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Biomedical subjects

Peter Gaustad

Publications and source records attributed to Peter Gaustad.

16 recordsLinked to original sources

Pneumocystis jirovecii pneumonia in B-cell lymphoma patients treated with the rituximab-CHOEP-14 regimen.

We report six cases of Pneumocystis jirovecii pneumonia (PCP) verified by immunoflourescence/polymerase chain reaction of bronchoalveolar fluid among 46 lymphoma patients (13%) who received rituximab-CHOEP-14 at our institution. PCP prophylaxis should be standard management for this group of patients and also considered for patients treated with rituximab-CHOP-14, CHOP-14 or CHOEP-14.

Adult↗

Diversity and significance of mold species in Norwegian drinking water.

In order to determine the occurrence, distribution, and significance of mold species in groundwater- and surface water-derived drinking water in Norway, molds isolated from 273 water samples were identified. Samples of raw water, treated water, and water from private homes and hospital installations were analyzed by incubation of 100-ml membrane-filtered samples on dichloran-18% glycerol agar. The total count (number of CFU per 100 ml) of fungal species and the species diversity within each sample were determined. The identification of mold species was based on morphological and molecular methods. In total, 94 mold species belonging to 30 genera were identified. The mycobiota was dominated by species of Penicillium, Trichoderma, and Aspergillus, with some of them occurring throughout the drinking water system. Several of the same species as isolated from water may have the potential to cause allergic reactions or disease in humans. Other species are common contaminants of food and beverages, and some may cause unwanted changes in the taste or smell of water. The present results indicate that the mycobiota of water should be considered when the microbiological safety and quality of drinking water are assessed. In fact, molds in drinking water should possibly be included in the Norwegian water supply and drinking water regulations.

Aspergillus↗

Sudden infant death syndrome (SIDS)--standardised investigations and classification: recommendations.

Sudden infant death syndrome (SIDS) still accounts for considerable numbers of unexpected infant deaths in many countries. While numerous theories have been advanced to explain these events, it is increasingly clear that this group of infant deaths results from the complex interaction of a variety of heritable and idiosyncratic endogenous factors interacting with exogenous factors. This has been elegantly summarised in the "three hit" or "triple risk" model. Contradictions and lack of consistencies in the literature have arisen from diverse autopsy approaches, variable applications of diagnostic criteria and inconsistent use of definitions. An approach to sudden infant death is outlined with discussion of appropriate tissue sampling, ancillary investigations and the use of controls in research projects. Standardisation of infant death investigations with the application of uniform definitions and protocols will ensure optimal investigation of individual cases and enable international comparisons of trends.

Bacteriological Techniques↗

In vitro activity of a cytotoxic factor isolated from human leukocytes.

The aim of the present study was to test the in vitro antimicrobial properties of a cytotoxic factor isolated from human leukocytes and for an effect on DNA synthesis. A microdilution broth method was used to determine MIC values for fungi and bacteria. Flow cytometry was used to examine the effect on DNA synthesis. The MIC values for fungi were in the range 1-128 microg CF/mL and concentrations 2-4 times the MIC were fungicidal. CF had no effect on bacteria (MIC and MBC values > 1024 microg CF/mL). Growth experiments performed with increasing concentration of CF showed a dose-dependent effect on growth of the yeasts tested. We confirmed that zinc ions could abrogate the antiproliferative effect of CF. Flow cytometric experiments showed that CF had no effect on the cell cyclus. The present study shows that this endogenous substance isolated from human leukocytes has growth inhibitory properties towards fungi. Because of the origin from human leukocytes, CF may have a role in the non-specific defense against fungal infections. The use of CF may potentially have a role in the treatment of infections caused by fungi. Further investigations to characterize CF chemically and to study the antifungal mechanism are necessary.

Anti-Bacterial Agents↗

Candidemia in Norway (1991 to 2003): results from a nationwide study.

A long-term, nationwide prospective candidemia study has been ongoing in Norway since 1991. All medical microbiological laboratories in the country have participated. During the period 1991 to 2003 a total of 1,393 episodes of candidemia occurred in 1,348 patients. The incidence of candidemia episodes per 100,000 inhabitants increased from approximately 2 episodes in the early 1990s to 3 episodes in 2001 to 2003. The average annual incidences varied markedly between the age groups. The incidence was high in patients aged < 1 year and in patients aged > or = 70 years. In patients > or = 80 years of age, the incidence has increased during the last 3 years from an annual average of 6.5 to 15.6 cases/100,000 inhabitants in 2003. Four Candida species (C. albicans [70%], C. glabrata [13%], C. tropicalis [7%], and C. parapsilosis [6%]) accounted for 95.5% of the isolates. The species distribution has been constant during the 13-year study period. The distribution of the most important species varied with the age of the patient. In patients < 1 year of age, the majority of episodes were caused by C. albicans (91%). The occurrence of C. glabrata increased with age. In patients > or = 80 years of age, approximately 1/3 of all episodes were due to this species. All C. albicans strains were susceptible to fluconazole. The percentage of yeast isolates with decreased susceptibility to fluconazole (MICs > or = 16 microg/ml) was 10.7% during the first period of this study (1991 to 1996) and 11.7% during the second period (1997 to 2003).

Adolescent↗

18S rDNA polymerase chain reaction and sequencing in onychomycosis diagnostics.

Diagnostic approaches to onychomycosis have traditionally been based on a combination of culture and microscopy. In the present study clinical specimens from 346 patients with suspected onychomycosis were analysed by 18S polymerase chain reaction (detection) followed by sequencing and subsequent database search (identification) in parallel with routine culture on agar (detection and identification). In 49 samples Trichophyton rubrum was identified by culture and sequencing. In 67 additional culture negative samples, a positive dermatophyte sequence was obtained (T. rubrum in 54, T. mentagrophytes in 5, and T. species in 8 samples). Fifteen samples cultured positive while no sequence was obtained. Two hundred and seven samples were negative by culture as well as by sequencing. Nails from 10 healthy controls were negative by culture and sequencing. In conclusion, the number of specimens that were positive by polymerase chain reaction was more than double the number that were positive by culture alone.

Adolescent↗

Clostridium tertium: 3 case reports.

Clostridium tertium is infrequently isolated from blood in patients with underlying diseases. Laboratory diagnosis is often delayed because Clostridium tertium is aerotolerant and resistant to metronidazole. Clinically it is a problem because it is commonly resistant to metronidazole, clindamycin and cephalosporins. We present 3 cases illustrating these characteristics.

Adult↗

Cytokine responses and regulation of interferon-gamma release by human mononuclear cells to Aspergillus fumigatus and other filamentous fungi.

There is substantial evidence that the production of proinflammatory cytokines is important in host resistance to invasive aspergillosis. Knowledge of the host response towards other filamentous fungi is scarce, as most studies have focused on Aspergillus fumigatus. In addition, interferon-gamma (IFNgamma) plays a crucial role in the control of invasive aspergillosis, but little is known about the regulation of IFNgamma after stimulation of mononuclear cells by A. fumigatus. Cytokine responses to four different Aspergillus spp., Scedosporium prolificans, and a Rhizopus oryzae strain were compared for their ability to induce the release of tumour necrosis factor-alpha (TNFalpha) and interleukin(IL)-6 by human monocytes. S. prolificans induced significantly more TNFalpha and IL-6 release compared to A. fumigatus, while the various Aspergillus spp. induce comparable levels of these cytokines. By using specific cytokine inhibitors we were able to show that endogenous IL-1, but not IL-18 and TNFalpha was required for IFNgamma and IL-10 release upon stimulation with A. fumigatus hyphae, whereas conidia induced IFNgamma stimulation is independent of these cytokines.

Antigens, Fungal↗

Phenotypic and genotypic aminoglycoside resistance in blood culture isolates of coagulase-negative staphylococci from a single neonatal intensive care unit, 1989-2000.

OBJECTIVES: To investigate the prevalence of aminoglycoside resistance and genes encoding aminoglycoside-modifying enzymes (AME) in blood culture isolates of coagulase-negative staphylococci (CoNS) from neonates. MATERIALS AND METHODS: A total of 180 isolates from 148 patients collected in a single neonatal unit over a 12 year period were examined for susceptibility to gentamicin, tobramycin, netilmicin, amikacin and arbekacin by Etest and/or disc diffusion. AME genes were detected by PCR. RESULTS: The overall non-susceptibility rates to gentamicin, tobramycin, netilmicin, amikacin and arbekacin were 66%, 68%, 52%, 38% and 1%, respectively. Gentamicin non-susceptibility rates were 4% and 91% in methicillin-susceptible and -resistant isolates, respectively. aac(6')-Ie-aph(2'')-Ia, aph(3')-IIIa and/or ant(4')-Ia were encountered in 125 (69%), 1 (0.5%) and 30 (16.6%) isolates, respectively. Forty-six (26%) isolates negative for AME genes were susceptible to all aminoglycosides. In contrast, 115 (92%), 91 (73%) and 66 (53%) of aac(6')-Ie-aph(2'')-Ia positive isolates were non-susceptible to gentamicin, netilmicin and amikacin, respectively. Only one isolate showed arbekacin resistance. However, aac(6')-Ie-aph(2'')-Ia positive isolates and isolates with gentamicin MIC > or =128 mg/L displayed a significant reduction in arbekacin inhibition zones. CONCLUSIONS: A high prevalence of aminoglycoside resistance was detected and associated with methicillin resistance. Discrepancies between phenotypic and genetic detection of aminoglycoside resistance were discerned. Gentamicin was the preferred substrate for phenotypic detection of aac(6')-Ie-aph(2'')-Ia. Arbekacin showed favourable antibacterial activity even in aac(6')-Ie-aph(2'')-Ia-positive isolates. We suggest including arbekacin in future clinical trials of empirical treatment of late onset neonatal sepsis.

Aminoglycosides↗

Susceptibility to quinupristin-dalfopristin and linezolid in 839 clinical isolates of Gram-positive cocci from Norway.

A total of 839 clinical isolates of Gram-positive cocci from Norway including Staphylococcus aureus (n = 214), coagulase negative Staphylococcus spp. (n = 100), Streptococcus pyogenes (n = 99), Streptococcus agalactiae (n = 80), Streptococcus pneumoniae (n = 127), Streptococcus spp. viridans group (n = 70), Enterococcus faecalis (n = 75), and Enterococcus faecium (n = 74), were tested by E-test for susceptibility to a range of antimicrobials including the novel antibiotics quinupristin-dalfopristin and linezolid. Subgroups of oxacillin resistant S. aureus and coagulase negative Staphylococcus spp., penicillin non-susceptible S. pneumoniae and vancomycin resistant Enterococcus spp. were specifically included as they are the intended targets for these new drugs. All isolates were susceptible to linezolid (MIC5o and MIC9o 0.25-2.0 mg/l, MIC range 0.12-2 mg/l). Staphylococcal and streptococcal isolates were also susceptible to quinupristin-dalfopristin except for some intermediately susceptible viridans group isolates (MIC54, and MIC90 0.25-2 mg/l, MIC range 0.125-2 mg/l). Enterococcus faecium (MIC90 = 4.0 mg/l) and Enterococcus faecalis (MIC50 = 8.0 mg/l, MIC90 > or = 32 mg/l) were less susceptible to this substance. There was no linkage between reduced susceptibility to linezolid or quinupristin-dalfopristin and resistance to other classes of antimicrobials. The study demonstrated a high prevalence of in vitro susceptibility to linezolid and quinupristin-dalfopristin, which is necessary for their use in the treatment of infections with resistant Gram-positive pathogens. The results were used to evaluate the appropriateness of breakpoints and to define a baseline for monitoring possible future emergence of resistance to quinupristin-dalfopristin and linezolid in Norway.

Acetamides↗

Cytokine release in healthy donors and patients with chronic granulomatous disease upon stimulation with Aspergillus fumigatus.

The release of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-10 upon stimulation with non-viable conidia and hyphal fragments from Aspergillus fumigatus was investigated in an ex vivo whole-blood model. In healthy volunteers, high numbers of conidia (between 10(6) and 3 x 10(8)/ml) induced a moderate release of TNF-alpha and IL-6. Hyphal fragments (2.5 x 10(5)/ml) were more potent in stimulating the release of these pro-inflammatory cytokines. Although some IL-10 release was observed upon stimulation with either conidia or hyphal fragments, it was not significantly different from that in unstimulated controls. In comparison, in whole blood obtained from 4 patients with chronic granulomatous disease (CGD), a high release of pro-inflammatory cytokines together with a significantly higher IL-10 release than in the healthy controls was seen after stimulation with A. fumigatus. In conclusion, A. fumigatus can trigger the release of pro-inflammatory cytokines in a human whole-blood system, which is likely to be central to the activation of antifungal defence mechanisms. In contrast, A. fumigatus stimulates a higher release of anti-inflammatory cytokines in CGD patients, which may suggest that a dysregulation between pro- and anti-inflammatory cytokines contributes to the increased susceptibility to invasive aspergillosis in this patient group.

Aspergillus fumigatus↗

Molecular epidemiology of Aspergillus fumigatus isolates recovered from water, air, and patients shows two clusters of genetically distinct strains.

There has been an increase in data suggesting that besides air, hospital water is a potential source of transmission of filamentous fungi, and in particular Aspergillus fumigatus. Molecular characterization of environmental and clinical A. fumigatus isolates, collected prospectively during an 18-month period, was performed to establish if waterborne fungi play a role in the pathogenesis of invasive aspergillosis. Isolates recovered from water (n = 54) and air (n = 21) at various locations inside and outside the hospital and from 15 patients (n = 21) with proven, probable, or possible invasive aspergillosis were genotyped by amplified fragment length polymorphism analysis. Based on genomic fingerprints, the environmental A. fumigatus isolates could be grouped into two major clusters primarily containing isolates recovered from either air or water. The genotypic relatedness between clinical and environmental isolates suggests that patients with invasive aspergillosis can be infected by strains originating from water or from air. In addition, 12 clusters with genetically indistinguishable or highly related strains were differentiated, each containing two to three isolates. In two clusters, clinical isolates recovered from patients matched those recovered from water sources, while in another cluster the clinical isolate was indistinguishable from one cultured from air. This observation might open new perspectives in the development of infection control measures to prevent invasive aspergillosis in high-risk patients. The genetic variability found between airborne and waterborne A. fumigatus strains might prove to be a powerful tool in understanding the transmission of invasive aspergillosis and in outbreak control.

Adult↗

Prevalence of gonococcal and chlamydial infections and sexual risk behavior among youth in Addis Ababa, Ethiopia.

BACKGROUND: No community-based study on the magnitude of sexually transmitted diseases (STDs) has ever been conducted among young people in Ethiopia. GOAL: To assess the magnitude of Chlamydia trachomatis and Neisseria gonorrhoeae infections and status of sexual risk behavior among youths (15-24 years old) in Addis Ababa, Ethiopia. STUDY DESIGN: Youths in or out of school residing in two (of the six) administrative zones in Addis Ababa served as the study population. Participants filled out a self-administered questionnaire related to sexuality and its sociocultural determinants. First-void urine (FVU) was analyzed for gonorrhea and chlamydial infection by polymerase chain reaction (PCR). RESULTS: A total of 561 youths took part in the study. Urine PCR was performed for 522 of them. Nine subjects (1.7%) were found to have and N gonorrhoeae and C trachomatis infections. There were five cases (1.0%) involving each agent. Double infection was noted in one female subject. All but one of the infections were detected among the out-of-school youths (chi-square = 4.5; < 0.05). None of these subjects complained of symptoms suggestive of an active STD. One-third (188/561) reported having had sexual intercourse. The prevalence among sexually active youths was thus 4.8% (9/188) for both infections combined (2.7% for each agent). While 7/52 (13.5%) of the sexually active females were found to also have STDs, only 2/136 (1.5%) of the males had an STD (chi-square = 8.0; < 0.01). Report of sexual activity was significantly associated with being male, an age of >/=20 years, out-of-school status, and report of alcohol/khat (amphetamine-like substance) consumption. Females reported less condom use, whether they were in or out of school and independent of age. CONCLUSIONS: Out-of-school youths, especially females, took more sexual risk and were exceedingly susceptible to STDs. This calls for alternative group-targeted strategies for sex education, disease prevention, and STD screening and management.

Adolescent↗

Competence without a competence pheromone in a natural isolate of Streptococcus infantis.

Many streptococcal species belonging to the mitis and anginosus phylogenetic groups are known to be naturally competent for genetic transformation. Induction of the competent state in these bacteria is regulated by a quorum-sensing mechanism consisting of a secreted peptide pheromone encoded by comC and a two-component regulatory system encoded by comDE. Here we report that a natural isolate of a mitis group streptococcus (Atu-4) is competent for genetic transformation even though it has lost the gene encoding the competence pheromone. In contrast to other strains, induction of competence in Atu-4 is not regulated by cell density, since highly diluted cultures of this strain are still competent. Interestingly, competence in the Atu-4 strain is lost if the gene encoding the response regulator ComE is disrupted, demonstrating that this component of the quorum-sensing apparatus is still needed for competence development. These results indicate that mutations in ComD or ComE have resulted in a gain-of-function phenotype that allows competence without a competence pheromone. A highly similar strain lacking comC was isolated independently from another individual, suggesting that strains with this phenotype are able to survive in nature in competition with wild-type strains.

Amino Acid Sequence↗