Study to determine the presence of antipolymer antibodies in a group of Dutch women with a silicone breast implant

OBJECTIVE: To determine whether there exists a population of Dutch women with a high prevalence of antipolymer antibodies (APA) and severe health complaints/symptoms, and exposure to a silicone breast implant (SBI). As the antigen-specific nature of the antipolymer antibody has not yet been established, we refer to the term polymer binding immunoglobulins. METHODS: The study population was selectedfrom a voluntary registry of SBI recipients of a Dutch consumers organisation. The final selection was based on the severity of self-reported complaints in a questionnaire. A total of 42 SBI recipients were included in the study, clinically examined and blood samples were obtained. RESULTS: In 12 of 42 SBI recipients an increase in the level of polymer binding immunoglobulins was detected compared to a negative reference sample, 3 of these 12 showing a positive and 9 a weakly positive response. In 3 out of 12 non-SBI recipients, included for control on the performance of the APA assay, an increased level of polymer binding immunoglobulins was demonstrated, 2 of these 3 showing a positive and 1 a weakly positive response. The study population of SBI recipients was categorised in severity subgroups (limited, mild, moderate, advanced) based on the fuctional capacity and the physicians general assessment of pain and disease activity. Most (34 of 42) SBI recipients belonged to the limited severity subgroup. CONCLUSION: Our methods failed to select a group of severely symptomatic Dutch SBI recipients reported to have a high prevalence of polymer binding antibodies. A discrepancy was present between the self reported severe complaints and the observed mild clinical symptoms. In the group of SBI recipients with self reported severe complaints recruited we did not find a high prevalence of polymer binding immunoglobulins. SBI exposure (mean 17 years) did not result in induction of polymer binding immunoglobulins in this minimal symptomatic study group.     

Change to abacavir-lamivudine-tenofovir combination treatment in patients with HIV-1 who had complete virological suppression

Patients who have not received previous antiretroviral treatment (ART) have a high failure rate on the combination treatment of abacavir, lamivudine, and tenovir. We assessed the virological failure rate in eight patients with HIV-1 who switched to this combination after having complete virological suppression from their previous long-term ART (median 8.0 months, range 7.5-18.0). Five of the eight patients showed virological failure. Four of these five patients had either the K65R mutation, the M184V/I mutation, or both. This combination of drugs cannot therefore be recommended as alternative treatment in patients with HIV-1 who are fully virologically suppressed.     

Closed-loop multivariable system identification for the characterization of the dynamic arm compliance using continuous force disturbances: a model study

This study presents a new multivariable closed-loop identification technique for estimating the dynamic compliance of the multijoint human arm during posture maintenance. The method is designed for the application of continuous force disturbances that facilitate interaction of the limb with the environment. The dynamic compliance of the arm arises from different physiological mechanisms and is important for maintaining stable postures and to suppress disturbances. Estimates can be useful to analyze the ability of the nervous system to adapt the arm compliance to different types of disturbances and environments. The technique is linear and requires no a priori knowledge of the system. Linear system behavior is justified for posture tasks where the hand position deviates slightly from a reference position. Interaction results in a closed-loop configuration of arm and environment. The problem with previous methods is the restriction to open-loop systems. With the current technique, the dynamic arm compliance is separately estimated from the closed-loop. The accuracy of the identification technique is tested by simulations for different values of the dynamic compliance of the arm and environment and for different methodological parameters. It is concluded that the identification technique is accurate, even for short observation periods and severe noise.     

Pain catastrophizing and kinesiophobia: predictors of chronic low back pain

By using a population-based cohort of the general Dutch population, the authors studied whether an excessively negative orientation toward pain (pain catastrophizing) and fear of movement/(re)injury (kinesiophobia) are important in the etiology of chronic low back pain and associated disability, as clinical studies have suggested. A total of 1,845 of the 2,338 inhabitants (without severe disease) aged 25-64 years who participated in a 1998 population-based questionnaire survey on musculoskeletal pain were sent a second questionnaire after 6 months; 1,571 (85 percent) participated. For subjects with low back pain at baseline, a high level of pain catastrophizing predicted low back pain at follow-up (odds ratio (OR) = 1.7, 95% confidence interval (CI): 1.0, 2.8) and chronic low back pain (OR = 1.7, 95% CI: 1.0, 2.3), in particular severe low back pain (OR = 3.0, 95% CI: 1.7, 5.2) and low back pain with disability (OR = 3.0, 95% CI: 1.7, 5.4). A high level of kinesiophobia showed similar associations. The significant associations remained after adjustment for pain duration, pain severity, or disability at baseline. For those without low back pain at baseline, a high level of pain catastrophizing or kinesiophobia predicted low back pain with disability during follow-up. These cognitive and emotional factors should be considered when prevention programs are developed for chronic low back pain and related disability.     

(N-3) fatty acids do not affect electrocardiographic characteristics of healthy men and women

(n-3) Fatty acids may reduce the risk of sudden death by preventing life-threatening cardiac arrhythmia. A standard electrocardiogram (ECG) may be used to detect clues as to the mechanism by which (n-3) fatty acids affect the electrophysiology of the heart. An earlier study showed that (n-3) fatty acids decreased the duration of the heart-rate corrected QT interval (QTc) in dogs. However, effects of (n-3) fatty acids on the standard ECG of humans have not been reported. Therefore, we investigated the effect of (n-3) fatty acids on QTc, QRS duration, apex-to-end-T duration, T-loop morphology and spatial QRS-T angle in apparently healthy men and women aged 50 to 70 y. Subjects (n = 42/group) received either capsules providing 1.5 g (n-3) fatty acids daily or placebo for 12 wk. ECG were recorded before and after intervention. None of the ECG characteristics were affected by (n-3) fatty acids. The QTc decreased by 0.8 ms or 0.2% (95% confidence interval, -6.1 to 4.4 ms) in subjects that consumed (n-3) fatty acids compared with the placebo group. These results do not support the hypothesis that (n-3) fatty acids prevent arrhythmia through electrophysiologic effects on heart cell membranes. However, an effect on the ECG in more susceptible populations can not be excluded.     

Identification of intrinsic and reflexive components of human arm dynamics during postural control

In this study a new methodology to quantify reflexive feedback gains from the mechanical behavior of the human arm during posture maintenance is proposed. Disturbance experiments were carried out on human subjects using continuous random force inputs. The task instruction was 'minimize displacements', prescribing a maximum performance task. For the separation of intrinsic and reflexive components, system identification in the frequency domain is applied. From the time records of position and force, frequency response functions (FRFs) are estimated. Given a model structure and an appropriate estimate of the intrinsic component, an estimate of the reflex gains for length and velocity are obtained from the FRFs. The feedback gains vary considerably with the frequency content of the disturbance signal. The results show that reflexive dynamics are substantial for narrow-band and especially low-frequency input signals. It is likely that high reflex gains are most effective for low-frequency inputs (< 3 Hz) that do not excite the closed-loop system's eigenfrequency. Also significant negative reflex gains are estimated for near-sinusoidal inputs (> 1.5 Hz). It is concluded that this new methodology can offer interesting insights into the ability of the central nervous system to modulate reflexive feedback gains.     

MTHFR 677C-->T polymorphism and risk of coronary heart disease: a meta-analysis

Context  In observational studies, individuals with elevated levels of plasma homocysteine tend to have moderately increased risk of coronary heart disease (CHD). The MTHFR 677CT polymorphism is a genetic alteration in an enzyme involved in folate metabolism that causes elevated homocysteine concentrations, but its relevance to risk of CHD is uncertain. Objective  To assess the relation of MTHFR 677CT polymorphism and risk of CHD by conducting a meta-analysis of individual participant data from all case-control observational studies with data on this polymorphism and risk of CHD. Data Sources  Studies were identified by searches of the electronic literature (MEDLINE and Current Contents) for relevant reports published before June 2001 (using the search terms MTHFR and coronary heart disease), hand searches of reference lists of original studies and review articles (including meta-analyses) on this topic, and contact with investigators in the field. Study Selection  Studies were included if they had data on the MTHFR 677CT genotype and a case-control design (retrospective or nested case-control) and involved CHD as an end point. Data were obtained from 40 (34 published and 6 unpublished) observational studies involving a total of 11 162 cases and 12 758 controls. Data Extraction  Data were collected on MTHFR 677CT genotype, case-control status, and plasma levels of homocysteine, folate, and other cardiovascular risk factors. Data were checked for consistency with the published article or with information provided by the investigators and converted into a standard format for incorporation into a central database. Combined odds ratios (ORs) for the association between the MTHFR 677CT polymorphism and CHD were assessed by logistic regression. Data Synthesis  Individuals with the MTHFR 677 TT genotype had a 16% (OR, 1.16; 95% confidence interval [CI], 1.05-1.28) higher odds of CHD compared with individuals with the CC genotype. There was significant heterogeneity between the results obtained in European populations (OR, 1.14; 95% CI, 1.01-1.28) compared with North American populations (OR, 0.87; 95% CI, 0.73-1.05), which might largely be explained by interaction between the MTHFR 677CT polymorphism and folate status. Conclusions  Individuals with the MTHFR 677 TT genotype had a significantly higher risk of CHD, particularly in the setting of low folate status. These results support the hypothesis that impaired folate metabolism, resulting in high homocysteine levels, is causally related to increased risk of CHD.      

The Dutch ‘Folic Acid Campaign’–have the goals been achieved?

Periconceptional folic acid use considerably reduces the risk of neural tube defects. The aim of this study was to measure the effect of the national and the local 'Folic Acid Campaign' on periconceptional folic acid use. Before (1995 survey) and 1 year after the campaign (1996 survey), the awareness and use of folic acid was measured among pregnant women in four regions of the Netherlands. To this end, pregnant women who visited the midwife, general practitioner or obstetrician for the first or second prenatal visit were asked to complete a questionnaire. The results showed that use of folic acid for any period around conception increased from 25.1% in 1995 to 53.5% in 1996. Appropriate use (4 weeks before until 8 weeks after conception) increased from 4.8% in 1995 to 21.0% in 1996. No additional effect of the local Folic Acid Campaign was found (adjusted odds ratio= 1.0; 95% confidence interval = 0.7, 1.4). It was possible to conclude that folic acid use at the recommended time increased considerably as a result of the national and the local Folic Acid Campaign, but the target (use in 46% of women wishing to conceive) was not achieved. New health education programmes are needed to increase further its use at the appropriate times.     

Consumption of fermented milk products and breast cancer: a case-control study in The Netherlands

In a case-control study in The Netherlands, we observed a significantly lower consumption of fermented milk products (predominantly yogurt and buttermilk) among 133 incident breast cancer cases as compared to 289 population controls (mean +/- SD among users only, 116 +/- 100 versus 157 +/- 144 g/day; P less than 0.01). The age-adjusted odds ratio of daily consumption of 1.5 glasses (greater than or equal to 225 g) of fermented milk versus none was 0.50 (95% confidence interval, 0.23-1.08). When fermented milk was entered as a continuous variable (per g) in either age-adjusted or multivariate analysis, the odds ratio expressed per 225 g was 0.63 (multivariate-adjusted 95% confidence interval, 0.41-0.96). After multivariate adjustment for intake of fat and other confounders, a statistically significant decrease in breast cancer risk was also observed for increasing intake of Gouda cheese. The multivariate-adjusted odds ratio expressed per 60 g of this fermented product was 0.56 (95% confidence interval, 0.33-0.95). For daily intake of milk, no statistically significant differences were observed between cases and controls. These results support the hypothesis that high consumption of fermented milk products may protect against breast cancer.