccines in different populations of 17- to 19-month-old children in the United States. DESIGN: Four immunogenicity trials with sera were assayed in one laboratory. Trials 1 and 2 each compared one vaccine in two regions, and trials 3 and 4 were randomized comparisons of multiple vaccines within a region. SUBJECTS: A convenience sample of 313 healthy children recruited from pediatric practices in Minneapolis, Minn., Dallas and Houston, Tex., and Sellersville, Pa. MEASUREMENTS AND RESULTS: Children with prevaccination antibody greater than 0.15 microgram/ml showed higher antibody responses to vaccination than children with less than or equal to 0.15 microgram/ml (p less than 0.001). Among the former, there were no significant differences in antibody response to vaccination with the different conjugates within any of the trials. Among children with less than or equal to 0.15 microgram/ml of antibody before vaccination, there were no significant differences in the geometric mean antibody responses of children in trial 1 vaccinated with polyribosylribitol phosphate-diphtheria toxoid (PRP-D) in Dallas or in Minneapolis, or of children in trial 3 in Dallas randomly assigned to receive Hib oligosaccharide-CRM197 (HbOC) or PRP-D. In contrast, in trial 2, children given PRP-tetanus toxoid (PRP-T) in Pennsylvania had a significantly higher geometric mean antibody response than children given PRP-T in Houston (13.5 vs 3.0 micrograms/ml; p = 0.005). In trial 4 in Minneapolis, the geometric mean antibody response was highest in children randomly assigned to receive PRP-outer membrane protein (OMP) (9.3 micrograms/ml), followed by PRP-D (5.0 micrograms/ml) and HbOC (2.3 micrograms/ml) (PRP-OMP vs HbOC; p = 0.005). In all four trials, IgG1 responses predominated compared with IgG2 responses. CONCLUSIONS: All four conjugate vaccines are immunogenic in children 17 to 19 months of age. However, the magnitude of the anticapsular antibody response varied by vaccine type, the level of antibody in prevaccination sera, and geographic location.

Antibodies, Bacterial

Hematogenous pneumococcal meningitis in the infant rat: description of a model.

Sensorineural deafness occurs in 20%-30% of children after Streptococcus pneumoniae meningitis. An infant rat model of S. pneumoniae meningitis was developed to study the pathogenesis of inner ear invasion by S. pneumoniae. S. pneumoniae type 6 was administered intraperitoneally (inoculum: 1-10 x 10(8) cfu) every 24 h for 3 days to 5-day-old rats. Bacteremia (12 [50%] of 24) and meningitis (11 [46%] of 24) were detected most frequently 4 days after the three doses. The mean cerebrospinal fluid (CSF) white blood count for rats with positive CSF cultures was 7271/mm3 (range, 81-20,475). Hematoxylin-eosin-stained brain tissue from the 11 rats with positive CSF cultures showed inflammation in the meninges and scala tympani in 9 each (82%), and scala vestibuli in 6 (55%), but none in the scala media. Gram's-stained brain and inner ear sections from the same 11 rats showed organisms in the meninges in 5 (45%) and scala tympani or vestibuli in 2 (18%). Perilymphatic inflammation occurred significantly (P less than .001) more than did endolymphatic inflammation.

Animals

Effect of dexamethasone or HWA-138 in combination with antibiotics in experimental Haemophilus influenzae type b infection.

Modulation of the host's inflammatory response in bacterial meningitis may be beneficial. In this study, the effects of dexamethasone and HWA-138, an analog of pentoxifylline, on CSF cultures and cochlear inflammation in an infant rat model of Haemophilus influenzae type b were studied. Five-day-old infant rats were inoculated once intraperitoneally with 1 x 10(4) to 10 x 10(4) CFU of H. influenzae type b (strain 1406). Twenty-four hours later, infant rats were treated intraperitoneally with one dose of ampicillin (0.1 mg/g of body weight), cefotaxime (0.05 mg/g), or cefuroxime (0.05 mg/g) alone or in combination with one dose of dexamethasone (0.00015 mg/g) or HWA-138 (0.005 mg/g). Twenty-four hours after treatment with cefuroxime plus dexamethasone, animals had a significantly (P less than or equal to 0.04) greater incidence of bacteremia and meningitis (eight of nine animals) than that in animals of the other treatment groups. Overall, dexamethasone was associated with less inflammation (P less than 0.04) of the cochlear nerve compared with that from antibiotic treatment alone. In this model, when suboptimal antimicrobial therapy is administered, anti-inflammatory agents may be beneficial with respect to reducing cochlear inflammation. However, dexamethasone and cefuroxime lead to a higher rate of positive blood and cerebral spinal fluid cultures than cefuroxime alone.

Ampicillin

Hormone ontogeny in the ovine fetus. XXVI. A sex difference in the effect of castration on the hypothalamic-pituitary gonadotropin unit in the ovine fetus.

The detection of pulsatile ovine LH (oLH) secretion in the sheep fetus by 81 days gestation (term 147 days), the suppression of fetal gonadotropin secretion by chronic administration of an LH-releasing factor agonist or antagonist, and the capacity of N-methyl; D-aspartate (a neuroexcitatory amino acid analog) to evoke a fetal oLH pulse strongly support a functional LH-releasing factor pulse-generator in the ovine fetus. In light of the sex difference in fetal gonadal function and gonadotropin secretion before day 114, we postulated that fetal castration would have a discordant effect on the pattern of gonadotropin secretion in males and females. Fetal sheep were either castrated (male = 11; female = 9) or sham operated (male = 9; female = 6) at 110-115 days gestation. Chronic indwelling arterial and venous catheters were implanted, and animals were studied for up to 30 days. During each study period fetal arterial blood samples were drawn every 15 min for 5 h and the plasma assayed for oFSH and oLH by specific RIAs. Multiple studies were performed on each fetus. In all fetuses (both intact and castrated) a decrease in oLH pulse frequency occurred after day 130. In female fetuses before day 130, castration had no effect on mean oLH pulse frequency (sham, 0.72 +/- 0.19 pulses/5 h; castrate, 0.50 +/- 0.13 pulses/5 h; P greater than 0.05). After day 130, pulsatile oLH secretion decreased in both intact and castrated female fetuses to undetectable levels during the sampling period. In contrast, castration significantly (P less than 0.001) increased mean oLH pulsatility in males before and after day 130 (less than 130 days, sham, 1.06 +/- 0.24 pulse/5 h; castrate, 2.70 +/- 0.22 pulse/5 h; greater than 130 days, sham, 0.18 +/- 0.12 pulses/5 h; castrate, 1.65 +/- 0.26 pulses/5 h). Mean oLH pulse amplitude was increased by castration only in the male fetuses (sham, 3.89 +/- 0.87 ng/ml; castrate, 6.02 +/- 0.39 ng/ml; P less than 0.05). oFSH pulses were infrequent in both sexes and not influenced by castration. The mean plasma concentration of oFSH was greater in intact female fetuses than in intact males (female, 5.65 +/- 1.15 ng/ml vs. male, 2.07 +/- 0.45 ng/ml; P less than 0.01). Castration increased the mean value for plasma oFSH in males (4.40 +/- 0.43 ng/ml; P less than 0.001) but had no effect in females (3.83 +/- 0.64 ng/ml; P greater than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

A preliminary report of ticarcillin and clavulanate versus triple antibiotic therapy in children with ruptured appendicitis.

Standard therapy for childhood ruptured appendicitis includes combination antibiotic therapy with ampicillin, gentamicin and clindamycin. Complicated dosing schedules and the possibility of aminoglycoside toxicity make alternatives desirable. One such alternative is Timentin (a combination agent of ticarcillin disodium and clavulanate potassium). This agent has a more convenient dose schedule than standard therapy and eliminates the possibility of aminoglycoside ototoxicity and nephrotoxicity. It is active in vitro against most pathogens associated with ruptured appendicitis in children. The preliminary results of an ongoing prospective, open label, randomized trial comparing ticarcillin and clavulanate with ampicillin, gentamicin and clindamycin in childhood ruptured appendicitis are reported herein. While further evaluation is necessary, we have found single agent therapy with ticarcillin and clavulanate to be equivalent in safety and efficacy to standard combination therapy. Also discussed are the relative merits of immediate versus delayed primary closure of the abdominal wound after appendectomy.

Anti-Bacterial Agents

Serious pediatric infections.

Third-generation cephalosporins are important additions to the range of antibiotics available for treating children with serious bacterial infections. They are highly active against the common pathogens, which cause bacterial meningitis in children. Strains of Haemophilus influenzae type b resistant to both ampicillin and chloramphenicol, and Streptococcus pneumoniae relatively resistant to penicillin remain susceptible to cefotaxime and ceftriaxone. Escherichia coli, Klebsiella pneumoniae, Citrobacter diversus, as well as the other more common gram-negative bacilli isolated from neonates and children are susceptible to these agents. However, Listeria monocytogenes is not cephalosporin-sensitive. Ceftazidime is the only third-generation cephalosporin useful for treating serious infections due to Pseudomonas aeruginosa in children. As with other beta-lactam antibiotics, the clearance of cephalosporins is prolonged in neonates, particularly premature babies. Cefotaxime and ceftriaxone are equivalent to ampicillin and chloramphenicol for the treatment of bacterial meningitis in children over two to three months of age with respect to neurologic outcome and safety, despite the in vitro activity of cefotaxime and ceftriaxone being much greater than the standard antibiotics for the meningeal pathogens. Cefotaxime and ceftriaxone are effective in the treatment of serious gram-negative infections in children. In many instances, ceftriaxone can be administered once daily, which allows for more convenient therapy, particularly on an outpatient basis. Although controversial, ceftazidime has been used as single-agent therapy for empiric treatment of neutropenic immunocompromised children with fever.

Bacterial Infections

Pilus- and non-pilus-mediated interactions of Haemophilus influenzae type b with human erythrocytes and human nasopharyngeal mucosa.

The role of pili of Haemophilus influenzae type b (Hib) in binding to human erythrocytes and in colonization and invasion of human nasopharyngeal (NP) organ cultures has been evaluated. Hib strains 1009 and 1007, NP and cerebrospinal fluid isolates from the same child with Hib meningitis, were studied. Strain 1009 was piliated (P+), produced pilin of approximately 24 kDa, and was hemadsorption-positive (HA+); strain 1007 was nonpiliated (P-), did not produce pilin, and was hemadsorption-negative (HA-). The rate of transition from one hemadsorption phenotype to the other in broth cultures and NP organ culture supernatants was 3 x 10(-4) per bacterium per generation for HA+ to HA- and 7 x 10(-4) per bacterium per generation for HA- to HA+. Growth in human NP organ culture supernatants of the P+HA+ strain was greater than that of the P-HA- strain at 6 and 12 h after infection. No difference was noted when the strains were grown in nutrient broth. Strain 1009 (P+HA+) attached in large clusters to cellular debris and nonciliated cells, a phenomenon never noted with strain 1007 (P-HA-). NP organ cultures infected with strain 1007 showed greater mucosal invasion than those infected with the 1009 strain. While P+HA+ and P-HA- Hib both attached to NP mucosa, P+HA+ strains may have a selective advantage in mucosal colonization but P-HA- strains may be more invasive.

Bacterial Adhesion

Hormone ontogeny in the ovine fetus. XXV. Somatotrope desensitization to growth hormone releasing factor (GRF) independent of short-latency, ultrashortloop GH feedback.

Plasma ovine growth hormone (oGH) concentrations are strikingly elevated in the ovine fetus and decline at birth towards the low levels observed in the newborn lamb. We postulated that developmental changes in somatotrope function secondary to GH-releasing factor (GRF) desensitization and GH feedback play a role in the developmental pattern of oGH secretion and tested this hypothesis in vito in chronically catheterized ovine fetuses (123-145 days gestation; term 147 days) and newborn lambs (1-18 days). In the first set of studies, two consecutive intravenous GRF(1-44 amide) boluses (1 microgram/kg) were administered. When the GRF boluses were given 90 min apart, they elicited similar oGH responses, both in fetuses and in newborn lambs. In contrast, when the GRF boluses were given 20 min apart, a significant oGH response was evoked by the first GRF but an oGH response was not detected after the second GRF, either in fetuses or in newborn lambs. When the oGH response GRF(1-44 amide; 1 microgram/kg i.v.) was evaluated 40 min after the start of a human GH infusion (25 micrograms/kg hGH bolus followed by 0.5 microgram/kg/min hGH for 80 min, resulting in mean hGH plasma concentrations of 80 ng/ml), the exogenous hGH did not after the oGH response to GRF, either in fetuses or in newborn lambs. The present in vivo results demonstrate that the fetal and the neonatal somatotrope can be desensitized to GRF and suggest that a short-term latency, ultrashortloop GH feedback mechanism is not operative, either in the ovine fetus or in the newborn lamb.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Corticosteroids and bacterial meningitis.

Despite timely and appropriate antimicrobial therapy of bacterial meningitis, neurologic sequelae still occur in some children. This also remains true for the third generation cephalosporins such as ceftriaxone and cefotaxime despite their extraordinary high bactericidal titers in the cerebrospinal fluid of children with bacterial meningitis. The most effective way to prevent neurologic damage in these patients is to prevent the infection from developing in the first place. This may be achievable in the very near future for meningitis due to Haemophilus influenzae type b, the most common organism causing meningitis in children in many parts of the world. Unfortunately, even though such means of prevention may be available or under development, ensuring that all children receive these immunizations is very difficult to accomplish. Furthermore, some forms of bacterial meningitis are not likely to be preventable by immunization or other methods and thus efforts to develop new means to minimize the neurologic damage due to meningitis remain important. One such effort involves the use of antiinflammatory agents in addition to antimicrobial therapy for the treatment of this infection. This review will focus on the role of one such antiinflammatory agent, corticosteroids, as adjunctive therapy for bacterial meningitis.

Adrenal Cortex Hormones

Effect of long-term bromocriptine infusion on plasma prolactin and ovine chorionic somatomammotropin in the pregnant ewe and fetal sheep.

It has been shown in previous studies that the continuous infusion of bromocriptine (CB 154) into either the sheep fetus or pregnant ewe was followed by pronounced ultrastructural changes in the binucleate (BN) cells of the ovine chorionic epithelium, which are a likely source of ovine chorionic somatomammotropin (oCS). We have examined ovine fetal and maternal plasma prolactin (PRL) and oCS concentrations following intravascular CB 154 infusion separately into either the fetus (0.03 mg/hour) or ewe (0.2 mg/hour). The CB 154 infusions significantly depressed fetal and maternal plasma radioimmunoassayable PRL concentrations within 24 hours of the commencement of infusion. Maternal plasma radioimmunoassayable oCS concentration was significantly depressed during infusion of CB 154 to the ewe, but the infusion of CB 154 to the fetus did not lower fetal plasma radioimmunoassayable oCS concentration or affect the duration of gestation.

Animals