Spaarne Hospital Hoofddorp

Hoofddorp, Netherlands

Spaarne Hospital Hoofddorp

Hoofddorp, Netherlands
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Lauria G.,Carlo BestaC Neurological Institute | Hsieh S.T.,National Taiwan University Hospital | Johansson O.,Karolinska Institutet | Kennedy W.R.,University of Minnesota | And 6 more authors.
European Journal of Neurology | Year: 2010

Background: Revision of the guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy, published in 2005, has become appropriate owing to publication of more relevant articles. Most of the new studies focused on small fiber neuropathy (SFN), a subtype of neuropathy for which the diagnosis was first developed through skin biopsy examination. This revision focuses on the use of this technique to diagnose SFN. Methods: Task force members searched the Medline database from 2005, the year of the publication of the first EFNS guideline, to June 30th, 2009. All pertinent articles were rated according to the EFNS and PNS guidance. After a consensus meeting, the task force members created a manuscript that was subsequently revised by two experts (JML and JVS) in the field of peripheral neuropathy and clinical neurophysiology, who were not previously involved in the use of skin biopsy. Results and Conclusions: Distal leg skin biopsy with quantification of the linear density of intraepidermal nerve fibers (IENF), using generally agreed upon counting rules, is a reliable and efficient technique to assess the diagnosis of SFN (Recommendation Level A). Normative reference values are available for bright-field immunohistochemistry (Recommendation Level A) but not yet for confocal immunofluorescence or the blister technique. The morphometric analysis of IENF density, either performed with bright-field or immunofluorescence microscopy, should always refer to normative values matched for age (Recommendation Level A). Newly established laboratories should undergo adequate training in a well-established skin biopsy laboratory and provide their own stratified for age and gender normative values, intra-and interobserver reliability, and interlaboratory agreement. Quality control of the procedure at all levels is mandatory (Good Practice Point). Procedures to quantify subepidermal nerve fibers and autonomic innervated structures, including erector pili muscles, and skin vessels, are under development but need to be confirmed by further studies. Sweat gland innervation can be examined using an unbiased stereologic technique recently proposed (Recommendation Level B).A reduced IENF density is associated with the risk of developing neuropathic pain (Recommendation Level B), but it does not correlate with its intensity. Serial skin biopsies might be useful for detecting early changes of IENF density, which predict the progression of neuropathy, and to assess degeneration and regeneration of IENF (Recommendation Level C). However, further studies are warranted to confirm its potential usefulness as an outcome measure in clinical practice and research. Skin biopsy has not so far been useful for identifying the etiology of SFN. Finally, we emphasize that 3-mm skin biopsy at the ankle is a safe procedure based on the experience of 10 laboratories reporting absence of serious side effects in approximately 35 000 biopsies and a mere 0.19% incidence of non-serious side effects in about 15 years of practice (Good Practice Point). © 2010 EFNS and PNS.


Van Gils E.J.M.,University Utrecht | Van Gils E.J.M.,Spaarne Hospital Hoofddorp | Veenhoven R.H.,Spaarne Hospital Hoofddorp | Hak E.,University Utrecht | And 10 more authors.
JAMA - Journal of the American Medical Association | Year: 2010

Context: The rapid increase in multiresistant serotype19Aas a cause of invasive and respiratory pneumococcal disease has been associated in time with the widespread implementation of 7-valent pneumococcal conjugate vaccination (PCV-7) in several countries. Because spontaneous fluctuations in time and antibiotic selective pressuremayhave induced this serotype 19A increase, controlled studies are needed to assess the role of PCV-7. Objective: To examine the association of PCV-7 vaccination and nasopharyngeal acquisition of serotype 19A pneumococci, their clonal distribution, and antibiotic susceptibility. Design, Setting, and Patients: Post hoc per-protocol completer's analysis as part of a randomized controlled trial of nasopharyngeal Streptococcus pneumoniae carriage enrolling 1003 healthy newborns with follow-up to the age of 24 months in the Netherlands, which has low antibiotic resistance rates. The study was conducted before widespread PCV-7 implementation in infants, between July 7, 2005, and February 14, 2008. Nasopharyngeal swabs were obtained at the age of 6 weeks and at 6, 12, 18, and 24 months. Intervention: Infants were randomly assigned to receive 2 doses of PCV-7 at 2 and 4 months; 2 + 1 doses of PCV-7 at 2, 4, and 11 months; or no dosage (unvaccinated control group). Main Outcome Measure: Cumulative proportion of children with nasopharyngeal acquisition of a new serotype 19A strain from 6 through 24 months of age. Results: Nine hundred forty-eight children completed the study. Fifty-four nasopharyngeal serotype 19A carriage isolates from 318 in the 2-dose group, 66 isolates from 327 in the 2 + 1-dose group, and 33 isolates from 303 in the unvaccinated were collected from 6 weeks through 24 months. The cumulative proportion who tested positive for new nasopharyngeal serotype 19A acquisition from 6 through 24 months of age was significantly higher in those having received the 2 + 1-dose PCV-7 schedule (16.2%;95% confidence interval [CI], 12.6%-20.6%) vs those who were unvaccinated (9.2%; 95% CI, 6.5%-13.0%; relative risk [RR], 1.75;95%CI, 1.14-2.70) but not after a 2-dose schedule (13.2%; 95% CI, 9.9%-17.4%; RR, 1.43; 95% CI, 0.91-2.25). There were 28 different sequence types identified, including 6 new types. The proportion of children with new 19A acquisition who had used antibiotics in the last 6 months (18.7%) did not differ among groups. Five isolates were penicillin-intermediate susceptible and another 3 were nonsusceptible to erythromycin and azithromycin, all in the vaccine groups. Conclusion: A 2 + 1-dose PCV-7 schedule was associated with an increase in serotype 19A nasopharyngeal acquisition compared with unvaccinated controls. Trial Registration: clinicaltrials.gov Identifier: NCT00189020. ©2010 American Medical Association. All rights reserved.


van Gils E.J.M.,University Utrecht | van Gils E.J.M.,Spaarne Hospital Hoofddorp | Hak E.,University of Groningen | Veenhoven R.H.,Spaarne Hospital Hoofddorp | And 6 more authors.
PLoS ONE | Year: 2011

Background: Heptavalent pneumococcal conjugate vaccine (PCV7) shifts nasopharyngeal colonisation with vaccine serotype pneumococci towards nonvaccine serotypes. Because of the reported negative association of vaccine serotype pneumococci and Staphylococcus aureus in the nasopharynx, we explored the effect of PCV7 on nasopharyngeal colonisation with S. aureus in children and parents. Methodology/Principal Findings: This study was part of a randomised controlled trial on the effect of PCV7 on pneumococcal carriage, enrolling healthy newborns who were randomly assigned (1:1:1) to receive PCV7 (1) at 2 and 4 months of age (2) at 2, 4 and 11 months or (3) no PCV7 (controls). Nasopharyngeal colonisation of S. aureus was a planned secondary outcome. Nasopharyngeal swabs were obtained from all children over a 2-year period with 6-months interval and from one parent at the child's age of 12 and 24 months and cultured for Streptococcus pneumoniae and S. aureus. Between July 2005 and February 2006, 1005 children were enrolled and received either 2-doses of PCV7 (n = 336), 2+1-doses (336) or no dose (n = 333) before PCV7 implementation in the Dutch national immunization program. S. aureus colonisation had doubled in children in the 2+1-dose group at 12 months of age compared with unvaccinated controls (10.1% versus 5.0%; p = 0.019). A negative association for co-colonisation of S. pneumoniae and S. aureus was observed for both vaccine serotype (adjusted odds ratio (aOR) 0.53, 95% confidence interval (CI) 0.38-0.74) and nonvaccine serotype pneumococci (aOR 0.67, 95% CI 0.52-0.88). Conclusions/Significance: PCV7 induces a temporary increase in S. aureus colonisation in children around 12 months of age after a 2+1-dose PCV7 schedule. The potential clinical consequences are unknown and monitoring is warranted. Trial Registration: ClinicalTrials.gov NCT00189020. © 2011 van Gils et al.


Vollebregt A.,Spaarne Hospital Hoofddorp | Fischer K.,University Utrecht | Gietelink D.,Amphia Hospital Breda | van der Vaart C.H.,University Utrecht
Journal of Sexual Medicine | Year: 2012

Introduction. In pelvic organ prolapse (POP) repair, the use of synthetic mesh is not only increasing but also a subject of discussion. The focus shifts from anatomical toward functional outcome, with sexual function being an important parameter. One of the concerns with mesh usage in POP surgery is the possible negative effect on sexual function. Aim. To compare and assess sexual function in women and men after primary cystocele repair with or without trocar-guided transobturator mesh. Methods. One hundred twenty-five women with a symptomatic cystocele stage≥II were included in this multicenter randomized controlled trial and assessed at baseline and 6-month follow-up. Main Outcome Measures. Female sexual function was measured by the Female Sexual Function Index (FSFI) and male sexual function by the Male Sexual Health Questionnaire. A subgroup analysis of women with a participating partner was performed. Results. In the mesh group, 54/59 women vs. 53/62 in the anterior colporrhaphy group participated. In men, 29 vs. 30 participated. After surgery, FSFI scores were comparable for both treatment groups. However, within group analysis showed significant improvement on the domains pain (effect size=0.5), lubrication (effect size=0.4), and overall satisfaction (effect size=0.5) in the colporrhaphy group. This improvement was not observed in the mesh group. A subgroup of women with a participating partner reported significantly higher baseline domain scores as compared with other women and did not report a significant improvement of sexual functioning irrespective of treatment allocation. Worsening of baseline sexual function was reported by 43% of women in the mesh group compared with 18% in anterior colporrhaphy group (P=0.05). Male sexual functioning did not change in either group. Conclusions. Women after an anterior colporrhaphy report a significant and clinically relevant improvement of their sexual functioning, whereas women after a mesh procedure did not. Vollebregt A, Fischer K, Gietelink D, and van der Vaart CH. Effects of vaginal prolapse surgery on sexuality in women and men; results from a RCT on repair with and without mesh. J Sex Med 12;9:1200-1211. © 2012 International Society for Sexual Medicine.


Hendrikx L.H.,National Institute for Public Health and the Environment | Hendrikx L.H.,Spaarne Hospital Hoofddorp | Ozturk K.,National Institute for Public Health and the Environment | de Rond L.G.H.,National Institute for Public Health and the Environment | And 4 more authors.
PLoS ONE | Year: 2011

Background: Whooping cough is a respiratory disease caused by Bordetella pertussis, which induces mucosal IgA antibodies that appear to be relevant in protection. Serum IgA responses are measured after pertussis infection and might provide an additional role in pertussis diagnostics. However, the possible interfering role for pertussis vaccinations in the induction of serum IgA antibodies is largely unknown. Methods/Principal Findings: We compared serum IgA responses in healthy vaccinated children between 1 and 10 years of age with those in children who despite vaccinations recently were infected with Bordetella pertussis. All children have been vaccinated at 2, 3, 4 and 11 months of age with either the Dutch whole-cell pertussis (wP) vaccine or an acellular pertussis (aP) vaccine and additionally received an aP booster vaccination at 4 years of age. Serum IgA responses to pertussis toxin (PT), filamentous heamagglutinin (FHA) and pertactin (Prn) were measured with a fluorescent multiplex bead-based immuno-assay. An ELISPOT-assay was used for the detection of IgA-memory B-cells specific to these antigens. Serum IgA levels to all pertussis vaccine antigens were significantly higher in infected children compared with healthy children. High correlations between anti-PT, anti-FHA or anti-Prn IgA and IgG levels were found in infected children and to some degree in wP primed children, but not at all in aP primed children. Highest numbers of IgA-pertussis-specific memory B-cells were observed after infection and generally comparable numbers were found after wP and aP vaccination. Conclusions: This study provides new insight in the diagnostic role for serum IgA responses against PT in vaccinated children. Since aP vaccines induce high serum IgG levels that interfere with pertussis diagnostics, serum IgA-PT levels will provide an additional diagnostic role. High levels of serum IgA for PT proved specific for recent pertussis infection with reasonable sensitivity, whereas the role for IgA levels against FHA and Prn in diagnosing pertussis remains controversial. © 2011 Hendrikx et al.


Hendrikx L.H.,National Institute for Public Health and the Environment | Hendrikx L.H.,Spaarne Hospital Hoofddorp | Ozturk K.,National Institute for Public Health and the Environment | de Rond L.G.H.,National Institute for Public Health and the Environment | And 4 more authors.
Vaccine | Year: 2011

Whooping cough is a respiratory disease caused by Bordetella pertussis. Since the 1950s in developed countries pertussis vaccinations are included in the national immunization program. However, antibody levels rapidly wane after both whole cell and acellular pertussis vaccination. Therefore protection against pertussis may depend largely on long-term B- and T-cell immunities. We investigated long-term pertussis-specific memory B-cell responses in children who were primed at infant age with the Dutch wP-vaccine (ISRCTN65428640). Purified B-cells were characterized by FACS-analysis and after polyclonal stimulation memory B-cells were detected by ELISPOT-assays specific for pertussis toxin, filamentous haemagglutinin, pertactin and tetanus. In addition, plasma IgG levels directed to the same antigens were measured by a fluorescent bead-based multiplex immunoassay. Two and 3 years after wP priming as well as 2 and 5 years after the aP booster at the age of 4, low plasma IgG levels to the pertussis proteins were found. At the same time, however pertussis protein-specific memory B-cells could be detected and their number increased with age. The number of tetanus-specific memory B-cells was similar in all age groups, whereas IgG-tetanus levels were high 2 years after tetanus booster compared to pre- and 5 years post-booster levels. This study shows the presence of long-term pertussis protein-specific memory B-cells in children despite waning antibody levels after vaccination, which suggests that memory B-cells in addition to antibodies may contribute to protection against pertussis. © 2010 Elsevier Ltd.


Hendrikx L.H.,National Institute for Public Health and the Environment | Hendrikx L.H.,Spaarne Hospital Hoofddorp | De Rond L.G.H.,National Institute for Public Health and the Environment | Ozturk K.,National Institute for Public Health and the Environment | And 4 more authors.
Vaccine | Year: 2011

Whooping cough, caused by Bordetella pertussis, is reemerging in the vaccinated population. Antibody levels to pertussis antigens wane rapidly after both whole-cell (wP) and acellular pertussis (aP) vaccination and protection may largely depend on long-term B- and T-cell immunity. We studied the effect of wP and aP infant priming at 2, 3, 4 and 11 months according to the Dutch immunization program on pertussis-specific memory B-cell responses before and after a booster vaccination with either a high- or low-pertussis dose vaccine at 4 years of age.Purified B-cells were characterized by FACS-analysis and after polyclonal stimulation, memory B-cells were detected by ELISPOT-assays specific for pertussis toxin, filamentous haemagglutinin and pertactin.Before and after the booster, higher memory B-cell responses were measured in aP primed children compared with wP primed children. In contrast with antibody levels, no dose-effect was observed on the numbers of memory B-cell responses. In aP primed children a fifth high-dose aP vaccination tended to induce even lower memory B-cell responses than a low-dose aP booster. In both wP and aP primed children, the number of memory B-cells increased after the booster and correlated with the pertussis-specific antibody concentrations and observed affinity maturation.This study indicates that aP vaccinations in the first year of life induce higher pertussis-specific memory B-cell responses in children 4 years of age compared with Dutch wP primary vaccinations. Since infant aP vaccinations have improved protection against whooping cough in children despite waning antibody levels, this suggests that an enhanced memory B-cell pool induction may have an important role in protection. However, the pertussis-dose of the preschool booster needs to be considered depending on the vaccine used for priming to optimize long-term protection against whooping cough. © 2011 Elsevier Ltd.


Hendrikx L.H.,National Institute for Public Health and the Environment | Hendrikx L.H.,Spaarne Hospital Hoofddorp | Schure R.-M.,National Institute for Public Health and the Environment | Ozturk K.,National Institute for Public Health and the Environment | And 5 more authors.
Vaccine | Year: 2011

The distribution of IgG-subclasses provides insight in the immunological mechanisms of protection against whooping cough. We investigated the effect of Dutch whole-cell pertussis and acellular pertussis vaccines administered in infancy on the IgG-subclass distributions in healthy children aged 12 months, 4 years and 9 years as well as in children who have been infected with Bordetella pertussis.A fluorescent bead-based multiplex immunoassay was used for the measurement of IgG1, IgG2, IgG3 and IgG4 responses against pertussis toxin, filamentous heamagglutinin and pertactin.Although IgG1 was the predominant subclass for all pertussis antigens in both healthy and infected children, elevated IgG4 levels were only present in children who had received repeated number of acellular pertussis vaccinations. IgG2 and IgG3 antibodies did not contribute to the IgG response. No differences in IgG-subclasses between healthy vaccinated or infected children were found.The pertussis vaccine used for priming seems to determine the IgG-subclass composition elicited after a secondary antibody response either induced by pertussis vaccination or infection. The pronounced anti-pertussis IgG4 response might reflect the Th2-skewing of the immune response after aP vaccination. © 2011 Elsevier Ltd.


Hendrikx L.H.,National Institute for Public Health and the Environment | Hendrikx L.H.,Spaarne Hospital Hoofddorp | Felderhof M.K.,Spaarne Hospital Hoofddorp | Ozturk K.,National Institute for Public Health and the Environment | And 5 more authors.
Vaccine | Year: 2011

Whooping cough has made its comeback and the incidence of pertussis in countries with widespread pertussis vaccination is most prominent in individuals above 9 years of age. To control the burden of infection, several countries already introduced acellular pertussis (aP) booster vaccination in adolescents and/or adults. However, antibody levels wane rapidly after vaccination even at older age. In this longitudinal study we investigated the effect of a second aP booster on the pertussis-specific memory B-cell immunity in children 9 years of age that have previously been vaccinated according to the national immunization program. Longitudinal blood samples were taken before, one month and one year after the booster. Purified B-cells were polyclonally stimulated and frequencies of memory B-cells were identified by ELISPOT-assays specific for various pertussis antigens. In addition, IgG levels and avidity indices were measured with fluorescent bead-based multiplex immunoassays. Starting with low pertussis-specific antibody and memory B-cell levels, a typical booster response was measured at one month after vaccination with increased antibody and memory B-cell responses. Although these responses declined slightly after one year, they substantially exceeded pre-booster levels and the avidity indices of the anti-pertussis antibodies remained high. Furthermore, high numbers of pertussisspecific memory B-cells at one-month post-booster correlate quite reliably with the corresponding high antibody response at one-year follow-up. In conclusion, booster vaccination in children 9 years of age induced an enhanced pertussis-specific memory immune response that sustained at least for one year. Therefore, this study supports the introduction of booster vaccination in older age groups. © 2011 Elsevier Ltd.


Vollebregt A.,Spaarne Hospital Hoofddorp | Fischer K.,University Utrecht | Gietelink D.,Amphia Hospital Breda | Van Der Vaart C.H.,University Utrecht
BJOG: An International Journal of Obstetrics and Gynaecology | Year: 2011

Objective To compare anterior colporrhaphy with a trocar-guided transobturator mesh procedure (Avaulta ® anterior). Design Randomised, controlled trial. Setting Three teaching hospitals. Population Women with a symptomatic cystocele at least stage II requiring primary surgical correction. Methods A total of 125 women were assessed at baseline and 1-year follow up. A sacrospinous hysteropexy or posterior colporrhaphy was performed when indicated. Main outcome measures The primary outcome was the difference in anatomical cure (defined as Pelvic Organ Prolapse-Quantification

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