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Biomedical subjects

C C Patrick

Publications and source records attributed to C C Patrick.

At least 19 recordsLinked to original sources
PubMed1997

Use of fluoroquinolones as prophylactic agents in patients with neutropenia.

BACKGROUND: The use of fluorinated quinolone antibiotics to selectively decontaminate the gastrointestinal tract is a reasonable alternative to prevent infection in neutropenic patients. The fluoroquinolones represent ideal antibiotics with which to achieve the principles of selective decontamination by allowing colonization of anaerobes to inhibit the adherence, colonization and proliferation of potentially pathogenic aerobic flora. OBJECTIVE: This report describes the prophylactic use of fluoroquinolones in neutropenic patients. RESULTS: The majority of studies of fluoroquinolone prophylaxis in neutropenic patients have shown a reduction in documented Gram-negative bacterial infections. However, Gram-positive infections, particularly those with viridans streptococci, present a major impediment to the use of single agent prophylaxis with a quinolone. CONCLUSION: Prophylaxis with fluoroquinolones in neutropenic patients was found to be advantageous, but it must be balanced against the risk of Gram-positive infections and the potential for antibiotic resistance.

Anti-Infective Agents↗
PubMed1996

Lipoteichoic acid from viridans streptococci induces the production of tumor necrosis factor and nitric oxide by murine macrophages.

Bacterial endotoxin or lipopolysaccharide is the major proinflammatory component of gram-negative bacteria, but the components of gram-positive bacteria that trigger the inflammatory cascade are poorly understood. Lipoteichoic acid (LTA) purified from 2 strains of viridans streptococci induced the accumulation of tumor necrosis factor (TNF) mRNA and protein by the murine macrophage cell line RAW 264.7 in a dose- and time-dependent manner. Furthermore, in the presence of recombinant interferon-gamma, LTA from both strains of viridans streptococci provoked the accumulation of inducible nitric oxide (NO) synthase mRNA and the production of NO. Together these observations indicate that LTA can trigger macrophage activation and the production of TNF and NO and suggest that LTA may be an important determinant of the host inflammatory response to gram-positive infection.

Animals↗
PubMed1995

Diagnostic utility of thoracentesis for neutropenic children with cancer.

Thoracentesis is a procedure often performed in children with pleural effusions to assist in diagnosis and management. Its safety and utility for immunocompromised patients with neutropenia (absolute neutrophil count, <1,500 polymorphonuclear leukocytes and band forms per microL) is unclear. We reviewed our experience over a 10-year period to evaluate the role of thoracentesis for neutropenic children with cancer who had pulmonary effusions of presumed infectious etiology. Twenty-two patients were identified, and 18 had absolute neutrophil counts of < or = 500/microL. Empirical antibiotics had been administered to 95% of these patients and antifungal agents to 72%. Two patients' cultures were positive for fungal organisms: Aspergillus terreus in one case and Candida albicans in the other. Both of these patients had been receiving antifungal therapy. Therapy was altered for these two patients plus one additional patient in whose pleural fluid tumor cells were unexpectedly found. Eight of the remaining 19 patients underwent another diagnostic procedure, yielding five additional diagnoses. In conclusion, thoracentesis is safe and should be considered as a diagnostic test for febrile neutropenic patients with pulmonary effusions of presumed infectious etiology, although more invasive tests may be warranted.

Adolescent↗
PubMed1995

Sequence and analysis of the rpoB gene of Mycobacterium smegmatis.

The rpoB gene encodes the beta subunit of the DNA-dependent RNA polymerase of bacteria. Mutations in defined areas result in resistance to rifampin. Mycobacterium smegmatis is naturally resistant to rifampin, but analysis of the rpoB gene revealed no identifiable rifampin resistance mutations. Another mechanism of resistance may be present.

Amino Acid Sequence↗
PubMed1995

Comparative virulence of Staphylococcus epidermidis isolates in a murine catheter model.

Among coagulase-negative staphylococci, Staphylococcus epidermidis is the species most commonly implicated in catheter-related infections. Whether some staphylococcal organisms are inherently more virulent than others, or whether their ability to infect relates more to the sheer numbers of organisms at the catheter site, remains unclear. We therefore compared eight S. epidermidis isolates and two other coagulase-negative staphylococci using a murine model that allowed us to quantify catheter colonization and abscess formation in the same animal. The organisms were isolated from different clinically relevant settings and were classified according to their slime phenotype. The ability to evoke abscesses or colonize catheters in half of the animals (ID50) was assessed. ID50 inoculum titers (log10 data +/- SD) ranged widely, from 8.5 +/- 0.3 to 10.2 +/- 0.2 for abscess formation (p < 0.005) and from 7.5 +/- 0.5 to 10.3 +/- 1.0 for catheter colonization (p < 0.005). ID50 values by statistical criteria suggested variability among organisms in the ability to induce abscess formation. High slime production correlated with both parameters, but not with the clinical source of the isolate. Our findings demonstrate impressive heterogeneity in the ability of a representative group of S. epidermidis isolates to colonize catheters and to evoke abscess formation and implicate slime productivity as a major virulence factor. The murine model used permitted simultaneous analysis of multiple factors involved in pathogenesis and should be useful in establishing the basis of S. epidermidis pathogenicity.

Abscess↗
PubMed1994

Pseudomonas aeruginosa bacteremia in immunocompromised children: analysis of factors associated with a poor outcome.

We identified 98 children and adolescents with cancer who were treated for Pseudomonas aeruginosa bacteremia over a 27-year period. The most common underlying disease was leukemia (lymphoblastic in 63 cases and myeloblastic in 17); in addition, 12 episodes were associated with solid tumors and 6 with other diagnoses. There were 29.5 episodes of P. aeruginosa bacteremia/1,000 cases of acute lymphoblastic leukemia, with a mortality of 27%, and 29.8 episodes/1,000 cases of acute myeloblastic leukemia, with a mortality of 24%; patients with solid tumors had an incidence of 5.0/1,000 cases and a mortality of 58% (P = .01 for mortality in leukemia vs. mortality in solid tumors, logistic regression analysis). Mortality was lower among children who developed bacteremia during remission therapy or induction therapy than among children who were being treated for relapse (P = .001). The majority (78%) of the 76 evaluated cases developed during periods when the absolute neutrophil count (ANC) was < 0.1 x 10(9)/L; mortality was higher among patients with such counts than among those with higher ANCs (36% vs. 14%, P = .04). Logistic regression analysis showed that perineal skin lesions were associated with higher mortality than were lesions at other sites of skin involvement (54% vs. 23%, P = .04).

Adolescent↗
PubMed1994

Monoclonal antibodies against a 97-kilodalton antigen from Aspergillus flavus.

We prepared a panel of five monoclonal antibodies (MAbs) directed against Aspergillus flavus that all reacted against one 97-kDa antigen by western blot (immunoblot). Flow cytometry demonstrated that these antibodies bound (in increasing degrees) to all morphologic stages of A. flavus growth: conidia, swollen conidia, and hyphae. Cross-reactivity among species was examined by enzyme-linked immunosorbent assay of fungal culture filtrates. Four MAbs reacted with 10 of 11 A. flavus isolates, and the fifth one reacted with 9 of them. One MAb also reacted with A. fumigatus, two reacted with A. niger, A. wentii, and A. nidulans, and all five reacted with A. ochraceus. None reacted with A. terreus, A. glaucus, A. versicolor, or a Penicillium species. Each MAb bound to A. flavus hyphae in formalin-fixed paraffin sections of a muscle biopsy from a confirmed human case of invasive aspergillosis. In summary, these MAbs identified a 97-kDa antigen found on A. flavus that is both surface bound and an exoantigen. Either the same or a cross-reacting antigen is present in A. fumigatus and other Aspergillus species.

Animals↗
PubMed1993

Variation in phenotypic expression of the Opa outer membrane protein and lipooligosaccharide of Neisseria meningitidis serogroup C causing periorbital cellulitis and bacteremia.

Expression of the Opa outer membrane protein varies widely among isolates of Neisseria meningitidis; the clinical significance of this variation is unclear. A sialic-acid acceptor is present in the lipooligosaccharide of some strains of Neisseria and has been shown to render Neisseria gonorrhoeae serum-resistant. We report the case of a patient who had an unusual clinical manifestation of infection due to N. meningitidis serogroup C, periorbital cellulitis with concomitant bacteremia. Clinical isolates from the blood and aspirate of the periorbital cellulitis were identical except for the phenotypic expression of the Opa outer membrane protein in the isolate from the periorbital cellulitis and in the lipooligosaccharide phenotype of the sialic-acid acceptor as defined by monoclonal antibodies. We discuss the laboratory and clinical implications of these findings.

Antigens, Bacterial↗
PubMed1993

Cunninghamella infections: review and report of two cases of Cunninghamella pneumonia in immunocompromised children.

Infections caused by Cunninghamella bertholletiae are being identified with increasing frequency in immunocompromised patients. We have treated two children with cancer for pulmonary infections caused by this rare fungus. Cunninghamella infection is found in a variety of populations of patients, including both children and adults undergoing chemotherapy. Clinical signs and symptoms are indistinguishable from those of other forms of zygomycosis. Outcome is poor: only three of 17 patients with such infection (including one of the two children described herein) have survived. Treatment involves aggressive surgical excision and administration of amphotericin B.

Child↗
PubMed1993

Typhlitis in children with cancer: a 30-year experience.

We identified 24 children treated for malignancies between 1962 and 1992 who had antemortem diagnoses of typhlitis that were confirmed on review. The study criteria specified the presence of fever, abdominal pain, and tenderness, with radiological evidence of right-sided colonic inflammation. Typhlitis was most frequent in patients treated for acute leukemias. Computed tomography and ultrasonography were more sensitive than plain radiography (false-negative rates, 15%, 23%, and 48%, respectively). The wider availability of these sensitive procedures and the increased intensity of chemotherapeutic regimens may account for a marked increase in the incidence of typhlitis over the past 5 years. Most patients responded to aggressive medical management, and typhlitis was fatal in only two cases (1 of 21 cases managed medically and 1 of 3 taken to surgery). Seven patients are alive > 1 year following the diagnosis. These findings contrast with prior descriptions of typhlitis as a preterminal event. Computed tomography and/or ultrasonography should be performed in all neutropenic patients with right-lower-quadrant signs to permit prompt diagnosis and treatment.

Adolescent↗
PubMed1993

Complications of bacteremia due to Stomatococcus mucilaginosus in neutropenic children.

Stomatococcus mucilaginosus, a normal inhabitant of the human oral cavity and upper respiratory tract, can cause fatal sepsis and meningitis in neutropenic patients. We identified eight cases of bacteremia due to S. mucilaginosus in children with cancer, of whom five developed complications despite receiving appropriate antibiotics. At the time cultures were positive, seven patients had profound neutropenia (< 100 neutrophils and band forms/mm3) and four had mucositis; five had central venous catheters. In two cases, there was unequivocal evidence of catheter-related sepsis. Bacteremia was eradicated in all patients within 48 hours after initiation of antibiotics. Despite prompt instigation of effective antibiotic therapy, the complication rates in this series were high: septic shock (50%), pneumonia (50%), dermatologic manifestations (38%), altered neurological status (25%), meningitis (13%), and adult respiratory distress syndrome (13%). No fatalities were attributable to S. mucilaginosus infection. These cases illustrate the virulence of S. mucilaginosus organisms in neutropenic children and suggest a substantial risk of sequelae even when adequate antibiotic therapy is given.

Adolescent↗
PubMed1993

Outer membrane protein binding sites of complement component 3 during opsonization of Haemophilus influenzae.

Complement component 3 (C3) binding to Haemophilus influenzae type b (Hib) is an important step in host defense against invasive disease, but the details of this process remain poorly understood. We have shown that the P1 and P2 outer membrane proteins (OMPs) serve as binding sites for C3 on serum-opsonized Hib. Whole-cell lysates of opsonized Hib were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the resolved proteins were transferred to nitrocellulose. Immunoblot analysis with monoclonal antibodies (MAbs) to the 49-kDa P1 and 39-kDa P2 OMPs demonstrated high-molecular-weight bands that were not present when the bacteria were opsonized with heat-inactivated or methylamine-treated serum. Immunoblot analysis with MAbs to the 98- or 16-kDa (P6) OMPs did not reveal additional bands. An unencapsulated Hib mutant still lacked C3 bound to the 98-kDa or P6 OMP, indicating that the absence of C3 binding to these proteins was not the result of epitope masking by the capsule. Studies with MAbs to C3 fragments confirmed that the anti-P1- and anti-P2-reactive bands were C3 fragments bound to these OMPs. The molecular weights of proteins reactive to anti-OMP and anti-C3 antibodies indicated that multiple C3 fragments may be bound to P1 or that C3 may be bound to P2 multimers. Finally, the presence of other anti-C3-reactive proteins indicated that several other proteins serve as C3 targets during the opsonization of Hib.

Amino Acid Sequence↗
PubMed1993

Modulating effect of dietary carbohydrate supplementation on Candida albicans colonization and invasion in a neutropenic mouse model.

We studied the effect of dietary carbohydrate supplementation on Candida albicans colonization and invasion of the gastrointestinal tract in a neutropenic mouse model. Mice inoculated with C. albicans were allowed free access to standard chow and drinking water supplemented with either glucose or xylitol or no carbohydrates (control). On days 33 through 36 postinoculation, the mean +/- standard error log10 CFU of C. albicans per gram on the mucosal surface, determined by quantitating CFU dislodged in the first wash of the gastric wall, was significantly higher in mice given the glucose supplement: 7.20 +/- 0.09 (glucose) versus 5.38 +/- 0.28 (xylitol) and 5.11 +/- 0.33 (control) CFU/g (P < or = 0.05 for each comparison by Fisher's protected least-significant-difference test). Fecal cultures also yielded the highest quantities of C. albicans in the glucose group. Invasion of the gastric wall by C. albicans correlated well with surface colonization in glucose-supplemented animals. Eight of 10 mice in this group, all with > 10(6) CFU/g, showed extensive invasive growth, as compared with only 2 of 26 mice in the remaining groups (P = 0.00006 by Fisher's exact test). These results indicate that dietary glucose intake is a key determinant of C. albicans growth in the gastrointestinal tract. The data provide an experimental rationale for clinical trials to decrease the intake of glucose or its utilization by C. albicans in immunocompromised patients.

Animals↗
PubMed1993

Cervical adenitis caused by Staphylococcus epidermidis.

Staphylococcus epidermidis, a human commensal, is a common cause of bacteremia in immunocompromised patients with indwelling medical devices. We report a case of isolated cervical adenitis caused by S. epidermidis in an immunocompetent patient and comment on the presumed pathogenesis.

Anti-Bacterial Agents↗
PubMed1993

Complement binding to Aspergillus conidia correlates with pathogenicity.

Complement has significant effects on the phagocytosis of Aspergillus organisms. We examined the amount and type of complement component C3 bound to the resting conidia of 29 isolates from nine Aspergillus species. The highly pathogenic species A. fumigatus and A. flavus bound fewer C3 molecules per unit of conidial surface area than did the less pathogenic species A. glaucus, A. nidulans, A. niger, A. ochraceus, A. terreus, A. versicolor, and A. wentii, as determined by quantitative flow cytometry. Immunoblot analysis of C3 fragments bound to conidia demonstrated that for all species most C3b was apparently converted to iC3b. For seven species, iC3b was clearly the major C3 product recognized by immunoblotting. However, A. niger and A. nidulans appear to promote further breakdown of opsonic C3 fragments to C3dg. We found significant variations in size and C3 binding among isolates within the same species. Intraspecies variation may contribute to seemingly discrepant results obtained in studies of Aspergillus phagocytosis.

Adult↗