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Biomedical subjects

B J Kullberg

Publications and source records attributed to B J Kullberg.

At least 109 records · Page 6Linked to original sources
PubMed1996

Low-density lipoprotein receptor-deficient mice are protected against lethal endotoxemia and severe gram-negative infections.

Lipoproteins can bind lipopolysaccharide (LPS) and decrease the LPS-stimulated production of pro-inflammatory cytokines. We investigated the effect of increased plasma concentrations of low-density-lipoproteins (LDL) on survival and cytokine production after a lethal challenge with either LPS or live Gram-negative bacteria in LDL receptor deficient mice (LDLR-/-). The LDLR-/- mice challenged with LPS had an eightfold increased LD50 when compared with the wild type controls (C57Bl/6J), while tumor necrosis factor alpha (TNFalpha) and interleukin-1 alpha (IL-1 alpha) plasma concentrations were decreased twofold. LDLR-/- mice had significantly lower and delayed mortality than control mice after infection with Klebsiella pneumoniae. No differences in the outgrowth of bacteria in the organs were present between the two groups, while circulating cytokine concentrations were decreased twofold in LDLR-/- mice. In contrast, the LPS-stimulated in vitro production of cytokines by peritoneal macrophages of LDLR-/- mice was significantly increased compared with controls. This increase was associated with enhanced specific binding of LPS to the macrophages of LDLR-/- mice. In conclusion, endogenous LDL can protect against the lethal effects of endotoxin and Gram-negative infection. At least part of this protection is achieved through decreased in vivo production of pro-inflammatory cytokines, in spite of increased cytokine production capacity.

Animals↗
PubMed1996

[The changing pattern of Candida infections: different species and increased resistance].

The incidence of invasive infections with Candida has strongly increased during the last few decades. Candida is now one of the commonest hospital pathogens. Many infections are nowadays caused by other species than C. albicans, notably C. tropicalis, C. krusei and C. glabrata. Particularly in HIV seropositive patients the yeast may develop resistance to fungistatic drugs. The altered species frequency and the resistance appear to be caused by the use of fungistatic agents of the imidazole group. To counter these developments the choice of antifungal therapeutics should be made very carefully.

Antifungal Agents↗
PubMed1995

Improving the quality of antimicrobial drug use can result in cost containment.

Antibiotic policies are implemented to optimize patient care, to limit antimicrobial resistance and to reduce costs. Before improving the use of antimicrobial drugs by monitoring, it is of primary importance to conduct a general utilization review to document problem areas within the hospital and to evaluate quality and costs. Subsequently, limited targets for an intervention can be defined. For the evaluation of quality, established criteria can be used to classify prescriptions into categories of appropriate use. Several classification systems are described in the literature. We have developed a classification method which allows evaluation of each relevant parameter associated with antimicrobial drug use and global (true) cost calculation. Data are processed in a computer program for Apple or Windows. Surgical prophylaxis is a target of choice to analyse at a hospital pharmacy level. Important cost savings can be obtained by implementing well-accepted standards of good antimicrobial prophylaxis.

Anti-Bacterial Agents↗
PubMed1995

An open study on the safety and efficacy of fluconazole in the treatment of disseminated Candida infections in patients treated for hematological malignancy.

Disseminated candidiasis is a serious infectious complication with a mortality as high as 50%. Standard therapy consists of parenteral amphotericin B which is associated with major side effects and prolonged hospitalization. The aim of the study was to assess the efficacy and safety of fluconazole in an open, noncomparative study. Fluconazole, as a single agent, was given intravenously for the first 3 days at a dose of 200 mg twice daily, followed by 200 mg twice daily orally until resolution of signs and symptoms or evident treatment failure. The study group comprised 24 consecutive patients of whom nine had acute and 15 chronic disseminated candidiasis. A clinical response was achieved in 67% of cases of acute disseminated candidiasis and in 86% of cases of chronic disseminated candidiasis. The median duration of therapy was 15 days and 6 months, respectively. Superinfections with Aspergillus fumigatus developed in five patients who were persistently neutropenic. No drug-related toxicity was registered.

Administration, Oral↗
PubMed1995

Pharmacologic inhibitors of tumor necrosis factor production exert differential effects in lethal endotoxemia and in infection with live microorganisms in mice.

Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) are principal mediators of septic shock; inhibition of TNF-alpha production may ameliorate outcome in severe infections. Pentoxifylline, chlorpromazine, and thalidomide inhibit TNF-alpha production. Their effects were tested in lethal endotoxemia in sensitized mice. Only chlorpromazine significantly improved survival. Chlorpromazine and pentoxifylline significantly reduced postendotoxin circulating TNF-alpha, by 89% and 76%, respectively. Chlorpromazine also significantly reduced IL-1 beta and soluble TNF receptor-P75. No drug improved survival in Klebsiella pneumoniae-infected mice despite significantly lower circulating TNF-alpha concentrations in chlorpromazine- or pentoxifylline-treated animals. The three compounds decreased circulating TNF-alpha in Candida albicans-infected mice, but survival was not influenced. In neutropenic mice, chlorpromazine had no influence on candida in organs, but in normal mice, Candida counts in kidneys were higher in chlorpromazine-treated mice. Thus, inhibition of TNF-alpha production was of no benefit in K. pneumoniae infection and worsened outcome in C. albicans infection.

Animals↗
PubMed1995

Phospholipase A2 is a circulating mediator in typhoid fever.

Circulating proinflammatory mediators have not been found in studies on typhoid fever, although the patients suffer from a systemic disease with characteristic protracted fever. The 14-kDa group II extracellular phospholipase A2 (PLA2) is induced by interleukin-1 and tumor necrosis factor and may mediate some of the effects of these cytokines. Circulating PLA2 concentrations were measured in 12 typhoid fever patients on various days after admission and after recovery. On admission, mean concentrations of PLA2 were elevated (1444 +/- 1560 ng/mL) and decreased gradually and significantly to day 14 (55 +/- 48 ng/mL). patients with complicated disease had significantly higher PLA2 levels on admission. PLA2 was not produced in a lipopolysaccharide-stimulated whole blood culture, indicating that PLA2 originates from other types of cells. These data indicate that PLA2 may be a mediator of disease in protracted inflammatory diseases such as thyroid fever.

Adolescent↗
PubMed1994

Interleukin-1 and related pro-inflammatory cytokines in the treatment of bacterial infections in neutropenic and non-neutropenic animals.

Bacterial infections in the immunocompromized host cause considerable mortality, and even the recently developed antimicrobial strategies often fail to cure these infections, especially in granulocytopenic patients. Cytokines and hematopoietic growth factors have been shown to stimulate host defense mechanisms in vitro and in vivo. We discuss the possible role of the pro-inflammatory cytokines interleukin-1, tumor necrosis factor-alpha, interleukin-6 and interleukin-8 as modulators of host resistance to bacterial infections. Interleukin-1 has been shown effective in various animal models of potentially lethal bacterial infection, even during severe granulocytopenia. The protective mechanism of interleukin-1 may be mediated via downregulation of cytokine receptors and cytokine production, and via induction of acute phase proteins. Moreover, in subacute and chronic infections interleukin-1 interferes with microbial outgrowth, via mechanisms that have only been partially elucidated.

Animals↗
PubMed1994

Cytokines in the treatment of fungal infections.

The incidence of invasive fungal infections in the immunocompromized host has increased during the past decade. Even the recently developed antifungal drugs are unable to cure these infections in patients with severely impaired host defense mechanisms. Cytokines have great potential to augment host resistance and as adjunctive therapy of invasive mycoses. We discuss the mechanisms of host defense against invasive candidiasis, aspergillosis, and cryptococcosis, and review the use of cytokines and growth factors in this setting. Interleukin-1 has been shown effective in an animal model of disseminated candidiasis, even during severe granulocytopenia. Interferon-gamma has been very effective as a modulator of resistance against a variety of fungal infections in vitro. The effect of interferon-gamma against disseminated candidiasis has been demonstrated in a mouse model. Activation of neutrophils is the main mechanism by which interferon-gamma enhances the elimination of Candida, and consequently the agent is not effective in severely granulocytopenic animals. Data on the role of colony-stimulating factors against fungal pathogens are accumulating, and trials with these agents for hematologic patients with invasive fungal infections are now being performed.

Animals↗
PubMed1994

Severe osteomyelitis due to the zygomycete Apophysomyces elegans.

We describe a previously healthy 69-year-old man presenting with osteomyelitis of the humerus due to the zygomycete Apophysomyces elegans. The infection was acquired in Aruba, The Netherlands Antilles. The skin provided the most likely portal of entry, although there was no history of a traumatic inoculation. The patient had no history of diabetes, and no underlying immune defects were found. Despite treatment with 7.9 g of amphotericin B, an interthoracoscapular amputation proved necessary to curtail the rapid spread of the fungus in this immunocompetent host.

Aged↗
PubMed1993

Recombinant interferon-gamma enhances resistance to acute disseminated Candida albicans infection in mice.

The effect of recombinant rat interferon-gamma (rIFN-gamma) on acute disseminated Candida albicans infection in mice was investigated. Outgrowth of C. albicans in kidneys, spleen, and liver of mice treated with one intravenous (iv) dose of rIFN-gamma before iv injection of 5 x 10(5) cfu of C. albicans was significantly lower than in controls over 7 days. rIFN-gamma was protective when given 1 day before, simultaneously with, or 1-3 days after infection but not when given 3 days before. In mice pretreated with hydrocortisone acetate, rIFN-gamma significantly reduced the outgrowth only when 10(3) cfu of C. albicans was injected. Injection of rIFN-gamma did not reduce the outgrowth of C. albicans in cyclophosphamide-pretreated mice and significantly increased the capacity of peripheral blood and exudate peritoneal granulocytes to kill C. albicans in vitro. Thus, rIFN-gamma enhances host resistance against acute disseminated C. albicans infection in mice through activation of polymorphonuclear leukocytes.

Analysis of Variance↗