Comparison of two methods for determining the cytogenetic effects induced by triethylenemelamine.

Triethylenemelamine (TEM), a known mutagen, induced marked cytogenetic effects on the bone marrow of rats as evaluated by cytogenetic analysis and the micronucleus test. At doses of 0.05, 0.15, and 0.30 mg/kg TEM, there was a dose-related increase in abnormal metaphase spreads. There was also a significant increase in polychromatic erythrocytes containing micronuclei, although there was no true dose-response relationship. The possible reasons for this difference, and problems inherent in comparing the sensitivity of the two methods are discussed. There was some correlation in the two procedures with respect to degree of damage in individual animals, and no overlap was found between treated and control rats with either method. These results support the usefulness of the micronucleus test as a relatively easy screening method for detecting chemically induced cytogenetic damage.     

Developing a vaccination evaluation model to support evidence-based decision making on national immunization programs

Among all public health provisions national immunization programs (NIPs) are beyond doubt one of the most effective in reducing mortality, morbidity, and costs associated with major infectious diseases. To maintain their success, NIPs have to modernize in response to many new and old demands regarding efficacy, safety, availability of new vaccines, emerging and evolving pathogens, waning immunity, altered epidemiological situations, and the public's trust in the program. In this paper we present an evaluation model in the form of a checklist that may help in collecting relevant scientific information that is necessary for evaluation and decision making when considering changes in a NIP. Such a checklist points to relevant information on the vaccine-preventable disease, the pathogen causing it, the vaccine, and the cost-effectiveness ratio of the vaccine. However, the final judgment on a potential change in the NIP cannot be based on a simple algorithm, as the relevant information reflects factors of a very different kind and magnitude, to which different value judgements may be added, and which may have certain degrees of uncertainty. Because any change in the NIP may be accompanied by more or less unforeseen changes in the vaccine's efficacy, evolutionary consequences, including the antigenic composition of the pathogen, and the vaccine's safety profile, an intensive surveillance program should accompany any NIP. Elements thereof include clinical-epidemiological surveillance, surveillance of vaccination coverage, immune surveillance, surveillance of microbial population dynamics, and surveillance of adverse events and safety issues. We emphasize that the decision to introduce a vaccine in the NIP should be taken as seriously, both scientifically and ethically, as the decision to withhold a vaccine from the NIP. In the latter case one might be responsible for vaccine-preventable disease and mortality.     

Assessing the introduction of universal varicella vaccination in the Netherlands

Although varicella is seen as a benign disease in the Netherlands, about 40,000 visits to a general practitioner (GP) are made, over 200 hospital admission occur, and 2.3 persons die on average each year. Most of this burden of disease can be prevented by universal varicella childhood vaccination. Ten years after the introduction of the single-shot, single-component varicella childhood vaccination in the USA, a major reduction in hospitalization, mortality, and burden of disease has been reported. Using our recently vaccine evaluation model for the introduction of a new vaccine in our national immunization program, we have analyzed the feasibility of universal varicella vaccination by replacing the measles-mumps-rubella (MMR) vaccine with a measles-mumps-rubella-varicella (MMRV) vaccine. After structuring and reviewing the available data, two major points of uncertainty remain: (1) the influence of universal childhood vaccination on the incidence of zoster later in life; (2) the cost-effectiveness ratio for the Dutch situation. Despite these uncertainties it is clear that universal childhood vaccination will prevent most of the varicella related GP-visits, hospitalizations, and deaths.     

Effects of visual processing and congenital nystagmus on visually guided ocular motor behaviour

Aim The aim of this study was to compare visually guided ocular motor behaviour in children with visual processing and/or motor deficits with an age‐matched comparison group and an adult group. Method Visual stimuli were shown to 28 children with visual processing and/or motor deficits (11 females, 17 males; mean age 7y 5mo, SD 2y 9mo, range 2–14y;) and an age‐matched comparison group of 213 typically developing children (115 females, 98 males; mean age 5y 8mo, SD 3y 5mo, range 0–12y). The adult group consisted of nine females and two males with (mean age of 24y 4mo, SD 4y 8mo). Individuals who had a likely diagnosis of cerebral visual impairment (CVI), an opticopathy with unknown location, nystagmus, glaucoma, or a cataract were included in the study. Exclusion criteria were a visual acuity below 0.2, a developmental age under 1 year, and the presence of brain tumours, autism, and anxiety disorders. Orientating eye movements to large cartoons were quantified using the reaction time to fixation (RTF) and gaze fixation area (GFA). A Mann–Whitney U test was used to compare the differences between groups and Bonferroni post‐hoc testing was used to analyse age dependence of RTF and GFA values within the comparison group. Results Individuals with CVI showed significantly prolonged RTF values; those with congenital nystagmus showed significantly increased GFA values. In the comparison group, RTF was significantly longer in children under the age of 2 years than in children aged 4 years and older (290 and 200ms respectively; p<0.001). No developmental change was found for GFA values. Interpretation Increased RTF values in individuals with CVI relate to visual processing deficits. The data suggest that visually guided ocular motor responses mature during the first 3 years of life.     

Heterogeneity and prediction of hemodynamic responses to dobutamine in patients with septic shock

OBJECTIVE: To establish the heterogeneity of hemodynamic responses to dobutamine in patients with septic shock and to identify the predictive factors of these hemodynamic responses. DESIGN: Prospective study. SETTING AND PATIENTS: A total of 12 patients with septic shock in a tertiary medical intensive care unit. INTERVENTIONS: A 20-min dobutamine infusion at 5 microg.kg(-1).min(-1) with subsequent increments to 8, 12.6, and 20 microg.kg(-1).min(-1), on two consecutive days. Responses were dichotomized into changes in heart rate (HR) or stroke volume index (SVI) of >10% and < or =10% at the maximal dobutamine infusion. MEASUREMENTS AND MAIN RESULTS: No differences were found in survival, Acute Physiology and Chronic Health Evaluation II score, maximal dobutamine doses, or pharmacokinetics of dobutamine between HR and SVI groups. In DeltaHR > 10% vs. DeltaHR < or = 10%, baseline HR was lower, and baseline mixed venous oxygen tension and saturation were higher. During dobutamine infusion, mean arterial pressure decreased in DeltaHR > 10%. Cardiac index and the systemic oxygen delivery index increased and the systemic vascular resistance index decreased at unchanged SVI. Pressure work index increased and the ratio of the diastolic to systolic aortic pressure time indices decreased but not to <0.6. In DeltaHR < or = 10%, systemic vascular resistance index and the ratio of the diastolic to systolic aortic pressure time indices decreased (but remained >0.6) without changes in SVI or cardiac index. Baseline hemodynamic and metabolic variables did not differ between SVI groups. In DeltaSVI > 10%, cardiac index increased with dobutamine, but Pao2 and the systemic oxygen delivery index decreased. In DeltaSVI < or = 10%, HR and the systemic oxygen delivery index increased; mean arterial pressure, left ventricular stroke work index, systemic vascular resistance index, and the ratio of the diastolic to systolic aortic pressure time indices decreased. CONCLUSIONS: Patients with a positive chronotropic response to dobutamine had lower baseline HR values, and a chronotropic rather than inotropic response predicted an increase in cardiac index and systemic oxygen delivery index. Incremental dosages of dobutamine did not compromise indirectly measured myocardial oxygen balance.     

Risk factors and prediction of postoperative delirium in elderly hip-surgery patients: implementation and validation of a medical risk factor model

OBJECTIVES: To evaluate risk factors for postoperative delirium in a cohort of elderly hip-surgery patients and to validate a medical risk stratification model. DESIGN: Prospective cohort study. SETTING: Medical school-affiliated general hospital in Alkmaar, the Netherlands. PARTICIPANTS: Six hundred three hip-surgery patients aged 70 and older screened for risk factors for postoperative delirium. MEASUREMENTS: Predefined risk factors for delirium were assessed on admission. One point was assigned for each of four risk factors present, resulting in three groups: low, intermediate, and high risk. Baseline screening and assessment included the Mini-Mental State Examination, the standardized Snellen test for visual impairment, chart review to determine Acute Physiological and Chronic Health Evaluation II score, and blood urea nitrogen to creatinine ratio. The primary outcome was postoperative delirium, as defined using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria. All patients were screened daily for delirium. RESULTS: Incidence of delirium was 3.8% in the low-risk group (P<.001), 11.1% in the intermediate-risk group (P=.27, relative risk (RR)=3.0), and 37.1% in the high-risk group (P<.001, RR=9.8). Cognitive impairment at admission had the highest predictive value for postoperative delirium (coefficient of determination=0.15). Contrary to previous findings, age was an independent predictive factor for delirium. Moreover, postoperative delirium was four times as frequent in acute patients as in elective hip-replacement patients. CONCLUSION: The medical risk factor model is valid for elderly hip-surgery patients. Cognitive impairment, age, and type of admission are important risk factors for delirium in this surgical population.     

Meningeal irritation

Diagnosing meningitis requires the information from both history-taking and physical examination in its entirety. In adults with a history that makes meningitis a possibility, specific tests used to diagnose meningeal irritation, such as for Kernig or Brudzinski signs or nuchal rigidity, probably do not affect the reliability of the diagnosis. In small children and the elderly, Kernig and Brudzinski signs are also probably of little or no diagnostic value.