Brain serotonin transporter binding in non-depressed patients with Parkinson's disease

Early post-mortem data suggest that damage to brain serotonin neurones might play a role in some features (e.g., depression) of Parkinson's disease (PD). However, it is not known whether such damage is a typical characteristic of living patients with PD or whether the changes are regionally widespread. To address this question we measured, by positron emission tomography imaging, levels of the brain serotonin transporter (SERT), a marker for serotonin neurones, as inferred from binding of [¹¹C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB), a second generation SERT radioligand, in subcortical and cerebral cortical brain areas of clinically advanced non-depressed (confirmed by structured psychiatric interview) patients with PD. SERT binding levels in PD were lower than those in controls in all examined brain areas, with the changes statistically significant in orbitofrontal cortex (−22%), caudate (−30%), putamen (−26%), and midbrain (−29%). However, only a slight non-significant reduction (−7%) was observed in dorsolateral pre-frontal cortex, an area implicated in major depression. Our imaging data suggests that a modest, regionally widespread loss of brain serotonergic innervation might be a common feature of advanced PD. Further investigation will be required to establish whether SERT binding is more or less decreased in those patients with PD who also have major depressive disorder.     

Small proportions: what to report for confidence intervals?

The original article to which this Erratum refers was published in Pharmacoepidemiology and Drug Safety 2005; 14: 239–247.     

Comparison of physiological responses to maximal arm exercise among able-bodied, paraplegics and quadriplegics

A comparison of pulmonary, cardiovascular and metabolic responses was made in 32 subjects consisting of 11 able-bodied, 8 paraplegics (T4-L3 lesions) and 13 quadriplegics (C5-C8 lesions) during maximal arm cranking exercise. A progressive continuous arm cranking test, modified for each group, was employed to elicit maximal responses with pulmonary and metabolic determinations made with open circuit spirometry and selected cardiovascular measurements made by impedance cardiography. Additionally, non-exercise static and dynamic lung function assessments were made. Quadriplegics had significantly lower (p less than 0.05) tidal volumes, vital capacities, forced expiratory volumes at 1 seconds, and maximal breathing capacities than the other two groups. The mean peak VO2 during maximal arm cranking was 28.2, 25.3 and 12.0 ml/kg.min for the able-bodied (AB), paraplegics (PP) and quadriplegics (QP), respectively. Furthermore, reduced cardiovascular function was observed in the QP as evident in the low peak HR (109 b/min), peak SV (52 ml/b) and peak Q (5.7 l/min). Values for the QP were 64% and 64% peak HR, 89% and 50% peak SV and 54% and 33% peak Q of values observed for the PP and AB groups, respectively. The peak SV and Q values were significantly lower (P less than 0.05) for the PP group when compared with the AB group. Although not statistically significant the estimated a-v O2 difference was higher for both spinal cord injured groups (14.0 and 14.6 ml O2/100 ml, PP and QP respectively). The impaired work capacity and reduced oxygen transport and utilisation of the QP group can be attributed to impaired sympathetic cardiac stimulation and a smaller available active muscle mass.     

Radical cystectomy after coronary artery bypass graft

Nine patients have undergone single-stage radical cystectomy and ileal conduit urinary diversion two to fifty-one months after coronary artery bypass procedures. Two patients presenting with intractable angina at the time their malignant disease was being evaluated required bypass surgery before cystectomy could be undertaken. No significant cardiac morbidity occurred postoperatively, and all remain alive without evidence of malignant disease.     

Evaluation and application of denaturing HPLC for mutation detection in Marfan syndrome: Identification of 20 novel mutations and two novel polymorphisms in the FBN1 gene

Mutations in the human fibrillin 1 gene (FBN1) cause the Marfan syndrome (MFS), an autosomal dominant connective tissue disorder. Knowledge about FBN1 mutations is important for early diagnosis, management, and genetic counseling. However, mutation detection in FBN1 is a challenge because the gene is very large in size ( approximately 200 kb) and the approximately 350 mutations detected so far are scattered over 65 exons. Conventional methods for large-scale detection of mutations are expensive, technically demanding, or time consuming. Recently, a high-capacity low-cost mutation detection method was introduced based on denaturing high-performance liquid chromatography (DHPLC). To assess the sensitivity and specificity of this method, we blindly screened 64 DNA samples of known FBN1 genotype exon-by-exon using exon-specific DHPLC conditions. Analysis of 682 PCR amplicons correctly identified 62 out of 64 known sequence variants. In three MFS patients of unknown FBN1 genotype, we detected two mutations and eight polymorphisms. Overall, 20 mutations and two polymorphisms are described here for the first time. Our results demonstrate 1) that DHPLC is a highly sensitive (89-99%, P = 0.05) method for FBN1 mutation detection; but 2) that chromatograms with moderate and weak pattern abnormalities also show false positive signals (in all 45-59%, P = 0.05); 3) that the difference in the chromatograms of heterozygous and homozygous amplicons is mostly independent of the type of sequence change; and 4) that DHPLC column conditions, additional base changes, and the amounts of injected PCR products influence significantly the shape of chromatograms. A strategy for FBN1 mutation screening is discussed.     

Fibrillin network in normal bone tissue

The molecular basis for Marfan's syndrome is known to reside in mutations in FBN1, the gene for fibrillin 1. The skeletal manifestations of Marfan syndrome include morphologic abnormalities and osteopenia. Presence and distribution of fibrillin 1 in adult bone (healthy or with Marfan syndrome) has not been studied extensively. We evaluated distribution of fibrillin and type III collagen in bone and cartilage of children and adults without bone disease, using monoclonal antibodies. Fibrillin is mostly present in attachment sites for tendons. In cartilage and bone tissue, fibrillin is identified at the junction between cartilage and bone in children, and in the areas with intense osteoblastic activity. These data suggest participation of fibrillin in bone formation and growth during youth and in bone mineralisation in adult.