Biomedical subjects

S H Heisterkamp

Publications and source records attributed to S H Heisterkamp.

At least 19 recordsLinked to original sources

PubMed2005

Mixed plaques: statistical evidence how plaque assays may underestimate virus concentrations.

Even at very low concentrations human pathogenic viruses may result in infection and possibly subsequent disease. Ideally, viruses are quantified by use of cell culture assays to determine their infectivity. Plaque assays are common tools for enumeration of viruses in inocula and this process is straightforward when a plaque results from the offspring of a single infectious virus particle. In the course of a study on the usefulness of sewage monitoring for surveillance of polio-virus transmission, sewage samples containing a mixture of two live polio vaccine strains (type 1 and type 3) were analyzed. The total poliovirus concentration in plaque forming units (pfu) was estimated by means of a monolayer plaque assay on L20B cells. Subsequent typing of virus directly by neutralisation of virus from excised plaques revealed the occurrence of plaques containing both type 1 and type 3 virus. This means that there must be plaques that originate from more than one initial infectious virus particle. As a consequence, the estimated virus concentration is incorrect. We present statistical methods that utilize these mixed plaque counts to estimate the concentrations of either virus type in our sewage samples. We can also calculate a correction factor for the error in virus concentration, which would result from equating a pfu to a single infectious particle. Since many quantitative methods in microbiology are based on colony counts, we conclude that such counts should be interpreted with caution, especially when data are used in quantitative microbial risk assessment to estimate the public health impact.

Colony Count, Microbial↗

PubMed2005

Dose dependency of adjuvant activity of particulate matter from five European sites in three seasons in an ovalbumin-mouse model.

Various particulate matter (PM) samples were tested for their adjuvant potency in an animal model of allergy (ovalbumin) in the European Union study entitled Respiratory Allergy and Inflammation Due to Ambient Particles. Coarse and fine ambient particles were collected during spring, summer, and winter in Rome, Oslo, Lodz, Amsterdam, and De Zilk. De Zilk, at the Dutch seaside, has mainly westerly winds and served as a negative pollution control. EHC-93 (Ottawa dust) was used as a positive control. We studied the adjuvant potency of the particle antibody responses to ovalbumin and histopathological changes in the lung. After a sensitization phase by coexposure to EHC-93 and ovalbumin, the antibody response to ovalbumin and inflammatory responses in the lung were huge. There was more adjuvant activity in reaction to 9-mg/ml samples than to 3-mg/ml samples. A best-fit analysis of these samples shows that the ambient coarse and fine particles at these sites, in combination with allergens, have severe to mild adjuvant activity in the order Lodz, Rome, Oslo, and Amsterdam. A high dose of the fine fraction was more potent than a high dose of the coarse fraction, except at De Zilk, where the reverse was true. Spring and winter PM was more potent than summer PM. Depending on the site, either a water-soluble or a water-insoluble fraction was responsible for the adjuvant activity. A concentration of 3 mg/ml is effective for screening high-activity samples, as is a concentration of 9 mg/ml for screening low-activity samples in the ovalbumin-mouse model.

Adjuvants, Immunologic↗

PubMed2004

Adjuvant activity of ambient particulate matter of different sites, sizes, and seasons in a respiratory allergy mouse model.

In the framework of an EU project entitled, "Respiratory Allergy and Inflammation due to Ambient Particles (RAIAP)", various ambient particulate matter samples were tested for their adjuvant potency in an animal allergy model to ovalbumin. Coarse (2.5-10 microm) and fine (0.15-2.5 microm) particles were collected during the spring, summer, and winter in Rome, Oslo, Lodz, and Amsterdam. Coarse and fine particles were also collected near a seaside location in the Netherlands, where prevailing winds are westerly. These latter particles served as a control, with a minimum contribution by traffic. Ottawa dust (EHC-93) was used as a standard reference sample. Immunoglobulins (IgE, IgG1, and IgG2a), histopathological changes in the lung, cytokines, and the number of cells and their differentiation in lung lavages were used as effect parameters to study the adjuvant potency of these particles. The particles (3 mg/ml) were mixed with ovalbumin (0.4 mg/ml) and intranasally administered during the sensitization or the challenge phase. Intranasal administration of ovalbumin only induced very little antibody response, but introduced a minor inflammatory response in the lung or BAL during the sensitization and challenge phase. On the contrary, after coexposure to EHC-93 and ovalbumin, a major increase was found in immunoglobulin levels specific for ovalbumin, and a major inflammatory response in lung and BAL was induced. Coexposure to ovalbumin with 4 out of 12 collected PM samples (3 mg/ml) resulted in an increase of mainly IgE and IgG1. The histopathological changes consisted of a small to severe peribronchial and perivascular inflammatory response, a hypertrophy of bronchiolar mucous cells and an increase in eosinophils and neutrophils in the BAL. Statistical evaluation of the above-mentioned parameters showed associations with PMx (coarse and fine), site, season, season x PMx, season x site and (PMx) x site. In addition, adjuvant activity of the PMx can be ranked as Lodz > Rome = Amsterdam > Oslo. When the different seasons were compared for IgE, PM from winter was found more active compared to PM from spring and summer. Only for the histopathological lesions, statistically significant difference in effects was found between coarse and fine (coarse > fine). No associations were found between the endotoxin content and the biological effects parameters, although endotoxin was much more confined to the coarse fraction. In conclusion, PM, both coarse and fine, and from various geographic sites, was found to differ in adjuvant activity; furthermore, winter was found more active than spring and summer.

Air Pollutants↗

PubMed2003

Acute effect of air pollution on respiratory complaints, exhaled NO and biomarkers in nasal lavages of allergic children during the pollen season.

During 2 months of the pollen season, the acute and putative adjuvant effect of traffic-related air pollution on respiratory health was investigated in children sensitised to grass pollen or house dust mite (HDM). Respiratory complaints were objectified via measurement of exhaled NO and inflammatory mediators in nasal lavage (NAL). During the study children, skin prick negative (n = 31) or positive to grass pollen (n = 22), HDM (n = 34) or grass pollen + HDM (n = 32), kept a daily diary on respiratory symptoms, and NAL and exhaled air was sampled twice a week. The level of air pollutants and pollen was monitored continuously. Like children sensitised to HDM, those sensitised to pollen reported respiratory complaints (shortness of breath, itchy eyes or blocked nose) more frequently than non-sensitised children during (but not before) the pollen season; the respiratory complaints of sensitised children were independent of the pollen level. In addition, exposure to increased levels of PM(10) induces 'shortness of breath' in pollen- and HDM-sensitised children, whereas ozone induces a blocked nose in HDM-sensitised children. Combined exposure to PM(10) + pollen and O(3) + pollen induces a blocked nose in both HDM-sensitised children and children sensitised to pollen + HDM. Significant positive associations were found between eNO and the levels of NO(2), CO, PM(2.5) and pollen in both sensitised and non-sensitised children. At the start of the pollen season, the NAL concentration of eosinophils and ECP in pollen-sensitised children was increased compared to winter, but their levels were not further affected by increased exposure to pollen or air pollution. In conclusion, during the pollen season, sensitised children continuously report a high prevalence of respiratory complaints which coincides with increased levels of upper and lower airway inflammatory markers. No additional pro-inflammatory effect of air pollution was observed, which indicates that air pollution does not facilitate allergen-induced inflammatory responses.

Air Pollution↗

PubMed2002

Palliative chemotherapy or watchful waiting? A vignettes study among oncologists.

PURPOSE: To determine the preferences of oncologists for palliative chemotherapy or watchful waiting and the factors considered important to that preference. METHODS: Sixteen vignettes (paper case descriptions), varying on eight patient and treatment characteristics, were designed to assess the oncologists' preferences. Their strength of preference was rated on a 7-point scale. An orthogonal main effects design provided a subset of all possible combinations of the characteristics, allowing estimations of the relative weights of the presented characteristics. A written questionnaire was sent to a random sample of oncologists (N = 1,235). RESULTS: The response rate was 67%, and 697 questionnaires were available for analysis. Eighty-one percent of the respondents were male. The mean age was 46 years. We found considerable variation among the oncologists. No major associations between physician characteristics and preferences were found. Of the patient and treatment characteristics affecting treatment preference, age was the strongest predictor, followed by the patient's wish to be treated and the expected survival gain. Other patient and treatment characteristics had a limited effect on preferences, except for psychologic distress, which had no independent impact. CONCLUSION: Patients will encounter different decisions depending on their oncologists' preferences and their own personal background. Therefore, to ensure adequate information for decision-making processes, decision aids are proposed.

Adult↗

PubMed2002

A Bayesian approach to parameter estimation in HIV dynamical models.

In the context of a mathematical model describing HIV infection, we discuss a Bayesian modelling approach to a non-linear random effects estimation problem. The model and the data exhibit a number of features that make the use of an ordinary non-linear mixed effects model intractable: (i) the data are from two compartments fitted simultaneously against the implicit numerical solution of a system of ordinary differential equations; (ii) data from one compartment are subject to censoring; (iii) random effects for one variable are assumed to be from a beta distribution. We show how the Bayesian framework can be exploited by incorporating prior knowledge on some of the parameters, and by combining the posterior distributions of the parameters to obtain estimates of quantities of interest that follow from the postulated model.

Bayes Theorem↗

PubMed2002

The proximal stomach and postprandial symptoms in functional dyspeptics.

OBJECTIVES: It remains unclear whether postprandial symptom profiles in patients with visceral hypersensitivity and in those with impaired fundic accommodation differ. Therefore, we evaluated the postprandial symptoms in functional dyspepsia (FD) patients classified according to proximal stomach function. In addition, the effect of gastric relaxation induced by sumatriptan on postprandial symptoms was studied in FD patients with impaired fundic accommodation. METHODS: Twenty-five healthy volunteers (HVs) and 44 FD patients filled out a disease-specific questionnaire (Nepean Dyspepsia Index) and underwent a gastric barostat study to evaluate visceral sensitivity, meal-induced fundic relaxation, and postprandial symptoms. Postprandial symptoms evoked by a drink test or reported during the barostat study were compared between FD patients subdivided according to the underlying pathophysiological mechanism. Finally, the effect of sumatriptan on postprandial symptoms evoked by a drink test was investigated in HVs and in FD patients with impaired fundic accommodation. RESULTS: There was no clear relationship between any of the 15 Nepean Dyspepsia Index symptoms and proximal stomach function. Postprandial symptoms evoked during the barostat study or after the drink tests were significantly higher in FD patients than in HVs; however, no clear differences in symptom profile could be demonstrated between the different subclasses of FD. Sumatriptan did not affect the maximal ingested volume or the postprandial symptoms in HVs or FD patients after a drink test. CONCLUSIONS: No clear relationship could be demonstrated between postprandial symptoms and proximal stomach function.

Adult↗

PubMed2002

Role of nitric oxide in gastric motor and sensory functions in healthy subjects.

BACKGROUND AND AIMS: Impaired accommodation and hypersensitivity to distension of the proximal stomach are considered to be important factors in the pathogenesis of dyspeptic complaints. As fundus relaxing agents may be effective in the treatment of these symptoms, insight into the mediators involved in fundic accommodation and associated perceptual responses is important. Therefore, we studied the effect of nitric oxide (NO) synthase inhibition by N(G)-monomethyl-L-arginine (L-NMMA) on fundic tone, postprandial sensations, and gastric perception in healthy volunteers. SUBJECTS AND METHODS: Eighteen healthy volunteers participated in a double blind, placebo controlled, randomised study. They underwent a gastric barostat study to evaluate the effect of L-NMMA on meal and distension induced sensations and on fundic relaxation in response to oral meal intake, intraduodenal lipid, and glucagon administration. RESULTS: Compared with placebo, L-NMMA decreased fundic volume after oral meal intake (438 (55) v 304 (67) ml; n=8; p<0.05) and during intraduodenal lipid infusion (384 (37) v 257 (43) ml; n=10; p<0.05) but not after glucagon injection (570 (62) v 540 (52) ml; n=4; p=0.4). In addition, basal fundic volume was significantly reduced by L-NMMA. Scores for nausea and satiation were decreased by L-NMMA after oral meal intake but not during intraduodenal lipid infusion. Perception scores to gastric distension were not altered by L-NMMA. CONCLUSIONS: NO is involved in maintaining basal fundic tone and in meal induced fundic relaxation in humans, but not in visceral perception.

Adaptation, Physiological↗

PubMed2002

Natural history of primary sclerosing cholangitis and prognostic value of cholangiography in a Dutch population.

BACKGROUND: Median survival of patients with primary sclerosing cholangitis (PSC) has been estimated to be 12 years. Cholangiography is the gold standard for diagnosis but is rarely used in estimating prognosis. AIMS: To assess the natural history of Dutch PSC patients and to evaluate the prognostic value of a cholangiographic classification system. PATIENTS: A total of 174 patients with established PSC attending a university hospital and three teaching hospitals from 1970 to 1999. METHODS: Charts were reviewed for validity and time of diagnosis, concurrent inflammatory bowel disease, interventions, liver transplantation, occurrence of cholangiocarcinoma, and death. Follow up data were obtained from the charts and from the attending clinician or family physician. Median follow up was 76 months (range 1-300). The earliest available cholangiography was scored using a radiological classification system for the severity of sclerosis, developed in our institution. Survival curves were computed by the Kaplan-Meier method. Cholangiographic staging was used to construct a prognostic model, applying Cox proportional hazards analysis. RESULTS: The estimated median survival from time of diagnosis to death from liver disease or liver transplantation was 18 years. Cholangiocarcinoma was found in 18 (10%) patients. Fourteen patients (8%) underwent liver transplantation. Cholangiographic scoring was inversely correlated with survival. A combination of intrahepatic and extrahepatic scoring, together with age at endoscopic retrograde cholangiopancreatography, proved strongly predictive of survival. CONCLUSIONS: The observed survival was considerably better than reported in earlier series from Sweden, the UK, and the USA. Classification and staging of cholangiographic abnormalities has prognostic value.

Adult↗

PubMed2001

Effect of preoperative oral immune-enhancing nutritional supplement on patients at high risk of infection after cardiac surgery: a randomised placebo-controlled trial.

BACKGROUND: Elderly patients and those with poor ventricular function have increased morbidity and mortality rates when undergoing surgery. We aimed to ascertain whether an oral immune-enhancing nutritional supplement could improve preoperative host defence, and subsequently lower postoperative infections and organ dysfunction in patients undergoing elective cardiac surgery who are at high risk of infection. METHODS: In this prospective, randomised, double-blind, placebo-controlled study, we randomly assigned 50 patients who were scheduled to undergo coronary artery bypass to receive either an oral immune-enhancing nutritional supplement containing L-arginine, omega3 polyunsaturated fatty acids, and yeast RNA (n=25), or a control (n=25) for a minimum of 5 days. Patients were included if they were aged 70 years or older, or had an ejection fraction of less than 0.4, or were scheduled to undergo mitral valve replacement. The main outcome was preoperative host defence (delayed-type hypersensitivity response to recall antigens, expression of HLA-DR epitopes on monocytes, and concentration of interleukin 6 in plasma). Analysis was per protocol. FINDINGS: Five patients (two in the treatment group) were excluded because they did not take the minimum dose. Preoperative expression of HLA-DR epitopes on monocytes was significantly higher in patients given the study treatment (109% [95% CI 92-128]) than those given the control (69% [58-82]) compared with baseline (100%) (p=0.02, repeated measures ANOVA). However, concentration of interleukin 6 was significantly lower in the treatment group (0.90 pg/L [0.69-1.18]) than in the control group (1.94 pg/L [1.45-2.59]) (p=0.032, repeated measures ANOVA). Additionally, delayed-type hypersensitivity response to recall antigens improved preoperatively and remained better until hospital discharge. INTERPRETATION: Intake of an oral immune-enhancing nutritional supplement for a minimum of 5 days before surgery can improve outlook in high-risk patients who are undergoing elective cardiac surgery.

Administration, Oral↗

PubMed2001

Impaired drinking capacity in patients with functional dyspepsia: relationship with proximal stomach function.

BACKGROUND & AIMS: Impaired fundic accommodation to a meal and hypersensitivity to distention are increasingly recognized as important mechanisms underlying functional dyspepsia (FD). In the present study, we evaluated whether a drink test can predict such abnormalities and thus represent a noninvasive tool to study proximal stomach motor function. METHODS: Healthy volunteers (HV), nonconsulters with mild dyspeptic symptoms (MS), and patients with FD filled out a disease-specific questionnaire and underwent a drink test with either water or with a high calorie fluid. The maximal ingested volume and the subsequent symptoms were meticulously recorded. In addition, all subjects underwent a gastric barostat study assessing meal-induced relaxation and sensation to distention. RESULTS: Drinking capacity was not significantly related to any particular dyspeptic symptom. FD were able to consume less water (893 +/- 70 mL) and caloric liquid (767 +/- 50 mL) compared with HV (water, 1764 +/- 120 mL; caloric liquid, 1308 +/- 96 mL) or MS (water, 1645 +/- 120 mL; caloric liquid, 973 +/- 45 mL). Approximately half of the FD had an abnormal water or Nutridrink test compared with 9% of MS and 4% of HV. Furthermore, FD developed significantly more symptoms than MS or HV after both drink tests. The drinking capacity did not predict impaired fundic accommodation or visceral hypersensitivity. CONCLUSIONS: FD, but not MS, have an impaired drinking capacity to both water and a nutrient liquid. The drinking capacity is not related to a specific dyspeptic symptom and does not predict proximal stomach motor function.

Adult↗

PubMed2000

Back-calculation by birth cohort, incorporating age- specific disease progression, pre-AIDS mortality and change in European AIDS case definition. European Union Concerted Action on Multinational AIDS Scenarios.

OBJECTIVES: To adapt and improve methodology for back-calculation of AIDS in Europe and to examine the feasibility of estimating past HIV incidence by birth cohort. METHODS: Empirical Bayesian back-calculation (EBBC) used Markov disease progression models, modified to allow for three diseases added to the AIDS case definition in 1993 and for pre-AIDS mortality, and estimation by penalized maximum likelihood with a neighbour prior. EBBC by 5-year birth cohort assumed a minimum age at infection and age-dependent progression rates; three versions, with varying age effects, were investigated using AIDS cases diagnosed prior to the introduction of highly active antiretroviral therapies (HAART). RESULTS: Compared with the no age-effect version, EBBC by birth cohort tended to produce flattened HIV incidence curves in country-exposure groups with < 1000 AIDS cases, reflecting effects of the neighbour prior when data become sparse. Otherwise, birth cohort analysis, with moderate effects of age on progression, gave initially increasing incidence curves and consistent patterns across countries, with the 1960-1964 cohort most affected. In the European Union, incidence is estimated to have peaked in 1983 among homosexual men and in 1988 among injecting drug users; 460000 persons were estimated to be living with HIV/AIDS at the end of 1995. CONCLUSIONS: Our improved methodology deals effectively with the change in AIDS case definition and has allowed quantitative assessments of the HIV epidemic by birth cohort using all AIDS cases diagnosed before 1996, thus providing a sound basis for public health policy at a time when estimation of more recent prevalence is compromised by the effects of HAART.

Acquired Immunodeficiency Syndrome↗

PubMed2000

[Practice of systematic reviews. VII. Pooling of results from observational studies].

Knowledge concerning aetiologic hypotheses can be obtained through systematic reviews of observational studies. In observational studies, heterogeneity between studies is expected, because of differences in study design and analysis. Data from observational studies have to be made comparable before pooling of results from component studies is possible. In this, definition of exposure and disease and adjustment for confounding have to be taken into account. Three methods to deal with heterogeneity are presented: ignoring (fixed effects model), modelling (random effects model) and exploring (meta regression). Any combination of data in meta-analysis of observational studies has to be based on statistical, methodological and clinical considerations. The same considerations are applied for the choice which method is used.

Confounding Factors, Epidemiologic↗

PubMed2000

Evidence for VIP(1)/PACAP receptors in the afferent pathway mediating surgery-induced fundic relaxation in the rat.

We previously reported activation of an inhibitory adrenergic and a non-adrenergic non-cholinergic (NANC) pathway during abdominal surgery relaxing the rat gastric fundus. In the present study, we investigated the possible role of nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) in the NANC part of the surgery-induced fundic relaxation. The effect of the NO biosynthesis inhibitor N(G)-nitro-L-arginine (L-NOARG), the non-selective VIP receptor antagonist [D-p-Cl-Phe(6),Leu(17)]-VIP and the selective VIP(1) receptor antagonist [Acetyl-His(1),D-Phe(2),Lys(15),Arg(16), Leu(17)]-VIP was investigated on the non-adrenergic fundic relaxation induced by manipulation of the small intestine followed by resection of the caecum. Guanethidine partly reduced the manipulation-induced fundic relaxation. Addition of L-NOARG reduced this non-adrenergic component, whereas the non-selective VIP receptor antagonist had no significant effect. Combination of L-NOARG and the non-selective VIP antagonist however further reduced the relaxation to manipulation. The selective VIP(1) receptor antagonist reduced the mean and maximal relaxation induced by abdominal surgery in the presence of guanethidine. When combined with L-NOARG, the relaxation of the gastric fundus was almost completely abolished. The VIP(1) receptor antagonist alone had no significant effect on the mean and maximal relaxation, but enhanced recovery of fundic tone. In conclusion, as VIP(1) receptors are not present in the rat gastric fundus, these results suggest that the NANC inhibitory pathway activated during abdominal surgery involves VIP(1) receptors, most likely in the afferent limb. The inhibitory neurotransmitters released at the level of the gastric fundus smooth muscle are NO and a substance different from VIP.

Abdomen↗

PubMed2000

USAGE: a web-based approach towards the analysis of SAGE data. Serial Analysis of Gene Expression.

MOTIVATION: SAGE enables the determination of genome-wide mRNA expression profiles. A comprehensive analysis of SAGE data requires software, which integrates (statistical) data analysis methods with a database system. Furthermore, to facilitate data sharing between users, the application should reside on a central server and be accessed via the internet. Since such an application was not available we developed the USAGE package. RESULTS: USAGE is a web-based application that comprises an integrated set of tools, which offers many functions for analysing and comparing SAGE data. Additionally, USAGE includes a statistical method for the planning of new SAGE experiments. USAGE is available in a multi-user environment giving users the option of sharing data. USAGE is interfaced to a relational database to store data and analysis results. The USAGE query editor allows the composition of queries for searching this database. Several database functions have been included which enable the selection and combination of data. USAGE provides the biologist increased functionality and flexibility for analysing SAGE data. AVAILABILITY: USAGE is freely accessible for academic institutions at http://www.cmbi.kun.nl/usage/. The source code of USAGE is freely available for academic institutions on request from the first author.

Databases, Factual↗

PubMed2000

Combinations of artemisinin and quinine for uncomplicated falciparum malaria: efficacy and pharmacodynamics.

Combinations of artemisinin and quinine for uncomplicated falciparum malaria were studied. A total of 268 patients were randomized to 7 days of quinine at 10 mg/kg of body weight three times a day (Q) or to artemisinin at 20 mg/kg of body weight followed by 3 (AQ3) or 5 (AQ5) days of quinine. Recrudescence rates were 16, 38, and 15% for the Q, AQ3, and AQ5 groups, respectively (P < 0.001). Recrudescence was associated with shorter parasite clearance time (PCT) and longer treatment after the blood smear had become negative (eradication time). However, classification of patients to outcome-recrudescence or radical cure-was correct in only 77% of patients. The population kinetics of the parasitemia was estimated with nonlinear mixed-effect models. Several models were tested, but the best model was a monoexponential decline of the parasitemia in which the mean parasite elimination half-life was shorter after artemisinin (5.1 h; 95% confidence interval [CI], 4.9 to 5.2 h) than after quinine (8.0 h [95% CI, 7.5 to 8.3 h]). Attempts to simulate the initial increase of the parasitemia did not result in better models with a biologically plausible interpretation. Recrudescence was associated with slower parasite clearance and a higher simulated terminal parasitemia (P(term)). The classification of patients to outcome groups based on P(term) was correct in 78% of patients. The data suggest that parasite strains with reduced sensitivity to quinine are prevalent in Vietnam, with slower parasite clearance and consequent recrudescence. A single dose of artemisinin induces rapid parasite reduction and lowers the value of P(term), but to prevent recrudescence, this should be followed by quinine for at least 3 days after parasite clearance, or 5 days in total.

Adolescent↗

PubMed2000

Neuroendocrine reactivity and recovery from work with different physical and mental demands.

OBJECTIVES: The purpose of this study was to examine the extent to which the type or nature (physical, mental or mixed mental and physical) of work and work characteristics is related to the course of neuroendocrine reactivity and recovery from work. METHODS: Neuroendocrine reactivity and recovery were studied by measuring the urinary excretion of adrenaline, noradrenaline, and cortisol during and after 3 workdays, 1 consecutive day off, and a baseline day. The assessment was made in 3 groups of Dutch male workers (N=60) who differed in the nature (mental, physical, and combined mental and physical demands) of their work. Multilevel analyses were performed to fit linear mixed-effects models for each hormone. RESULTS: Main or interaction effects with time of day were found between the workers in combined mental and physical work and the 2 other groups of workers for cortisol, adrenaline, and noradrenaline excretion. In addition, the baseline levels of the 3 hormones were higher in the workers with combined mental and physical work when compared with the other 2 groups. The excretion rates during the workdays were higher than those on the day off, but a trend towards mobilizing less activity was found from the 1st to the 3rd workday. Job demands were negatively related to cortisol excretion. Job control and social demands at work did not affect the excretion rates of the hormones. CONCLUSIONS: Unfavorable effects on cortisol and adrenaline reactivity or recovery was found for workers with combined mental and physical demands when compared with workers doing mainly mental or mainly physical work. The results of the present study are in accordance with the cognitive activation theory and the allostatic load model.

Adult↗

PubMed1999

Placebo effect in the treatment of duodenal ulcer.

AIMS: To assess whether frequency of placebo administration is associated with duodenal ulcer healing. METHODS: A systematic literature review of randomized clinical trials was undertaken. 79 of 80 trials that met the inclusion criteria. The pooled 4 week placebo healing rate of all duodenal ulcer trials that employed a four times a day regimen was compared with the rate obtained from trials with a twice a day regimen. RESULTS: The pooled 4 week healing rate of the 51 trials with a four times a day regimen was 44. 2% (805 of 1821 patients) compared with 36.2% (545 of 1504 patients) in the 28 trials with a twice a day regimen (difference, 8.0% [equal effects model]; 95% confidence interval, 4.6% to 11.3%). Depending on the statistical analysis, the rate difference ranged from 6.0% (multivariable random effects model) to 8.0% (equal effects model). A number of sensitivity analyses showed comparable differences between the two regimens. Most of these sensitivity analyses were not significant, probably because a number of trials were excluded resulting in a loss of power. CONCLUSIONS: We found a relation between frequency of placebo administration and healing of duodenal ulcer. We realize that the comparison was based on nonrandomized data. However, we speculate that the difference between regimens was induced by the difference in frequency of placebo administration. A better knowledge of various placebo effects is required in order to make clinically relevant assessments of treatment effects derived from placebo-controlled trials.

Duodenal Ulcer↗