How to improve screening in first-degree relatives of patients with premature coronary heart disease.

BACKGROUND: Guidelines on the prevention of cardiovascular disease recommend screening in close relatives of patients with premature coronary heart disease (CHD). This family history puts them at increased risk for CHD, independent of other major risk factors, but screening for CHD risk factors in these relatives is not widely practiced in Europe. This demonstration project examined how to improve screening of close relatives of patients with premature CHD in daily practice. METHODS: A controlled study design was used. Four hospitals were compared in a pre-test as to the actual screening of relatives of patients with premature CHD. Then they were arranged in pairs and randomly assigned to the Usual care (U) or Intervention group (I). An information and health education program--involving patients, relatives and family doctors--was developed in I to improve screening by the family doctor. RESULTS: The pre-test confirmed that screening of relatives of patients with premature CHD is poorly practiced in the four regions; no significant differences between I and U were observed. The screening of relatives during the study period reached 63.9% in I compared to 25.4% in U. This difference between I and U was present in siblings and offspring. The cardiovascular risk profile of the relatives of I was not optimal and needed improvement. CONCLUSION: Screening of first-degree relatives of patients with premature CHD can be significantly improved through a health education program. This is the first and necessary step to improve the management of risk factors in these people, who are at increased risk for CHD.     

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.     

Immunological Aspects of Alzheimer’s Disease

Alzheimer’s disease (AD) is a chronic neurodegenerative disease causing progressive impairment of memory and cognitive function. The amyloid cascade hypothesis suggests that mismetabolism of the β-amyloid (Aβ) precursor protein (APP) followed by subsequent formation of non-fibrillar and fibrillar Aβ deposits leads to glial activation and eventually to neurotoxicity, causing cognitive impairment. Several lines of evidence indicate that an inflammatory process contributes to the pathology of AD. First, inflammatory proteins have been identified as being associated with neuritic plaques and in glial cells surrounding these plaques. Second, certain polymorphisms of acute-phase proteins and cytokines associated with AD plaques increase the risk or predispose for earlier onset of developing AD. Third, epidemiological studies indicate that anti-inflammatory drugs can retard the development of AD. Several steps in the pathological cascade of AD have been identified as possible targets for actions of nonsteroidal anti-inflammatory drugs. For instance, microglia are considered a target because this cell type is closely involved in AD pathology through secretion of neurotoxic substances and by modulating a positive feedback loop of the inflammatory mechanism that may be involved in the pathological cascade in AD. On the basis of studies in APP transgenic mice, immunisation with Aβ was recently suggested as a novel immunological approach for the treatment of AD. Immunisation elicits Aβ-specific antibodies that could affect several early steps of the amyloid-driven cascade. Antibodies could prevent Aβ from aggregating into fibrils and accelerate clearance of Aβ by stimulating its removal by microglial cells. This review outlines the pathological and genetic evidence that an inflammatory mechanism is involved in AD and the therapeutic approaches based on inhibition or mediation of inflammation.     

Early, discontinuous, high dose growth hormone treatment to normalize height and weight of short children born small for gestational age: results over 6 years.

Most children born small for gestational age (SGA) normalize their size through spontaneous catch-up growth within the first 2 yr after birth. Some SGA children fail to do so and maintain an abnormally short stature throughout childhood. We have previously reported that high dose GH treatment (66 or 100 microg/kg x day s.c. over 2 yr; age at start, 2-8 yr; n = 38) induces pronounced catch-up growth in short children born SGA, thereby normalizing their height and weight in childhood. Here, we report on the further prepubertal growth course of these children over the first 4 yr after withdrawal of early, high dose GH treatment. Of the 38 treated children, none developed precocious puberty, and 22 remained prepubertal. Mean age of the latter at start of GH was 4.4 yr, height was -3.7 SD score, and height after adjustment for midparental height was -2.9 SD score. Height increased by an average of 2.5 SD during the 2 yr of GH treatment and decreased by 0.4 and 0.3 SD, respectively, during the first and second year after GH withdrawal. Subsequently, when stature was not extremely short at the start (mean adjusted height SD score, -2.7; n = 13), no further GH treatment was given, and the adjusted height was stabilized around -1.0 SD score; when stature was very short at the start (mean adjusted height, -3.3 SD score; n = 9), a second course of GH treatment (66 microg/kg x day s.c.) was initiated either 2 yr (n = 5) or 3 yr (n = 4) after initial GH withdrawal. This second course was associated with renewed catch-up growth and also resulted in a mean adjusted height of -1.0 SD score. In each subgroup, the pattern of the weight course paralleled that of the height course; GH treatment was well tolerated. In conclusion, early, discontinuous, high dose GH treatment appears to be a safe and efficient option to normalize prepubertal height and weight in the majority of short SGA children. It remains to be examined whether the normalized stature will be maintained during pubertal development, either with or without further GH treatment.     

Susceptibility of the PER.C6 cell line for infection with clinical human respiratory syncytial virus isolates

Human respiratory syncytial virus (HRSV) is one of the most important agents causing upper respiratory infection in infants. The susceptibility of the PER.C6 cell line for infection with clinical HRSV strains was investigated. During the HRSV season of 2006/2007 in Belgium, 90 isolates were inoculated into the PER.C6 and HEp-2 cells and viral growth was evaluated by quantification of the extracellular viral RNA concentration. Initially, viral growth of HRSV strains was observed after 7 days of inoculation in the PER.C6 cells, demonstrated by an increase in HRSV RNA levels. However, HRSV strains that were selected for continued propagation in the PER.C6 cells no longer seemed to replicate, which was reflected by consecutive decreasing viral RNA levels. Several approaches that were investigated to improve the efficiency of infection of clinical HRSV isolates in the PER.C6 cells, such as the influence of rotation and centrifugation of the virus inoculum into the cells were unsuccessful. In contrast, when clinical HRSV strains were inoculated in the HEp-2 cells substantial virus stocks could be produced and the virus could be propagated up to infectious titers of 5 logPFU per ml. In conclusion, the PER.C6 cell line was not permissive for persistent HRSV infection in our experiments and did not support long term production of large virus stocks at high titers. This possibly limits the use of this cell line for many in vitro applications using HRSV, e.g. plaque or virus yield reduction assays or the preparation of virus stocks for in vivo challenge experiments or in vitro vaccine production.     

Malaria and human immunodeficiency virus infection as risk factors for anemia in infants in Kisumu,western Kenya

The role of maternal and pediatric infection with human immunodeficiency virus type 1 (HIV-1) and malaria as risk factors for anemia was determined in a birth cohort of infants born to mothers participating in a study of the interaction between placental malaria and HIV infection, in Kisumu, Kenya. Between June 1996 and April 2000, 661 infants born to 467 HIV-seropositive and 194 HIV-seronegative mothers were monitored monthly from birth. At each visit a questionnaire was completed and a blood sample was collected for the determination of hemoglobin levels and detection of malaria and HIV. Anemia was common and increased from 13.6% at one month to 75% at six months and remained high throughout the second half of infancy. Placental malaria, infant malaria, and HIV infection of the infant were all associated with infant anemia in a multivariate model, adjusting for other co-variates found to be associated with infant anemia. The HIV-infected infants with malaria parasitemia had lower mean hemoglobin levels compared with HIV-uninfected infants, or HIV-infected infants without malaria, suggesting that HIV-infected infants are particularly vulnerable to the adverse consequences of malaria at this age. Early detection and prompt treatment of infant malaria and treatment of anemia as part of the study protocol failed to prevent most of the infants from becoming anemic. Although not proven effective in this study, micronutrient supplementation should be prospectively assessed in HIV-infected infants as a means of preventing anemia.     

Effects of vision and arm position on amplitude of arm postural tremor in patients with multiple sclerosis

Feys P, Helsen WF, Liu X, Lavrysen A, Nuttin B, Ketelaer P. Effects of vision and arm position on amplitude of arm postural tremor in patients with multiple sclerosis. Arch Phys Med Rehabil 2004;85:1031-3.

Objectives

To quantify the effects of vision and arm position on arm postural tremor, comparisons were made between flexed and extended arm positions performed with the eyes open and closed.

Design

Case-control study.

Setting

National multiple sclerosis (MS) center in Belgium.

Participants

Sixteen patients (32 arms) with MS who had intention tremor and 16 healthy controls (32 arms).

Interventions

Not applicable.

Main outcome measure

The amplitude of postural tremor was assessed by a magnetic position sensor attached to the index finger.

Results

The amplitude of postural tremor was not influenced by changes in visual condition or different arm positions. Both healthy controls and MS patients made more directional changes in the flexed, compared with the extended arm position.

Conclusions

The amplitude of the arm postural tremor in MS is independent of vision and arm position. Selecting 1 arm position is sufficient to assess postural tremor amplitude.     

The relevance of therapeutic drug monitoring in plasma and erythrocytes in anti-cancer drug treatment.

Therapeutic drug monitoring generally focuses on the plasma compartment only. Differentiation between the total plasma concentration and the free fraction (plasma water) has been described for a number of limited drugs. Besides the plasma compartment, blood has also a cellular fraction which has by far the largest theoretical surface and volume for drug transport. It is with anti-cancer drugs that major progress has been made in the study of partition between the largest cellular blood compartment, i.e., erythrocytes, and the plasma compartment. The aim of the present review is to detail the progress made in predicting what a drug does in the body, i.e., pharmacodynamics including toxicity and plasma and/or red blood cell concentration monitoring. Furthermore, techniques generally used in anti-cancer drug monitoring are highlighted. Data for complex Bayesian statistical approaches and population kinetics studies are beyond the scope of this review, since this is generally limited to the plasma compartment only.