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Jan Verhoef

Publications and source records attributed to Jan Verhoef.

At least 19 recordsLinked to original sources
PubMed2003

APHS can act synergically with clinically available HIV-1 reverse transcriptase and protease inhibitors and is active against several drug-resistant HIV-1 strains in vitro.

OBJECTIVES: The use of multiple drug combinations in current anti-human immunodeficiency virus (HIV) therapy allows lower dosages of individual drugs and results in enhancement of the therapeutic effect due to synergic interactions between different drugs. We have shown that o-(acetoxyphenyl)hept-2-ynyl sulphide (APHS), a recently developed non-steroidal anti-inflammatory drug, shows anti-HIV activity in a dose-dependent manner. The first aim of this study was to investigate whether APHS can act synergically with the clinically available reverse transcriptase and protease inhibitors (RTIs and PIs, respectively) in vitro. Because of the increasing prevalence of RTI- and PI-resistant HIV-1 strains, the second aim of this study was to assess the antiviral activity of APHS against drug-resistant HIV-1 strains in vitro. MATERIALS AND METHODS: HIV-infected peripheral blood mononuclear cells (PBMC) were treated for 7 days with different combinations of APHS and RTIs or PIs. The MT-2 cell line was infected with different HIV-1 strains and treated with APHS for 5 days. RESULTS: APHS showed synergic interactions with the RTIs zidovudine, lamivudine and efavirenz and with the PIs indinavir and ritonavir. The 50% inhibitory concentration (IC50) of APHS in this assay dropped from 13 microM when used alone, to 5 micro M after combination with an RTI or PI. In combination with APHS the IC50 of the RTI and PI drugs tested also dropped. APHS inhibits the replication of HIV-1 strains resistant to zidovudine, lamivudine, stavudine, didanosine, zalcitabine and ritonavir. CONCLUSIONS: These results indicate that APHS can be combined with RTIs and PIs and can inhibit several NRTI and PI-resistant HIV-1 strains.

Alkynes↗
PubMed2003

Aspirin-like molecules that inhibit human immunodeficiency virus 1 replication.

Some anti-inflammatory molecules are also known to possess anti-human immunodeficiency virus (HIV) activity. We found that o-(acetoxyphenyl)hept-2-ynyl sulfide (APHS), a recently synthesized non-steroidal anti-inflammatory molecule can inhibit HIV-1 replication. The aim of this study was to clarify the mechanism of action of APHS. When administered during the first steps of the infection, APHS was capable of inhibiting the replication of several HIV-1 strains (macrophage-tropic and/or lymphocytotropic) in a dose-dependent manner in both peripheral blood mononuclear cells (PBMC), monocyte-derived macrophages and peripheral blood lymphocytes with 50% inhibitory concentration values of approximately 10 microM. The 50% toxic concentration of APHS varied between 100 and 200 microM in the different primary cells tested. APHS did not affect HIV-1 replication once the provirus was already inserted into the cellular genome. APHS also did not inhibit HIV-1 entry into the host cells as determined by quantification of gag RNA inside PBMC 2h after infection. However, APHS did inhibit gag DNA synthesis during reverse transcription in primary cells, which indicates that APHS may target the reverse transcription process.

Acetylene↗
PubMed2003

Resistant Haemophilus influenzae in community-acquired respiratory tract infections: a role for cefixime.

An increase in Haemophilus influenzae resistance has been documented around the world during the last 30 years. Resistance is due to the production of beta-lactamases, and/or changes to penicillin-binding protein (PBP) targets. The resistance problem has led to the need for new therapeutic strategies aimed at maintaining effective management of both upper respiratory tract infections (URTIs) and lower respiratory tract infections (LRTIs). Among antimicrobial agents tested, third-generation cephalosporins have been shown to possess excellent in vitro activity against beta-lactamase-positive and -negative isolates, corresponding with proven clinical efficacy in a wide range of RTIs. The role of H. influenzae in RTIs is outlined, changing trends in epidemiological surveillance studies monitored and implications for therapy, based upon results of clinical trials discussed.

Anti-Bacterial Agents↗
PubMed2003

Surveillance for hospital-acquired infections on surgical wards in a Dutch university hospital.

OBJECTIVES: To determine incidence rates of hospital-acquired infections and to develop preventive measures to reduce the risk of hospital-acquired infections. METHODS: Prospective surveillance for hospital-acquired infections was performed during a 5-year period in the wards housing general and vascular, thoracic, orthopedic, and general gynecologic and gynecologic-oncologic surgery of the University Medical Center Utrecht, the Netherlands. Data were collected from patients with and without infections, using criteria of the Centers for Disease Control and Prevention. RESULTS: The infection control team recorded 648 hospital-acquired infections affecting 550 (14%) of 3,845 patients. The incidence density was 17.8 per 1,000 patient-days. Patients with hospital-acquired infections were hospitalized for 19.8 days versus 7.7 days for patients without hospital-acquired infections. Prolongation of stay among patients with hospital-acquired infections may have resulted in 664 fewer admissions due to unavailable beds. Different specialties were associated with different infection rates at different sites, requiring a tailor-made approach. Interventions were recommended for respiratory tract infections in the thoracic surgery ward and for surgical-site infections in the orthopedic and gynecologic surgery wards. CONCLUSIONS: Surveillance in four surgical wards showed that each had its own prominent infection, risk factors, and indications for specific recommendations. Because prospective surveillance requires extensive resources, we considered a modified approach based on a half-yearly point-prevalence survey of hospital-acquired infections in all wards of our hospital. Such surveillance can be extended with procedure-specific prospective surveillance when indicated.

Academic Medical Centers↗
PubMed2003

Lipoprotein metabolism in patients with severe sepsis.

OBJECTIVE: Lipoproteins have been implicated to play a role in innate immunity. Changes in lipoprotein levels have been reported in a variety of inflammatory disorders. Not much is known about lipoprotein metabolism in patients with severe sepsis. We conducted an ancillary study in a multiple-center phase III sepsis trial to investigate the dynamics of plasma lipoproteins in patients with severe sepsis. DESIGN: Prospective analysis in patients meeting criteria for severe sepsis as part of a multiple-center sepsis study (KyberSept) with antithrombin III (Kybernin P). SETTING: University hospital intensive care unit. PATIENTS: Seventeen patients were included in the study. INTERVENTIONS: Randomized patients received a loading dose of 6000 IU of antithrombin III (Kybernin P) or placebo followed by a 96-hr continuous infusion of 250 IU/hr antithrombin III (Kybernin P) or placebo. In each patient, serial blood samples for total cholesterol, lipoprotein cholesterol, triglycerides, apolipoprotein A-1, apolipoprotein B, and C-reactive protein determination as well as clinical data were collected over 28 days. MEASUREMENTS AND MAIN RESULTS: Plasma cholesterol levels rapidly decreased from 2.67 +/- 2.02 mmol/L on day 0 to a nadir of 1.41 +/- 0.70 mmol/L on day 3, followed by a slow increase to 4.18 +/- 1.94 mmol/L on day 28. High-density lipoprotein (HDL) cholesterol concentrations decreased rapidly from 0.84 +/- 0.92 mmol/L to a nadir of 0.42 +/- 0.35 mmol/L on day 3, to show a slow increase during the following 4 wks to 0.84 +/- 0.42 mmol/L. The low-density lipoprotein (LDL) cholesterol concentrations were already low (0.94 +/- 0.81 mmol/L) at study entry, to show a progressive increase to subnormal values (2.01 +/- 0.94 mmol/L) at 4 wks. Nadir and recovery lipoprotein concentrations were significantly different (paired Student's t-test, p <.05). A significant correlation was found between HDL cholesterol and apolipoprotein A-1 (r =.714, p <.05) and between LDL cholesterol and apolipoprotein B (r =.733, p <.05). There was no statistical difference in lipoprotein concentrations either between survivors and nonsurvivors or between patients receiving antithrombin III or placebo. Serum amyloid A was a major apoprotein (45%) in HDL at the start of the sepsis and was slowly replaced by apolipoprotein A-1 during recovery. A positive correlation was found between plasma C-reactive protein concentrations and serum amyloid A concentrations in HDL (r =.684, p <.05). No other relevant correlations were found between inflammatory and lipoprotein parameters. CONCLUSIONS: In patients with severe sepsis, lipoprotein concentrations rapidly change and can be reduced to 50% of recovery concentrations. The pattern of early rapid decline is found primarily in the HDL and a slow recovery in both HDL and LDL fractions. The correlation between apolipoprotein and lipoprotein cholesterol concentrations suggests a decline in lipoprotein particles. During severe sepsis, HDL is shifted to acute phase HDL, which is enriched in serum amyloid A and depleted of cholesterol and apolipoprotein A-1. Lipoprotein concentrations are unable to discriminate between survivors and nonsurvivors.

APACHE↗
PubMed2002

Multidrug resistance among Enterobacteriaceae is strongly associated with the presence of integrons and is independent of species or isolate origin.

This study investigated the extent to which multidrug resistance (MDR) among Enterobacteriaceae is related to DNA elements called "integrons," whether the relationship is species dependent or origin dependent, and which resistance patterns are associated with integrons. Analysis of 867 nonrepeat isolates comprising 8 species and originating from the community and 23 European hospitals showed a significant relation between MDR and integrons, independent of species or origin. Although resistance to each tested antimicrobial agent was significantly associated with integrons, only resistance to sulfamethoxazole, cotrimoxazole, gentamicin, tobramycin, ampicillin, piperacillin, and cefuroxime predicted the presence of integrons. Combined resistance to both ampicillin and sulfamethoxazole-trimethoprim was the starting point for the development of resistance to additional beta-lactams, aminoglycosides, cephalosporins, and ciprofloxacin, a development paralleled by an increasing prevalence of integrons. The acquisition of resistance genes is not random, and the transfer of integron-carrying elements plays a dominant role in the development of MDR by Enterobacteriaceae.

Anti-Bacterial Agents↗
PubMed2002

Evidence of extensive interspecies transfer of integron-mediated antimicrobial resistance genes among multidrug-resistant Enterobacteriaceae in a clinical setting.

Multidrug resistance in gram-negative bacteria appears to be primarily the result of the acquisition of resistance genes by horizontal transfer. To what extent horizontal transfer may be responsible for the emergence of multidrug resistance in a clinical setting, however, has rarely been investigated. Therefore, the integron contents of isolates collected during a nosocomial outbreak of genotypically unrelated multidrug-resistant Enterobacteriaceae were characterized. The integron was chosen as a marker of transfer because of its association with multiresistance. Some genotypically identical isolates harbored different integrons. Grouping patients carrying the same integron yielded 6 epidemiologically linked clusters, with each cluster representing a different integron. Several patients carried multiple species harboring the same integron. Conjugation experiments with these strains resulted in the transfer of complete resistance patterns at high frequencies (10(-2) to 10(-4)). These findings provide strong evidence that the horizontal transfer of resistance genes contributed largely to the emergence of multidrug-resistant Enterobacteriaceae in this clinical setting.

Anti-Bacterial Agents↗
PubMed2002

Amyloid-beta-induced chemokine production in primary human macrophages and astrocytes.

In Alzheimer's disease (AD), chemotaxis might be responsible for attracting glial cells towards the neuritic plaque. Using primary monocyte-derived macrophages and primary adult astrocytes as a model, amyloid-beta (Abeta) (1-42) was able to stimulate the production, as measured by RT-PCR, of MIP-1alpha and MIP-1beta mRNA in macrophages and MCP-1 in astrocytes. Cocultures showed in unstimulated as well as in Abeta-stimulated cells an increase in MIP-1alpha, MIP-1beta and MCP-1 mRNA. ELISAs of supernatant samples of stimulated macrophages and astrocytes also showed an increase in MIP-1alpha and MIP-1beta in macrophages and MCP-1 in astrocytes. Stimulated cocultures showed an increase in MIP-1alpha, MIP-1beta and MCP-1 protein levels in contrast to unstimulated cocultures.

Adult↗
PubMed2002

Antimicrobial susceptibility and serotypes of nasopharyngeal Streptococcus pneumoniae in children with pneumonia and in children attending day-care centres in Fortaleza, Brazil.

The susceptibility of nasopharyngeal Streptococcus pneumoniae to eight antibiotics was studied in 482 children under 5 years of age with community-acquired pneumonia and in 429 healthy pneumococci carriers in Fortaleza, Brazil. Serotyping of strains with pooled and type-specific antisera was also performed. Overall, S. pneumoniae was isolated from 499/911 (55%) children. The carriage rate in children attending day-care centres was higher (72%) than in children with pneumonia (50%) (P<0.001). MIC determination in 441 strains revealed 45% to be intermediate penicillin-resistant and 4% high penicillin-resistant strains. Resistance rates to co-trimoxazole and erythromycin were 42 and 23%, respectively. Serotyping of 211 penicillin-resistant and 58 randomly selected penicillin-susceptible isolates showed that 78% of the strains belonged to paediatric serogroups 6, 14, 19 and 23 (86% of the penicillin-resistant and 51% of the penicillin-susceptible strains, P=0.001). Resistance rates of S. pneumoniae to penicillin and co-trimoxazole in Fortaleza were higher than previously reported in Brazil and associated with paediatric serogroups 6, 14, 19 and 23.

Anti-Bacterial Agents↗
PubMed2002

Is methicillin-resistant Staphylococcus aureus more contagious than methicillin-susceptible S. aureus in a surgical intensive care unit?

BACKGROUND AND OBJECTIVE: In the Netherlands, the prevalence of methicillin resistance among Staphylococcus aureus isolates has been kept to less than 1% by using active screening programs and isolation. At the University Medical Center Utrecht (UMCU), an active screening program for methicillin-resistant S. aureus (MRSA) in the surgical intensive care unit (ICU) was implemented in 1986. Between 1992 and 2001, only 6 patients with MRSA were admitted to the surgical ICU. However, 4 of these 6 strains were able to spread to 23 other patients and 15 healthcare workers (HCWs). We were surprised by the epidemic behavior of these strains and wondered whether this was exceptional for S. aureus or whether methicillin-susceptible S. aureus (MSSA) was also spreading in the ICU. DESIGN: A 2-month, prospective, observational study to investigate the incidence and spread of MSSA in the surgical ICU of UMCU and historical data collected during a 10-year period regarding MRSA. SETTING: A 10-bed surgical ICU in a 1,042-bed teaching hospital. RESULTS: Weekly swabs revealed the presence of MSSA in 11 (24%) of 45 patients and 16 (22%) of 72 HCWs. Of all 4,105 patient-HCW contacts, there were only 21 episodes in which both the patient and the HCW were found to carry MSSA. With the use of pulsed-field gel electrophoresis, no identical strains could be identified. CONCLUSION: In our surgical ICU, MRSA seems to spread more easily than MSSA, probably because of selection under antibiotic pressure or a still unknown intrinsic factor within MRSA.

Academic Medical Centers↗