Statins are associated with a reduced infrarenal abdominal aortic aneurysm growth.

OBJECTIVE: To evaluate the effect of statins on aneurysm growth in a group of consecutive patients under surveillance for infrarenal aortic aneurysms (AAA). MATERIALS AND METHODS: All patients (59 statin users, 91 non-users) under surveillance between January 2002 and August 2005 with a follow-up for aneurysm growth of at least 12 months and a minimum of three diameter evaluations were retrospectively included in the analysis. Multiple regression analysis, weighted with the number of observations, was performed to test the influence of statins on AAA growth rate. RESULTS: During a median period of 3.1 (1.1-13.1) years the overall mean aneurysm growth rate was 2.95+/-2.8 mm/year. Statin users had a 1.16 mm/year lower AAA growth rate compared to non-users (95% CI 0.33-1.99 mm/year). Increased age was associated with a slower growth (-0.09 mm/year per year, p = 0.003). Female gender (+1.82 mm/year, p = 0.008) and aneurysm diameter (+0.06 mm/year per mm, p = 0.049) were associated with increased AAA growth. The use of non-steroidal anti-inflammatory drugs, chronic lung disease, or other cardiovascular risk factors were not independently associated with AAA growth. CONCLUSIONS: Statins appear to be associated with attenuation of AAA growth, irrespective of other known factors influencing aneurysm growth.     

Accuracy of an anthropometric estimate of the muscle and bone area in a transversal cross-section of the arm

To standardize the maximal static force (Fo) of the arm flexors, the accuracy of an anthropometric method for estimating the mid-arm cross-sectional muscle and bone area (MBA) was investigated. This was done by comparing the anthropometrically determined area (MBA.A) with the area measured by means of computerized tomography (MBA.S). In the same way, the accuracy of Heymsfield's equations (Heymsfield et al., 1982) for predicting MBA (MBA.H) from anthropometric measures was tested. MBA.A was significantly larger than MBA.S, the relative difference increasing with the thickness of the subcutaneous fat layer. This difference was attributed to a 27% underestimation of the fat layer thickness as measured with the skinfold caliper. Women being fatter than men, this caused the standardized maximal static force (Fo/MBA) to be lower in women than in men. MBA.H was 12% smaller than MBA.S. This may have been due to a difference in the way of measuring the arm circumference between the present authors and Heymsfield et al.     

Acute intermittent porphyria and primary liver-cell carcinoma.

A patient known with acute intermittent porphyria who developed primary liver-cell carcinoma is described. No other risk factors were found. A possible association of acute intermittent porphyria with the development of primary liver-cell carcinoma has been suggested in recent, mainly Scandinavian literature. So far this association has never been described in The Netherlands.     

On the synthesis of time‐varying LQG weights and noises along optimal control and state trajectories

A general approach to control non‐linear uncertain systems is to apply a pre‐computed nominal optimal control, and use a pre‐computed LQG compensator to generate control corrections from the on‐line measured data. If the non‐linear model, on which the optimal control and LQG compensator design is based, is of sufficient quality, and when the LQG compensator is designed appropriately, the closed‐loop control system is approximately optimal. This paper contributes to the selection and computation of the time‐varying LQG weighting and noise matrices, which determine the LQG compensator design. It is argued that the noise matrices may be taken time‐invariant and diagonal. Three very important considerations concerning the selection of the time‐varying LQG weighting matrices are turned into a concrete computational scheme. Thereby, the selection of the time‐varying LQG weighting matrices is reduced to selecting three scalar design parameters, each one weighting one consideration. Although the three considerations seem straightforward they may oppose one another. Furthermore, they usually result in time‐varying weighting matrices that are indefinite, rather than positive (semi) definite as required for the LQG design. The computational scheme presented in this paper addresses and resolves both problems. By two numerical examples the benefits of our optimal closed‐loop control system design are demonstrated and evaluated using Monte Carlo simulation. Copyright © 2005 John Wiley & Sons, Ltd.     

T-cell receptor usage of interleukin-2-responsive peripheral gamma delta T cells.

The majority of human peripheral gamma delta T cells express the V gamma 9 gene in combination with the V delta 2 gene. The diversity of this subset of gamma delta T cells is limited by a preferential usage of the J gamma P gene segment and a highly distinctive junctional motif of the T-cell receptor (TCR) delta chain. We and others have observed that peripheral blood derived V gamma 9+V delta 2+ gamma delta T cells of healthy individuals are activated after stimulation with interleukin-2 (IL-2) in vitro, but only a small percentage of gamma delta T cells subsequently proliferates. To assess whether the proliferating, IL-2-responsive gamma delta T cells represent a selective group of T cells, we have analysed TCR junctional features of IL-2-responsive gamma delta T cells. Out of 30 individuals studied, nine were identified as IL-2-responders and three as IL-2-hyperresponders. The TCR V(D)J gene usage from IL-2 stimulated peripheral blood lymphocytes of these IL-2-(hyper)responsive individuals was analysed. The results showed that in most individuals gamma delta T cells polyclonally expanded after stimulation with IL-2. In two IL-2-hyperresponder individuals, however, a monoclonal expansion of a particular V gamma 9+V delta 2+ gamma delta T cell was found. In one of these individuals, this V gamma 9+V delta 2+ T-cell clone expressed a very rare gamma delta TCR type because of the presence of an Ala within the junctional region at a conserved position relative to V delta framework residues (delta 97), which is very infrequently used by peripheral blood V gamma 9+V delta 2+ cells. This particular clonotype could also be detected in unstimulated PBL samples taken from that individual, and made up for 30% of the total peripheral gamma delta T-cell pool. These data indicate that in general IL-2-responsive V gamma 9+V delta 2+ gamma delta T cells represent a polyclonal population, reflecting in vivo stimulation with multiple antigens or superantigens. In contrast, monoclonal expansions of gamma delta T cells after stimulation with IL-2 can also occur, which may be related to an in vivo stimulation by one particular antigen, rendering this gamma delta T-cell type dominant in the peripheral blood.     

Gene conversion is a likely cause of mutation in PKD1

Approximately 70% of the gene responsible for the most common form of autosomal dominant polycystic kidney disease ( PKD1 ) is replicated in several highly homologous copies located more proximally on chromosome 16. We recently have described a novel technique for mutation detection in the duplicated region of PKD1 that circumvents the difficulties posed by these homologs. We have used this method to identify two patients with a nearly identical cluster of base pair substitutions in exon 23. Since pseudogenes are known to be reservoirs for mutation via gene conversion events for a number of other diseases, we decided to test whether these sequence differences in PKD1 could have arisen as a result of this mechanism. Using changes in restriction digest patterns, we were able to show that these sequence substitutions are also present in N23HA, a rodent-human somatic cell hybrid that contains only the PKD1 homologs. Moreover, these changes were also detected in total DNA from several affected and unaffected individuals that did not harbor this mutation in their PKD1 gene copy. This is the first example of gene conversion in PKD1 , and our findings highlight the importance of using gene-specific reagents in defining PKD1 mutations.      

Incipient ovarian failure and premature ovarian failure show the same immunological profile

PROBLEM: Incipient ovarian failure (IOF) is characterized by regular menstrual cycles, infertility and a raised early-follicular FSH in women under 40. IOF might be a precursor or a mitigated form of premature ovarian failure (POF). Disturbances in the immune system may play a role in ovarian failure. METHOD OF STUDY: Autoantibodies and lymphocyte subsets were determined in 63 POF patients, 50 IOF patients, and 27 controls. RESULTS: The prevalence of autoantibodies did not differ between the groups. There was a statistically significant difference in lymphocyte subsets between the control group and the POF group, with the IOF group taking an intermediate position. We found a decrease in percentage of T-suppressor cells with a rise in T-helper/T-suppressor cell ratio, a decrease in natural killer cells, and an increase in B lymphocytes and HLA-DR positive T cells. CONCLUSIONS: These data support the concept that IOF is a mitigated form of POF. The question remains whether these changes are the cause or the consequence of the ovarian failure.     

The force-velocity relationship of arm flexion in untrained males and females and arm-trained athletes

Summary The force-velocity curve (FVC) of arm flexion was established in 123 untrained males and 110 untrained females aged from 15 to 36 years, and 48 arm-trained athletes competing in different sport disciplines. The FVC was described by Hill's equation and defined by the parameters: maximal static moment (M₀), maximal angular velocity (₀), maximal power (P₀) and the concavity of the FVC (H). Within the given age range the level of the curve parameters of both untrained men and women was independent of age.On average, H was the same in all three groups. As compared to M₀ of the untrained males, M₀ of the athletes was 33% higher and M₀ of the females was 38% lower; with regard to P₀ these differences were +30% and –43% respectively. ₀ was the same for trained and untrained males, wherease ₀ of the women was 10% lower than ₀ of the men.     

Identification of an HLA-DQ2 peptide binding motif and HLA-DPw3-bound self-peptide by pool sequencing

Molecules of the major histocompatibility complex (MHC) present antigenic peptides to T cells. Sequencing peptide pools eluted from MHC class I molecules has established allele-specific peptide binding motifs. We applied pool sequencing to analyze human MHC class II-bound peptides and found that HLA-DQ2-eluted peptides predominantly contained lysine, isoleucine, and phenylalanine at relative position i, i + 3 and i + 8, respectively. These residues putatively represent anchor residues for MHC binding. Analysis of a heterogeneous HLA-DPw3/DPw4-eluted peptide pool yielded a sequence matching an epitope from the endogeneous enzyme glyceraldehyde-3-phosphate dehydrogenase. This self-peptide and a partially identical, known allo-epitope bound specifically to DPw3 and DR13 molecules, suggesting the sharing of a binding motif. In particular, the presence of an arginine at relative position 4 appeared important for binding to these HLA class II specificities. Thus, pool sequencing is applicable for the analysis of MHC class II-eluted peptides.