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Biomedical subjects

R G Westendorp

Publications and source records attributed to R G Westendorp.

At least 19 recordsLinked to original sources
PubMed1999

Protection against influenza after annually repeated vaccination: a meta-analysis of serologic and field studies.

BACKGROUND: According to common recommendations, influenza vaccination should be performed annually. It has been suggested that vaccination in previous years reduces vaccine efficacy in the long term. OBJECTIVE: To determine whether the protection of influenza vaccine decreases when vaccination is repeated annually. METHODS: Articles published between 1966 and 1997 were selected from MEDLINE. The end point for field studies was the influenza-related morbidity or mortality during influenza outbreaks (resulting in field protection rates). The end point for serologic studies was exceeding a protective postvaccination hemagglutination-inhibition titer (serologic protection rates). Protection rate differences between groups with single and multiple vaccinations were subjected to meta-analysis. RESULTS: Seven field studies (including 13 trials) supported the hypothesis that protection in multiple-vaccination groups is at least as good as that in single-vaccination groups. Ten trials with 5117 observations could be subjected to meta-analysis. The pooled protection-rate difference was close to 0 (1.1%; 95% confidence interval, -0.2% to 2.4%), thus detecting no difference between single or multiple vaccination. Twelve serologic studies (including 53 trials) showed heterogeneous results: 9 trials were significantly in favor of single vaccination, and 7 were in favor of multiple vaccination, but in most cases, there was no significant difference between the 2 vaccination groups. The pooled serologic protection-rate difference from 52 trials (12341 observations) was again close to 0 (1.7%; 95% confidence interval, -1.3% to 4.8%). CONCLUSIONS: We did not detect any evidence for a decreasing protection with annually repeated influenza vaccination. Annual vaccination should not be discouraged in populations at risk.

Antibodies, Viral↗
PubMed1999

Quality and quantity of the humoral immune response in healthy elderly and young subjects after annually repeated influenza vaccination.

Doubt about the serologic efficacy of annually repeated influenza vaccination prompted investigations into the course of hemagglutination-inhibiting (HI), IgG, and IgA antibody titers and the IgG and IgA avidity index to influenza A/Taiwan/1/86 and A/Beijing/353/89 after annual vaccination. Fifty-four healthy elderly persons >70 years of age and 24 healthy young adults <30 years of age received standard influenza vaccine during 3 consecutive years. On average, prevaccination HI, IgG, and IgA titers to both influenza virus strains increased >=4 fold between the first and the third vaccination (analysis of variance, P<.001). The postvaccination HI and IgG titers remained unchanged after annual vaccination. The avidity index of IgG and IgA antibodies increased somewhat after annual vaccination, although the increase was statistically significant only in the young subjects. These data indicate that annual influenza vaccination of healthy elderly and young subjects results in an overall increase in protective antibodies.

Adolescent↗
PubMed1999

Mortality in patients with epilepsy: 40 years of follow up in a Dutch cohort study.

To investigate the extent of and the causes of excess mortality in patients with epilepsy, mortality was studied in a cohort of patients with newly diagnosed epilepsy over an extended follow up period. All patients (both inpatients and outpatients) of the Instituut voor Epilepsiebestrijding in Heemstede, the Netherlands between 1953 and 1967 were included in the study. Complete follow up was obtained for 1355 patients, 746 men and 609 women. The mean follow up was 28 years (range 6 months-41 years). In total, 38 665 person years were surveyed, in which 404 patients died. All cause mortality was threefold increased (risk ratio (RR) 3.2; 95%CI 2.9-3. 5), and was only slightly higher for men than for women. Mortality was highest under 20 years of age (RR 7.6; 95%CI 6.5-8.7), and during the first 2 years of follow up (RR 16; 95%CI 12-20). Mortality directly related to epilepsy accounted for 18 of the 53 deaths in the first 2 years after diagnosis, which is equivalent to an incidence rate of 6.8 per 1000 person-years (95% CI 4.1-10). After 2 years 110 of the 351 deaths could be attributed to epilepsy itself, or were epilepsy related, with an incidence rate of 3.1 per 1000 person-years (95% CI 2.5-3.6). The data presented suggest that the increased mortality risk in patients with epilepsy is attributable in part to epilepsy itself, and is predominantly present at younger age and early after diagnosis. However, the absolute risk is moderate.

Cause of Death↗
PubMed1999

The DD genotype of the ACE gene polymorphism is associated with progression of diabetic nephropathy to end stage renal failure in IDDM.

BACKGROUND: The insertion-deletion (I/D) polymorphism of the angiotensin converting enzyme gene is a diallelic polymorphism that constitutes a genetic influence on the progression of renal diseases such as IgA nephropathy. Patients with the DD genotype have an accelerated progression towards end stage renal failure in these diseases. The role of the I/D polymorphism in the pathogenesis of diabetic nephropathy in IDDM is unresolved. PATIENTS AND METHODS: We therefore set out to study the contribution of the I/D polymorphism in 79 patients (age 39.5 +/- 7.6 years (mean +/- SD) with end stage renal failure due to diabetic nephropathy, who were recipients of a combined kidney-pancreas transplantation (n = 60), or who were on the waiting list for such a procedure (n = 19). The control series consisted of 82 patients (age 39.5 +/- 9.6 years) without microalbuminuria after fifteen years of IDDM. RESULTS: The ACE genotype distribution in patients was not in accordance with the Hardy-Weinberg equilibrium due to a significant overrepresentation of the DD genotype (X2 = 8.9, p = 0.01). This resulted in a significant increase of the D-allele frequency in the cases compared to controls (X2 = 4.9, p = 0.03). The presence of one D-allele did not increase the risk of end stage renal failure (odds ratio ID/II = 1.0, 95% CI 0.4-2.2). The presence of the DD genotype increased the risk of end stage renal failure twofold compared to the other genotypes (odds ratio 2.1, 95% CI 1.1-4.0). The risk estimate seemed slightly higher in patients with good metabolic control (odds ratio 2.6, 95% CI 1.0-7.1), than in patients with poor control (odds ratio 1.6, 95% CI 0.59-4.3). CONCLUSION: It is concluded that the risk of end-stage renal failure in patients with IDDM is twofold increased in patients with the DD genotype as compared to patients with other genotypes.

Adult↗
PubMed1998

Determination of tumour necrosis factor-alpha and interleukin-10 production in a whole blood stimulation system: assessment of laboratory error and individual variation.

Ex vivo production of cytokines as determined by whole blood stimulation and supernatant ELISA is partly determined by heritability. To assess the ability of this system to distinguish between high and low producers the laboratory error and individual variation were investigated. Whole blood samples from healthy volunteers were collected using endotoxin-free tubes and were incubated with 0 to 1000 ng/ml lipopolysaccharide concentrations for 4 and 24 h, and subsequently centrifuged. In the supernatants, TNF-alpha and IL10 were measured by ELISA. Coefficients of variation for the day-to-day variation in the blood sampling, transport and stimulation as well as in the whole blood stimulation per se ranged from 7.5% to 12.3%. The intra-individual variation was 15% (TNF-alpha) and 19% (IL10) in contrast to the inter-individual variation of, on average, 35%. No interchanging of ranks between high and low producers was observed after repeating the whole blood stimulation on distinct days. The whole blood stimulation system is able to distinguish high and low producers of TNF-alpha and IL10.

Blood↗
PubMed1998

[Roaming through methodology. VI. Medical perspective on the causes of death].

The Central Statistics Office (CBS) annually publishes the causes of death of decreased Dutch residents. It is generally assumed that the registration of causes of death is unreliable and provides only limited additional information. It is a fact that the physicians who perform the post mortems may supply incomplete or incorrect information. Hence, individual causes of death are sometimes coded incorrectly. This necessitates specific instruction of medical students. For studies of large groups, misclassification of individual causes of death is of less importance. However, the systematics of the registration has to be taken into account. It is important that causes of death are registered uniformly facilitating (inter)national comparisons. With the aid of a causes of death register, characteristics of (groups of) the population can be related to the distribution of the causes of death; at the level of the individual patient the causes of death may afford insight into causes and effects of disease. The latter is possible by a temporary link of patient data with the individual causes of death.

Cause of Death↗
PubMed1998

Interleukin 10 secretion in relation to human IL-10 locus haplotypes.

Stimulation of human blood cultures with bacterial lipopolysaccharide (LPS) shows large inter-individual variation in interleukin 10 (IL-10) secretion, which has been shown to have a genetic component of over 70%. Alleles at two microsatellite loci in the 4 kb immediately upstream of the human IL-10 transcription initiation site in 132 individuals from 56 Dutch families were defined and assigned as haplotypes. LPS-induced IL-10 secretion was measured by ELISA and related to the IL-10 promoter haplotypes present in 78 unrelated individuals obtained from these families. Analysis showed that LPS-induced IL-10 secretion from unrelated individuals varied with IL-10 promoter haplotypes (P = 0.024; Kruskal-Wallis test). Two observations were made in relation to secreted IL-10 levels and promoter haplotypes; first, those haplotypes containing the allele IL10.R3 were associated with lower IL-10 secretion than haplotypes containing any other IL10.R allele. Second, the haplotype IL10.R2/IL10.G14 was associated with highest IL-10 secretion overall, whereas the haplotype IL10.R3/IL10.G7 was associated with lowest IL-10 secretion. These data demonstrate that the ability to secrete IL-10 can vary in man according to the genetic composition of the IL-10 locus.

Alleles↗
PubMed1998

Anti-inflammatory cytokine profile and mortality in febrile patients.

BACKGROUND: An anti-inflammatory cytokine profile on whole-blood stimulation in vitro is associated with fatal outcome of meningococcal disease. We investigated whether an anti-inflammatory cytokine profile in the circulation is associated with adverse outcome in other infectious diseases. METHODS: We enrolled 464 consecutive patients (272 men, 192 women) who presented to hospital with fever (> or = 38.2 degrees C). On admission we measured plasma interleukin 10 (IL-10) and tumour necrosis factor alpha (TNF alpha), and collected clinical and microbiological data on the febrile illness, then followed up all patients for clinical outcome. FINDINGS: In at least 399 of the 464 patients fever was caused by infection. 33 patients died after a median hospital stay of 11 days (interquartile range 3-20). Concentrations of IL-10 were significantly higher in non-survivors (median 169 pg/mL [IQR 83-530]) than in survivors (median 88 pg/mL [42-235], p=0.042). When dichotomised around the median, the mortality risk was two times higher in patients who had high concentrations of IL-10 than in those with low concentrations (relative risk 2.39 [95% CI 1.07-5.33]), in patients with low and high concentrations of TNF alpha. In the 406 patients without haemodynamic deterioration in the first 24 h, IL-10 was higher and TNF alpha lower in patients who died than in those who survived. The ratio of IL-10 to TNF alpha was higher in non-survivors (median 6.9 [3.0-21.0]) than in survivors (median 3.9 [2.0-7.0], p=0.040). This ratio was highest in patients who died without underlying disease (median 21.5 [5.0-25.0]). Age, sex, and duration of fever before admission did not explain the differences in IL-10 and TNF alpha. INTERPRETATION: An anti-inflammatory cytokine profile of a high ratio of IL-10 to TNF alpha is associated with fatal outcome in febrile patients with community-acquired infection. Our findings caution against a widespread use of proinflammatory cytokine inhibition in patients with sepsis.

Adolescent↗
PubMed1998

Similar response to simvastatin in patients heterozygous for familial hypercholesterolemia with mRNA negative and mRNA positive mutations.

In patients heterozygous for familial hypercholesterolemia, the low-density lipoprotein (LDL) cholesterol lowering effect of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors may depend on the nature of the mutation in the LDL receptor gene. To test this hypothesis, we compared the response to simvastatin, 20 mg daily for 9 weeks, between heterozygous carriers of functionally different classes of mutations, i.e. mRNA negative or mRNA positive mutations. Out of 116 consecutive, unrelated patients with familial hypercholesterolemia, 27 patients were selected for molecular analyses: 14 patients with mRNA negative and 13 with mRNA positive mutations. Before simvastatin treatment, patients with mRNA negative mutations had higher levels of LDL cholesterol, lower levels of high-density lipoprotein (HDL) cholesterol and significantly more often tendon xanthomas, compared to patients with mRNA positive mutations. Simvastatin reduced the mean fasting LDL cholesterol levels to a similar percentage in the mRNA negative and mRNA positive patients (37, 36%, respectively, 95% CI of difference--8 to 5%, P = 0.2). This effect was similar to the 37% decrease observed in our total series of patients with familial hypercholesterolemia (n = 116). The increase in mean concentration of HDL cholesterol was greater in the mRNA negative group than in the mRNA positive group (16, 0%, respectively, 95%, CI of difference 8-25%, P = 0.002) independent of the response of total triglycerides to simvastatin. The percentage LDL cholesterol lowering response varied among multiple carriers of the same mutation, even in the case of mRNA negative mutations. We conclude that the percentage LDL lowering response to simvastatin treatment was similar in patients with mRNA negative and mRNA positive mutations. Moreover, variation of this response within multiple carriers of the same mutation suggests an influence of additional factors.

Anticholesteremic Agents↗
PubMed1998

The plea against annual influenza vaccination? 'The Hoskins' Paradox' revisited.

Three papers by Hoskins and collaborators published in The Lancet in the 70s, have been challenging the common policy to annually vaccinate people at risk with inactivated influenza virus vaccine. From an analysis of a vaccination campaign in adolescent pupils of a boarding school and four influenza outbreaks in the period 1970-76, Hoskins et al. concluded that annually repeated vaccinations would not confer protection against epidemic influenza in the long-term ('Hoskins' Paradox'). A review of the papers revealed, however, that most of the study subjects were not consequently vaccinated every year and that most of the presented data were, therefore, not relevant for the problem of annually repeated influenza vaccination. When applying strict definitions of single vaccination (immunised immediately prior to the epidemic, but not in the years before) and multiple vaccination (immunised immediately prior to the epidemic, and also in the year(s) before), only two of four epidemics (A/England/42/72 (H3N2) in 1972/73 and A/Port Chalmers/1/73 (H3N2) in 1973/74) could be evaluated: in one case, no negative effect of repeated vaccination could be detected, in the second case, the attack rate difference between groups with single and multiple vaccination was of borderline significance. Data on two other epidemics (B/Hong Kong/8/73 in 1973/74 and A/Victoria/3/75 (H3N2) in 1975/76) could not be interpreted because of incomplete vaccination strategies. In conclusion, Hoskins' Paradox cannot be substantiated by Hoskins' own data. Considering other published data on the subject, it is suggested that no negative effect of annually repeated vaccination on protection against epidemic influenza exists.

Adolescent↗
PubMed1998

Differences in age, site distribution, and sex between nodular and superficial basal cell carcinoma indicate different types of tumors.

Basal cell carcinomas (BCC) are among the most common cancers in white subjects. Etiologic factors include ultraviolet and ionizing radiation, chemical carcinogens, and possibly infection with human papillomaviruses. Because of clinical and histologic differences, differential pathogenetic mechanisms have been suggested for different BCC subtypes. We studied the patient and tumor characteristics of all BCC diagnosed and/or treated at the departments of Dermatology and Plastic Surgery of our hospital between 1985 and 1996, and a review of the literature was carried out. Some important differences between patients with nodular BCC and patients with superficial BCC were observed. The frequency of superficial BCC was higher in females and was seen in younger patients as compared with nodular BCC. The latter occurred mainly in the head/neck region: in males they were seen more frequently on the ears, and in females they were predominantly seen on the eyelids, the lips, and in the neck. Superficial BCC occurred mainly on the trunk, and occurred significantly more often on the trunk in males than in females, where the legs were the most common site. These findings strongly suggest that the superficial subtype is a separate group within the clinical entity of BCC. Furthermore, our findings seem to support the etiologic role of sun exposure in these tumors; however, this role may be different for each subtype. Chronic sun exposure may be an etiologic factor in nodular BCC as compared with intermittent sun exposure in superficial BCC. Other factors, such as differences in site specific host factors and referral bias, may also play a role in the differences found between the subtypes.

Abdomen↗
PubMed1998

Effect of hyperinsulinemia on plasma leptin concentrations and food intake in rats.

We investigated the dose- and time-dependent effect of insulin infusion on peripheral and portal plasma leptin concentrations in normal rats. Three groups were studied: group I: euglycemic (6 mmol/l) insulin (6 mU . kg-1 . min-1) clamps for 0, 2, 4, 12, and 24 h; group II: euglycemic insulin (18 mU . kg-1 . min-1) clamp for 2 h; and group III: euglycemic insulin (3 mU . kg-1 . min-1) clamp for 7 days. In group III, food intake was quantified during days 1-7. After an overnight fast, peripheral and portal plasma leptin levels were identical (1.5 +/- 0.2 and 1.6 +/- 0.2 ng/ml). Insulin infusion (6 mU . kg-1 . min-1) for 2 h had no effect on plasma leptin levels (1.5 +/- 0.2 ng/ml). After 4 h (2.0 +/- 0.2 ng/ml), 12 h (2.2 +/- 0. 4 ng/ml), and 24 h (2.7 +/- 0.6 ng/ml; all P < 0.05) of insulin infusion, a progressive time-related increase in plasma leptin concentration was observed; portal vein leptin levels rose in parallel and were similar to peripheral levels. When insulin (18 mU . kg-1 . min-1) was infused for 2 h, plasma leptin levels increased to 3.0 +/- 0.3 ng/ml (P < 0.01). Seven days of constant insulin infusion (3 mU . kg-1 . min-1) resulted in a progressive increase in fasting plasma leptin and a parallel decrease in food intake. A mean increase in plasma leptin concentration of 1 ng/ml during the 7-day insulin infusion period was associated with a mean decrease in food intake of 2.5 g/day (multivariate ANOVA, P < 0.05). We conclude that the insulin-induced rise in peripheral and portal vein leptin levels is similar and both dose and time dependent. The inverse relationship between plasma leptin concentration and food intake during prolonged hyperinsulinemia, but not during short-term hyperinsulinemia, supports the role of leptin in long-term food consumption.

Animals↗
PubMed1998

A risk model approach to the prediction of fetal acidemia.

Known risk factors for adverse perinatal outcome were related to severe fetal acidemia during labor and at birth. Severe fetal acidemia was defined as a fetal scalp or umbilical artery pH > 3 SD below the mean for normal pregnancy. pH values were available for 1,524 singleton births without congenital anomalies. Of these births, 83 (5.4%) had at least one pH value > 3 SD below the reference mean. Known risk factors in the group with severe acidemia were compared with those in a random sample of the remaining 94.6% births. The strongest predictor of severe fetal acidemia was an abnormal cardiotocogram with a Hammacher score > 8. Risk factors shown to lower pH values significantly were combined in a prediction model based on multiple regression analysis. Back-validation of the model showed that half of all cases of severe fetal acidemia could not be adequately predicted. It is concluded that such prediction models do not contribute to a more effective detection of severe fetal acidemia.

Acidosis↗
PubMed1998

Histomorphometric correlates of renal failure in IgA nephropathy.

It is generally accepted that the severity of renal insufficiency in patients correlates with the severity of tubulointerstitial abnormalities, but not with the severity of glomerular abnormalities in kidney biopsies. We recently challenged this view by demonstrating significant correlations of glomerular structural abnormalities with renal function in a histomorphometric study of biopsies from patients with various kidney diseases. We set out to confirm these findings in biopsies from patients with a single disease entity. IgA nephropathy was selected. An additional objective of the study was to determine the prognostic value of our histological predictors of renal function. Histomorphometric measurements were done in silver- and PAS-stained paraffin sections of biopsies from 83 patients with primary IgA nephropathy. The results were correlated with creatinine clearance at the time of biopsy. The prognostic value of the histomorphometric parameters and of several clinical characteristics were determined in a Cox proportional hazard model. All glomerular histomorphometric indices correlated with the severity of renal insufficiency, but quantitative estimates of the glomerular deposition of periodic acid-Schiff positive extracellular matrix (PAS-index) seemed to be the most important glomerular structural-functional correlate (r = 0.53, p<0.001). However, the correlation of quantitative estimates of the severity of interstitial extracellular matrix accumulation with renal function (quantitative interstitial index) was superior (r = 0.76, p<0.001). Creatinine clearance at biopsy and initial proteinuria were the strongest clinical predictors of renal survival. The severity of tubulointerstitial extracellular matrix accumulation was the strongest histological predictor of an adverse outcome. In conclusion, quantitative estimates of the severity of glomerular and tubulointerstitial extracellular matrix accumulation both correlate well with the severity of renal failure in biopsies from patients with IgA nephropathy. Creatinine clearance at biopsy, initial proteinuria and the severity of tubulointerstitial extracellular matrix accumulation are the best predictors of renal survival. On a more general note, the paradigm of the absence of correlation of glomerular pathology with renal function should be abandoned.

Adult↗
PubMed1998

The risk of mortality and the factor V Leiden mutation in a population-based cohort.

The factor V Leiden mutation (conferring resistance to activated protein C) has been implicated in the risk of arterial thrombosis and is a well-established risk factor for venous thrombosis especially in the elderly. We studied whether the disease association of the factor V mutation is reflected in an increased all-cause and cause-specific mortality. First, the prevalence of the factor V Leiden mutation was determined in a population-based study among subjects aged 85 years and over (4.7%, n = 660) and was found to correspond to the prevalence in young subjects aged 18 to 40 years (5.0%, n = 321). Secondly, we studied the association of factor V Leiden with the risk of all-cause mortality and specific causes of death in the elderly cohort during a 10-year follow-up period. Neither the all-cause mortality risk (RR 1.0; 95% CI, 0.7-1.5), nor the risk of death due to cardiovascular disease (RR 0.9; 95% CI, 0.5-1.7) were increased in elderly subjects heterozygous for factor V Leiden. Our study thus indicates that heterozygosity for factor V Leiden does not affect population mortality.

Adolescent↗
PubMed1997

[Daily functioning and health care utilization among persons 85 years old and older].

OBJECTIVE: Description of the activities of daily living and the use of care in relation to several determinants in persons aged 85 years and over. DESIGN: Cross-sectional survey. SETTING: General population from the city of Leiden, the Netherlands. METHOD: A representative sample from the inhabitants aged 85 years and over of the city of Leiden was enrolled. A physician visited 239 'oldest old' (response rate 83%) at their places of residence, in 1991/'92. Data were obtained on health (joint disorder, cardiovascular disease, diabetes mellitus, Parkinson's disease; disorders in cognition, eyesight, hearing; limitation of mobility), self care and household activities in daily living and the use of care (informal care by neighbours or family, (geriatric) home help, district nurse, private help). Statistical analysis was performed by non-parametric tests and logistic regression. RESULTS: Of the 'oldest old' 111 (46%) lived independently, and 67 of them (28% of the total group) had no professional help. Almost all 'oldest old' had at least one health disorder. In all, 129 women (77%) and 43 men (61%) had restrictions in basic and (or) instrumental activities of daily living. These restrictions were strongly related to disorders in cognition, vision and mobility, less related to chronic disease and not related to hearing disorders. Restrictions in the activities of daily living were also related to the living condition. This relation was particularly strong for women. Men living without a partner were more likely to be institutionalised. Among the 'oldest old' who lived independently, restrictions in the activities of daily living were related to the use of care, with the exception of privately organised care. CONCLUSION: One out of four persons aged 85 years and over lived without professional help. Marked differences between the sexes were found for the interrelation between activities in daily living and the use of care.

Activities of Daily Living↗