Infections in patients hospitalized for fever as related to duration and other predictors at admittance.

PURPOSE: To find the underlying diagnoses of patients admitted to a medical department with symptoms of fever to ascertain whether the duration of fever, temperature readings, and common laboratory tests could give a clue to the final diagnosis. METHODS: A retrospective study of the records of 299 patients admitted to the Medical Department, Haukeland University Hospital from July 1st, 2001 until June 30th, 2004 for fever without any diagnosis suggesting the cause of the fever. RESULTS AND CONCLUSIONS: Infections were the most common diagnoses, but the proportion of patients with infections declined with increasing duration of fever before admission (63.7 % when <7 days, 45.8 % when >21 days). A group of patients on immunosuppressive therapy were all hospitalized within 1 week from the debut of fever, and their causes of fever were comparable to those of non-immunocompromised patients with fever of the same duration. With fever <7 days, patients with bacterial or viral infection had higher maximum temperatures (medians 39.2 and 38.9 °C, respectively) than those without infection (median 38.0 °C). Patients with bacterial infection had higher C-reactive protein (CRP) levels than patients in the other groups, whereas viral infection was associated with higher lymphocyte counts. The neutrophil:lymphocyte ratio was higher in patients with fever due to bacterial infections than in those with viral infections. For patients with fever for <1 week, neutrophil [area under the curve (AUC) 0.723], white blood cell (WBC, AUC 0.692), and monocyte (AUC 0.691) counts and CRP levels (AUC 0.684) were the best single indicators of bacterial infection.

Flow cytometry technique for analysing Leishmania promastigote phagocytosis by human polymorphonuclear leucocytes and monocytes.

In this study, we developed a flow cytometry technique for studying Leishmania (L.) mexicana phagocytosis by human polymorphonuclear leucocytes (PMNs) and monocytes. Leishmania promastigotes are elongated in shape and flagellated. This influences the light scatter when phagocytosis is measured by flow cytometry. Accordingly, we developed an oxidative burst method for measuring the phagocytic process. As this is an indirect marker of phagocytosis, we used confocal, light and electron microscopy to verify that promastigotes were, indeed, internalized by the phagocytes. For both PMNs and monocytes, the optimal conditions for achieving high sensitivity in flow cytometry detection were 5% pooled human serum and 15 min. incubation time. Incubations at 35, 37 and 39°C were also equally efficient for both PMNs and monocytes. Optimal parasite ratios were 10 parasites per PMN and 20 parasites per monocyte. Under these conditions, Leishmania were readily phagocytosed by human PMNs and monocytes and the effects of other influences, such as treatment, would be readily detectable. This indicated that these cells may play a role in the immune response against Leishmania.

Bacterial findings in infected hip joint replacements in patients with rheumatoid arthritis and osteoarthritis: a study of 318 revisions for infection reported to the norwegian arthroplasty register.

High rates of Staphylococcus aureus are reported in prosthetic joint infection (PJI) in rheumatoid arthritis (RA). RA patients are considered to have a high risk of infection with bacteria of potentially oral or dental origin. One thousand four hundred forty-three revisions for infection were reported to the Norwegian Arthroplasty Register (NAR) from 1987 to 2007. For this study 269 infection episodes in 255 OA patients served as control group. In the NAR we identified 49 infection episodes in 37 RA patients from 1987 to 2009. The RA patients were, on average, 10 years younger than the OA patients and there were more females (70% versus 54%). We found no differences in the bacterial findings in RA and OA. A tendency towards a higher frequency of Staphylococcus aureus (18% versus 11%) causing PJI was found in the RA patients compared to OA. There were no bacteria of potential odontogenic origin found in the RA patients, while we found 4% in OA. The bacteria identified in revisions for infection in THRs in patients with RA did not significantly differ from those in OA. Bacteria of oral or dental origin were not found in infected hip joint replacements in RA.

Pandemic influenza vaccination elicits influenza-specific CD4+ Th1-cell responses in hypogammaglobulinaemic patients: four case reports.

In these case reports, we investigated pandemic influenza 2009 vaccination of primary hypogammaglobulinaemic patients. Three combined variable immunodeficiency (CVID) patients and one X-linked agammaglobulinaemia (XLA) patient were vaccinated with the pandemic vaccine A/California/7/2009 (H1N1)-like split virus (X179a) adjuvanted with the oil-in-water emulsion AS03. Subsequently, serum and peripheral blood mononuclear cells were sampled and used to measure the haemagglutination inhibition (HI) and antibody-secreting cell (ASC) responses. In addition, the IFN-γ, IL-2 and TNF-α producing CD4(+) Th1-cell response was determined as these cytokines are important indicators of cell-mediated immunity. Two of the CVID patients responded to vaccination as determined by a >4-fold rise in HI antibodies. These subjects also had influenza-specific ASC numbers, which, albeit low, were higher than prevaccination levels. In addition, vaccination induced CD4(+) Th1-cell responses in both the XLA patient and the CVID patients, although the frequency of influenza-responsive cells varied amongst the patients. These results suggest that hypogammaglobulinaemia patients can mount a CD4(+) Th1 cell-mediated response to influenza vaccination and, additionally, that influenza vaccination of some hypogammaglobulinaemia patients can produce an influenza-specific humoral immune response. The findings should be confirmed in larger clinical studies.

The effect of zanamivir treatment on the early immune response to influenza vaccination.

Zanamivir is licensed for influenza treatment, but may also play a role in prophylaxis either alone or in combination with vaccine in epidemic periods. We conducted a double blind placebo controlled trial to investigate the effect of zanamivir treatment on the humoral immune response to influenza vaccine. Forty young healthy volunteers were vaccinated with licensed trivalent influenza vaccine and received 20 mg zanamivir (24 subjects) or placebo (16 subjects) daily for a period of 14 days. No significant differences were observed in the magnitude or the time course of the antibody response to the influenza H3N2 and B strains between the two groups, in contrast the placebo group responded with higher antibody titres to the H1N1. Our results suggest that during an influenza epidemic, volunteers would only need to continue zanamivir treatment for the initial 12 days after vaccination whilst the vaccine induced protective antibody response developed.

Enhanced drought tolerance of a soil-dwelling springtail by pre-acclimation to a mild drought stress.

The springtail Folsomia candida has a highly permeable cuticle, but is able to survive several weeks at 98.2%RH. This corresponds to a water potential deficit of about 17bars between the environment and the normal osmotic pressure of the body fluids of this animal. Recent studies have shown a water vapour absorption mechanism by accumulation of sugars and polyols (SP) in F. candida, which explains how this species can survive dehydrating conditions. In the present study, adult F. candida were pre-acclimated at 98.2%RH to induce the accumulation of SP, and were subsequently exposed for additional desiccating conditions from 98 to 94%RH. Activity level, water content, osmotic pressure of body fluids and SP composition were investigated. After the desiccation period, the animals were rehydrated at 100%RH and survival was assessed. The results showed that F. candida survived a more severe drought stress when it had been pre-acclimated to 98.2%RH before exposure to lower humidity. This species was able to maintain hyperosmosity to the surroundings at 95.5%RH, suggesting that it can absorb water vapour down to this limit. Below this limit, trehalose levels increased while myo-inositol levels decreased. We propose that this is a change of survival strategy where F. candida at mild desiccation levels seek to retain water by colligative means (remain hyperosmotic), but at severe desiccation levels switches to an anhydrobiotic strategy.

Antibiotic susceptibility of blood culture isolates of Enterobacteriaceae. A Norwegian multicenter study.

From May to November 1997 each of six major hospitals throughout Norway collected 72 to 104 consecutive blood culture isolates of Enterobacteriaceae, altogether 563 isolates. Escherichia coli was the predominating organism (69%), followed by Klebsiella spp. (15%), Enterobacter spp. (6%), and Proteus mirabilis (4%). The susceptibility of the isolates to ampicillin, cefuroxime, ceftazidime, imipenem, tobramycin, and ciprofloxacin was determined by the E-test. 37% and 7% of the isolates were resistant to ampicillin and cefuroxime, respectively, and 1% were resistant to ceftazidime and tobramycin. Only one isolate of P. mirabilis was imipenem resistant. All isolates were susceptible to ciprofloxacin. The prevalence of ampicillin-resistant isolates at each hospital varied from 21 to 45%, and of cefuroxime-resistant isolates from 3 to 9%. The results were compared with those of a similar study performed in 1991-1992. No significant changes in the susceptibility to the various agents could be demonstrated. The high frequency of isolates resistant to ampicillin has clearly limited the usefulness of this agent in the treatment of septicemia and other serious infections caused by Enterobacteriaceae.

[Treatment of acute bacterial meningitis]. / Behandling av akutt bakteriell meningitt.

BACKGROUND: Acute bacterial meningitis requires immediate antimicrobial therapy. MATERIALS AND METHODS: Guidelines to antimicrobial treatment of children and adults with acute bacterial meningitis are presented. RESULTS: The most common agents causing acute bacterial meningitis are Streptococcus agalactiae in children less than one month of age, and Streptococcus pneumoniae and Neisseria meningitidis in individuals more than one month of age. If the causative bacterial agent is not known, children below one month of age should be given ampicillin and gentamicin, whereas older children and adults should be given benzylpenicillin in combination with either cefotaxime or ceftriaxone. We suggest treatment with specific antibiotic regimens in cases of known aetiology.

[Antibiotic treatment of infectious endocarditis]. / Antibiotikabehandling ved infeksiøs endokarditt.

BACKGROUND: Infective endocarditis is a septic condition in which the heart valves and the endocardial surfaces are infected, causing bacteraemia. In Norway, infective endocarditis is the most common infectious disease of the heart and accounts for approximately one case per 1,000 hospital admissions. The mortality rate is 15-40%. MATERIAL AND METHODS: This article presents a review of antimicrobial treatment of infective endocarditis, based on relevant literature and the author's clinical experience. Prophylactic treatment is not described. RESULTS AND INTERPRETATION: Early start of antimicrobial treatment is extremely important in order to avoid destruction of the heart valves and should always be started as soon as endocarditis is suspected and blood cultures have been drawn. The patient must be treated with bactericidal antibiotics in high doses given intravenously for four to eight weeks, depending on the aetiologic agents and the response. Only antibiotics that have been proven effective against endocarditis should be used. The minimal inhibitory concentration (MIC) should be determined for all antibiotics used.

Effects of polycyclic aromatic compounds on the drought tolerance of Folsomia fimetaria (Collembola, Isotomidae).

Drought tolerance (survival at 98.2% relative humidity and 20 degress C) was investigated for adult individuals of the springtail Folsomia fimetaria after three weeks of exposure to different polycyclic aromatic compounds (PACs). Seven PACs were investigated (acridine, dibenzofuran, carbazole, fluorene, dibenzothiophene, fluoranthene, and pyrene), with each substance used at several exposure concentrations. Sublethal concentrations of dibenzothiophene, fluorene, fluoranthene, and pyrene caused a dose-related decrease in drought tolerance in exposed adults, whereas no such relationship was found for acridine, dibenzofuran, and carbazole. The organisms used in the drought tolerance study were taken directly from standard ecotoxicity tests that had just been completed, hence the concentrations causing subsequent effects on drought tolerance and those affecting survival and reproduction in the ecotoxicity tests could be compared. Some of the tested substances significantly reduced the drought tolerance of F. fimetaria at concentrations that had little effect on survival, indicating a synergistic effect of the two stressors. However, drought tolerance was affected at concentrations below the threshold value for toxicity in standard tests (no-observed-effect concentration for reproduction) only for dibenzothiophene. In the field, soil organisms exposed to contaminants also face multiple environmental stressors such as drought and cold. Because the reduced drought tolerance is a side effect of chemical exposure, such effects should be considered when extrapolating from laboratory to field conditions.

Freeze induced glucose accumulation in the enchytraeid, Fredericia ratzeli from Greenland.

The tolerance of freezing and associated accumulation of cryoprotectants was studied in an Arctic population of the enchytraeid Fredericia ratzeli. At -3 and -5 degrees C specimens readily froze when slowly cooled in contact with moist soil. A small fraction of the animals (10-20 %) survived internal ice formation under these circumstances. Frozen specimens had elevated glucose concentrations as compared to unfrozen control animals acclimated at 0 degrees C. In a fraction of the animals, equal to the fraction surviving freezing, a high concentration of glucose was detected. The highest values amounted to ca. 150 microg mg(-1) dry weight, corresponding to ca. 270 mmoles L(-1). It is argued that the physiology of freeze tolerance in this enchytraeid resembles the physiology described for freeze tolerant earthworms and frogs.

Immunodeficiency in alpha-mannosidosis: a matched case-control study on immunoglobulins, complement factors, receptor density, phagocytosis and intracellular killing in leucocytes.

UNLABELLED: Patients with the autosomal recessive lysosomal storage disease alpha-mannosidosis suffer from recurrent infections. To study the mechanisms of this immunodeficiency, six patients were matched against six healthy controls and their humoral and cellular immunocompetence investigated. No differences in the number of circulating leucocytes including B-cells, levels of immunoglobulin main classes, nor IgG subclasses were observed. However, post-immunisation serum levels of specific antibodies against poliovirus, diphtheria toxin and tetanus toxin were significantly reduced. In patients, the density of the complement-binding receptor CD11b and the Fc-receptor CD16 was significantly enhanced on monocytes and polymorphonuclear neutrophils (PMN) and the number of phagocytosing PMN was significantly increased in the presence of pooled human serum. This was not observed in the presence of autologous serum, indicating altered opsonic properties. Also in normal PMN, phagocytosis was inhibited by a factor in the serum from the patients. Despite maintained oxidative burst, patient PMN demonstrated insufficient intracellular bacterial killing. CONCLUSION: Our data indicate that patients with alpha-mannosidosis have an immunodeficiency at both the humoral and cellular level.

Immunity to diphtheria among children in Northern Norway and North-Western Russia.

In 1990, diphtheria re-emerged in Russia and during the following four-year period the resulting epidemic reached all the Newly Independent States (NIS) of the former Soviet Union. Several neighbouring countries of NIS, Norway included, have experienced sporadic imported cases. A sero-epidemiological study among children in Northern Norway and North-Western Russia was performed in order to evaluate protection against diphtheria and how differences in vaccination programmes affect immunity. A total of 664 sera, 400 from Norwegian and 264 from Russian children, were examined for antibodies against diphtheria, using an in vitro toxin neutralisation method. The Russian children studied had satisfactory protection in all age groups examined. The Norwegian children had poor protection against diphtheria from the age of 7 years until they received the booster dose at the age of 11. Therefore, a revision of the Norwegian vaccination programme, including a booster dose at school-entry age, seems warranted.

Seasonal changes in tolerance to cold and desiccation in Phauloppia sp. (Acari, Oribatida) from Finse, Norway.

In the alpine region at Finse, Norway, Phauloppia spp. (Acari, Oribatida) inhabit lichens on top of boulders. Adult mites are about 0.5 mm in length and have a mean weight of ca. 15 µg. Temperatures in the lichens may drop below -35 degrees C in winter and increase to 55 degrees C in the summer. Large seasonal variations were recorded in supercooling points and body fluid osmolality. Mean January values of SCPs and osmolality were -35.3 degrees C and 3756 mOsm, while July values were -9.4 degrees C and 940 mOsm, respectively. Thermal hysteresis proteins were present in both summer and winter acclimated mites. In mid-winter, some of the mites survived more than 49 days in a water vapor saturated atmosphere at -19 degrees C, and more than 42 days enclosed in ice at the same temperature.The mites showed high tolerance to desiccation. Specimens collected in October survived up to 23 days at 22 degrees C and 5% RH. The tolerance to desiccation was lower in specimens collected during the winter. Some mites survived the loss of up to 90% of their total water content and were reactivated when given access to water. Length measurements of individual Phauloppia sp. showed that both male and female mites are clearly divided in two size groups, suggesting that they belong to two closely related species or different populations.

Interactions between environmental pollution and cold tolerance of soil invertebrates: a neglected field of research.

The adaptations to climatic stress of invertebrates have been extensively studied and the underlying physiology is relatively well understood. It is therefore possible to predict critical lower temperature and moisture limits at which a species will suffer increased mortality. Environmental pollution can reduce the tolerance to climatic stress considerably but it is not known how significant these synergistic effects are in polluted areas. Results are presented showing examples of synergism between toxic and climatic stress. The physiological mechanisms involved in the synergistic effects are discussed.

[Once-daily dosage of aminoglycosides--a therapeutic simplification and an economical benefit]. / Dosering av aminoglykosider en gang i døgnet--en terapeutisk forenkling og et økonomisk fremskritt.

Conventionally, aminoglycosides have been administered in two or three daily doses. Numerous in-vitro and animal experiments and several clinical trials favour a once-daily dosage regimen of aminoglycosides, which provides a more rapid concentration-dependent bacterial killing and is probably less toxic than two or three dosage regimens. In this article the pharmacological and microbiological background for once-daily aminoglycoside administration is reviewed, and some controlled trials are discussed. Recommendations for clinical practice are given.

Detection of diphtheria antitoxin by four different methods.

OBJECTIVE: To investigate the reliability of the different methods used in Norway and Russia for detection of diphtheria antitoxin. METHODS: One hundred and twenty-two sera were selected among Russian serum samples previously collected for seroepidemiologic studies of diphtheria antitoxin. The sera were selected to cover the total antitoxin range and were analyzed by four different antidiphtheria toxin assays: an in vitro toxin neutralization test using Vero cells (in vitro NT), an in vivo neutralization test using rabbit skin inoculation (in vivo NT), an indirect enzyme immunoassay (EIA) and a passive hemagglutination assay (PHA). The results were expressed according to the international standard as: not protected (<0.01 IU/mL), relatively protected (0.01-0.1 IU/mL) or protected (≥0.1 IU/mL). The sensitivity, specificity and inter-rater agreement (K or Kw) of each method were related to the in vitro NT selected as the reference method. RESULTS: The in vivo NT test corresponded very well with the in vitro NT in its ability to differentiate between protection/relative protection and no protection (sensitivity 97%, specificity 87% and K=0.84). The EIA test showed a high sensitivity (96%), but since many sera were categorized as protected rather than not protected, the specificity (30%) and inter-rater agreement (K=0.29) were low. The PHA test had a very high specificity (100%) but a low sensitivity (86%). CONCLUSIONS: The agreement between the two neutralization tests was high. If none of the neutralization assays is routinely available, the PHA test can be used to predict the need for vaccination on an individual basis but should not be used for seroepidemiologic studies, since the protection rate for diphtheria would be falsely too low, due to the lower sensitivity. The indirect EIA test used in this study should not be used routinely.

Leukocyte adhesion deficiency in a Norwegian boy.

A Norwegian boy suffering from recurrent urinary and respiratory tract infections was examined. It was found that granulocyte random migration, respiratory burst activity and the proportions of CD11/CD18 receptor positive leukocytes were reduced, consistent with a diagnosis of leukocyte adhesion deficiency. An increased proportion of Fc gammaI-receptor-bearing granulocytes did not compensate for the CR3 deficiency.

Antibiotic susceptibility of blood culture isolates of Enterobacteriaceae from six Norwegian hospitals 1991-1992.

From August 1991 to February 1992, each of the six largest hospitals throughout Norway collected 84 to 107 consecutive blood culture isolates of Enterobacteriaceae, altogether 571 isolates. The distribution of various species and genera at the different hospitals was uniform; Escherichia coli being most prevalent (57-67%), followed by Klebsiella spp. (12-18%) and Proteus mirabilis (7-11%). Twenty-one and 4% of E. coli isolates were resistant to ampicillin and cefuroxime, respectively, and 11% of Klebsiella isolates were cefuroxime resistant. Five Enterobacter isolates and one Citrobacter isolate were resistant to ceftazidime, and one Salmonella isolate was resistant to imipenem. All isolates were susceptible to ciprofloxacin and tobramycin. These results were compared with the antibiotic consumption in each hospital region. Although hospitals in the regions with the highest consumption of ampicillin tended to have a higher percentage of isolates resistant to this agent, no significant differences were found. There was no significant difference between hospitals regarding prevalence of cefuroxime-resistant isolates.