First case of severe pneumonic tularemia in an immunocompetent patient in the Netherlands.

Tularemia is a zoonosis caused by different subspecies of the Gram-negative bacterium Francisella tularensis. We report the first case in the Netherlands of pneumonic tularemia caused by the F. tularensis subspecies holarctica after probable occupational inhalation of contaminated aerosols. Notification of cases of tularemia has been mandatory by law in the Netherlands since 1 November 2016.

Lessons learned from enrollment in the BEST study--a multicenter, randomized trial of group psychosocial support in metastatic breast cancer.

The BEST study, a multicenter randomized trial of group psychosocial support in metastatic breast cancer, had several unusual features that may have influenced recruitment, notably the group nature of the intervention and the need for close collaboration between medical and psychosocial investigators. The recruitment process was examined in light of these features. Establishment of study centers was facilitated by involvement of experienced medical investigators who had successfully collaborated in previous research projects. Systematic evaluation of potential subjects or direct recruitment by psychosocial investigators optimized recruitment; however, the group nature of the intervention prolonged recruitment. Overall, 652 women were approached and 237 (43.3% of those medically eligible) randomized. Using population-based estimates, 24.3% of women with metastatic breast cancer were assessed for the study and 8.7% randomized. A randomization ratio of 2:1 was required to form and maintain groups. Competing clinical trials were the greatest barrier to recruitment. Five lessons were learned during recruitment for this trial: (1) multicenter randomized trials of psychosocial interventions are feasible, even in very ill patients, (2) the use of a group intervention effectively increased the required sample size by 50%, (3) similarity of randomization rates suggests that generalizability of study results will probably be comparable to that of other randomized cancer trials, (4) multidisciplinary collaborations and involvement of experienced researchers facilitated enrollment, and (5) most challenges encountered in recruitment were similar to those seen in all clinical trials.

Cryopreservation of porcine fetal ventral mesencephalic tissue for intrastriatal transplantation in Parkinson's disease.

In this study we examined the efficacy of cryopreserving porcine fetal mesencephalic tissue. After microscopical dissection of the ventral mesencephalon (VM) from E28 pig fetuses, the collection of explants was randomly divided into two equal parts. One part was directly prepared as cell suspension. The other part was stored in hibernation medium for less than 2 days and then cryopreserved as tissue fragments and stored in liquid nitrogen. After 2 weeks up to 1 year, these tissue fragments were thawed and processed as cell suspensions. After cell counting and assessment of viability, these cell suspensions were used to examine survival, morphology, and neurite formation of the dopaminergic neurons in cell culture as well as after intrastriatal implantation in 6-OHDA-lesioned rats. Comparison of cryopreserved with fresh VM cell suspensions showed no significant difference with respect to cell viability and the average number of living cells per VM explant. The morphology of cultured dopaminergic neurons after cryopreservation was identical to that of fresh cells. After intrastriatal implantation, survival and outgrowth of cryopreserved dopaminergic neurons as well as functional effects did not differ from those of fresh cells. In conclusion, the cryopreservation technique we used proves to be a reliably effective method for storing porcine fetal VM tissue.

Genetic and social influences on starting to smoke: a study of Dutch adolescent twins and their parents.

In a study of 1600 Dutch adolescent twin pairs we found that 59% of the inter-individual variation in smoking behaviour could be attributed to shared environmental influences and 31% to genetic factors. The magnitude of the genetic and environmental effects did not differ between boys and girls. However, environmental effects shared by male twins and environmental effects shared by female twins were imperfectly correlated in twins from opposite-sex pairs, indicating that different environmental factors influence smoking in adolescent boys and girls. In the parents of these twins, the correlation between husband and wife for 'currently smoking' (r = 0.43) was larger than for 'ever smoked' (r = 0.18). There was no evidence that smoking of parents (at present or in the past) encouraged smoking in their offspring. Resemblance between parents and offspring was significant but rather low and could be accounted for completely by their genetic relatedness. Moreover, the association between 'currently smoking' in the parents and smoking behaviour in their children was not larger than the association between 'ever smoking' in parents and smoking in their children.

Left-handedness in twins: genes or environment?

Twin family data can cast light on the longstanding problem about the influences of genes and environment on the etiology of left-handedness. Therefore, hand preference was assessed in 1700 adolescent twin pairs and their parents. Left-handedness (LH) appeared not significantly enhanced among twins compared to the general population. In addition the following observations were made: (1) Significant more LH in first born twins than in second born twins. (2) Significant higher left-handedness association in MZmm pairs compared to DZmm pairs and not or may be marginally so in MZff versus DZff pairs. These results, combined with the observations that (a) left-handed fathers increase the probability of LH in sons but not in daughters; (b) LH in mothers increases LH prevalence in both sons and daughters to the same degree; and (c) very low birth weight, corrected for the effect of gestational age, increases LH prevalence in first born twins only, make an environmental explanation more likely. The possibility that exposure to prenatal male hormones - to which low birth weight and high birth stress children are more vulnerable - might be a crucial condition for the etiology of LH, is discussed.

Familial resemblances in alcohol use: genetic or cultural transmission?

OBJECTIVE: Resemblances between parents and children for alcohol use can be due both to cultural transmission and genetic inheritance. We examined the genetic and environmental determinants of the familial resemblances in alcohol use. METHOD: With a parent-twin design a distinction was made between the contribution of genetic effects, the environmental influences shared by siblings and the effects of cultural transmission from parents to offspring. By questionnaire data on whether subjects had ever used alcohol were obtained from 403 Dutch families with a twin aged 15-16 years old and from 805 families with a twin aged 17 years and older. RESULTS: For 15-16 year olds, the resemblance between parents and offspring could be explained either by genetic inheritance or cultural transmission. Shared environment explained between 58% and 88% of the individual differences in adolescent alcohol use. For twins aged 17 years and older, 43% of the individual differences in alcohol use could be attributed to genetic factors and 37% to shared environment. There was no evidence for cultural transmission in this age group. CONCLUSIONS: For adolescents aged 17 years and older parental alcohol use did not create an environment that stimulated alcohol use in children. The resemblance for alcohol use between parents and their children aged 17 years and older could be explained by their genetic relatedness. For 15-16 year old adolescents, shared environmental influences were more important than for older adolescents. Only 10% of this shared environmental variance might be influenced by parental alcohol use due to cultural transmission.

Impaired initial cell reaction in CAPD-related peritonitis.

Our objective was to determine the incidence of peritonitis episodes with an impaired initial cell reaction (IICR:neutrophil number < 100 x 10(6)/L) over a period of ten years, and to find possible explanations for this unusual presentation of peritonitis. A retrospective review of the files of continuous ambulatory peritoneal dialysis (CAPD) patients included in the CAPD program 1984 and 1993 was done. Analysis of cytokine and prostanoid patterns during four peritonitis episodes with an IICR was compared to 12 episodes with a normal initial cell reaction (NICR). Dialysate cell numbers and immunoeffector characteristics of peritoneal cells were compared in 7 IICR patients in a stable situation and a control group of 70 stable CAPD patients. The setting was a CAPD unit in the Academic Medical Center in Amsterdam. Thirty-five CAPD patients who had one or more peritonitis episodes with an IICR and a control group of 249 CAPD patients were included in the study. The incidence of peritonitis with an IICR was 6%. These episodes occurred more than once in 51% of the patients who presented with IICR. In 72% the cell reaction was only delayed: a cell number exceeding 100 x 10(6)/L was reached later. Staphylococcus aureus was significantly more frequently the causative microorganism compared to all peritonitis episodes (PE) that occurred during the study period. Patients with IICR had lower dialysate cell counts in a stable situation, compared to a control group (p < 0.01). This was caused by a lower number of macrophages and CD4 positive lymphocytes. The phagocytosis capacity of the macrophages appeared to be normal. In a comparison of four PE with an IICR and 12 episodes with an NICR, the tumor necrosis factor-alpha (TNF-alpha) response was similar and occurred on day 1, also pointing to normally functioning macrophages. However, the maximal appearance rates of interleukin-6 (IL-6) and IL-8 occurred later in the episodes with IICR compared to NICR (day 2 vs day 1, p < 0.05). No differences were found in vasodilating prostaglandins, mesothelial cell markers (cancer antigen 125, phospholipids, hyaluronan), and mesothelial cell numbers in the stable situation nor during peritonitis. Peritonitis can present as abdominal pain in the absence of a cloudy dialysate. In some of the patients this presentation occurred more than once. This impaired, most often delayed, cell reaction was associated with a delayed secondary cytokine response. As IL-6 and IL-8 can be synthesized by mesothelial cells, this suggests an impaired functioning mesothelium. This could not be confirmed, however, by a lower number of mesothelial cells in effluent or lower dialysate levels of mesothelial cell markers.

Eight-year follow-up of a community-based large group behavioral smoking cessation intervention.

OBJECTIVE: To evaluate the effectiveness of a large group community-based behavioral smoking cessation intervention over an 8-year follow-up period and to determine precessation predictors of cessation at each follow-up time. RESEARCH APPROACH: Behavioral intervention followed by three longitudinal follow-up interviews. SETTING: Regional Outpatient Cancer Centre. STUDY PARTICIPANTS: 971 participants in smoking cessation clinics held between 1986 and 1990. INTERVENTION: Eight 90-minute sessions over 4 months utilizing education, self-monitoring, nicotine fading, a group quit date and behavioral modification techniques. Up to 110 smokers participated in each group program. MAIN OUTCOME MEASURES: Cessation rates at 3, 6, and 12 months postquit and at 8-year follow-up. Differences between successful and unsuccessful participants in precessation demographic, smoking history, and smoking behavior variables. RESULTS: At 3 months postquit date, 39.3% of the 971 participants reported that they were not smoking, decreasing to 32.1% at 6 months and 26.0% at 12 months. At the 8-year follow-up, 33.9% of the original sample were contacted, and of those, 47.7% reported that they were currently not smoking. There were nine predictors of cessation at the end of the program (3 months), which were similar to those previously reported in the literature. Similarly, at 6 and 12 months, six factors were associated with not smoking. At the 9-year follow-up the only variable predictive of continued abstinence was being female (p < .05). CONCLUSIONS: This program was successful in promoting smoking cessation and maintenance, even with its large-group format. Predictive factors were similar to those previously reported in the literature.

Restriction coefficients of low molecular weight solutes and macromolecules during peritoneal dialysis.

The intrinsic permeability of the peritoneal membrane can be functionally represented by the restriction coefficient (RC). The RC can be calculated as the exponent of the power relation between the mass transfer area coefficients (MTACs) of various solutes and their free diffusion coefficients in water. When the RC = 1.0, transport is determined by free diffusion only, as is expected for low molecular weight (LMW) solutes. A RC > 1.0 suggests that transport is restricted by the peritoneal membrane in a size-selective way, as has been found previously for macromolecules (MM). RCLMW can be calculated using the MTACs of urea, creatinine, urate, and beta 2-microglobulin, whereas RCMM can be calculated from clearances of beta 2-microglobulin, albumin, IgG, and alpha 2-macroglobulin. RCLMW and RCMM were determined in 108 peritoneal dialysis (PD) patients. In 36 patients, 3 or more (range 3-13) observations for RCLMW during a period of at least 2 years were available. RCMM were analyzed when present in the same patients. The median cross sectional values (n = 108) were: RCLMW: 1.22 (range 0.75-2.18) and RCMM: 2.30 (range 1.86-3.27). RCLMW was not correlated with time on PD, neither cross sectionally (r = -0.07, NS) nor after analysis of trend (mean regression coefficient t = 0.26, SD = 0.07). For RCMM a positive correlation with duration of PD was demonstrated (cross sectionally r = -0.18, p = 0.02, analysis of trend: t = 2.27, SD = 0.11, n = 27). Both RCs were not interrelated (r = -0.18, NS). The absence of a relation between both RCs suggests that LMW solutes and MM are transported by different pathways. The mean value of 1.22 for the RCLMW illustrates that the transport of LMW solutes is mainly by free diffusion, through the small-pore system. MM, which have to pass through the large-pore system, are restricted by the peritoneal membrane in a size-selective way, as shown by the high value of the RCMM. The lack of a correlation between the RCLMW and duration of PD indicates that no systematic changes occur in the small pores of the peritoneal vessels. In contrast, the increase of RCMM with duration of PD suggests restrictive changes at the level of the large-pore system.

Adding salmeterol to an inhaled corticosteroid: long term effects on bronchial inflammation in asthma.

BACKGROUND: Addition of the long acting beta2 agonist salmeterol to inhaled corticosteroids leads to better symptomatic asthma control than increasing the dose of inhaled corticosteroids. However, little is known about the long term effects of adding salmeterol on the asthmatic inflammatory process, control of which is considered important for the long term outcome of asthma. METHODS: After a 4 week fluticasone run-in period, 54 patients with allergic asthma were randomised to receive twice daily treatment with fluticasone 250 microg with or without salmeterol 50 microg for 1 year in a double blind, parallel group design (total daily dose of fluticasone 500 microg in both treatment groups). Primary outcomes were sputum eosinophil numbers and eosinophil cationic protein concentrations. Secondary outcomes were neutrophil associated sputum parameters and a respiratory membrane permeability marker. The effects on allergen induced changes were determined before and at the end of the treatment period. RESULTS: Adding salmeterol to fluticasone resulted in improved peak expiratory flow, symptom scores, rescue medication usage, and bronchial hyperresponsiveness (p < 0.05 for all). There was no sustained effect on sputum cell differential counts and cytokine concentrations during the treatment period or on changes induced by allergen challenge at the end of treatment (p > 0.05). However, adding salmeterol significantly reduced sputum ratios of alpha2-macroglobulin and albumin during the treatment period (p = 0.001). CONCLUSIONS: The addition of salmeterol to fluticasone produces no sustained effect on allergen induced cellular bronchial inflammation but leads to a significant improvement in size selectivity of plasma protein permeation across the respiratory membrane. This may contribute to the improved clinical outcome seen in patients with allergic asthma when a long acting beta2 agonist is combined with inhaled corticosteroids.

Costs of MRI. A calculation for the Netherlands.

A calculation of the costs of magnetic resonance (MR) using a machine with a field strength of 0.5 and 1.5 T is presented for the Netherlands. The costs per patient are 1,000 Dfl. and approximately 1,200 Dfl., respectively. Because the total number of MRI facilities in the Netherlands is strictly limited, also the costs of scientific research in the field of MRI have to be taken into account. It is possible to calculate the hourly costs of research on a time-sharing basis for a 1.5-Tesla machine. Combining patient care and scientific research on one machine has a reciprocal influence on the costs.

Psychosocial impact of laryngectomy mediated by perceived stigma and illness intrusiveness.

In addition to prolonging life, successful treatment by laryngectomy also results in functional disability (loss of speech) and physical disfigurement (stoma). It was hypothesized that these after-effects contribute to perceived stigma which, in turn, compromises quality of life. The hypothesis that the psychosocial impact of perceived stigma operates through illness intrusiveness--illness-induced disruptions that interfere with continued involvements in valued activities and interests--was tested. Data were collected from 51 laryngectomy recipients via standardized interviews. As hypothesized, results indicated that: 1. both perceived stigma and illness intrusiveness are related to psychosocial well-being and emotional distress; 2. illness intrusiveness mediates the relation between perceived stigma and psychosocial outcomes; 3. the psychosocial impact of illness intrusiveness is most devastating in the context of highly stigmatized self-perception; and 4. unique profiles of illness intrusiveness across individual life domains may be associated with specific psychosocial outcomes. Findings are discussed in relation to the hypothesis that illness intrusiveness is a common underlying determinant of the psychosocial impact of chronic illness.

Association between alcohol use and smoking in adolescent and young adult twins: a bivariate genetic analysis.

The association between alcohol use and smoking was examined in a large population-based sample of Dutch twins consisting of three age groups; young adolescent twins aged 12-14 years (n = 650 twin pairs), 15-16-years-old adolescent twins (n = 705 twin pairs), and young adult twins aged 17-25 years (n = 1266 twin pairs). For all three age groups, alcohol use and smoking were correlated (r = 0.5-0.6). Adolescents and young adults who smoked were more likely to drink alcohol than nonsmokers. The relation between alcohol use and smoking was also found within a twin pair; alcohol use in one twin was correlated with smoking in the cotwin. This finding suggested that familial factors contribute to the association between alcohol and tobacco use. With a bivariate genetic model, it was examined to what extent the comorbidity was due to genetic and environmental factors that predispose to both alcohol use and smoking. The genetic analyses showed that the underlying factors that influence alcohol and tobacco use and cause their association were different for adolescent and young adult twins. Initiation of alcohol use and smoking in adolescents (aged 12-16 years) was substantially influenced by the same shared environmental features. Alcohol and tobacco use in young adults were associated due to the same genetic risk factors.

Similar levels of nitric oxide in exhaled air in non-asthmatic rhinitis and asthma after bronchial allergen challenge.

BACKGROUND: Nitric oxide in exhaled air (eNO) is elevated in allergic asthma compared with healthy subjects and has been proposed as a marker of bronchial inflammation. However, eNO is elevated to a lesser extent in allergic non-asthmatic rhinitis as well. Considering the distinctive clinical appearances of both allergic diseases, differences in eNO are expected to persist after allergen exposure. The aim of the study was to compare allergen-induced changes in eNO in house dust mite sensitized patients with asthma and patients with perennial rhinitis without asthma symptoms. METHODS: Bronchial allergen challenge was performed in 52 patients sensitized to house dust mite (Dermatophagoides pteronyssinus), of whom 26 had non-asthmatic rhinitis and 26 had asthma. Levels of eNO were measured before and 1 h, 1 day and 1 week after challenge. RESULTS: At baseline eNO was significantly lower in non-asthmatic rhinitis compared with asthma (geometric mean eNO (SEM): 121 (1.1) in non-asthmatic rhinitis vs 197 (1.1) nl/min in asthma, P < 0.006). However, the increase in eNO after bronchial allergen challenge in non-asthmatic rhinitis, in particular in those patients with a dual asthmatic response, significantly exceeded the increase in asthma resulting in similar levels of eNO after challenge (geometric mean eNO (SEM) at 24 h postchallenge 204 (1.1) in non-asthmatic rhinitis vs 244 (1.1)nl/min in asthma, P = 0.3). CONCLUSION: The difference in eNO between non-asthmatic rhinitis and asthma at baseline is abolished after allergen exposure due to a significantly greater increase in eNO in non-asthmatic rhinitis.

A multivariate genetic analysis of sensation seeking.

The genetic architecture of sensation seeking was analyzed in 1591 adolescent twin pairs. Individual differences in sensation seeking were best explained by a simple additive genetic model. Between 48 and 63% of the total variance in sensation seeking subscales was attributable to genetic factors. There were no sex differences in the magnitude of the genetic and environmental effects. The different dimensions of sensation seeking were moderately correlated. The strongest correlations were between the subscales Thrill and Adventure Seeking and Experience Seeking (r = 0.4) and between Boredom Susceptibility and Disinhibition (r = 0.4 in males, r = 0.5 in females). A triangular decomposition showed that the correlations between the sensation seeking subscales were induced mainly by correlated genetic factors and, to a smaller extent, by correlated unique environmental factors. The genetic and environmental correlation structures differed between males and females. For females, higher genetic correlations for Experience Seeking with Boredom Susceptibility and Disinhibition and higher correlations among the unique environmental factors were found. There was no evidence that sex-specific genes influenced sensation seeking behavior in males and females.

A religious upbringing reduces the influence of genetic factors on disinhibition: evidence for interaction between genotype and environment on personality.

Information on personality, on anxiety and depression and on several aspects of religion was collected in 1974 Dutch families consisting of adolescent and young adult twins and their parents. Analyses of these data showed that differences between individuals in religious upbringing, in religious affiliation and in participation in church activities are not influenced by genetic factors. The familial resemblance for different aspects of religion is high, but can be explained entirely by environmental influences common to family members. Shared genes do not contribute to familial resemblances in religion. The absence of genetic influences on variation in several dimensions of religion is in contrast to findings of genetic influences on a large number of other traits that were studied in these twin families. Differences in religious background are associated with differences in personality, especially in Sensation Seeking. Subjects with a religious upbringing, who are currently religious and who engage in church activities score lower on the scales of the Sensation Seeking Questionnaire. The most pronounced effect is on the Disinhibition scale. The resemblances between twins for the Disinhibition scale differ according to their religious upbringing. Receiving a religious upbringing seems to reduce the influence of genetic factors on Disinhibition, especially in males.

The influence of religion on alcohol use initiation: evidence for genotype X environment interaction.

We examined the possible role of religious upbringing as a mediator of the shared environmental influences and as a moderator of the genetic influences on the risk of alcohol use initiation in a large population-based sample of Dutch adolescent and young adult twins (1967 twin pairs). There was not a significant association between religious participation and alcohol use initiation among Dutch adolescents and young adults. We also hypothesized that the relative magnitude of the genetic influences on the risk of alcohol use initiation would be greater for those adolescents and young adults who were raised in a less religious environment compared to those adolescents and young adults who were raised in a more religious environment. We indeed found higher heritabilities for females without a religious upbringing compared to females with a religious upbringing. Genetic influences accounted for 40% of the variance in alcohol use initiation in nonreligious females, compared to 0% in religiously raised females. Shared environmental influences accounted for 54% of the variance for nonreligious females and 88% of the variance in religious females. For males, the genetic variance was also higher in the nonreligious group compared to the religious group, but this difference was not statistically significant. Whether or not they were raised religiously, the liability to alcohol use initiation in males was moderately influenced by genetic factors (30%) and substantially influenced by shared environmental factors (60%).

The genetics of smoking initiation and quantity smoked in Dutch adolescent and young adult twins.

Not much is known about the genetic and environmental determinants of various aspects of substance use in adolescents. This study examined whether the inheritance of initiation of tobacco use in adolescents is independent of the inheritance of the number of cigarettes smoked. Alternative multifactorial threshold models were applied to data on tobacco use in 1676 Dutch adolescent twin pairs. The three models that were considered are (i) the single liability dimension model, (ii) the independent liability dimension model, and (iii) the combined model (CM). The results showed that there is not one underlying continuum of liability to smoking. The CM was the best-fitting model. This model postulates that there are separate initiation and quantity dimensions but allows for the possibility that there are some individuals who are so low on the liability to level of consumption that they are not using tobacco. There were no differences between males and females in the magnitude of the genetic and environmental influences on individual differences in smoking initiation and quantity smoked. Smoking initiation was influenced by genetic factors (39%) and shared environmental influences (54%). Once smoking is initiated genetic factors determine to a large extent (86%) the quantity that is smoked.