A population-based study on motor performance and white matter lesions in older women

OBJECTIVE: To investigate the relationship between motor performance and white matter lesions (WMLs) on computed tomography (CT) of the brain in older women. DESIGN: Cross-sectional study. SETTING: Population-based study in G?teborg, Sweden. PARTICIPANTS: A total of 248 women aged 70, 74, and 78 years. MEASUREMENTS: Motor performance was measured by a Postural-Locomotion-Manual (PLM) test using an optoelectronic technique. WMLs on CT scans were rated as no, mild, moderate, or severe. RESULTS: White matter lesions were associated with impaired mobility of the lower extremities, that is, prolonged locomotion phase in the PLM test. This association was also present after controlling for age, hypertension, coronary heart disease, stroke, diabetes mellitus, chronic bronchitis, intermittent claudication, and smoking. CONCLUSIONS: Cerebral white matter lesions may contribute to motor impairments in older adults.     

The toxicity of D-penicillamine in systemic sclerosis

We studied D-penicillamine toxicity in 259 patients with systemic sclerosis treated since 1972. The average daily dose of 635 mg was given for a mean of 1.8 years. Of patients with systemic sclerosis, 47% has side effects from D-penicillamine treatment, similar to the 56% of 807 patients with rheumatoid arthritis in seven separate series. Individual manifestations of toxicity included rash, proteinuria, gastrointestinal symptoms, dysgeusia, oral ulcers, thrombocytopenia, and neutropenia. Four episodes each of myasthenia gravis and pemphigus occurred in our patients; both were reported rarely in patients with rheumatoid arthritis. Adverse effects occurred more frequently after rapid increases in dosage. Treatment had to be discontinued due to toxicity in 29% of patients with systemic sclerosis and in 33% of those with rheumatoid arthritis. Although toxic, with a high frequency of adverse effects, D-penicillamine can be used safely in the treatment of systemic sclerosis. Pemphigus and myasthenia gravis may occur more frequently with therapy for systemic sclerosis than with that for rheumatoid arthritis.     

Predictors of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement

OBJECTIVE: To determine whether there are factors, such as the diffusing capacity for carbon monoxide (DLCO) or pulmonary artery pressure (PAP) on echocardiogram, that can predict the development of pulmonary hypertension (PHT) in patients with limited scleroderma. METHODS: Using the large Pittsburgh Scleroderma Databank, 106 patients who had the diagnosis of PHT after January 1, 1982, were matched with 106 controls by scleroderma subtype, age, sex, race, disease duration, and the mean time to the diagnosis of PHT after the initial Pittsburgh visit. Autoantibodies, vascular features, use of calcium channel blockers, extent of pulmonary function, and echocardiogram findings were determined at any time prior to the diagnosis of PHT (or prior to the matched time in controls). RESULTS: Patients with PHT had a mean DLCO of 52% of predicted at an average of 4.5 years prior to the diagnosis of PHT. This was markedly decreased compared with the values in controls, whose mean DLCO was 81% of predicted (P < 0.0001). The estimated mean PAP on echocardiogram was only slightly higher in the PHT patients compared with controls (34 mm Hg versus 29 mm Hg; P not significant). Nineteen PHT patients had 4 serial measurements of the DLCO during the 15 years prior to the diagnosis of PHT. The initial mean DLCO was 80% of predicted, which decreased in a linear manner to a mean of 35% of predicted at the time of diagnosis of PHT, whereas the value in controls remained at approximately 80% of predicted (P < 0.0001). PHT patients had more severe Raynaud's phenomenon and more severe digital tip ulcers, but they used calcium channel blockers significantly less frequently (37% versus 61% of controls; P < 0.01). The predominance of nucleolar autoantibodies and the absence of anti-Scl 70 antibody were associated with PHT. CONCLUSION: A decreasing DLCO is an excellent predictor of the subsequent development of isolated PHT in limited scleroderma. The DLCO may be significantly decreased for many years prior to the diagnosis of PHT. The presence of autoantibodies and the PAP may also be helpful predictors. The long-term use of calcium channel blockers may be protective, but newer agents that are more effective in treating PHT may also be helpful in altering the natural history of this serious complication in limited scleroderma.     

Small and large fiber sensory polyneuropathy in type 2 diabetes: Influence of diagnostic criteria on neuropathy subtypes

Diabetic polyneuropathy (DPN) can be classified based on fiber diameter into three subtypes: small fiber neuropathy (SFN), large fiber neuropathy (LFN), and mixed fiber neuropathy (MFN). We examined the effect of different diagnostic models on the frequency of polyneuropathy subtypes in type 2 diabetes patients with DPN. This study was based on patients from the Danish Center for Strategic Research in Type 2 Diabetes cohort. We defined DPN as probable or definite DPN according to the Toronto Consensus Criteria. DPN was then subtyped according to four distinct diagnostic models. A total of 277 diabetes patients (214 with DPN and 63 with no DPN) were included in the study. We found a considerable variation in polyneuropathy subtypes by applying different diagnostic models independent of the degree of certainty of DPN diagnosis. For probable and definite DPN, the frequency of subtypes across diagnostic models varied from: 1.4% to 13.1% for SFN, 9.3% to 21.5% for LFN, 51.4% to 83.2% for MFN, and 0.5% to 14.5% for non‐classifiable neuropathy (NCN). For the definite DPN group, the frequency of subtypes varied from: 1.6% to 13.5% for SFN, 5.6% to 20.6% for LFN, 61.9% to 89.7% for MFN, and 0.0% to 6.3% for NCN. The frequency of polyneuropathy subtypes depends on the type and number of criteria applied in a diagnostic model. Future consensus criteria should clearly define sensory functions to be tested, methods of testing, and how findings should be interpreted for both clinical practice and research purpose.     

High frequency of MYC gene amplification is a common feature of radiation‐induced sarcomas. Further results from EORTC STBSG TL 01/01

Irradiation is a major causative factor among the small subgroup of sarcomas with a known etiology. The prognosis of radiation‐induced sarcomas (RIS) is significantly worse than that of their spontaneous counterparts. The most frequent histological subtypes include undifferentiated pleomorphic sarcomas, angiosarcomas, and leiomyosarcomas. A high frequency of MYC amplifications in radiation‐induced angiosarcomas, but not in primary angiosarcomas, has recently been described. To investigate whether MYC amplifications are also frequent in RIS other than angiosarcomas, we analyzed the MYC amplification status of 83 RIS and 192 sporadic sarcomas by fluorescence in situ hybridization. We found significantly higher numbers of MYC amplifications in RIS than in sporadic sarcomas (P < 0.0001), especially in angiosarcomas, undifferentiated pleomorphic sarcomas, and leiomyosarcomas. Angiosarcomas were special in that MYC amplifications were particularly frequent and always high level, while other RIS showed low‐level amplifications. We conclude that MYC amplifications are a frequent feature of RIS as a group and may contribute to the biology of these tumors. © 2012 Wiley Periodicals, Inc.     

Combinations of self‐reported rhinitis,conjunctivitis, and asthma predicts IgE sensitization in more than 25,000 Danes

BackgroundAllergic rhinitis (AR), allergic conjunctivitis (AC), and asthma composing multiple phenotypes and improved understanding of these phenotypes and their respective risk factors are needed.ObjectivesThe objective of this study was to define the prevalence of AR, AC, and asthma and their association with allergen‐specific immunoglobulin E (sIgE) sensitization in a large cohort of blood donors and identify risk factors.MethodsFrom the nationwide population‐based Danish Blood Donor Study, 52,976 participants completed an electronic questionnaire including AR, AC, asthma, allergic predisposition, and childhood residence. Of these, 25,257 were additionally tested for sIgE to inhalation allergens (Phadiatop).ResultsThe prevalence of sIgE sensitization, AR, AC, and asthma was 30%, 19%, 15%, and 9%, respectively. The youngest birth cohorts had the highest prevalence of sIgE sensitization and symptoms of asthma, AR, and AC, and for asthma, they apparently experienced symptoms at an earlier age. The sIgE sensitization was positively associated with male sex. The sIgE seroprevalence was higher in participants with both AR and AC (ARC) than in participants with either AR or AC. Allergic predisposition and sIgE sensitization increased the risk of the diseases, while farm upbringing was associated with reduced prevalence of ARC, however, only in sIgE sensitized participants.ConclusionBirth year, childhood residence, sIgE sensitization, and allergic predisposition were associated with asthma, AR, and AC prevalence. Individuals with self‐reported ARC represent a primarily sIgE‐positive phenotype, while those with either AR or AC represent more diverse phenotypes.     

Intraplaque Hemorrhage and the Plaque Surface in Carotid Atherosclerosis: The Plaque At RISK Study (PARISK)

BACKGROUND AND PURPOSE:An important characteristic of vulnerable plaque, intraplaque hemorrhage, may predict plaque rupture. Plaque rupture can be visible on noninvasive imaging as a disruption of the plaque surface. We investigated the association between intraplaque hemorrhage and disruption of the plaque surface.MATERIALS AND METHODS:We selected the first 100 patients of the Plaque At RISK study, an ongoing prospective noninvasive plaque imaging study in patients with mild-to-moderate atherosclerotic lesions in the carotid artery. In carotid artery plaques, disruption of the plaque surface (defined as ulcerated plaques and/or fissured fibrous cap) and intraplaque hemorrhage were assessed by using MDCTA and 3T MR imaging, respectively. We used a χ² test and multivariable logistic regression to assess the association between intraplaque hemorrhage and disrupted plaque surface.RESULTS:One hundred forty-nine carotid arteries in 78 patients could be used for the current analyses. Intraplaque hemorrhage and plaque ulcerations were more prevalent in symptomatic compared with contralateral vessels (hemorrhage, 38% versus 11%; P < .001; and ulcerations, 27% versus 7%; P = .001). Fissured fibrous cap was more prevalent in symptomatic compared with contralateral vessels (13% versus 4%; P = .06). After adjustment for age, sex, diabetes mellitus, and degree of stenosis, intraplaque hemorrhage was associated with disrupted plaque surface (OR, 3.13; 95% CI, 1.25–7.84) in all vessels.CONCLUSIONS:Intraplaque hemorrhage is associated with disruption of the plaque surface in patients with a carotid artery stenosis of <70%. Serial studies are needed to investigate whether intraplaque hemorrhage indeed increases the risk of plaque rupture and subsequent ischemic stroke during follow-up.

The need to identify patients with mild-to-moderate carotid artery stenosis and an increased stroke risk who might benefit from surgical treatment has shifted research interest from assessment of the degree of carotid stenosis to assessment of vulnerable plaque characteristics.¹ Vulnerable plaques are atherosclerotic plaques more prone to rupture and are associated with a higher risk for thromboembolism and ischemic stroke.^2,3 Intraplaque hemorrhage is an important characteristic of the vulnerable plaque.⁴ Prevalence of intraplaque hemorrhage has been shown to be higher in symptomatic than in asymptomatic lesions.⁵ Moreover, the presence of intraplaque hemorrhage in carotid artery disease is associated with an increased risk of cerebral ischemic events.^6–8The pathophysiologic mechanism leading to intraplaque hemorrhage is a topic of debate. However, a common viewpoint is that small leaky neovessels in the atherosclerotic plaques are a likely source of intraplaque hemorrhage.^5,9,10 The presence of intraplaque hemorrhage is thought to initiate several biologic processes like phagocytosis and local inflammation, leading to the release of proteolytic enzymes, deposition of free cholesterol and subsequently plaque growth, plaque destabilization, and possible plaque rupture.^5,9–12 Plaque rupture can be visible on imaging as a disruption of the atherosclerotic plaque surface (plaque ulceration and/or a fissured fibrous cap).^13,14 A previous study reported that plaque ulceration on CTA was useful for the prediction of intraplaque hemorrhage on MR imaging in a broad group of symptomatic patients referred for carotid artery imaging.¹⁵ Ulcerated plaques themselves are independently associated with an increased risk of ipsilateral ischemic events as well.^16,17The aim of the current study was to investigate the association between intraplaque hemorrhage, as assessed on MR imaging, and disruption of the plaque surface, assessed on MDCTA, in symptomatic patients with a carotid artery stenosis of <70%.