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Biomedical subjects

B Hofmann

Publications and source records attributed to B Hofmann.

At least 55 records · Page 3Linked to original sources
PubMed1998

Relationship between ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin and moxifloxacin (BAY 12-8039) MICs and mutations in grlA, grlB, gyrA and gyrB in 116 unrelated clinical isolates of Staphylococcus aureus.

The in-vitro activities of five fluoroquinolones were tested against 70 ciprofloxacin-resistant and 46 ciprofloxacin-susceptible unrelated isolates of Staphylococcus aureus. All 116 S. aureus isolates were studied for the presence of mutations in the grl and gyr loci. The order of efficacy of the fluoroquinolones tested, from least to most active, was: ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin and moxifloxacin (BAY 12-8039), in response to all characterized mutations in grlA, grlB, gyrA and gyrB. Moxifloxacin was active against most S. aureus isolates tested (MIC90 = 1 mg/L for ciprofloxacin-resistant isolates) and was less influenced by known mutations.

Anti-Infective Agents↗
PubMed1998

The prevalence of low- and high-level mupirocin resistance in staphylococci from 19 European hospitals.

The topical agent mupirocin plays a crucial role in strategies designed to control outbreaks of methicillin-resistant Staphylococcus aureus. The extent of high- or low-level mupirocin resistance amongst S. aureus from European hospitals is not known. Six hundred and ninety-nine S. aureus and 249 coagulase-negative staphylococci (CNS) derived from blood, hospital-acquired pneumonia or skin and soft tissue infections from 19 European hospitals were tested for susceptibility to mupirocin and oxacillin. Methicillin sensitivity was found in 72% and 32% of S. aureus and CNS, respectively. High-level mupirocin resistance was detected in 1.6% of S. aureus and 5.6% of CNS isolates, while low-level mupirocin resistance was detected in 2.3% of S. aureus and 7.2% of CNS isolates. Amongst S. aureus, methicillin-resistant isolates were twice as likely to have high- or low-level mupirocin resistance. This difference was less pronounced in CNS. No relationship was found between the site of infection and prevalence of mupirocin resistance. High- and low-level mupirocin resistance was detected amongst staphylococci from 10 and 16 of the hospitals studied, respectively. To maintain the relatively low prevalence of mupirocin resistance in Europe amongst both S. aureus and CNS, the prudent use of mupirocin restricted to defined infection control strategies should be emphasized.

Anti-Bacterial Agents↗
PubMed1998

The effect of reserpine, an inhibitor of multidrug efflux pumps, on the in-vitro activities of ciprofloxacin, sparfloxacin and moxifloxacin against clinical isolates of Staphylococcus aureus.

In Staphylococcus aureus, in addition to mutations in the grl and gyr gene loci, multidrug efflux pumps like NorA contribute to decreased fluoroquinolone susceptibility. Efflux pumps can be inhibited by the plant alkaloid reserpine, which, at 20 mg/L, reduced sparfloxacin, moxifloxacin and ciprofloxacin IC50s and MICs by up to four-fold in 11, 21 and 48 of the 102 unrelated clinical isolates tested, respectively. The effect was less pronounced with the hydrophobic drugs sparfloxacin and moxifloxacin than with the hydrophilic drug ciprofloxacin and was stable in all 25 clonally related isolates tested.

Anti-Infective Agents↗
PubMed1998

Development of a multiplex-PCR for direct detection of the genes for enterotoxin B and C, and toxic shock syndrome toxin-1 in Staphylococcus aureus isolates.

As well as conventional methods such as immunodiffusion, ELISA, or agglutination for the detection of toxin production in Staphylococcus aureus, amplification techniques like PCR allow a very sensitive and specific identification of the genes responsible for enterotoxin B and C, and TSST-1 production. These toxins might be a cause of the toxic shock syndrome (TSS). For that reason an easy and quick test system for determining the toxin production pattern of S. aureus isolates is desirable so that strains suspected to be toxin producers may be identified much faster and easier. In the present investigation, a new multiplex-PCR method was used that allowed single bacterial colonies grown on agar plates to be used directly in the PCR assay without preceding preparation. This procedure generated information concerning the presence of seb, sec-1 and tst genes within 4 h in a single test. To analyse the sensitivity and the specificity of this procedure, 100 methicillin-resistant S. aureus (MRSA), 50 coagulase-negative staphylococci and 50 other eubacterial isolates were tested initially with sets of single primer pairs followed by a combined multiplex-PCR. Results of this amplification technique were compared to a conventional and widely used method for toxin detection, reversed passive latex agglutination (RPLA). With the RPLA assay results as the basis, sensitivity and specificity of the seb and tst primer sets were 100%, whereas sensitivity and specificity of the sec-1 primer set were 100% and 82%, respectively. With the sec-1 primer set, two isolates were identified as carrying the corresponding toxin gene although the RPLA test did not show any detectable toxin. The multiplex-PCR rapidly generated reliable information concerning the toxin-producing capacity of staphylococcal strains and could be easily integrated into a multiplex procedure described previously. The latter enabled the identification of specific PCR products for eubacteria and staphylococci as well as the detection of the coa and mecA genes.

Bacterial Toxins↗
PubMed1998

Typing of methicillin-resistant Staphylococcus aureus isolates from Düsseldorf by six genotypic methods.

Nosocomial infections caused by methicillin-resistant Staphylococcus aureus (MRSA) represent an increasing problem in hospitals. Quick and reliable typing methods are required to obtain information about the relatedness of MRSA isolates and to allow faster implementation of appropriate infection control measures. This investigation describes the distribution of MRSA isolates from 11 hospitals in the Düsseldorf region of Germany, and the ability of six different genotypic typing techniques -- pulsed-field gel electrophoresis (PFGE), random amplification of polymorphic DNA (RAPD), 16S-23S rDNA spacer amplification, protein A-gene PCR, PCR characterisation of the hypervariable region (HVR) adjacent to mecA, and coagulase gene-PCR -- to detect different unrelated types. Of 7814 S. aureus isolates tested, 489 (6.3%) were MRSA, of which 183 were selected for subsequent molecular analyses on the basis of being the first MRSA isolated from colonised or infected patients. Larger hospitals had a higher incidence of MRSA and a greater variability in genotypes than smaller hospitals. All methods confirmed the presence of two main clonal types. The ability of techniques to detect different unrelated types was found to be as follows: PFGE, 28 types; 16S-23S rDNA spacer-amplification, 10 types; RAPD, nine types; protein A-gene PCR, five types; HVR-PCR, five types; and coa gene-PCR, two types. Combination of PFGE and one other PCR-based method (spacer-amplification, RAPD or protein-A gene PCR) provided the best resolution of types and allowed the identification of subtypes. Similar molecular types were identified with international MRSA isolates. Although PCR-based techniques have the advantage of rapid performance and easy handling, their discriminatory capacity is inferior compared to the more labour intensive PFGE.

Bacterial Typing Techniques↗
PubMed1998

Characterization of grlA, grlB, gyrA, and gyrB mutations in 116 unrelated isolates of Staphylococcus aureus and effects of mutations on ciprofloxacin MIC.

One hundred sixteen unrelated clinical isolates of Staphylococcus aureus (70 ciprofloxacin resistant and 46 ciprofloxacin susceptible) from eight countries were studied for the presence of mutations in the grlA, grlB, gyrA, and gyrB gene loci. Two mutations within grlA (located at codons 80 and 84) and two mutations within gyrA (located at codons 84 and 88) were clearly associated with ciprofloxacin resistance, although other mutations detected within the four genes studied may also contribute to decreased susceptibility.

Anti-Infective Agents↗
PubMed1998

[Cleavage and biotransformation of the central muscle relaxant chlormezanone].

Chlormezanone, a chiral centrally acting muscle relaxant, will be cleaved at its S-C-1 bond by an autoprotolytic process. The optimum of chemical stability exists between pH 2 up to pH 9 with a maximum at pH 7.4. The plasma half life at 37 degrees C is 76 h. Enzymes do attack the products of cleavage namely 4-chlorobenzaldehyde and 2-carboxyethane-sulfinic-acid-N-methyl-amide. The main metabolite in urine is 4-chlorohippuric acid in the range of up to 70% of the oral administered dose to humans. No cytochrome P-450 is engaged in the cleavage of the S-C-bond.

Biotransformation↗
PubMed1997

[From the history of electrocardiography].

The basis of electrocardiography was established in the innovative years between 1850 and 1930. Men like Waller, DuBois-Reymond, and Einthoven were the innovators of what we today recognize as modern electrocardiography. Others, like Lewis and Bedford, introduced analysis of cardiac arrhythmias, of the S-T segment and the QRS complex. The article gives an overview of this innovative period and its instrumentation.

Electrocardiography↗
PubMed1997

[Medical equipment--errors, causes and risks].

Development in technology has introduced advanced technological apparatus into the health care sector. New technology has led to increased possibilities in diagnostics and treatment, but it also represents a substantial risk. A survey at the Lillehammer Hospital showed a relatively high rate of apparatus failure. However, only in a few cases was this of any consequence to the patient or the operator. The survey showed that preventive maintenance reduces the failure rate and that operator training and user checks reduce the risk related to medical apparatus.

Equipment Failure↗
PubMed1997

HIV-infected individuals with the CCR delta32/CCR5 genotype have lower HIV RNA levels and higher CD4 cell counts in the early years of the infection than do patients with the wild type. Copenhagen AIDS Cohort Study Group.

The relations among serum HIV RNA levels, CD4 cell counts, presence of the mutant CCR5-allele in heterozygous form, and clinical outcome was analyzed in 96 patients from the Copenhagen AIDS Cohort. In the early years of the infection, patients with the CCR5 delta32/CCR5 genotype had significantly lower HIV RNA levels (p = 0.005) and higher CD4 cell counts (p < 0.005) than did patients homozygous for the normal allele. The long-term clinical benefit of being heterozygous is small and cannot solely explain the large interpatient variation in progression rates. The beneficial effect of being heterozygous seems to be mediated by events in the early stages of the HIV infection.

CD4 Lymphocyte Count↗
PubMed1997

[Holistic health and specific disease].

Health and disease are cardinal concepts in all medical activity. There are two main theories of the conceptual structure of medicine. The reductionist theory defines the concept of disease as deviation of bodily or mental functions, while the holistic theory tries to establish a positive concept of health. The reductionist theory claims to be essensialistic, descriptive and objective, while the holistic theories are supposed to be nominalistic, normative and subjective. A presentation of the theories show that both positions involve conceptual difficulties.

Europe↗
PubMed1997

Susceptibility to HIV infection and progression of AIDS in relation to variant alleles of mannose-binding lectin.

BACKGROUND: Low serum concentrations of mannose-binding lectin (MBL) are associated with increased susceptibility to recurrent infection. Three variant alleles in the MBL gene (B, C, and D), cause low serum concentrations of the protein. We investigated whether variant alleles of MBL affect susceptibility to infection with HIV and progression of AIDS. METHODS: Between 1983 and 1986, all men who attended two clinics in Copenhagen for HIV screening were invited to take part in our study. We investigated the prevalence of variant alleles of MBL (detected by PCR) and assessed the prognostic value of these alleles and the corresponding serum MBL concentrations (measured by ELISA) in 96 homosexual men with HIV infection and in two control groups (123 healthy adults and 36 HIV-negative homosexual men at high risk of HIV infection because of their sexual behaviour). Follow-up was for up to 10 years. FINDINGS: Eight (8%) of the HIV-infected men were homozygous for the variant MBL alleles compared with one (0.8%) of the healthy controls (p = 0.005) and none of the high-risk homosexual controls (p = 0.05). We found no significant association between MBL genotype and time from first positive HIV test to progression of AIDS (p = 0.8). However, in the 61 HIV-infected men who developed AIDS, the median survival time was significantly shorter after the AIDS diagnosis for men who were carriers of the variant alleles (both homozygous and heterozygous) than for men homozygous for the normal MBL allele (11 [IQR 4-21] vs 18 months [9-44], p = 0.007). Among men who developed AIDS, there was a significant difference in survival time between those with serum MBL concentrations below the lower quartile, those within the IQR, and those above the upper quartile (p = 0.02). Multivariate analysis showed that men who developed AIDS and had low serum MBL concentrations had an increased rate of rapid death, independently of CD4 T-cell counts at AIDS diagnosis. INTERPRETATION: Our findings suggest that homozygous carriers of variant MBL alleles are at increased risk of HIV infection, either directly or indirectly because of increased susceptibility to coinfections. These alleles are also associated with a significantly shorter survival time after a diagnosis of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Serotonin modulates immune function in T cells from HIV-seropositive subjects.

We have shown earlier increased intracellular levels of cAMP in peripheral lymphocytes from HIV-seropositive subjects and that a chemically induced decrease in this level increases cell proliferation and cytotoxicity. Others have shown that serotonin indirectly decreases intracellular cAMP levels in normal peripheral lymphocytes. In this study, we show that addition of serotonin decreases intracellular levels of cAMP in lymphocytes from HIV-seropositive subjects and significantly increases the proliferative capacity in vitro. However, the effect of serotonin varies with the initial proliferative response; e.g., these with the highest initial responses have the highest increases. An increase in IL-2 production may be a part of this mechanism since addition of serotonin to in vitro cultures of PHA-stimulated cells increases the expression of mRNA for IL-2 and IFN-gamma. The effect on lymphocyte proliferation was most likely mediated through the serotonin 5HT1a receptor because similar results could be obtained by using DPAT, a specific activator of this receptor. Changes in the expression of 5HT1a receptors as judged by the expression of mRNA could not explain why serotonin in vitro had a stronger enhancing effect on cell proliferation in some HIV-seropositive individuals than in others.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Liposomal 1,25 (OH)2 vitamin D3 compounds block proliferation and induce differentiation in myelomonocytic leukaemia cells.

The vitamin D3 derived hormone 1.25 (OH)2 vitamin D3 (1,25 D3) is able to induce growth arrest and differentiation in myelomonocytic leukaemia cells. In order to allow for specific delivery to leukaemic cells the lipophilic compound was incorporated into the lipid membranes of liposomes. Liposomal 1.25 D3 reduced proliferation as measured by 3H-thymidine incorporation in HL60 leukaemia cells by up to 60%. When liposomes were prepared at different concentrations of 1,25 D3 65% inhibition was achieved at 48 nM. The MC 1288 stereoisomer of 1,25 D3 was more potent and had the same activity at 4.8 nM. The effect of the liposomal compounds was specific to myeloid cells as they reduced proliferation in myelomonocytic HL60, monoblastic U937 and monocytic Mono Mac 6 cells but not in the T-cell lines Jurkat and Molt 4. The antiproliferative effect of liposomal 1,25 D3 was associated with an induction of differentiation since treated HL60 cells showed a monocytic morphology, increased expression of CD14 and decreased expression of CD33. When peripheral blood leukaemic cells from M4 and M5 acute myeloid leukaemia (AML) patients were admixed with liposomal compounds an antiproliferative effect was seen in all five cases, including the two cases where free compounds led to enhanced growth. Liposomal delivery of 1,25 (OH)2 vitamin D3 may offer a novel approach to treatment of myelomonocytic leukaemia.

Cell Differentiation↗
PubMed1997

Development of cytomegalovirus (CMV) disease may be predicted in HIV-infected patients by CMV polymerase chain reaction and the antigenemia test.

OBJECTIVE: Cytomegalovirus (CMV) is a frequent opportunistic viral pathogen in patients with AIDS leading to retinitis and other serious manifestations. CMV disease may be successfully treated. Prophylactic antiviral therapy has been shown to reduce the risk of CMV disease if initiated early. We evaluated PCR and the antigenemia tests as methods for early detection of CMV disease. METHODS: Two-hundred HIV-seropositive subjects with CD4 T-cell counts below 100 x 10(6)/l were monitored with CMV polymerase chain reaction (PCR), the antigenemia test, blood cultures and CMV immunoglobulin (Ig) G and IgM titres every second month for 1 year. RESULTS: Thirty-eight patients (19%) developed CMV disease. The PCR test detected CMV DNA a median of 46 days before onset of disease. This was earlier than the median of 34 for the antigenemia test and a median of 1 day for CMV blood cultures. Univariate analysis showed that the CMV PCR, the antigenemia test and blood cultures all had significant predictive values for subsequent development of CMV disease with odds ratios (OR) of 30, 22 and 20. CMV serology had no predictive value. Multivariate analysis showed that the PCR method was superior to the other tests; OR: CMV PCR 10.0, antigenemia test 4.4 and CMV cultures 4.3. No clinical parameters had any significant predictive value in the stepwise multivariate model. CONCLUSIONS: The CMV PCR and the CMV antigenemia tests are both sensitive methods that may predict development of CMV disease up to several months prior to clinical disease. These methods make it possible to select patients at high risk for CMV disease and suitable for prophylactic therapy against CMV.

AIDS-Related Opportunistic Infections↗