Jacob de Vries

Time to stop ovarian cancer screening in BRCA1/2 mutation carriers?

Women at high risk of ovarian cancer due to a genetic predisposition may opt for either surveillance or prophylactic bilateral salpingo‐oophorectomy (pBSO). Main objective of our study was to determine the effectiveness of ovarian cancer screening in women with a BRCA1/2 mutation. We evaluated 241 consecutive women with a BRCA1 or BRCA2 mutation who were enrolled in the surveillance program for hereditary ovarian cancer from September 1995 until May 2006 at the University Medical Center Groningen (UMCG), The Netherlands. The ovarian cancer screening included annual pelvic examination, transvaginal ultrasound (TVU) and serum CA125 measurement. To evaluate the effectiveness of screening in diagnosing (early stage) ovarian cancer sensitivity, specificity, positive and negative predictive values (PPV and NPV) of pelvic examination, TVU and CA125 were calculated. Three ovarian cancers were detected during the surveillance period; 1 prevalent cancer, 1 interval cancer and 1 screen‐detected cancer, all in an advanced stage (FIGO stage IIIc). A PPV of 20% was achieved for pelvic examination, 33% for TVU and 6% for CA125 estimation alone. The NPV were 99.4% for pelvic examination, 99.5% for TVU and 99.4% for CA125. All detected ovarian cancers were in an advanced stage, and sensitivities and positive predictive values of the screening modalities are low. Restricting the analyses to incident contacts that contained all 3 screening modalities did not substantially change the outcomes. Annual gynecological screening of women with a BRCA1/2 mutation to prevent advanced stage ovarian cancer is not effective.

Bond Strengthening in Oral Bacterial Adhesion to Salivary Conditioning Films

ABSTRACT Transition from reversible to irreversible bacterial adhesion is a highly relevant but poorly understood step in initial biofilm formation. We hypothesize that in oral biofilm formation, irreversible adhesion is caused by bond strengthening due to specific bacterial interactions with salivary conditioning films. Here, we compared the initial adhesion of six oral bacterial strains to salivary conditioning films with their adhesion to a bovine serum albumin (BSA) coating and related their adhesion to the strengthening of the binding forces measured with bacteria-coated atomic force microscopy cantilevers. All strains adhered in higher numbers to salivary conditioning films than to BSA coatings, and specific bacterial interactions with salivary conditioning films were accompanied by stronger initial adhesion forces. Bond strengthening occurred on a time scale of several tens of seconds and was slower for actinomyces than for streptococci. Nonspecific interactions between bacteria and BSA coatings strengthened twofold faster than their specific interactions with salivary conditioning films, likely because specific interactions require a closer approach of interacting surfaces with the removal of interfacial water and a more extensive rearrangement of surface structures. After bond strengthening, bacterial adhesion forces with a salivary conditioning film remained stronger than those with BSA coatings.

Oral bacterial adhesion forces to biomaterial surfaces constituting the bracket–adhesive–enamel junction in orthodontic treatment

Bacterial adhesion to biomaterial surfaces constituting the bracket-adhesive-enamel junction represents a growing problem in orthodontics, because bacteria can adversely affect treatment by causing demineralization of the enamel surface around the brackets. It is important to know the forces with which bacteria adhere to the surfaces of these junction materials, as the strength of these forces will determine how easy it will be to remove the bacteria. We compared the adhesion forces of five initially colonizing and four cariogenic strains of bacteria to an orthodontic adhesive, stainless steel, and enamel, with and without a salivary conditioning film. Adhesion forces were determined using atomic force microscopy and a bacterial probe. In the absence of a salivary conditioning film, the strongest bacterial adhesion forces occurred to the adhesive surface (-2.9 to -6.9 nN), while adhesion forces to the enamel surfaces were lowest (-0.8 to -2.7 nN). In the presence of a salivary conditioning film, adhesion forces were reduced strongly, to less than 1 nN, and the differences between the various materials were reduced. Generally, however, initial colonizers of dental hard surfaces presented stronger adhesion forces to the different materials (-4.7 and -0.6 nN in the absence and presence of a salivary conditioning film, respectively) than cariogenic strains (-1.8 and -0.5 nN).

Weibull analyses of bacterial interaction forces measured using AFM

Statistically significant conclusions from interaction forces obtained by AFM are difficult to draw because of large data spreads. Weibull analysis, common in macroscopic bond-strength analyses, takes advantage of this spread to derive a Weibull distribution, yielding the probability of occurrence of a force value and the dependability of the data set. Here we propose Weibull distribution as a new way to present nanoscopic bacterial interaction forces obtained using AFM.

Surfactive and antibacterial activity of cetylpyridinium chloride formulations in vitro and in vivo

AIMnTo compare effects of three cetylpyridinium chloride (CPC) formulations with and without alcohol and Tween80 on physico-chemical properties of salivary pellicles, bacterial detachment in vitro and bacterial killing in vivo.nnnMATERIAL AND METHODSnAdsorption of CPC to salivary pellicles in vitro was studied using X-ray photoelectron spectroscopy and water contact angle measurements. Adhesion and detachment of a co-adhering bacterial pair was determined in vitro using a flow chamber. Killing was evaluated after live/dead staining after acute single use in vivo on 24- and 72-h-old plaques after 2-week continuous use.nnnRESULTSnThe most pronounced effects on pellicle surface chemistry and hydrophobicity were observed after treatment with the alcohol-free formulation, while the pellicle thickness was not affected by any of the formulations. All CPC formulations detached up to 33% of the co-adhering pair from pellicle surfaces. Bacterial aggregate sizes during de novo deposition were enhanced after treatment with the alcohol-free formulation. Immediate and sustained killing in 24 and 72 h plaques after in vivo, acute single use as well as after 2-week continuous use were highest for the alcohol-free formulation.nnnCONCLUSIONSnCPC bioavailability in a formulation without alcohol and Tween80 could be demonstrated through measures of pellicle surface properties and bacterial interactions in vitro as well as bacteriocidal actions on oral biofilms in vivo.

Force Analysis of Bacterial Transmission from Contact Lens Cases to Corneas, with the Contact Lens as the Intermediary

PURPOSEnTo determine the probability of transmission of a Staphylococcus aureus strain from a contact lens case, to the contact lens (CL) surfaces, to the cornea, on the basis of bacterial adhesion forces measured by using atomic force microscopy (AFM).nnnMETHODSnAdhesion forces between S. aureus strain 835 probes with rigid and soft CLs, storage cases, and porcine corneas were measured with AFM and used to calculate Weibull distributions, from which the transmission probability from one surface to another was derived. Bacterial transmission probabilities from force analyses were compared with experimentally obtained transmission data.nnnRESULTSnAfter bond-strengthening, S. aureus adhered to the surface of a lens case with a median force of 10.8 nN. Adhesion forces were different on the soft and rigid CLs (7.7 and 13.6 nN, respectively). Adhesion forces on porcine corneas amounted to 11.8 nN. Data variations were used to calculate the Weibull distribution, from which the probability of transmission from the lens case to a CL and from the CL to the cornea can be directly read. Final transmission probabilities from lens case to the cornea were slightly higher for the rigid (24%) than for the soft (19%) CL. Bacterial transmission determined experimentally increased with increasing contact times, but were within the range of the probabilities derived from Weibull analyses.nnnCONCLUSIONSnProbabilities of bacterial transmission from contaminated lens cases to corneas can be derived from Weibull analyses of measured forces of adhesion to the surfaces involved.

Measurements of softness of microbial cell surfaces.

Publisher Summary This chapter compares the dependence of the electrophoretic mobility on the ionic strength of a fibrillated and a nonfibrillated oral streptococcal strain. It reports that a soft, ion-penetrable strain was fibrillated, while an electrophoretically harder strain was devoid of a proteinaceous fibrillar surface layer, demonstrable by electron microscopy after negative staining. The bald streptococcal strain had a diffusion coefficient, as measured by dynamic light scattering that was independent of ionic strength and composition of the suspending fluid. The fibrillar strain shows an almost twofold decrease in diffusion coefficient on increasing the suspension pH from 2 to 7. Direct probing of the softness of microbial cell surfaces has been described using atomic force microscopy and suggested that the mechanical softness of microbial cell surfaces related with the electrophoretic one and the dynamic nature of microbial cell surfaces upon changes of their ionic environment. Thus, particulate microelectrophoresis, dynamic light scattering, and atomic force microscopy have become valuable, partly complementary methods to assess the softness and related ion penetrability of microbial cell surfaces. Considering the implications of these dynamic properties of microbial cell surfaces for their adhesion to surfaces, the chapter describes the application of these three methods as geared toward the analysis of microbial cell surfaces.