Mapping preclinical compensation in Parkinson's disease: An imaging genomics approach

Mutations in the Parkin (PARK2) and PINK1 gene (PARK 6) can cause recessively inherited Parkinson's disease (PD). The presence of a single Parkin or PINK1 mutation is associated with a dopaminergic nigrostriatal dysfunction and conveys an increased risk to develop PD throughout lifetime. Therefore neuroimaging of non‐manifesting individuals with a mutant Parkin or PINK1 allele opens up a window for the investigation of preclinical and very early phases of PD in vivo. Here we review how functional magnetic resonance imaging (fMRI) can be used to identify compensatory mechanisms that help to prevent development of overt disease. In two separate experiments, Parkin mutation carriers displayed stronger activation of rostral supplementary motor area (SMA) and right dorsal premotor cortex (PMd) during a simple motor sequence task and anterior cingulate motor area and left rostral PMd during internal movement selection as opposed to externally cued movements. The additional recruitment of the rostral SMA and right rostral PMd during the finger sequence task was also observed in a separate group of nonmanifesting mutation carriers with a single heterozygous PINK1 mutation. Because mutation carriers were not impaired at performing the task, the additional recruitment of motor cortical areas indicates a compensatory mechanism that effectively counteracts the nigrostriatal dysfunction. These first results warrant further studies that use these imaging genomics approach to tap into preclinical compensation of PD. Extensions of this line of research involve fMRI paradigms probing nonmotor brain functions. Additionally, the same fMRI paradigms should be applied to nonmanifesting mutation carriers in genes linked to autosomal dominant PD. This will help to determine how “generically” the human brain compensates for a preclinical dopaminergic dysfunction. © 2009 Movement Disorder Society     

Antimicrobial effects of an NO-releasing poly(ethylene vinylacetate) coating on soft-tissue implants in vitro and in a murine model

Infection of surgical meshes used in abdominal wall reconstructions often leads to removal of the implant and increases patient morbidity due to repetitive operations and hospital administrations. Treatment with antibiotics is ineffective due to the biofilm mode of growth of the infecting bacteria and bears the risk of inducing antibiotic resistance. Hence there is a need for alternative methods to prevent and treat mesh infection. Nitric oxide (NO)-releasing coatings have been demonstrated to possess bactericidal properties in vitro. It is the aim of this study to assess possible benefits of a low concentration NO-releasing carbon-based coating on monofilament polypropylene meshes with respect to infection control in vitro and in vivo. When applied on surgical meshes, NO-releasing coatings showed significant bactericidal effect on in vitro biofilms of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and CNS. However, using bioluminescent in vivo imaging, no beneficial effects of this NO-releasing coating on subcutaneously implanted surgical meshes in mice could be observed.     

Favorable Glucose Tolerance and Lower Prevalence of Metabolic Syndrome in Offspring without Diabetes Mellitus of Nonagenarian Siblings: The Leiden Longevity Study

OBJECTIVES: To explore measures of metabolic syndrome and glucose metabolism in families with exceptional longevity. DESIGN: Case–control study. SETTING: A university hospital in Leiden, the Netherlands. PARTICIPANTS: One hundred twenty‐one offspring of nonagenarian siblings, who were enriched for familial factors promoting longevity, and 113 of their partners. No subject had diabetes mellitus. MEASUREMENTS: Prevalence of metabolic syndrome was determined according to the criteria of the Third Report of the National Cholesterol Education Program. Glucose tolerance was assessed according to a 2‐hour oral glucose tolerance test. RESULTS: The offspring of nonagenarians siblings had a lower prevalence of metabolic syndrome (P=.03), similar body composition, lower mean fasting blood glucose levels (4.99 vs 5.16 mmol/L; P=.01), lower mean fasting insulin levels (5.81 vs 6.75 mU/L; P=.04), a higher mean homeostasis model assessment of insulin sensitivity (0.78 vs 0.65; P=.02), and a more‐favorable glucose tolerance (mean area under the receiver operating characteristic curve for glucose (13.2 vs 14.3; P=.007) than their partners. No significant differences were observed between the offspring and their partners in β‐cell function (insulogenic index 13.6 vs 12.5; P=.38). CONCLUSION: Despite similar body composition, the offspring of nonagenarian siblings showed a lower prevalence of metabolic syndrome and better glucose tolerance than their partners, centralizing the role of favorable glucose metabolism in familial longevity.     

A weak balance: the contribution of muscle weakness to postural instability and falls

Muscle strength is a potentially important factor contributing to postural control. In this article, we consider the influence of muscle weakness on postural instability and falling. We searched the literature for research evaluating muscle weakness as a risk factor for falls in community-dwelling elderly individuals, for evidence that strength training reduces falls, and for pathophysiological evidence from patients with neuromuscular disease that supports the link between muscle weakness and falls. In virtually all studies that included strength testing, muscle weakness was a consistent risk factor for falls in the elderly. Studies that evaluated the merits of muscle strength training often showed a reduction in fall rates, particularly when strength training was a component of a multifactorial intervention, although it was unclear whether strength training alone led to a fall reduction. Surprisingly few studies addressed the pathophysiological relationship between muscle strength and balance control. We conclude that muscle weakness is an important risk factor for falls that is potentially amenable to therapeutic intervention, and that future studies should further clarify the role of muscle weakness in balance control and the pathophysiology of falls.     

Correlates of thenar near-infrared spectroscopy-derived tissue O2 saturation after cardiac surgery

We studied the significance of near-infrared spectroscopy (NIRS), for measuring tissue oxygenation (S(t)O(2)) and perfusion adequacy, and thus for haemodynamic monitoring of patients after cardiac surgery. We compared NIRS-derived S(t)O(2) of the thenar muscle to haemodynamic variables, oxygenation indices, temperature, lactate levels and urinary output, in 23 patients in the course of time after cardiac surgery and admission into the intensive care unit. Clinical variables, global haemodynamics and NIRS% total haemoglobin (%HT) and S(t)O(2) in the thenar for up to 18-22 h after admission were measured. The S(t)O(2) declined concomitantly with a rise in the body-finger temperature difference. Cardiac output did not change but mean arterial pressure rose, concomitantly with tapering doses of nitroglycerine, indicative of an increase in vascular tone during recovery from surgery. From all variables, changes in body-finger temperature difference best correlated to changes in S(t)O(2) (r(s)=-0.48, P<0.001). As judged from clinical and haemodynamic correlates, thenar NIRS S(t)O(2) is a non-invasive measure of peripheral rather than global perfusion adequacy, after cardiac surgery. This may help to define the role of thenar NIRS monitoring after cardiac surgery in future studies.     

Osteoarticular infections in HIV-infected patients: 23 cases among 1,515 HIV-infected patients

Background The reported incidence of osteoarticular infections in HIV-infected patients has varied in the literature.

Patients and methods We determined the incidence and characteristics of osteoarticular infections reported in a database of 1,515 HIV-infected patients between 1983 and 2003.

Results 23 HIV-infected patients were identified with an osteoarticular infection, 11 of whom had a spondylodiscitis. 16 were intravenous drug abusers; this was identified as a risk factor for developing an osteoarticular infection. The most common agent was Staphylococcus aureus. 6 patients required surgical intervention and in a worst-case scenario more than one-fifth had recurrence of their infection.

Conclusion Development of an osteoarticular infection is a rare complication in this group of HIV-infected patients, but a remarkably high number of infections of the spine were seen.     

Sweating dysfunction in Parkinson's disease.

We sought to determine the prevalence and nature of sweating disturbances in patients with Parkinson's disease (PD), and investigated their correlation with other clinical features and with Quality of Life (QoL) measures. A questionnaire on symptoms and consequences of sweating dysfunction was completed by 77 consecutive outpatients, from three movement disorder clinics, and 40 controls. QoL was assessed using the disease-specific Parkinson's Disease Questionnaire (PDQ)-39 and generic EuroQoL (EQ)-5D rating scales. Patients also underwent a clinical examination, including assessment with the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr staging system. Sweating disturbances, either hypohidrosis or in particular, hyperhidrosis, were reported by 64% of patients and by 12.5% of controls (P < 0.005) and were often localised or asymmetric. Complaints of sweating disturbances were not correlated with disease severity, but did correlate with other symptoms of autonomic dysfunction. Sweating problems occurred predominantly in off periods and in on periods with dyskinesias. Sweating disturbances were not correlated with overall QoL scores, but we did observe a significant correlation with the pain dimension of the PDQ-39 and the visual analogue scale of the EQ-5D. Furthermore, many patients reported physical, social, and emotional impairment due to sweating. Sweating disturbances are common and distressing symptoms of PD that are related mainly to autonomic dysfunction, off periods, and dyskinesias.