Clinical features and predictors for disease natural progression in adults with Pompe disease: a nationwide prospective observational study

Background

Due partly to physicians’ unawareness, many adults with Pompe disease are diagnosed with great delay. Besides, it is not well known which factors influence the rate of disease progression, and thus disease outcome. We delineated the specific clinical features of Pompe disease in adults, and mapped out the distribution and severity of muscle weakness, and the sequence of involvement of the individual muscle groups. Furthermore, we defined the natural disease course and identified prognostic factors for disease progression.

Methods

We conducted a single-center, prospective, observational study. Muscle strength (manual muscle testing, and hand-held dynamometry), muscle function (quick motor function test), and pulmonary function (forced vital capacity in sitting and supine positions) were assessed every 3–6 months and analyzed using repeated-measures ANOVA.

Results

Between October 2004 and August 2009, 94 patients aged between 25 and 75 years were included in the study. Although skeletal muscle weakness was typically distributed in a limb-girdle pattern, many patients had unfamiliar features such as ptosis (23%), bulbar weakness (28%), and scapular winging (33%). During follow-up (average 1.6 years, range 0.5-4.2 years), skeletal muscle strength deteriorated significantly (mean declines of ?1.3% point/year for manual muscle testing and of ?2.6% points/year for hand-held dynamometry; both p<0.001). Longer disease duration (>15 years) and pulmonary involvement (forced vital capacity in sitting position <80%) at study entry predicted faster decline. On average, forced vital capacity in supine position deteriorated by 1.3% points per year (p=0.02). Decline in pulmonary function was consistent across subgroups. Ten percent of patients declined unexpectedly fast.

Conclusions

Recognizing patterns of common and less familiar characteristics in adults with Pompe disease facilitates timely diagnosis. Longer disease duration and reduced pulmonary function stand out as predictors of rapid disease progression, and aid in deciding whether to initiate enzyme replacement therapy, or when.

     

Ovules and seeds ofDirachma socotrana (Dirachmaceae)

Dirachma has a bitegmic, crassinucellate and anatropous ovule with a single median provascular tegumentary bundle. The seed coat is characterized by an exotesta and an endotegmic pigment layer. Although the fruit ofDirachma superficially resembles that of theGeraniaceae s. str., the characters of ovule and seed do not support a relationship with that family. Also a relationship withBarbeyaceae, as suggested by recentrbcL studies, is not supported by seed anatomical characters. The true relationships ofDirachma are difficult to assess on the basis of ovule and seed characters alone. TheRhamnaceae may be a closer relative.     

Crop performance, nitrogen and water use in flooded and aerobic rice

Irrigated aerobic rice is a new system being developed for lowland areas with water shortage and for favorable upland areas with access to supplementary irrigation. It entails the cultivation of nutrient-responsive cultivars in nonsaturated soil with sufficient external inputs to reach yields of 70–80% of high-input flooded rice. To obtain insights into crop performance, water use, and N use of aerobic rice, a field experiment was conducted in the dry seasons of 2002 and 2003 in the Philippines. Cultivar Apo was grown under flooded and aerobic conditions at 0 and at 150 kg fertilizer N ha^–1. The aerobic fields were flush irrigated when the soil water potential at 15-cm depth reached –30 kPa. A ¹⁵N isotope study was carried out in microplots within the 150-N plots to determine the fate of applied N. The yield under aerobic conditions with 150 kg N ha^–1 was 6.3 t ha^–1 in 2002 and 4.2 t ha^–1 in 2003, and the irrigation water input was 778 mm in 2002 and 826 mm in 2003. Compared with flooded conditions, the yield was 15 and 39% lower, and the irrigation water use 36 and 41% lower in aerobic plots in 2002 and 2003, respectively. N content at 150 kg N ha^–1 in leaves and total plant was nearly the same for aerobic and flooded conditions, indicating that crop growth under aerobic conditions was limited by water deficit and not by N deficit. Under aerobic conditions, average fertilizer N recovery was 22% in both the main field and the microplot, whereas under flooded conditions, it was 49% in the main field and 36% in the microplot. Under both flooded and aerobic conditions, the fraction of ¹⁵N that was determined in the soil after the growing season was 23%. Since nitrate contents in leachate water were negligible, we hypothesized that the N unaccounted for were gaseous losses. The N unaccounted for was higher under aerobic conditions than under flooded conditions. For aerobic rice, trials are suggested for optimizing dose and timing of N fertilizer. Also further improvements in water regime should be made to reduce crop water stress.     

Silicone genital prosthesis for female-to-male transsexuals.

In the case of a female-to-male transsexual who has not yet undergone phalloplasty, one of the greatest concerns is how to give the appearance of having male external genitals. Many methods have been attempted by patients. We helped develop a silicone prosthesis after obtaining information on the demands of female-to-male transsexuals through a questionnaire sent to 120 of them. Three different models of the prosthesis were designed to enable three different methods of fixation. One of the methods of fixation involves the creation of a bipedicled skin flap in the pubic area. Thus this is the first of such prostheses that can be worn directly fixed to the body. It seems that the prosthesis developed in close cooperation with our department fulfills most of the needs of our patients.     

Drosophilid Assemblages at Different Urbanization Levels in the City of Porto Alegre, State of Rio Grande do Sul, Southern Brazil

The present study analyzed the drosophilid assemblages in different levels of urbanization in the city of Porto Alegre, Rio Grande do Sul, Brazil. Collections were carried out in 2008 in three different environments: a highly urbanized area????Jardim Botanico,?? a forested area with intermediary urbanization????Parque Gabriel Knijnik,?? and in a relatively well-preserved forested area, although threatened by the urban growth????Morro Santana.?? In Jardim Botanico, 36 species belonging to four genera were found, with high abundance of exotic species as Drosophila simulans Sturtevant and Zaprionus indianus (Gupta). In Parque Gabriel Knijnik, 33 species that belonged to four genera were found, with higher abundances of native species belonging to the Drosophila tripunctata species group and Drosophila willistoni species subgroup, and lower abundance of exotic species. As for Morro Santana, 32 species and three genera were found, with higher abundances of native groups, low representativeness of exotic species, and absence of Zaprionus indianus. The analysis of the Jaccard index showed higher similarity in the species composition between samples collected in summer and autumn, and between samples collected in winter and spring. On the other hand, the Morisita index differentiated Jardim Botanico from the other two studied sites. Our results show that Morro Santana is an important area of native biodiversity, reinforcing, therefore, the inclusion of this area in the project for the creation of an ecological corridor as proposed by the Ministry of the Environment of Brazil.     

Functional aspects of mature seed coat of theCannaceae

Cannaceae seeds have been analysed regarding seed coat structure, germination and macromolecular composition of the seed coats. Data of several mass spectrometric techniques were combined with those of microscopic and histochemical techniques to acquire insight into the functions of the seed coat.Cannaceae seeds have an exotestal layer of Malpighian cells with a hydrophobic and a hydrophilic part. The hydrophobic part is mainly responsible for the impermeability of the seed and contains silica, callose, lignin as water repellent substances. Water can only enter the seed after a certain temperature-induced opening of an imbibition lid. During imbibition the hydrophilic part of the Malpighian cells swells and the seed coat ruptures due to differences in pressure in the upper and lower part of the Malpighian cells.     

Paraoxonase-1 is a major determinant of clopidogrel efficacy

Clinical efficacy of the antiplatelet drug clopidogrel is hampered by its variable biotransformation into the active metabolite. The variability in the clinical response to clopidogrel treatment has been attributed to genetic factors, but the specific genes and mechanisms underlying clopidogrel bioactivation remain unclear. Using in vitro metabolomic profiling techniques, we identified paraoxonase-1 (PON1) as the crucial enzyme for clopidogrel bioactivation, with its common Q192R polymorphism determining the rate of active metabolite formation. We tested the clinical relevance of the PON1 Q192R genotype in a population of individuals with coronary artery disease who underwent stent implantation and received clopidogrel therapy. PON1 QQ192 homozygous individuals showed a considerably higher risk than RR192 homozygous individuals of stent thrombosis, lower PON1 plasma activity, lower plasma concentrations of active metabolite and lower platelet inhibition. Thus, we identified PON1 as a key factor for the bioactivation and clinical activity of clopidogrel. These findings have therapeutic implications and may be exploited to prospectively assess the clinical efficacy of clopidogrel.