Association of Bone Morphogenetic Proteins With Otosclerosis

We studied the role of polymorphisms in 13 candidate genes on the risk of otosclerosis in two large independent case‐control sets. We found significant association in both populations with BMP2 and BMP4, implicating these two genes in the pathogenesis of this disease. Introduction : Otosclerosis is a progressive disorder of the human temporal bone that leads to conductive hearing loss and in some cases sensorineural or mixed hearing loss. In a few families, it segregates as a monogenic disease with reduced penetrance, but in most patients, otosclerosis is more appropriately considered a complex disorder influenced by genetic and environmental factors. Materials and Methods : To identify major genetic factors in otosclerosis, we used a candidate gene approach to study two large independent case‐control sets of Belgian‐Dutch and French origin. Tag single nucleotide polymorphisms (SNPs) in 13 candidate susceptibility genes were studied in a stepwise strategy. Results : Two SNPs were identified that showed the same significant effect in both populations. The first SNP, rs3178250, is located in the 3′ untranslated region of BMP2. Individuals homozygote for the C allele are protected against otosclerosis (combined populations: p = 2.2 × 10^?4; OR = 2.027; 95% CI = 1.380–2.979). The second SNP, rs17563, is an amino acid changing (p.Ala152Val) SNP located in BMP4. The G allele, coding for the amino acid alanine, confers susceptibility in both populations (combined populations: p = 0.002; OR = 1.209; 95% CI: 1.070–1.370). Conclusions : These results indicate that polymorphisms in the BMP2 and BMP4 genes, both members of the TGF‐β superfamily, contribute to the susceptibility to otosclerosis and further strengthen the results from the recently reported association of TGFB1 with this disease.     

Attention-deficit-hyperactivity disorder and reward deficiency syndrome

Molecular genetic studies have identified several genes that may mediate susceptibility to attention deficit hyperactivity disorder (ADHD). A consensus of the literature suggests that when there is a dysfunction in the “brain reward cascade,” especially in the dopamine system, causing a low or hypo-dopaminergic trait, the brain may require dopamine for individuals to avoid unpleasant feelings. This high-risk genetic trait leads to multiple drug-seeking behaviors, because the drugs activate release of dopamine, which can diminish abnormal cravings. Moreover, this genetic trait is due in part to a form of a gene (DRD₂ A1 allele) that prevents the expression of the normal laying down of dopamine receptors in brain reward sites. This gene, and others involved in neurophysiological processing of specific neurotransmitters, have been associated with deficient functions and predispose individuals to have a high risk for addictive, impulsive, and compulsive behavioral propensities. It has been proposed that genetic variants of dopaminergic genes and other “reward genes” are important common determinants of reward deficiency syndrome (RDS), which we hypothesize includes ADHD as a behavioral subtype. We further hypothesize that early diagnosis through genetic polymorphic identification in combination with DNA-based customized nutraceutical administration to young children may attenuate behavioral symptoms associated with ADHD. Moreover, it is concluded that dopamine and serotonin releasers might be useful therapeutic adjuncts for the treatment of other RDS behavioral subtypes, including addictions.     

The effect of arteriovenous fistulae in haemodialysis patients on whole body and segmental bioelectrical impedance

BACKGROUND: Bioelectrical impedance (BIA) is a potentially useful method for measuring body water and soft-tissue composition in patients with chronic renal failure. The majority of whole body impedance is derived from the limbs with only a small contribution from the trunk, and thus abnormalities of the limbs could have an exaggerated effect on estimates of total body impedance. METHODS: This study investigated the effect of arteriovenous fistulae in the arm in haemodialysis patients on body composition measurement by whole body BIA. Body composition estimates from measurements on fistula and non-fistula sides of the body were compared and segmental impedance measurements of the arms were also performed. RESULTS: Whole body resistance was markedly lower on the fistula side of the body compared with the nonfistula side at 517.1 (124.3) omega compared with 561.5 (121.2) omega, P < 0.0005. This difference was accounted for by differences in the arm segments. This was attributed to swelling of the fistula arm which had a greater mid- arm circumference at 28.5 (2.1) cm compared with the contralateral side at 27.5 (2.0) cm, P < 0.05. This resulted in greater estimates for total body water from the fistula side at 38.6 (10.0) kg compared with 36.6 (8.6) kg from the non-fistula side, P < 0.05 and fat-free mass at 51.1 (11.8) kg from the fistula side compared with 49.1 (11.2) kg from the non-fistula side, P < 0.005. Estimates of body fat from the fistula side, 13.1 (6.9) kg, were less than the nonfistula side, 15.0 (6.0), P < 0.005. CONCLUSIONS: The presence of arteriovenous fistulae for vascular access in haemodialysis patients may have a significant effect on estimates of body composition by BIA.      

Histamine inhalation is a specific but insensitive laboratory test for migraine

Migraine is a subjective complaint and no laboratory test has until now been of value. The aim of the present study is to evaluate whether histamine inhalation may be used as a diagnostic test for migraine. In a double blind study design, 15 migra neurs and 15 control subjects scored headache intensity and characteristics before, during, and in the subsequent 12 h after inhalation of increasing doses of histamine (0, 2, 4, 8, 16, 32 and 64 mg/ml). During the histamine inhalations, headaches increased dose-dependently in both groups Eleven of the migraineurs and eight of the healthy controls experienced headaches after the inhalations These headaches fulfilled the IHS criteria for migraine without aura in six of the migraineurs, but in none of the control subjects. Using this as a test parameter, the specificity of the test was 1, but the sensitivity was only 0.4. Our results indicate that histamine inhalation is a specific but insensitive laboratory test for migraine. Migraineurs should be informed about the risk of a migraine attack being provoked before histamine inhalation in pulmonary laboratories.     

Quality-of-life assessment during palliative radiotherapy

A total of 164 consecutive patients with a range of biopsy-proven locally advanced or metastatic cancers were interviewed t o assess quality of life using the Rotterdam Symptom Check List (RSCL) at three longitudinal time intervals during a course of palliative radiotherapy. Of the 164 patients, 120 were able to complete all 3 question-naires. Paired t-tests were used t o assess the significance of changes in the patients mean scores over time. Of the 33 symptoms assessed in the RSCL, changes in the degree o f symptomatology were highly consistent with changes expected in clinical practice, as a result of either disease progression or side effects o f treatment. It is concluded that the RSCL provides a practical assessment of various symptoms in patients receiving palliative radiotherapy, and that the changes in symptom profile over time are relevant to clinical practice. The RSCL has never been previously used in the assessment of palliative radiotherapy, and the present study validates this instrument.