[Combined hepatitis A/B vaccination: evaluation of a vaccination schedule in facilities for handicapped people]. / Hepatitis A/B-Kombinationsimpfung: Evaluation eines Impfprogramms in Werkstätten für Menschen mit Behinderung.

AIM OF THE STUDY: People with mental and physical disabilities have a higher risk of infection with hepatitis viruses. Studies conducted so far show contradictory results on the success of vaccination in this population. These people live and work under special conditions and sometimes have immune defects. METHODS: We investigated the antibody response after combined vaccination against hepatitis A and B in facilities for handicapped people in the city of Essen/Germany. Antibodies were determined in people with disabilities (n=949) and also in social workers taking care of handicapped people (n=115). RESULTS: Protective antibodies against hepatitis A were detected in 98.9% in people with disabilities and social workers. The seroconversion rate against hepatitis B in handicapped people was 90.2% and was comparable to the seroconversion rate in social workers (91.3%). Re-vaccinations were offered to all people with anti-HBs titres below 100 IU/L (28% of handicapped and 23.5% of social workers). In the group of low responders in handicapped people about 50% developed anti-HBs concentration above 100 IU/L. Non-responders showed 30-40% seroconversion rate after re-vaccination. CONCLUSION: Based on this study we would recommend serological tests about 4-8 weeks after vaccination to confirm seroconversion. By this procedure people who need a booster vaccination will be recognized and non-responders should be offered another HBV vaccination. In about 20% of the non-responders included in this study HBs antigen was detected.

Management and outcomes after multiple corneal and solid organ transplantations from a donor infected with rabies virus.

BACKGROUND: This article describes multiple transmissions of rabies via transplanted solid organ from a single infected donor. The empirical Milwaukee treatment regimen was used in the recipients. METHODS: Symptomatic patients were treated by deep sedation (ketamine, midazolam, and phenobarbital), ribavirin, interferon, and active and passive vaccination. Viral loads and antibodies were continuously monitored. RESULTS: Recipients of both cornea and liver transplants developed no symptoms. The recipient of the liver transplant had been vaccinated approximately 20 years before transplantation. Two recipients of kidney and lung transplants developed rabies and died within days of symptomatic disease. Another kidney recipient was treated 7 weeks before he died. The cerebrospinal fluid viral load remained at constant low levels (<10,000 copies/mL) for approximately 5 weeks; it increased suddenly by almost 5 orders of magnitude thereafter. After death, no virus was found in peripheral compartments (nerve tissue, heart, liver, or the small intestine) in this patient, in contrast to in patients in the same cohort who died early. CONCLUSIONS: Our report includes, to our knowledge, the longest documented treatment course of symptomatic rabies and the first time that the virus concentration was measured over time and in different body compartments. The postmortem virus concentration in the periphery was low, but there was no evidence of a reduction of virus in the brain.

Lack of de novo hepatitis C virus infections and absence of nosocomial transmissions of GB virus C in a large cohort of German haemodialysis patients.

To determine the prevalence and incidence of hepatitis C virus (HCV) infections among haemodialysis patients, a large prospective multicentre trial was conducted in the German Federal State of North Rhine-Westphalia. Sera obtained from the recruited patients in two separate sampling rounds run 1 year apart were analysed for both anti-HCV antibodies and HCV RNA. HCV RNA positive samples were also genotyped by direct sequencing of an HCV core fragment. In the first and second rounds, 150 (5.2%) of 2909 and 114 (5.4%) of 2100 patients were anti-HCV positive, respectively, and 4% of individuals were viraemic. Evaluation of potential risk factors in a case-control study indicated that the factors 'foreign country of birth', 'blood transfusions given before 1991' and 'duration of treatment on haemodialysis' were associated with the risk of HCV infection. Among the 2100 patients of whom 'paired' serum samples from both rounds were available for testing, not a single 'de novo' HCV infection could be recorded. The fact that in a subset of about 20% of these patients no nosocomial GB virus C (GBV-C) transmission occurred during the observational period suggests that the lack of HCV seroconversions was not only attributable to the isolation of HCV-infected patients but also to the strict adherence to so-called universal hygienic precautions for infection control maintained in the participating dialysis centres.

Norovirus outbreaks in nursing homes: the evaluation of infection control measures.

Effective infection control measures during norovirus outbreaks are urgently needed in places where vulnerable individuals gather. In the present study, the effect of a number of measures was investigated in daily practice. Forty-nine Dutch nursing homes were monitored prospectively for norovirus outbreaks during two winter seasons. A total of 37 norovirus outbreaks were registered. Control measures were most effective when implemented within 3 days after onset of disease of the first patient. Measures targeted at reduced transmission between persons, via aerosols, and via contaminated surfaces reduced illness in staff and in residents. Reducing illness in staff results in fewer costs for sick leave and substitution of staff and less disruption in the care of residents. The effect of control measures on outbreak duration was limited. This is the first intervention study examining the effect of control measures. Further research is needed to extend and refine the conclusions.

Towards a better resolution of hepatitis C virus variants: CLIP sequencing of an HCV core fragment and automated assignment of genotypes and subtypes.

Commercially available assays for typing of hepatitis C virus (HCV) isolates satisfy the current clinical needs. They are, however, limited in their ability to identify the multitude of existing HCV subtypes correctly. Therefore, these kits should only be used cautiously in epidemiological studies and will also not meet future clinical demands which might arise, e.g., from the application of HCV subtype-specific antiviral compounds. In an attempt to overcome the drawbacks of commercial typing procedures based on the analysis of the 5' untranslated region (5' UTR), an approach was developed which relies on CLIP sequencing of an HCV core fragment with automated assignments of types and subtypes via an originally created "core-specific" sequence database. The performance characteristics of the new technique were evaluated in comparison to the Trugene 5' NC Genotyping Kit. The core-based sequencing method could regularly detect HCV isolates of genotypes 1-6 with an analytical sensitivity of 5000 IU/ml. The accuracy of typing results obtained by the Trugene test was 97% (genotypes) and 81% (subtypes). The core-linked approach classified all HCV strains correctly on the level of genotypes and led to an adequate subtype assignment in 96% of all cases. This analytical performance characteristics recorded for the newly devised typing technique was superior to those reported for all commercially available assays, including a most recently released new generation of the line probe assay. Consequently, CLIP sequencing of an HCV core fragment with subsequent automated assignment of types and subtypes can be confidently used in clinical laboratory practice to answer current and also future questions in the context of HCV typing.

Patient-specific initial wall stress in abdominal aortic aneurysms with a backward incremental method.

Patient-specific wall stress simulations on abdominal aortic aneurysms may provide a better criterion for surgical intervention than the currently used maximum transverse diameter. In these simulations, it is common practice to compute the peak wall stress by applying the full systolic pressure directly on the aneurysm geometry as it appears in medical images. Since this approach does not account for the fact that the measured geometry is already experiencing a substantial load, it may lead to an incorrect systolic aneurysm shape. We have developed an approach to compute the wall stress on the true diastolic geometry at a given pressure with a backward incremental method. The method has been evaluated with a neo-Hookean material law for several simple test problems. The results show that the method can predict an unloaded configuration if the loaded geometry and the load applied are known. The effect of incorporating the initial diastolic stress has been assessed by using three patient-specific geometries acquired with cardiac triggered MR. The comparison shows that the commonly used approach leads to an unrealistically smooth systolic geometry and therefore provides an underestimation for the peak wall stress. Our backward incremental modelling approach overcomes these issues and provides a more plausible estimate for the systolic aneurysm volume and a significantly different estimate for the peak wall stress. When the approach is applied with a more complex material law which has been proposed specifically for abdominal aortic aneurysm similar effects are observed and the same conclusion can be drawn.

Assessment of endoleak significance after endovascular repair of abdominal aortic aneurysms: a lumped parameter model.

The outcome of endovascular repair of abdominal aortic aneurysms (AAAs) is greatly compromised by the possible occurrence of endoleak. Previously, the causes and effects of endoleak on a patient-specific basis have mainly been investigated in experimental studies. In order to both reconcile and physically substantiate the various experimental findings, a lumped parameter model of an incompletely excluded AAA was developed. After experimental validation, the model was applied to study the effects on the intrasac pressure of the degree of endoleak, the degree of stent-graft compliance, and the resistance of a possible outflow tract formed by a branching vessel. It is concluded that the presence of endoleak leads to elevated intrasac pressure, the mean of which is mainly governed by the outflow tract resistance, while the pulse pressure is governed by both the endoleak resistance and the stent-graft compliance. Based on the agreement of the current results with previous findings, it is further concluded that the lumped parameter modelling method provides a useful numerical tool for validating experimental endoleak studies.

[Two patients with Hantavirus infection in The Netherlands; substantial increase in incidence in neighbouring countries]. / Twee patiënten met een Hantavirus-infectie in Nederland; sterke toename van de incidentie in de ons omringende landen.

A 12-year-old girl and a 57-year-old woman were admitted with fever, general malaise, abdominal pain, nausea and vomiting. Both patients had acute renal insufficiency based on tubulointerstitial nephritis caused by the genus Hantavirus, which was confirmed by blood tests. Both patients recovered spontaneously. The neighbouring countries of France, Germany and Belgium have recently reported 2- to 7-fold increases in the number of Hantavirus infections. Hantavirus is a zoonotic viral disease that is transmitted by mice and is found in humans worldwide. Infection with Hantavirus is associated with severe renal impairment and thrombocytopenia, which usually resolves spontaneously. Recognition of the clinical signs and targeted serological testing can lead to adequate management of the disease. Diagnosing patients with Hantavirus infections will also help to prevent infections in The Netherlands and track epidemiological changes.

A patient-specific computational model of fluid-structure interaction in abdominal aortic aneurysms.

It is generally believed that knowledge of the wall stress distribution could help to find better rupture risk predictors of abdominal aortic aneurysms (AAAs). Although AAA wall stress results from combined action between blood, wall and intraluminal thrombus, previously published models for patient-specific assessment of the wall stress predominantly did not include fluid-dynamic effects. In order to facilitate the incorporation of fluid-structure interaction in the assessment of AAA wall stress, in this paper, a method for generating patient-specific hexahedral finite element meshes of the AAA lumen and wall is presented. The applicability of the meshes is illustrated by simulations of the wall stress, blood velocity distribution and wall shear stress in a characteristic AAA. The presented method yields a flexible, semi-automated approach for generating patient-specific hexahedral meshes of the AAA lumen and wall with predefined element distributions. The combined fluid/solid mesh allows for simulations of AAA blood dynamics and AAA wall mechanics and the interaction between the two. The mechanical quantities computed in these simulations need to be validated in a clinical setting, after which they could be included in clinical trials in search of risk factors for AAA rupture.

Extremely obese children respond better than extremely obese adolescents to lifestyle interventions.

UNLABELLED: What is already known about this subject Lifestyle intervention is regarded as therapy of choice in obese children and adolescents. It is unclear whether extremely obese children and adolescents respond to lifestyle intervention. What this study adds Extremely obese children respond better than obese children to a lifestyle intervention. In contrast, most extremely obese adolescents achieved no weight loss in lifestyle intervention suggesting that other treatment approaches are needed for them. BACKGROUND: There are conflicting results of treating extreme obesity in childhood by lifestyle interventions in the literature. METHODS: We analysed the outcome of a 1-year lifestyle intervention in an intention-to-treat approach in 1291 children (mean age 11.0 ± 2.5 years, mean body mass index [BMI] 27.5 ± 4.7 kg m(-2), 55.8% female, 62.4% obese, 37.6% extremely obese (defined by BMI-SDS >2.3) at end of intervention and 1 year later. RESULTS: The mean BMI-SDS reduction was -0.20 ± 0.32 at end of intervention and -0.14 ± 0.37 1 year after end of intervention compared to baseline (comparing intervention vs. 1 year later P = 0.010). Extremely obese children ≤10 years demonstrated a significantly greater BMI-SDS reduction than obese children ≤10 years (-0.24 ± 0.38 vs. -0.16 ± 0.38, P = 0.021). Extremely obese adolescents >10 years demonstrated a significantly lower BMI-SDS reduction compared to obese adolescents >10 years (-0.05 ± 0.30 vs. -0.15 ± 0.39, P < 0.001). Comparing the BMI-SDS reduction between obese children <10 years and >10 years revealed no significant difference (P = 0.195) in contrast to the comparison between extremely obese children <10 years and >10 years (P < 0.001). The same findings were observed in the follow-up period after the end of intervention. CONCLUSIONS: Our study demonstrated an encouraging effect of lifestyle intervention in extremely obese children ≤10 years at the end of intervention and 1 year later, but only a limited effect in extremely obese adolescents >10 years.

Effects of 6 months of moderate aerobic exercise training on immune function in the elderly.

The purpose of this study was to determine the effects of 6 months of moderate aerobic exercise on age-dysregulated measures of T lymphocyte and natural killer (NK) cell number and function. Previously sedentary elderly (age = 65 +/- 0.8 years) subjects were randomly assigned to supervised 3 time/week exercise intervention group (EXC, n = 14) or flexibility/toning control group (FT-CON, n = 15). Fasting resting blood samples were drawn prior to and after the 6 month intervention. The EXC group exhibited a significant (P < 0.05) 20% increase in VO2 max, whereas the FT-CON group had a smaller non-significant (P = 0.07) increase (9%). Immune results revealed that, in general, changes in immune function in response to 6 months of exercise training at an average intensity of 52% heart rate reserve (HRR) were similar when compared to FT-CON who exercised at approximately 21% HRR. There were no intervention-induced changes in total white blood cell, neutrophil, lymphocyte, monocyte, eosinophil, or basophil blood counts. Furthermore, the percentage and number of CD3+, CD4+ and CD8+ T cells in the blood remained unchanged. There was a tendency for the percentage and number of CD4+ and CD8+ näive cells (CD45RA+) to increase and for CD4+ memory cells (CD45RO+) to decrease post-intervention, especially in FT-CON. Both groups exhibited a small intervention-induced increase in the T-cell proliferative response to mitogenic stimulation: the percentage change of which was higher in the EXC group at several doses of Con A. Unstimulated NK cell cytolysis versus K562 cells tended to increase (P < 0.1) in the EXC group with little change in FT-CON. We conclude that 6 months of supervised exercise training can lead to nominal increases in some measures of immune function, while not affecting others, in previously sedentary elderly.

Effects of maximal exercise on natural killer (NK) cell cytotoxicity and responsiveness to interferon-alpha in the young and old.

We investigated the effects of a graded maximal exercise treadmill test on natural killer (NK) cell number, activity, and responsiveness to interferon-alpha (IFN-alpha) in young (22+/-0.7 yrs) and elderly (65+/-0.8 yrs) sedentary subjects. NK cell cytotoxicity (NKCC) was determined using Ficoll purified peripheral blood mononuclear cells (PBMCs) by a 51Cr release assay against NK-sensitive (K562) and NK-insensitive (Daudi) target cells at various effector:target (E:T) ratios before and immediately after exercise. PBMCs were incubated with rhu IFN-alpha (125 and 250u/10(6) PBMCs) or without for 2 hrs before addition to the 51Cr release assay. There were no differences in unstimulated NKCC against K562 or Daudi targets between the old and the young despite significantly (p=.01) higher percentages of CD56+ NK cells (21.1+/-2.3% in old vs 12.5+/-2.5% in young, pre-exercise). IFN-alpha increased NKCC versus both targets, and NK cells from old subjects were hyporesponsive to IFN-alpha stimulation; this was especially evident at low E:T ratios versus Daudi cells. Maximal exercise significantly increased (50-200%) unstimulated NKCC versus K562 and Daudi targets similarly in both young and old and increased the percentage of CD56+ cells in the PBMC fraction to 33.3+/-3.7% and 23.3+/-3.6% in old and young, respectively. We found a significant correlation between %CD56+ and basal NKCC versus K562s and Daudi cells in the young (i.e., r=.55; p=.02 vs K562s), but not the old (i.e., r=.20; p=.29 vs K562s) subjects. This indicates that, in the young, part of the exercise-induced increase in NKCC is due to an increase in NK cell number. Maximal exercise did not affect unstimulated per cell killing of K562s, but tended to increase per cell killing of Daudis. These results indicate that CD56+ cells from old subjects have an intrinsic defect in their ability to perform cytolysis and respond to IFN-alpha. Furthermore, a single bout of maximal exercise increases NKCC and CD56+ cell number similarly in both young and old subjects regardless of the target cell used.

[Not more symptoms with mefloquine use than with other drugs in malaria prophylaxis]. / Niet meer klachten bij mefloquinegebruik dan bij malariaprofylaxe met andere middelen.

OBJECTIVE: To investigate the prevalence of health problems and compliance with respect to malaria prophylaxis of travellers to the (sub)tropics. SETTING: Travel department of the Public Health Care Centre Groningen, the Netherlands. DESIGN: Retrospective follow-up study. METHODS: A questionnaire was sent out to 450 visitors to the Public Health Care Centre. They had stayed in the (sub)tropics for at most three months. Two subgroups used malaria prophylaxis (mefloquine or proguanil/proguanil-chloroquine): the control group used no prophylaxis. RESULTS: 40% of the 321 responders reported health problems during their stay in the (sub)tropics. Users of proguanil (with or without concurrent chloroquine prophylaxis) reported significantly more health problems (55%). Symptoms reported most frequently were vomiting and diarrhoea. Insomnia and neuropsychiatric disorders were reported only rarely (1%) and these complaints were equally distributed over the prophylaxis subgroups. The reported compliance with chemoprophylaxis was 77%. CONCLUSIONS: The frequently reported psychiatric complaints during use of mefloquine were not confirmed by this study. The compliance with malaria prophylaxis in this study was similar to that in other studies.

Analyses of non-synonymous obesity risk alleles in SH2B1 (rs7498665) and APOB48R (rs180743) in obese children and adolescents undergoing a 1-year lifestyle intervention.

Association of obesity risk alleles of single nucleotide polymorphisms (SNPs) near or in the SH2B adaptor protein 1 gene (SH2B1) and increased body mass index (BMI) has been often described. A gene in close proximity, apolipoprotein B48 receptor gene (APOB48R), is tagged by the same SNP(s).We analyzed 454 overweight and obese children and adolescents (10.8±2.6 years, BMI-SDS 2.4±0.5; 55% girls) who completed a 1-year lifestyle intervention ('Obeldicks' program). Carriers of obesity risk alleles of non-synonymous SNPs in SH2B1 (rs7498665, Thr484Ala) or APOB48R (rs180743, Pro419Ala), as genotyped by TaqMan, were analysed for changes in anthropometrics (body-mass index (BMI), and standardized BMI (BMI-SDS)), blood pressure (systolic and diastolic) and plasma parameters (total cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglycerides, glucose, insulin, and HOMA).We observed no evidence for an association of the obesity risk alleles to alterations in any of the analyzed phenotypes. Both mean BMI and BMI-SDS improved during the intervention independent of genotype. The mean systolic blood pressure was lowered and concentrations of HDL-cholesterol increased significantly.The obesity risk alleles of non-synonymous SNPs at SH2B1 and APOB48R have no strong effect on weight loss-related phenotypes in overweight children after a 1-year lifestyle intervention.

Which factors are important in adults' uptake of a (pre)pandemic influenza vaccine?

Since 2008, (pre)pandemic vaccines against H5N1 influenza have been available and pandemic vaccines against new influenza H1N1 are currently produced. In The Netherlands, the vaccination call for seasonal influenza among the recommended groups approximates 70%. These statistics raise the question if adults in Western societies are willing to get a (pre)pandemic influenza vaccination, for example, against avian H5N1 or swine-like H1N1 virus. A questionnaire was performed to determine the predictors of a negative intention to be immunized against pandemic influenza among adults. Demographical, behavioural and organisational determinants were studied. Thirty-four and five percent of the respondents were negatively intended to get a pandemic influenza vaccination in a pre-pandemic or pandemic phase, respectively. On the basis of six behavioural determinants negative intention to get a pandemic influenza vaccination can be predicted correctly in almost 80% of the target group. These determinants should be targeted in pandemic preparedness plans.

Towards patient-specific risk assessment of abdominal aortic aneurysm.

Diagnosis of vascular disease and selection and planning of therapy are to a large extent based on the geometry of the diseased vessel. Treatment of a particular vascular disease is usually considered if the geometrical parameter that characterizes the severity of the disease, e.g. % vessel narrowing, exceeds a threshold. The thresholds that are used in clinical practice are based on epidemiological knowledge, which has been obtained by clinical studies including large numbers of patients. They may apply "on average", but they can be sub-optimal for individual patients. To realize more patient-specific treatment decision criteria, more detailed knowledge may be required about the vascular hemodynamics, i.e. the blood flow and pressure in the diseased vessel and the biomechanical reaction of the vessel wall to this flow and pressure. Over the last decade, a substantial number of publications have appeared on hemodynamic modeling. Some studies have provided first evidence that this modeling may indeed be used to support therapeutic decisions. The goal of the research reported in this paper is to go one step further, namely to investigate the feasibility of a patient-specific hemodynamic modeling methodology that is not only effective (improves therapeutic decisions), but that is also efficient (easy to use, fast, as much as possible automatic) and robust (insensitive to variation in the quality of the input data, same outcome for different users). A review is presented of our research performed during the last 5 years and the results that were achieved. This research focused on the risk assessment for one particular disease, namely abdominal aortic aneurysm, a life-threatening dilatation of the abdominal aorta.

[Laboratory diagnosis of rheumatic diseases. Part 3: arthritides caused by infection]. / Labordiagnostik rheumatischer Erkrankungen: Teil 3: Infektbedingte Arthritiden.

This third part of this series of articles on laboratory diagnostics of rheumatic diseases considers the rheumatic diseases caused by infection by microorganisms, or reactive arthritides. The basis for laboratory diagnostics of infection-reactive arthritides is the investigation of anti-infection antibodies. In some situations, DNA amplification methods may be helpful. Bacterially infected joints should be immediately examined by arthrocentesis and microscopic examination and laboratory culture of the synovial fluid.

[Saponins as plant fungistatic compounds : On the antibiotic action of saponins. III]. / Saponine als pflanzliche Pilzabwehrstoffe : Zur antibiotischen Wirkung von Saponinen. III.

The action of 19 saponins and saponin fractions on 15 species of fungi, mostly plant pathogenes, was tested. The fungi showed different sensitivity, but no fungus was generally resistant to saponins. The fungistatic action on several species was observed at concentrations often below the real saponin content of many plants.

[Intranasal extradural meningiomas. Case report and review of the literature]. / Intranasale extradurale meningeome. Fallbericht und Literaturzusammenstellung.

Report on an extradural meningioma of the left nasal cavity and ethmoid sinus with secondary extension into the subfrontal region in an 18-year old male. Review of 37 similar cases reported in literature. These slowly growing non-infiltrating tumours cause nasal obstruction and sinusitis but have no characteristical clinical symptoms. The origins of these tumours are obviously arachnoideal meningocytes which accompany the olfactory filaments through the lamina cribrosa to the extradural site.