PubMed Health⌕ Search

Biomedical subjects

F Mattner

Publications and source records attributed to F Mattner.

At least 19 recordsLinked to original sources
PubMed2007

[Prevention and control of the spread of vancomycin-resistant enterococci: results of a workshop held by the German Society for Hygiene and Microbiology].

The incidence of vancomycin-resistant enterococci (VRE), especially E. faecium, is increasing in several German hospitals and some facilities have experienced VRE outbreaks. The German National Nosocomial Infection Surveillance System has also noticed a sharp increase in the incidence of nosocomial VRE infections per 10,000 patients from 0.5 in 2003 to 11.0 in 2005 accompanied by a rise in VRE-associated mortality. However, the reasons of this increase remain unknown. As VRE may cause severe nosocomial infections, transmission must be restricted. This article provides the guidelines as defined by the workshop of the German Society for Hygiene and Microbiology for the prevention of VRE transmission in both, endemic and epidemic, settings. The following topics are discussed: indication for VRE screening, microbiological diagnostics, general infection control measures (isolation precautions and use of protective clothing) and additional hygiene measures in the nosocomial VRE outbreak setting.

Cross Infection↗
PubMed2006

[Control of methicillin-resistant S. aureus by active surveillance. Results of a workshop held by the Deutsche Gesellschaft für Hygiene und Mikrobiologie].

In Germany, methicillin-resistant S. aureus (MRSA) is increasing continuously. To control the spread of MRSA, active surveillance and admission screening are recommended. In most cases, screening cultures of patients at risk for MRSA will be sufficient. Screening of all patients admitted to an ICU is cost-effective when the incidence of MRSA and nosocomial MRSA infections is high (>2 cases/100 patients and 0.3 MRSA infections/100 patients, respectively): Under these circumstances, a decrease in the incidence of nosocomial MRSA infections of 50% leads to cost-effectiveness at costs of 16 Euro/sample (including subsequent costs). If the incidence of nosocomial MRSA infections decreases by 75%, costs of 24 Euro/sample (including subsequent costs) are cost-effective. If the incidence of MRSA is high, screening by PCR may be cost-effective for patients at high risk for MRSA, especially if they are isolated prophylactically. Recently, PCR methods have been developed which allow the specific identification of MRSA even from nasal swabs.

Cost-Benefit Analysis↗
PubMed2006

Risk groups for clinical complications of norovirus infections: an outbreak investigation.

Norovirus infections have been described as self-limiting diseases of short duration. An investigation of a norovirus outbreak in a university hospital provided evidence for severe clinical features in patients with several underlying diseases. Clinical outcomes of norovirus infection were defined. Risk-factor analysis targeting underlying diseases and medication was performed using multivariate analyses. In five outbreak wards, 84 patients and 60 nurses were infected (an overall attack rate of 32% in patients, and 76% in nurses). The causative agent was the new variant Grimsby virus. Severe clinical features, including acute renal failure, arrhythmia and signs of acute graft organ rejection in renal transplant patients, were observed in seven (8.3%) patients. In multivariate analyses, cardiovascular disease (OR 17.1, 95% CI 2.17-403) and renal transplant (OR 13.0, 95% CI 1.63-281) were risk-factors for a potassium decrease of >20%. Age >65 years (OR 11.6, 95% CI 1.89-224) was a risk-factor for diarrhoea lasting >2 days. Immunosuppression (OR 5.7, 95% CI 1.78-20.1) was a risk-factor for a creatinine increase of >10%. Norovirus infections in patients with underlying conditions such as cardiovascular disease, renal transplant and immunosuppressive therapy may lead to severe consequences typified by decreased potassium levels, increased levels of C-reactive protein and creatine phosphokinase. In the elderly, norovirus infection may lead to an increased duration of diarrhoea. Therefore patients at risk should be hospitalised early and monitored frequently. Strict preventional measures should be implemented as early as possible to minimise the risk of nosocomial outbreaks.

Aged↗
PubMed2005

[Guidelines for preventing health-care-associated pneumonia].

Because of the high morbidity and mortality associated with health-care-associated pneumonia, it is important to implement evidence-based prevention measures. Recently by CDC published Guidelines for Preventing Health-Care-Associated Pneumonia describe prevention measures based on evaluated studies, randomized controlled trials or meta-analyses. In this paper the most important prevention measures are given, as well as the evidence classification. "Among the changes in the recommendations to prevent bacterial pneumonia, especially ventilator-associated pneumonia, are the preferential use of or tracheal rather than naso-tracheal tubes in patients who receive mechanically assisted ventilation, the use of noninvasive ventilation to reduce the need for and duration of endotracheal intubation, changing the breathing circuits of ventilators when they malfunction or are visibly contaminated, and (when feasible) the use of an endotracheal tube with a dorsal lumen to allow drainage of respiratory secretions."

Anti-Bacterial Agents↗
PubMed2004

Evaluation of a radiolabelled peripheral benzodiazepine receptor ligand in the central nervous system inflammation of experimental autoimmune encephalomyelitis: a possible probe for imaging multiple sclerosis.

PURPOSE: Peripheral benzodiazepine receptors (PBRs) are upregulated on macrophages and activated microglia, and radioligands for the PBRs can be used to detect in vivo neuroinflammatory changes in a variety of neurological insults, including multiple sclerosis. Substituted 2-phenyl imidazopyridine-3-acetamides with high affinity and selectivity for PBRs have been prepared that are suitable for radiolabelling with a number of positron emission tomography and single-photon emission computed tomography (SPECT) isotopes. In this investigation, the newly developed high-affinity PBR ligand 6-chloro-2-(4'-iodophenyl)-3-(N,N-diethyl)imidazo[1,2-a]pyridine-3-acetamide, or CLINDE, was radiolabelled with 123I and its biodistribution in the central nervous system (CNS) of rats with experimental autoimmune encephalomyelitis (EAE) evaluated. METHODS: EAE was induced in male Lewis rats by injection of an emulsion of myelin basic protein and incomplete Freund's adjuvant containing Mycobacterium butyricum. Biodistribution studies with 123I-CLINDE were undertaken on EAE rats exhibiting different clinical disease severity and compared with results in controls. Disease severity was confirmed by histopathology in the spinal cord of rats. The relationship between inflammatory lesions and PBR ligand binding was investigated using ex vivo autoradiography and immunohistochemistry on rats with various clinical scores. RESULTS: 123I-CLINDE uptake was enhanced in the CNS of all rats exhibiting EAE when compared to controls. Binding reflected the ascending nature of EAE inflammation, with lumbar/sacral cord>thoracic cord>cervical cord>medulla. The amount of ligand binding also reflected the clinical severity of disease. Ex vivo autoradiography and immunohistochemistry revealed a good spatial correspondence between radioligand signal and foci of inflammation and in particular ED-1+ cells representing macrophages and microglia. CONCLUSION: These results demonstrate the ability of 123I-CLINDE to measure in vivo inflammatory events represented by increased density of PBRs and suggest that 123I-CLINDE warrants further investigation as a potential SPECT marker for imaging of CNS inflammation.

Animals↗
PubMed2004

Two case reports: fatal Absidia corymbifera pulmonary tract infection in the first postoperative phase of a lung transplant patient receiving voriconazole prophylaxis, and transient bronchial Absidia corymbifera colonization in a lung transplant patient.

Absidia corymbifera is a rare cause of pulmonary tract infection. There exist only 5 case reports predominantly diagnosed in bone marrow transplant patients. Lung transplant patients are at high risk for invasive fungal infections. Due to A. corymbifera as pathogen, known to be voriconazole resistant, a fatal invasive pulmonary mycosis occurred. In the present case voriconazole prophylaxis failed. A second patient showed a transient colonization of the bronchi. To prevent airborne transmitted invasive pulmonary mycosis in the first postoperative period of lung transplantation the patient should be situated in a room ventilated by HEPA-filtered air. The specific treatment should start very early when first suspicion arises. A review of the literature on pulmonary tract infections induced by Absidia corymbifera is provided.

Absidia↗
PubMed2002

Improvement of the enzymatic stability of a cytotoxic T-lymphocyte-epitope model peptide for its oral administration.

Oral administration of peptide antigens, to provide proper mucosal and/or systemic immunity, is largely ineffective. This is mainly due to the very small quantity of antigen that survives degradation in the intestine and that crosses the intestinal absorption membrane. The present study focuses on the improvement of the enzymatic stability of a 13 amino acid long peptide containing a cytotoxic T-lymphocytes (CTL)-epitope. Within this study, it is shown, that simple chemical modification at the N- and C-terminus of the peptide can provide significant stability towards enzymatic attack by intestinal exopeptidases. Around 50% of the modified peptide resisted enzymatic attack on native porcine intestinal mucosa within 3h of incubation at pH 6.8 and 37 degrees C, whereas unmodified control peptide was almost completely degraded within the same time period. Additionally, a mucoadhesive drug carrier matrix with specific inhibitory properties towards luminally secreted endopeptidases has been generated. The incorporation of the simply modified peptide in this delivery system should enhance the amount of biologically active antigen being available at the mucosal site for further presentation to immunomodulating systems. This might open the door for a successful oral immunotherapy.

Administration, Oral↗
PubMed2001

Pharmacological evaluation of (+)-2- [123I]A-69024: a radioligand for in vivo studies of dopamine D1 receptors.

(+)-2-[123I] A-69024, [(+)-1-(2-[123I] iodo-4,5-dimethoxy-benzyl)-7-hydroxy-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline], is a specific and enantioselective dopamine D1 receptor radioligand. The in vivo biodistribution of this radioligand in rats showed high brain uptake and a distribution consistent with the density of dopamine D1 receptors. Highest uptake was observed in the striatum (0.65 %ID/g) at 5 min followed by clearance. As a measure of specificity the striatum/cerebellar ratio reached a maximum of 3.9 at 30 min post-injection. Radioactivity in the striatum was reduced by 68% by pre-administration of the D1 antagonist SCH 23390. Pre-administration of other dopamine binding drugs, spiperone (D2), 7-OH-DPAT (D3), and clozapine (D4) displayed no inhibitory effect on (+)-2-[123I]A-69024 accumulation in any brain region. Ketanserin (5-HT2/5-HT2C) and haloperidol (D2 receptor antagonist/sigma receptor ligand) also displayed no inhibitory effect in any brain region studied. With the pharmacologically inactive enantiomer, (-)-2-[123I]A-69024, the brain uptake was determined to be non-specific since a striatum/cerebellar ratio of near 1 was observed throughout the time course of the experiment. (+)-2-[123I]A-69024 displays enantioselectivity for dopamine D1 receptors and may deserve further investigation as a possible SPECT radioligand.

Animals↗
PubMed2001

Defined synthetic vaccines.

Although vaccines have proven very successful in preventing certain infectious diseases, progress in the field has been slowed by the tediousness of developing classical vaccines consisting of whole pathogens. Thus, there is great need for improvement in several areas: firstly, the range of diseases which can be treated has to be expanded. Secondly, antigens have to be defined to make the use of whole pathogens as antigen obsolete. And thirdly, new adjuvants have to be developed which show low toxicity, high potency and are also able to drive the immune response in the desired direction. Ideally, a vaccine would only consist of well-characterized, synthetic materials. This review summarizes the different approaches for the development of completely defined synthetic vaccines.

Adjuvants, Immunologic↗
PubMed2000

Inhibition of Th1 development and treatment of chronic-relapsing experimental allergic encephalomyelitis by a non-hypercalcemic analogue of 1,25-dihydroxyvitamin D(3).

1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] inhibits production of IL-12, a cytokine involved in the development of Th1 cells and in the pathogenesis of Th1-mediated autoimmune diseases. Here, we show that 1,25(OH)(2)D(3) and a non-hypercalcemic analogue are selective and potent inhibitors of Th1 development in vitro and in vivo without inducing a deviation to the Th2 phenotype. Administration of 1,25(OH)(2)D(3) or its analogue prevents chronic-relapsing experimental allergic encephalomyelitis (CR-EAE) induced by the myelin oligodendrocyte glycoprotein (MOG) peptide 35 - 55 (MOG(35 - 55)) in Biozzi AB / H mice. The inhibition of EAE induction is associated with a profound reduction of MOG(35 - 55)-specific proliferation and Th1 cell development. Importantly, the non-hypercalcemic analogue also provides long-term protection from EAE relapses induced by immunization with spinal cord homogenate when administered for a short time at symptom onset or even after the first peak of disease. Neuropathological analysis shows a reduction of inflammatory infiltrates, demyelinated areas and axonal loss in brains and spinal cords of treated mice. These resuls indicate that inhibition of IL-12-dependent Th1 cell development is associated with effective treatment of CR-EAE and suggest the feasibility of an approach based on low molecular weight inhibitors of IL-12 production in the treatment of multiple sclerosis.

Animals↗
PubMed1999

Synthesis and evaluation of [123I]labelled analogues of the partial inverse agonist Ro 15-4513 for the study of diazepam-insensitive benzodiazepine receptors.

The imidazobenzodiazepines ethyl 8-iodo-5,6 dihydro-5-methyl-6-oxo-4H-imidazo[1,5a][1,4] benzodiazepine-3-carboxylate 1 and tert-butyl 8-iodo-5,6 dihydro-5-methyl-6-oxo-4H-imidazo [1,5a][1,4] benzodiazepine-3-carboxylate 2 were prepared to study the diazepam-insensitive (DI) benzodiazepine receptor (BZR) subtype. The [123I] analogues were prepared via iododestannylation reactions in radiochemical yields of 70-80% and a specific activity >2,500 Ci/mmol. The tert-butyl analogue [123I]-2 exhibited nanomolar affinity for BZRs in homogenate membranes of rat cerebellum with Kd values for the diazepam-sensitive (DS) and DI receptors of 3.18 +/- 0.58 and 13.55 +/- 2.72 nM, respectively. The Bmax for cerebellar DS and DI receptors were 1,276 +/- 195 and 518 +/- 26 fmol/mg protein, respectively.

Animals↗
PubMed1998

Interleukin-12 is essential for a protective Th1 response in mice infected with Cryptococcus neoformans.

To analyze the roles of interleukin-12 (IL-12) and the IL-12-dependent Th1 response in resistance to Cryptococcus neoformans, we have established a chronic infection model in wild-type mice and in mice with targeted disruptions of the genes for the IL-12p35 and IL-12p40 subunits (IL-12p35(-/-) and IL-12p40(-/-) mice, respectively) as well as in mice with a targeted disruption of the IL-4 gene. Long-term application of exogenous IL-12 prevented death of infected wild-type mice for the entire period of the experiment (up to 180 days) but did not resolve the infection. Infected IL-12p35(-/-) and IL-12p40(-/-) mice died significantly earlier than infected wild-type mice, whereas infection of IL-4-deficient mice led to prolonged survival. Interestingly, infected IL-12p40(-/-) mice died earlier and developed higher organ burdens than IL-12p35(-/-) mice, which, for the first time in an infection model, suggests a protective role of the IL-12p40 subunit independent of the IL-12 heterodimer. The fungal organ burdens of IL-4-deficient mice and IL-12-treated wild-type mice were significantly reduced compared to those of untreated wild-type mice and IL-12-deficient mice. Histopathological analysis revealed reduction of the number of granulomatous lesions following treatment with IL-12. Susceptibility of both IL-12p35(-/-) and IL-12p40(-/-) mice was associated with marginal production of gamma interferon and elevated levels of IL-4 from CD4(+) T cells, which indicates Th2 polarization in the absence of IL-12, whereas wild-type mice developed a Th1 response. Taken together, our data emphasize the essential role of IL-12 for protective Th1 responses against C. neoformans.

Animals↗
PubMed1997

Interleukin-12 is indispensable for protective immunity against Leishmania major.

Interleukin-12 (IL-12)-deficient mice derived from a strain genetically resistant to infection with Leishmania major were recently shown to be susceptible toward this parasite, developing a strong Th2 response after injection of a large number of parasites. We further investigated the role of IL-12 in L. major infection by studying the responses of mutant mice against smaller numbers of parasites. IL-12-deficient mice infected with only small numbers of parasites showed the progressive lesion development and high parasite burden associated with a polarized Th2 response. Our data show that IL-12 is indispensable for protective immunity against L. major. Even at low inocula, no salvage pathway appears to compensate for the lack of IL-12. However, genetically susceptible BALB/c mice infected with small numbers of parasites were able to resolve lesions and restrict the parasite burden to levels which were 10(5)-fold lower than those in IL-12-deficient mice. In contrast to mutant mice, BALB/c mice mounted a type 1 response against low inocula of L. major. IL-12-deficient BALB/c mice, however, developed a type 2 response. These data emphasize the essential role of IL-12 in resistance against L. major. In addition, this study suggests that in the absence of IL-12, susceptibility to L. major is determined by the inability to induce a Th1 response rather than the development of a Th2 response. Our results are relevant for potential vaccination strategies that use low inocula of infective microorganisms which fail to induce a protective type 1 response at higher inocula.

Animals↗
PubMed1997

Treatment with homodimeric interleukin-12 (IL-12) p40 protects mice from IL-12-dependent shock but not from tumor necrosis factor alpha-dependent shock.

The role of interleukin-12 (IL-12) was investigated in different shock models using anti-IL-12 reagents. IL-12 is composed of two disulfide-bonded subunits, p35 and p40. The IL-12 p40 homodimer (p40)2 has been shown to be a potent IL-12 antagonist in vitro. We investigated its in vivo inhibitory capacity in different shock models of mice. We could demonstrate that (p40)2 is able to protect mice from septic shock in primarily IL-12-dependent models such as the Shwartzman reaction and lipopolysaccharide (LPS)-induced shock, whereas (p40)2 has no effect in the tumor necrosis factor alpha-dependent LPS/D-GalN shock model. In IL-12-dependent shock models, (p40)2 inhibits IL-12-induced gamma interferon production and thereby interferes with the cascade of cytokine release, finally leading to death.

Animals↗
PubMed1996

Genetically resistant mice lacking interleukin-12 are susceptible to infection with Leishmania major and mount a polarized Th2 cell response.

Mice with homologous disruption of the gene coding for either the p35 subunit or the p40 subunit of interleukin-12 (IL-12) and derived from a strain genetically resistant to infection with Leishmania major have been used to study further the role of this cytokine in resistance to infection and the differentiation of functional CD4+ T cell subsets in vivo. Wild-type 129/Sv/Ev mice are resistant to infection with L. major showing only small lesions which resolve spontaneously within a few weeks and develop a type 1 CD4+ T cell response. In contrast, mice lacking bioactive IL-12 (IL-12p35-/- and IL-12p40-/-) developed large, progressing lesions. Whereas resistant mice were able to mount a delayed-type hypersensitivity (DTH) response to Leishmania antigen, susceptible BALB/c mice as well as IL-12-deficient 129/Sv/Ev mice did not show any DTH reaction. To characterize the functional phenotype of CD4+ T cells triggered in infected wild-type mice and IL-12-deficient mice, the expression of mRNA for interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) in purified CD4+ lymph node cells was analyzed. Wild-type 129/Sv/Ev mice showed high levels of mRNA for IFN-gamma and low levels of mRNA for IL-4 which is indicative of a Th1 response. In contrast, IL-12- deficient mice and susceptible BALB/c mice developed a strong Th2 response with high levels of IL-4 mRNA and low levels of IFN-gamma mRNA in CD4+ T cells. Similarly, lymph node cells from infected wild-type 129 mice produced predominantly IFN-gamma in response to stimulation with Leishmania antigen in vitro whereas lymph node cells from IL-12-deficient mice and susceptible BALB/c mice produced preferentially IL-4. Taken together, these results confirm in vivo the importance of IL-12 in induction of Th1 responses and protective immunity against L. major.

Animals↗