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M E Brandt

Publications and source records attributed to M E Brandt.

At least 19 recordsLinked to original sources
PubMed2005

Candidemia in pediatric outpatients receiving home total parenteral nutrition.

This is a cohort study of pediatric outpatients receiving total parenteral nutrition (TPN) and follow-up care in a Tennessee hospital between January and June 1999. The study was conducted following an increase in the incidence of candidemia. Of 13 children receiving home TPN, five had candidemia; three were due to Candida parapsilosis. Case patients were more likely to have an underlying hematologic disease (P = 0.02) as well as previous history of fungemia (P = 0.02). Two case patients had successive candidemia episodes 3 months apart; karyotypes and RAPD profiles of each patient's successive C. parapsilosis isolates were similar. Candida spp. were frequently detected in hand cultures from cohort members (four of 10) and family member caregivers (nine of 11); C parapsilosis was isolated from five caregivers. Our findings underscore the challenges of maintaining stringent infection control practices in the home health care setting and suggest the need for more intensive follow-up and coordination of home TPN therapy among pediatric patients.

Adolescent↗
PubMed2003

Epidemiology, clinical manifestations, and therapy of infections caused by dematiaceous fungi.

The dematiaceous (brown-pigmented) fungi are a large and heterogenous group of moulds that cause a wide range of diseases including phaeohyphomycosis, chromoblastomycosis, and eumycotic mycetoma. Among the more important human pathogens are Alternaria species, Bipolaris species, Cladophialophora bantiana, Curvularia species, Exophiala species, Fonsecaea pedrosoi, Madurella species, Phialophora species, Scedosporium prolificans, Scytalidium dimidiatum, and Wangiella dermatitidis. These organisms are widespread in the environment, being found in soil, wood, and decomposing plant debris. Cutaneous, subcutaneous, and corneal infections with dematiaceous fungi occur worldwide, but are more common in tropical and subtropical climates. Infection results from traumatic implantation. Most cases occur in immunocompetent individuals. Dematiaceous moulds are also important causes of invasive sinusitis and allergic fungal sinusitis. Infection is thought to follow inhalation. Although cerebral infection is the commonest form of systemic phaeohyphomycosis, other localized deep forms of the disease, such as arthritis, and endocarditis, have been reported. Disseminated infection is uncommon, but its incidence is increasing, particularly among immunocompromised individuals. Scedosporium prolificans is the most frequent cause. A number of dematiaceous fungi are neurotropic, including Cladophialophora bantiana, Ramichloridium mackenziei, and Wangiella dermatitidis. Although cases have occurred in immunocompromised persons, cerebral phaeohyphomycosis is most common in immunocompetent individuals with no obvious risk factors. Most forms of disease caused by dematiaceous fungi require both surgical and medical treatment. Itraconazole is currently the most effective antifungal agent for chromoblastomycosis and subcutaneous phaeohyphomycosis, while ketoconazole remains useful for mycetoma. Extensive surgical debridement combined with amphotericin B treatment is recommended for chronic invasive sinusitis. Long-term treatment with itraconazole has led to improvement or remission in some patients that had failed to respond to amphotericin B. Allergic fungal sinusitis requires surgical removal of impacted mucin combined with postoperative oral corticosteroids. Antifungal treatment is not usually of benefit, but post-operative itraconazole may reduce the need for reoperation. The clinical outcome of cerebral and other deep-seated forms of phaeohyphomycosis is dismal, with long-term survival being reported only when complete surgical resection of discrete lesions is possible. The development of new antifungal agents and combination treatment may help to improve the management of these infections.

Antifungal Agents↗
PubMed2002

Population-based surveillance and a case-control study of risk factors for endemic lymphocutaneous sporotrichosis in Peru.

Population-based surveillance and a case-control study were conducted in Abancay, Peru, to estimate the burden of disease and to determine risk factors for sporadic lymphocutaneous sporotrichosis (LS). Laboratory records from local hospitals were reviewed for the years of 1997 and 1998, and prospective surveillance was conducted for the period of September 1998 through September 1999. A case-control study was conducted with 2 matched control subjects per case patient. The mean annual incidence was 98 cases per 100,000 persons. Children had an incidence 3 times higher than that for adults and were more likely to have LS lesions on the face and neck. Identified risk factors included owning a cat, playing in crop fields, having a dirt floor in the house, working mainly outdoors, and having a ceiling made of raw wood or conditions associated with a lower socioeconomic status. Decreased environmental exposure, such wearing protective clothing during construction activities for adults or limiting contact with cats and soil for children, and improvements in living spaces may decrease the incidence of LS.

Adolescent↗
PubMed2001

Identification of functionally important amino-terminal arginines of Agrobacterium tumefaciens ADP-glucose pyrophosphorylase by alanine scanning mutagenesis.

Treatment of the Agrobacterium tumefaciens ADP-glucose pyrophosphorylase with the arginyl reagent phenylglyoxal resulted in complete desensitization to fructose 6-phosphate (F6P) activation, and partial desensitization to pyruvate activation. The enzyme was protected from desensitization by ATP, F6P, pyruvate, and phosphate. Alignment studies revealed that this enzyme contains arginine residues in the amino-terminal region that are relatively conserved in similarly regulated ADP-glucose pyrophosphorylases. To functionally evaluate the role(s) of these arginines, alanine scanning mutagenesis was performed to generate the following enzymes: R5A, R11A, R22A, R25A, R32A, R33A, R45A, and R60A. All of the enzymes, except R60A, were successfully expressed and purified to near homogeneity. Both the R5A and R11A enzymes displayed desensitization to pyruvate, partial activation by F6P, and increased sensitivity to phosphate inhibition. Both the R22A and R25A enzymes exhibited reduced V(max) values in the absence of activators, lower apparent affinities for ATP and F6P, and reduced sensitivities to phosphate. The presence of F6P restored R22A enzyme activity, while the R25A enzyme exhibited only approximately 1.5% of the wild-type activity. The R32A enzyme displayed an approximately 11.5-fold reduced affinity for F6P while exhibiting behavior identical to that of the wild type with respect to pyruvate activation. Both the R33A and R45A enzymes demonstrated a higher activity than the wild-type enzyme in the absence of activators, no response to F6P, partial activation by pyruvate, and desensitization to phosphate inhibition. These altered enzymes were also insensitive to phenylglyoxal. The data demonstrate unique functional roles for these arginines and the presence of separate subsites for the activators.

Adenosine Triphosphate↗
PubMed2001

Feedback control of a biodynamical model of HIV-1.

We describe a continuous differential equation model of the interaction dynamics of HIV-1 and CD4 and CD8 lymphocytes in the human body. We demonstrate several methods of stable control of the HIV-1 population using an external feedback control term that is analogous to the introduction of a therapeutic drug regimen. We also show how the immune system components can be bolstered against the virus through a feedback control approach.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Trends in antifungal drug susceptibility of Cryptococcus neoformans isolates in the United States: 1992 to 1994 and 1996 to 1998.

The antifungal drug susceptibilities of two collections of Cryptococcus neoformans isolates obtained through active laboratory-based surveillance from 1992 to 1994 (368 isolates) and 1996 to 1998 (364 isolates) were determined. The MICs of fluconazole, itraconazole, and flucytosine were determined by the National Committee for Clinical Laboratory Standards broth microdilution method; amphotericin B MICs were determined by the E-test. Our results showed that the MIC ranges, the MICs at which 50% of isolates are inhibited (MIC(50)s), and the MIC(90)s of these four antifungal agents did not change from 1992 to 1998. In addition, very small numbers of isolates showed elevated MICs suggestive of in vitro resistance. The MICs of amphotericin B were elevated (>or=2 microg/ml) for 2 isolates, and the MICs of flucytosine were elevated (>or=32 microg/ml) for 14 isolates. Among the azoles, the fluconazole MIC was elevated (>or=64 microg/ml) for 8 isolates and the itraconazole MIC (>or=1 microg/ml) was elevated for 45 isolates. Analysis of 172 serial isolates from 71 patients showed little change in the fluconazole MIC over time. For isolates from 58 patients (82% of serial cases) there was either no change or a twofold change in the fluconazole MIC. In contrast, for isolates from seven patients (12% of serial cases) the increase in the MIC was at least fourfold. For isolates from another patient there was a 32-fold decrease in the fluconazole MIC over a 1-month period. We conclude that in vitro resistance to antifungal agents remains uncommon in C. neoformans and has not significantly changed with time during the past decade.

Antifungal Agents↗
PubMed1999

Neuroanatomic and neuropsychological outcome in school-age children with achondroplasia.

We previously reported on cognitive and respiratory factors in a series of infants with achondroplasia (ACH). We now present the results of neuropsychological evaluation and magnetic resonance imaging in 16 school-age children with ACH, 7 of whom had been included as infants in our previous report. We examined the neuroanatomic and cognitive status of this sample, as well as the predictive stability of the prior infant assessment. Seventeen normally developing children of average stature and 21 preterm children with arrested (compensated, unshunted) hydrocephalus constituted the comparison groups. Brain volumes of children with ACH were significantly larger than those of the comparison groups. In addition, children with ACH exhibited kinking of the medulla and neuroanatomic abnormalities consistent with arrested hydrocephalus, including enlarged ventricles and hypoplasia of the corpus callosum. Cognitive abilities at school age were average, although mild deficits were seen on visual-spatial tasks, similar to those obtained by the hydrocephalic comparison group. Only gross motor coordination deficits distinguished the ACH group from the hydrocephalic controls. Infant assessment overestimated later school-age IQ scores in those infants with ACH who scored above average. These findings point to generally preserved cognitive skills in selected children with ACH at early school age, although children with ACH should be evaluated individually as they are at risk for cognitive, academic, and motor deficits.

Achondroplasia↗
PubMed1999

Trends in species distribution and susceptibility to fluconazole among blood stream isolates of Candida species in the United States.

National surveillance of blood stream infections (BSI) attributable to Candida spp. has been limited to date. Recent studies have suggested in increase in the proportion of BSI attributable to non-Candida albicans species and have also raised concerns regarding the emergence of antifungal resistance among Candida spp. The increased utilization of broad-spectrum antifungal agents and the recognition of Candida spp. as prominent pathogens with the potential for developing antifungal resistance, emphasize the need for ongoing surveillance of antifungal susceptibility patterns. In this investigation trends in species distribution and susceptibility to fluconazole among BSI isolates of Candida spp. referred to our laboratory by United States hospitals were evaluated over the 7-year period from 1992 to 1998. A total of 1579 BSI isolates from more than 50 medical centers were processed. Overall, C. albicans accounted for 52% of isolates followed by C. glabrata (18%), C. parapsilosis (15%), C. tropicalis (11%), and C. krusei (2%). The proportion of BSI isolates that were C. albicans ranged from 45% in 1992 to 60% in 1998. Among the non-C. albicans isolates, C. glabrata succeeded C. parapsilosis as the most common species beginning in 1995. Overall, the susceptibility of all Candida species (C. albicans plus all other species) to fluconazole remained stable (MIC90, 16 micrograms/mL). The fluconazole MIC90 for C. albicans was 0.5-2.0 micrograms/ml for all years studied except 1995 (8.0 micrograms/mL) and was 1.0 microgram/mL overall. The present study suggests a continued prominent role of C. albicans as a cause of BSI, and a constant level of susceptibility of Candida BSI isolates to fluconazole over 7 years. These data should serve as a baseline for future surveillance efforts for anti-fungal agents tested against yeast BSI isolates.

Antifungal Agents↗
PubMed1999

The epidemiology of candidemia in two United States cities: results of a population-based active surveillance.

We conducted prospective, active population-based surveillance for candidemia (defined as any Candida species isolated from blood) in Atlanta and San Francisco (total population, 5.34 million) during 1992-1993. The average annual incidence of candidemia at both sites was 8 per 100,000 population. The highest incidence (75 per 100,000) occurred among infants </=1 year old. In 19% of patients, candidemia developed prior to or on the day of admission. Underlying medical conditions included cancer (26%), abdominal surgery (14%), diabetes mellitus (13%), and human immunodeficiency virus infection (10%). In 47% of cases, species of Candida other than Candida albicans were isolated, most commonly Candida parapsilosis, Candida glabrata, and Candida tropicalis. Antifungal susceptibility testing of 394 isolates revealed minimal levels of azole resistance among C. albicans, C. tropicalis, and C. parapsilosis. These data document the substantial burden of candidemia and its changing epidemiology. Continued surveillance will be important to monitor the epidemiology of candidemia and to detect emergence of resistance to azoles.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Cryptococcosis: population-based multistate active surveillance and risk factors in human immunodeficiency virus-infected persons. Cryptococcal Active Surveillance Group.

To determine the incidence of cryptococcosis and its risk factors among human immunodeficiency virus (HIV)-infected persons, population-based active surveillance was conducted in four US areas (population, 12.5 million) during 1992-1994, and a case-control study was done. Of 1083 cases, 931 (86%) occurred in HIV-infected persons. The annual incidence of cryptococcosis per 1000 among persons living with AIDS ranged from 17 (San Francisco, 1994) to 66 (Atlanta, 1992) and decreased significantly in these cities during 1992-1994. Among non-HIV-infected persons, the annual incidence of cryptococcosis ranged from 0.2 to 0.9/100,000. Multivariate analysis of the case-control study (158 cases and 423 controls) revealed smoking and outdoor occupations to be significantly associated with an increased risk of cryptococcosis; receiving fluconazole within 3 months before enrollment was associated with a decreased risk for cryptococcosis. Further studies are needed to better describe persons with AIDS currently developing cryptococcosis in the era of highly active antiretroviral therapy.

AIDS-Related Opportunistic Infections↗
PubMed1999

In vitro activities of voriconazole, fluconazole, and itraconazole against 566 clinical isolates of Cryptococcus neoformans from the United States and Africa.

We investigated the in vitro activity of voriconazole compared to those of fluconazole and itraconazole against 566 clinical isolates of Cryptococcus neoformans from Africa (164) and the United States (402). Isolates were obtained from cerebrospinal fluid (362), blood (139), and miscellaneous sites (65). Voriconazole (MIC at which 90% of the isolates are inhibited [MIC90], 0.12 to 0.25 microg/ml) was more active than either itraconazole (MIC90, 0.5 microg/ml) or fluconazole (MIC90, 8.0 to 16 microg/ml) against both African and U. S. isolates. Isolates inhibited by >/=16 microg of fluconazole per ml were almost all (99%) inhibited by </=1 microg of voriconazole per ml. These results suggest that voriconazole may be useful in the treatment of cryptococcosis.

Africa↗
PubMed1998

Memory functions in children with early hydrocephalus.

Children with arrested, shunted, and no hydrocephalus were compared on verbal and nonverbal memory tasks assessing multiple components of memory. A gradient of severity was hypothesized, with the shunted hydrocephalus group expected to exhibit the most significant memory impairments and the arrested group expected to perform more poorly than children with no hydrocephalus. Etiologies of prematurity, spina bifida, and aqueductal stenosis were represented by 157 participants. Results supported the hypothesis; the shunted hydrocephalus group performed poorer on all memory measures. Differences for the arrested group were less frequently statistically significant relative to children with no hydrocephalus. Irrespective of etiology, the shunted hydrocephalus group exhibited a pattern of performance suggestive of encoding and retrieval deficits on both verbal and nonverbal tasks, showing a pervasive disturbance of memory processes.

Analysis of Variance↗
PubMed1998

In vitro susceptibilities of Candida bloodstream isolates to the new triazole antifungal agents BMS-207147, Sch 56592, and voriconazole.

BMS-207147, Sch 56592, and voriconazole are three new investigational triazoles with broad-spectrum antifungal activity. The in vitro activities of these three agents were compared with those of itraconazole and fluconazole against 1,300 bloodstream isolates of Candida species obtained from over 50 different medical centers in the United States. The MICs of all of the antifungal drugs were determined by broth microdilution tests performed according to the National Committee for Clinical Laboratory Standards method using RPMI 1640 as a test medium. BMS-207147, Sch 56592, and voriconazole were all quite active against all Candida sp. isolates (MICs for 90% of the isolates tested [MIC90s], 0.5, 1.0, and 0.5 microgram/ml, respectively). Candida albicans was the most susceptible species (MIC90s, 0.03, 0.06, and 0.06 microgram/ml, respectively), and C. glabrata was the least susceptible (MIC90s, 4. 0, 4.0, and 2.0 microgram/ml, respectively). BMS-207147, Sch 56592, and voriconazole were all more active than itraconazole and fluconazole against C. albicans, C. parapsilosis, C. tropicalis, and C. krusei. There existed a clear rank order of in vitro activity of the five azoles examined in this study when they were tested versus C. glabrata: voriconazole > BMS-207147 = Sch 56592 = itraconazole > fluconazole (MIC90s, 2.0, 4.0, 4.0, 4.0, and 64 microgram/ml, respectively). For isolates of Candida spp. with decreased susceptibility to both itraconazole and fluconazole, the MICs of BMS-207147, Sch 56592, and voriconazole were also elevated. These results suggest that BMS-207147, Sch 56592, and voriconazole all possess promising antifungal activity and that further in vitro and in vivo investigations are warranted to establish the clinical value of this improved potency.

Antifungal Agents↗
PubMed1998

Correlation between serological and sequencing analyses of the PorB outer membrane protein in the Neisseria meningitidis serotyping system.

The current serological typing scheme for Neisseria meningitidis is not comprehensive; a proportion of isolates are not serotypeable. DNA sequence analysis and predicted amino acid sequences were used to characterize the structures of variable-region (VR) epitopes on N. meningitidis PorB proteins (PorB VR typing). Twenty-six porB gene sequences were obtained from GenBank and aligned with 41 new sequences. Primary amino acid structures predicted from those genes were grouped into 30 VR families of related variants that displayed at least 60% similarity. We correlated VR families with monoclonal antibody (MAb) reactivities, establishing a relationship between VR families and epitope locations for 15 serotype-defining MAbs. The current panel of serotype-defining MAbs underestimates by at least 50% the PorB VR variability because reagents for several major VR families are lacking or because a number of VR variants within some families are not recognized by serotype-defining MAbs. These difficulties, also reported for serosubtyping based on the PorA protein, are shown as inconsistent results between serological and sequence analyses, leading to inaccurate strain identification and incomplete epidemiological data. The information from this study enabled the expansion of the panel of MAbs currently available for serotyping, by including MAbs of previously undetermined specificities. Use of the expanded serotype panel enabled us to improve the sensitivity of serotyping by resolving a number of formerly nonserotypeable strains. In most cases, this information can be used to predict the VR family placement of unknown PorB proteins without sequencing the entire porB gene. PorB VR typing complements serotyping, and a combination of both techniques may be used for full characterization of meningococcal strains. The present work represents the most complete and integrated data set of PorB VR sequences and MAb reactivities of serogroup B and C meningococci produced to date.

Amino Acid Sequence↗
PubMed1998

Proposed standardization of Neisseria meningitidis PorA variable-region typing nomenclature.

Neisseria meningitidis isolates are conventionally classified by serosubtyping, which characterizes the reactivities of the PorA outer membrane protein variable-region (VR) epitopes with monoclonal antibodies (MAbs). A newer method (PorA VR typing) uses predicted amino acid sequences derived from DNA sequence analysis. The resulting classification schemes are not standardized, offering conflicting and sometimes irreconcilable data from the two methods. In this paper, we propose a standardization of the PorA VR typing nomenclature that incorporates serologic information from traditional PorA serosubtyping with molecular data from predicted VR sequences. We performed a comprehensive literature and database search, generating a collection of strains and DNA sequences that reflects the diversity within PorA that exists to date. We have arranged this information in a comprehensive logical model that includes both serosubtype and PorA VR type assignments. Our data demonstrate that the current panel of serosubtype-defining MAbs underestimates PorA VR variability by at least 50%. Our proposal for VR typing is informative because amino acid sequence and serologic information, when serosubtype-defining MAbs are available, can be deduced simultaneously from the PorA VR designation. This scheme will be useful in future classification and applied epidemiologic studies of N. meningitidis, being a systematic way of selecting PorA vaccine candidates and analyzing vaccine coverage and failure.

Amino Acid Sequence↗
PubMed1998

Utility of random amplified polymorphic DNA PCR and TaqMan automated detection in molecular identification of Aspergillus fumigatus.

We developed a method for the identification of Aspergillus fumigatus fungal isolates by using random amplified polymorphic DNA (RAPD) PCR (RAPD-PCR) cloning and the TaqMan LS50B fluorogenic detection system (Perkin-Elmer Corp., Applied Biosystems, Foster City, Calif.). DNA from seven clinically important Aspergillus species was screened by RAPD-PCR to identify section- or species-specific amplicons. With the OPZ19 RAPD primer a 1,264-bp product was amplified from all A. fumigatus strains initially examined but not from other species. A partial DNA sequence of this product was used to design a specific primer pair, which generated a single 864-bp fragment with DNA from 90 of 100 A. fumigatus isolates when a "touchdown" (65-->55 degrees C) annealing protocol was used. The TaqMan system, a fluorogenic assay which uses the 5'-->3' endonuclease activity of Taq DNA polymerase, detected this 864-bp product with DNA from 89 of these 90 A. fumigatus strains; 1 DNA sample generated an indeterminate result. With DNA from three morphologically typical A. fumigatus isolates, six white ("albino") A. fumigatus isolates, and five of six Neosartorya species (non-A. fumigatus members of the section Fumigati), the 864-bp product was amplified differentially at an annealing temperature of 56 degrees C but not with the touchdown annealing format. No amplicon was detected with DNA from 56 isolates of heterologous Aspergillus, Penicillium, and Paecilomyces species or from Neosartorya fennelliae; TaqMan assay results were either negative (51 isolates) or indeterminate (5 isolates) for all isolates. This RAPD-PCR and TaqMan assay offers promise as a nucleic acid-based system that can be used for the identification of filamentous fungal isolates and that requires no postamplification sample manipulations.

Aspergillosis↗
PubMed1998

The epidemiological features of invasive mycotic infections in the San Francisco Bay area, 1992-1993: results of population-based laboratory active surveillance.

Population-based active laboratory surveillance for invasive mycotic infections was conducted during 1992 and 1993 in three California counties: Alameda, Contra Costa, and San Francisco (population, 2.94 million). The cumulative incidence of invasive mycotic infections was 178.3 per million per year. Invasive mycoses were most commonly caused by Candida (72.8 per million per year), Cryptococcus (65.5), Coccidioides (15.3), Aspergillus (12.4), and Histoplasma (7.1). The clinical significance of other, less common fungi was determined by detailed chart review. The cumulative incidence was determined for zygomycosis (1.7 per million per year), hyalohyphomycosis (1.2), and phaeohyphomycosis (1.0). The most common underlying conditions were human immunodeficiency virus infection (47.4%), nonhematologic malignancy (14.7%), diabetes mellitus (9.9%), and chronic lung disease (9.3%). This represents the first population-based epidemiological assessment of invasive mycoses in the United States.

Age Distribution↗