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Biomedical subjects

P Sandven

Publications and source records attributed to P Sandven.

At least 37 records · Page 2Linked to original sources

Epidemiology, diagnosis and treatment of systemic Candida infection in surgical patients under intensive care.

The incidence of systemic Candida infections in patients requiring intensive care has increased substantially in recent years as a result of a combination of factors. More patients with severe underlying disease or immunosuppression from anti-neoplastic or anti-rejection chemotherapy and at risk from fungal infection are now admitted to the ICU. Improvements in supportive medical and surgical care have led to many patients who would previously have died as a result of trauma or disease surviving to receive intensive care. Moreover, some therapeutic interventions used in the ICU, most notably broad-spectrum antibiotics and intravascular catheters, are also associated with increased risks of candidiasis. Systemic Candida infections are associated with a high morbidity and mortality, but remain difficult to diagnose and ICU staff need to be acutely aware of this often insidious pathogen. A number of studies have identified risk factors for systemic Candida infection which may be used to identify those at highest risk. Such patients may be potential candidates for early, presumptive therapy. Here we review the epidemiology, pathogenesis, morbidity and mortality of systemic Candida infections in the ICU setting, and examine predisposing risk factors. Antifungal treatment, including the use of amphotericin B, flucytosine and fluconazole, and the roles of early presumptive therapy and prophylaxis, is also reviewed.

Antifungal Agents↗

Does the mycotoxin citrinin function as a sun protectant in conidia from Penicillium verrucosum.

Our results demonstrate high concentrations of the UV absorbing mycotoxin citrinin in the outer layer of spores from three citrinin-producing strains of Penicillium verrucosum, which is released in an aqueous environment. An important function of the toxin could be to act as a sun protectant in order to create favorable conditions during the initial germination process. When spores from these strains of P. verrucosum were examined by confocal microscopy, a clearly visible fluorescent layer associated with the cell wall was observed. The strains were grown on agar plates, and the mycelial mat was washed with saline. This suspension contained at least 95% of the spores and particulate material, which was removed by filtration after counting the conidia. An aliquot of this filtrate was extracted and citrinin was purified by high pressure liquid chromatography. The absorbance at 319 nm was used to calculate the amount of UV absorbing material released from the spores. Based on the spore numbers in the suspension of the saline extract, we estimated that this material released was 1.4-4.1 pg per spore or 8-24% of the spore weight. Citrinin (and minor amounts of ochratoxin A and some other unidentificable fluorescent compounds) were observed in the filtrate when subjected to thin layer chromatography.

Journal Article↗

Constant low rate of fungemia in norway, 1991 to 1996. The Norwegian Yeast Study Group.

Since 1991 information on yeast isolates from blood cultures has been recorded prospectively from all microbiological laboratories (5 university and 16 county or local hospital laboratories) in Norway (population, 4.3 million). From 1991 to 1996 a total of 571 episodes of fungemia in 552 patients occurred (1991, 109 episodes; 1992, 81 episodes; 1993, 93 episodes; 1994, 89 episodes; 1995, 98 episodes; and 1996, 101 episodes). The fungemia rates per 10,000 patient days were 0.29 in 1991 and 0.27 in 1996. The average rates for the years 1991 to 1996 were 0.37 for the university laboratories and 0.20 for the other laboratories. These rates are low compared to the rate (0. 76) in five Dutch university hospitals in 1995 and the rate (2.0) in Iowa in 1991. The four most frequently isolated species were Candida albicans (66%), Candida glabrata (12.5%), Candida parapsilosis (7.6%), and Candida tropicalis (6.4%). The incidences of both C. albicans (range, 63 to 73%) and C. glabrata (range, 8.4 to 15.7%) varied somewhat throughout this period, but no significant increase or decrease was noted. MICs of amphotericin B, flucytosine, and fluconazole were determined for 89% of the isolates. All were susceptible to amphotericin B, and only 29 (5.6%) strains had decreased susceptibility to flucytosine. All C. albicans isolates were susceptible to fluconazole. The percentage of yeast isolates with decreased susceptibility to fluconazole (MICs, >/=16 microgram/ml) did increase, from 9.6% in 1991 and 1992 to 12.2% in 1994, 16.1% in 1995, and 18.6% in 1996. This was largely due to increases in the percentages of resistant C. glabrata and Candida krusei strains in the last 2 years. Compared to the incidence in other countries, it is remarkable that Norway has such a low and constant incidence of fungemia. A possible reason for this difference might be a restricted antibiotic use policy in Norway.

Adult↗

Candida norvegensis: a fluconazole-resistant species.

Candida norvegensis has been an unusual cause of infections in humans. In Norway this species was isolated from eight patients from 1990 to 1996 and was of probable pathogenic significance in four of them. All isolates were resistant to fluconazole. The same was true for two C. norvegensis isolates from before 1940, and it is therefore assumed that the fluconazole resistance is inherent.

Adult↗

Detection of rifampin resistance among isolates of Mycobacterium tuberculosis from Mozambique.

Rifampin resistance in respiratory isolates of Mycobacterium tuberculosis from Mozambique was detected by screening for point mutations using polymerase chain reaction (PCR) and DNA sequence analysis. The target template was a 350-bp fragment of rpoB encoding the beta-subunit of the RNA polymerase. Of the 66 strains studied, 38 were rifampin resistant by susceptibility testing with the radiometric method, 3 were intermediately resistant, and 25 were susceptible to rifampin. In 39 of the 41 rifampin-resistant strains, base-substitutions in the rpoB fragment were detected, and a total of 13 distinct mutations affecting 6 amino acids were observed. One of these mutations (His-->Thr in amino acid 526) was not previously described. The isolates were also investigated by restriction fragment length polymorphism (RFLP) analysis using the insertion element IS6110 as a hybridization probe. A total of 47 RFLP patterns were identified, with up to 9 isolates having the same RFLP pattern. Strains with the same RFLP pattern harbored different mutations in rpoB, suggesting that acquisition of rifampin resistance followed the spread of a rifampin-susceptible clone. The data showed that rifampin resistance can be detected with a high sensitivity by DNA sequence analysis of this fragment of rpoB. However, a few strains with rifampin resistance due to factors other than base substitutions in rpoB could be missed.

Amino Acid Sequence↗

The physical nature of a large bowel perforation predicts severity of the subsequent inflammatory response.

The aim of the study was to determine how the physical nature of a large bowel perforation influences the host inflammatory response. Two rat models were used: a 4 mm cecal perforation (CP) and a cecal ligation with 23 gauge needle puncture (CLP). CP gave a more fulminant course and this was reflected in higher levels of bacteria, endotoxin, tumor necrosis factor, interleukin-1 (IL-1), and IL-6, which were all strongly compartmentalized in the peritoneal cavity. Despite a sustained enhancement of cytokines in peritoneal fluid, only a temporary burst of tumor necrosis factor, and no release of IL-1, were seen in serum, whereas IL-6 was continuously released. Depletion of leukocytes was more pronounced in CP than CLP. In summary, a large bowel perforation like CP triggers an overwhelming host reaction with leukocytopenia, cytokine release, dehydration, hypoperfusion, and death. The smaller fecal inoculum in CLP gives a more subacute inflammatory response.

Animals↗

Serum IgG antibodies to mold spores in two Norwegian sawmill populations: relationship to respiratory and other work-related symptoms.

Wood trimmers and planing operators from two separate sawmill populations (N = 303 and 170) were studied by serology assessment and a self-administered questionnaire. IgG antibodies to Rhizopus microsporus ssp. rhizopodiformis, Paecilomyces variotii, and Aspergillus fumigatus were measured by ELISA. The questionnaire included questions about general respiratory symptoms and symptoms after handling moldy timber. Personal exposure of wood trimmers to mold spores and wood dust was measured in one part of the sawmills. R. microsporus was the most prevalent mold assessed by serology. Antibody levels were higher and symptoms suggestive of mucous membrane irritation, chronic nonspecific lung disease, allergic alveolitis, and organic dust toxic syndrome were more frequently reported by wood trimmers than by planing operators. The mean level of IgG antibodies to R. microsporus in sawmill workers working in the same work area was the best predictor of symptoms in both populations. The consistent results indicate that exposure to spores of R. microsporus may cause several respiratory symptoms in wood trimmers.

Adult↗

Susceptibilities of Norwegian Candida albicans strains to fluconazole: emergence of resistance. The Norwegian Yeast Study Group.

All Candida albicans isolates in Norwegian microbiological laboratories in 1991 judged clinically important (except vaginal isolates) were collected. The isolates were tested for susceptibility to fluconazole with an agar dilution test and a commercially available agar diffusion test. A total of 212 strains (95%) were susceptible to fluconazole, and MICs for most of the strains (92%) were < or = 1.56 micrograms/ml. The agar diffusion test using a 15-micrograms tablet and a 48-h incubation period separated resistant from susceptible strains with a wide margin. The only exception was a strain for which the MIC was 6.25 micrograms/ml. The difference in zone size between the resistant and the susceptible populations of strains was 11 mm. Accordingly, it appears that the agar diffusion test is an appropriate method for detecting fluconazole resistance. The 12 fluconazole-resistant isolates originated from eight AIDS patients with oral or esophageal Candida infections. Seven of the patients had been given fluconazole for 1 month or more, often as self medication. Four had infections that were clinically resistant to fluconazole; one additional patient responded only when the dose was increased. All isolates recovered from these patients were analyzed by multilocus enzyme electrophoresis. The 12 C. albicans isolates belonged to five electrophoretic types, but three of four patients attending one hospital had isolates belonging to one electrophoretic type. One possible explanation for this finding could be that a nosocomial spread of resistant strains has occurred.

Acquired Immunodeficiency Syndrome↗

Epidemiological analysis of Candida albicans strains by multilocus enzyme electrophoresis.

Genotypic diversity in a collection of 98 isolates of Candida albicans was assessed by multilocus enzyme electrophoresis. Four of the 10 enzyme loci studied were polymorphic. The electrophoretic patterns observed were compatible with those expected for a diploid organism. The 98 isolates were assigned to 14 electrophoretic types, each of which was represented by from 1 to 21 isolates. Samples from various clinical sites of seven bone marrow transplant patients treated in the same unit within a 13-month period were obtained repeatedly. Three patients were found to be colonized with more than one strain. In one patient, flucytosine-resistant strains were isolated after systemic antifungal treatment was started. These isolates had electrophoretic types different from those of the strains that colonized the patient before treatment. There was no evidence that cross-infection between these patients occurred in the hospital. The population structure of C. albicans is discussed in regard to the multilocus genotype data.

Antifungal Agents↗

[Infection problems in the leukopenia phase after autologous bone marrow transplantation].

Between 1986 and 1991, 29 patients with malignant lymphomas were treated with total body irradiation and high-dose chemotherapy followed by autologous bone marrow transplantation at the Norwegian Radium Hospital. Owing to treatment-induced bone marrow toxicity, the leucocyte count in peripheral blood rapidly fell to zero. The aplastic phase lasted for 25 days (median). All patients experienced fever in the posttransplant period and needed broad-spectrum antibiotics. 12 patients had documented bacteremia, mostly with Gram-positive isolates. There were seven cases of documented focal infections, and antibiotic-associated colitis was seen in two cases. Other complications included bleedings and skin rashes. Four patients died in the post-transplant period from complications related to the cytotoxic treatment. We discuss guidelines for antimicrobial treatment of suspected and confirmed infections in neutropenic patients.

Adolescent↗

Detection and quantitation of antibodies against Rhizopus by enzyme-linked immunosorbent assay.

In sawmills high concentrations of spores from the mould Rhizopus microsporus may occur, causing allergic alveolitis in exposed workers. Both symptomatic and asymptomatic exposed workers may develop antibodies. An enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to Rhizopus has been developed in order to study the relationship between antibody levels and exposure levels. The precision of the measurements of Rhizopus antibodies by ELISA carried out on the same microtiter plate was estimated to be 11%. It is therefore possible to detect changes in antibody levels of approximately 25% or more. Antibodies were studied longitudinally by ELISA in 60 wood trimmers. The observed changes in antibody levels exceeded the precision of the ELISA method substantially, indicating significant variability in antibody levels in wood trimmers. The ELISA test was compared with the double immunodiffusion test (DID). Sera from 67 wood trimmers were analyzed by both methods. Antibodies were detected by ELISA in 70% and by DID in 28% of the workers in this group, clearly demonstrating that the ELISA test is the most sensitive method for the detection of antibodies to Rhizopus.

Antibodies, Fungal↗

Relationships between exposure to spores from Rhizopus microsporus and Paecilomyces variotii and serum IgG antibodies in wood trimmers.

A longitudinal study of wood trimmers exposed to mould spores was carried out from 1985 to 1988. Exposure to airborne spores from Rhizopus microsporus ssp. rhizopodiformis and Paecilomyces variotii was measured by scanning electron microscopy of filter samples. Specific IgG antibodies to these moulds were measured by ELISA in serum samples collected at half-year intervals. Antibody levels to R. microsporus and P. variotii were higher in wood trimmers than in other sawmill workers whose jobs had an assumed lower exposure to mould spores. Antibody levels were significantly elevated after periods with high exposure compared to antibody levels in the same wood trimmers after periods with low exposure. Antibodies were also found in newly employed wood trimmers. These wood trimmers were exposed to 1,300 x 10(3) R. microsporus spores/m3 and 130 x 10(3) P. variotii spores/m3 (arithmetic mean exposure). Antibody levels in the newly employed wood trimmers were similar to antibody levels in wood trimmers who had already worked in the trimming department before the start of the study. Antibody levels to R. microsporus and P. variotii in wood trimmers can be regarded as indicators of fairly recent exposure. There were, however, large differences between the individual antibody levels of similarly exposed wood trimmers.

Adult↗

Aureobasidium infection of the jaw.

A 32-yr-old white North American male resident of Norway presented with an asymptomatic radiolucency first identified 3 yr after the removal of an impacted mandibular right third molar in Southern California 16 yr previously. Surgical exploration revealed an intraosseous cavity filled with a black, homogeneous, gelatinous substance thought to be foreign material, but which was diagnosed histologically as containing black yeasts. Cultivation of a microbiologic sample for 6 wk grew black yeast-like colonies. The yeast isolate was identified as an Aureobasidium species different from the typical A. pullulans. A blood sample was negative with regard to antibodies both with double diffusion technique and ELISA. Also, examination with respect to dermatologic manifestations gave negative results. Flucytocin 10 g/d was administered systemically for 30 d. Six months postoperatively bone regeneration was satisfactory radiologically.

Adult↗

Laboratory identification and sensitivity testing of yeast isolates.

Methods used for identification and sensitivity testing of yeasts are presented. Identification depends on both morphologic features and biochemical characteristics. The germ tube test is a simple test for the identification of the commonest yeast pathogen, Candida albicans. Species not identified by this method can be identified by means of several other tests, the most important being the carbohydrate assimilation test. Several kits are commercially available and most appear to be satisfactory. Antifungal susceptibility tests are not standardized, and results are often subject to considerable variation. Until improved methods are developed, it might be advisable that smaller laboratories only do a preliminary screening test for flucytosine susceptibility and, if indicated, also for amphotericin B susceptibility. Important isolates should be sent to laboratories with a special interest in antifungal susceptibility testing for more extensive testing.

Antifungal Agents↗

[Candida albicans--is it causing a new national disease?].

A hypothesis concerning a chronic candida hypersensitivity syndrome caused by the presence of Candida albicans in the gut was put forward in the USA a decade ago. Lately this theory has gained much publicity in Norway through articles in the press and programs on the national radio and television. The purpose of this article is to give a presentation and critical evaluation of this syndrome. It is concluded that the theory of a chronic Candida hypersensitivity syndrome is speculative and devoid of experimental support.

Candidiasis↗