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Biomedical subjects

M C Fisher

Publications and source records attributed to M C Fisher.

At least 37 records · Page 2Linked to original sources
PubMed1996

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.

Adjuvants, Immunologic↗
PubMed1995

Effect of rifampin on Staphylococcus aureus colonization in children on chronic peritoneal dialysis.

The efficacy of rifampin in eliminating Staphylococcus aureus colonization was evaluated in a pediatric peritoneal dialysis population. Six children with documented nasal colonization were treated for 7 days with rifampin and cloxacillin. Although antimicrobial therapy eliminated nasal carriage in all patients, recolonization occurred in 66%. Exit site colonization proved difficult to eradicate with negative cultures documented in only 3 of 5 children after rifampin/cloxacillin therapy. Although S. aureus carriage is a risk factor for S. aureus infections, efforts to eradicate carriage with rifampin are hindered by rapid recolonization.

Antibiotics, Antitubercular↗
PubMed1995

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.

Bacteriological Techniques↗
PubMed1995

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.

Central Nervous System Diseases↗
PubMed1994

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.

Bacteriological Techniques↗
PubMed1993

Source of Pseudomonas cepacia: ribotyping of isolates from patients and from the environment.

Ribotyping, an analysis of bacterial strain identity based on chromosomal restriction fragment length polymorphisms, was performed on 68 isolates of Pseudomonas cepacia recovered from patients receiving care at the two children's hospitals in Philadelphia and from environmental samples. Twenty different ribotypes were identified. Ribotype R3 predominated among isolates from all three sources. These findings are consistent with the acquisition of P. cepacia from the environment or by person-to-person transmission.

Burkholderia cepacia↗
PubMed1992

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.

Animals↗
PubMed1992

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.

Analgesics↗
PubMed1991

Ribotype stability of serial pulmonary isolates of Pseudomonas cepacia.

Eighty-three isolates of Pseudomonas capacia were recovered from respiratory secretions from 12 chronically colonized cystic fibrosis patients and examined by ribotype analysis. In 9 patients, the ribotype of the cultured P. cepacia remained unchanged throughout the entire period of observation, indicating chronic pulmonary colonization with a single strain. In each of the remaining 3 patients, two genetically distinct strains were detected among serial P. cepacia isolates. No significant change in clinical condition was correlated with the change in identity of the colonizing strain. In control experiments, the stability of strain ribotype was demonstrated among isolated that had been subcultured 100 times in vitro and among isolates recovered from chronically colonized mice. These data demonstrate the utility of ribotype analysis and indicate that most chronically colonized cystic fibrosis patients harbor a single strain of P. cepacia for prolonged periods.

Animals↗
PubMed1990

Prolonged bacteremia with catheter-related central venous thrombosis.

Infection of a central venous thrombus is a serious but rarely recognized complication of the use of central venous catheters in children. We report the cases of seven children with persistent bacteremia or fungemia in which central venous thrombosis was demonstrated by ultrasonography after removal of the catheter. All patients had signs and symptoms of infection, but only one had clinical evidence of central venous stasis. Bacteremia persisted from 6 to 35 days. Infection did not resolve in any patient prior to catheter removal, and five patients had positive blood cultures for 5 or more days after removal of the catheter. Six patients, including all who survived, were treated parenterally with antibiotics for more than 28 days. Two patients died; neither death was directly attributable to infection. Central venous thrombosis should be suspected in patients with persistent catheter-related bacteremia. Optimal treatment of this problem is not yet known.

Adolescent↗
PubMed1990

Impact of treatment guidelines on use of ribavirin.

During the 1987 through 1988 seasonal peak of respiratory syncytial virus (RSV), 177 courses of ribavirin were administered at St Christopher's Hospital for Children, a tertiary care medical center in Philadelphia, Pa. Charts were reviewed on 100 treated patients with proved or suspected RSV disease to determine adherence to American Academy of Pediatrics treatment guidelines. Ninety-four percent fulfilled criteria for the risk of significant morbidity: cardiac, pulmonary, or immunodeficiency conditions (38%); an age of 6 weeks or younger (35%); or severe illness (21%). Severe illness was defined as hypoxemia, hypercapnia, or marked tachypnea. Of those treated because of underlying conditions, 71% had RSV documented, as did 71% of patients aged 6 weeks or younger and 81% of patients with severe disease. A study of 80 consecutive patients who were hospitalized with illness compatible with RSV infection revealed that 56% of patients were treated with ribavirin. Adherence to guidelines led to ribavirin use in half of the hospitalized patients with suspected RSV infection. The majority of these patients received therapy because of underlying conditions or very young age.

Drug Prescriptions↗
PubMed1989

Emergence of isolates resistant to ampicillin.

Clinical isolates of Streptococcus faecium demonstrating ampicillin resistance were recovered from eight pediatric patients. Sites of isolation included blood, surgical wound, bile drainage, urine, burns, and peritoneal fluid. Seven patients had prolonged hospitalization, and all had been treated with broad-spectrum antibiotics prior to isolation of the resistant enterococcus. One isolate was from an ill, bacteremic patient; the others were in mixed culture and were not considered causes of disease. The isolates were not epidemiologically related. Minimal inhibitory concentrations for various antibiotics included ampicillin (16 to 32 mg/L), penicillin (128 mg/L), gentamicin (16 mg/L), and vancomycin (2 mg/L). Three isolates demonstrated high-level resistance (greater than 2000 mg/L) to streptomycin; none did so to gentamicin. In vitro synergy testing performed on seven available isolates for ampicillin and gentamicin demonstrated no synergy to this combination. None produced beta-lactamase. Combined antibiogram and plasmid data showed at least five distinct patterns. These strains present a new clinical problem in their high level of resistance to ampicillin and to the combination of ampicillin and gentamicin.

Ampicillin Resistance↗
PubMed1989

Outbreak of pertussis in a residential facility for handicapped people.

An outbreak of pertussis was recognized and investigated in a home for neurologically impaired people. Of 66 residents, 44 (67%) had evidence of recent pertussis infection, although only 12 (27%) had respiratory symptoms. Pertussis was diagnosed by culture, direct fluorescent antibody testing of nasal secretions, agglutinating antibody titer, pertussis antitoxin titer, IgG antibody to pertussis toxin, IgA antibody to pertussis toxin, IgA antibody to filamentous hemagglutinin, or IgG antibody to filamentous hemagglutinin. No single test identified more than 66% of people with pertussis. Of those with positive serologic findings, 95% had a positive test result for IgA antibody to filamentous hemagglutinin or for IgG antibody to pertussis toxin or for both. Pertussis occurred in both immunized and unimmunized residents. Seven carriers were identified; these residents had positive cultures or positive direct fluorescent antigen test results but negative serologic findings. Treatment of residents and caretakers with erythromycin halted the outbreak.

Adolescent↗