Nociceptive aspects of fibromyalgia

Although characterized by a variety of symptoms, chronic widespread pain is the primary complaint bringing most patients with fibromyalgia syndrome (FMS) into the clinic. The etiology of this painful condition is unknown, and any possible relationship between pain and the many other symptoms of FMS is unclear. This article focuses on the unique characteristics of nociception in patients with FMS. The intent is to present criteria that should be considered in the search for biological events that contribute to FMS pain. Based on this approach, examples are proposed of factors that fulfill some criteria and may, therefore, deserve further study for their possible role in pain associated with FMS.     

Screening for venous thromboembolism in traumatic brain injury: limitations of D-dimer assay

OBJECTIVES: To assess whether 2 different D-dimer fibrin degradation assays-a second-generation latex immunosorbent agglutination (LIA) and an enzyme-linked immunosorbent assay (ELISA)-are predictive for the development of deep venous thrombosis (DVT) at the currently accepted level of 500 microg/L of D-dimer assay during the first weeks after traumatic brain injury (TBI) and to correlate over 8 weeks the second-generation LIA assay with the ELISA assay after acute TBI. DESIGN: A case series of persons with TBI were screened for DVT at 2 weeks (+/-3d) using real-time, spectral Doppler ultrasound, as well as D-dimer fibrin split products. All persons were rescreened at 4, 6, and 8 weeks (+/-3d) after injury using D-dimer LIA and ELISA assays. SETTING: A university hospital with a directly connected comprehensive in- and outpatient rehabilitation center that are part of the Traumatic Brain Injury Model Systems. PARTICIPANTS: Over 3 years, 35 TBI subjects with a mean Glasgow Coma Scale score of 6.5 were consecutively enrolled into the trial while on acute care. Persons were at least 16 years of age with no history of treatment for DVT. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Data were analyzed for the levels of D-dimer and risk as established by a predictive value of 500 microg/L. Changes in D-dimer values over time and within subjects were assessed by analysis of variance (ANOVA) with repeated measures, and the methods were correlated. RESULTS: The mean LIA level at 2 weeks was 4.3mg/L and averaged 1.6 mg/L at 8 weeks from injury (P=.012, ANOVA), and the ELISA dropped from 4,748 microg/L to 1.695 microg/L (P=.0022, ANOVA). Except for 1 ELISA value in 1 patient, D-dimer levels were elevated beyond 500 microg/L at 2 weeks. There was a very good correlation between the LIA and the ELISA at 2, 4, 6, and 8 weeks after TBI (P<.0001). In individual cases, there were only occasional discrepancies between the LIA and ELISA methods. There were no positive DVTs at 2 weeks using ultrasound, so prediction of the sensitivity and the specificity of D-dimer with DVT was not possible. CONCLUSION: Using the currently recommended levels of D-dimer to predict DVT is not clinically useful in the acute TBI population.     

Central venous access and handwashing: variability in policies and practices

This study examined variability in handwashing policy between hospitals, variability in handwashing practices in nurses and how practice differed from policy in tertiary paediatric hospitals in Australia and New Zealand. Eight of the possible nine major paediatric hospitals provided a copy of their handwashing and/or central venous access device (CVAD) policies, and 67 nurses completed a survey on their handwashing practices associated with CVAD management. A high degree of variability was found in relation to all the questions posed in the study. There was little consistency between policies and little agreement between policies and clinical practice, with many nurses washing for longer than required by policy. Rigour of handwashing also varied according to the procedure undertaken and the type of CVAD with activities undertaken farther from the insertion site of the device more likely to be performed using a clean rather than an aseptic handwashing technique. As both patients and nursing staff move within and between hospitals, a uniform and evidence-based approach to handwashing is highly desirable.     

Paradoxical fall in proteinuria during pregnancy in an LCAT-deficient patient—A case report

A 29-year-old lady was diagnosed with lecithin:cholesterol acyltransferase (LCAT) deficiency having presented with bilateral corneal clouding, severely reduced high density lipoproteins cholesterol, and proteinuria. She is a compound heterozygote with two LCAT gene mutations, one of which is novel, c.321C>A in exon 3. Surprisingly, the level of proteinuria significantly improved during pregnancy, despite stopping the angiotensin-converting enzyme inhibitor. However, LCAT concentration and activity remained identical during pregnancy and postpartum. Her pregnancy was complicated by rising triglyceride levels from the second trimester requiring treatment with omega-3 fatty acid and fenofibrate. In the last trimester, a further complication arose when she became hypertensive and proteinuria worsened. She was diagnosed with pre-eclampsia and had an emergency cesarean section at 39 weeks delivering a healthy baby. This case adds to the knowledge of the pathophysiology of LCAT deficiency during pregnancy and will be useful in future patient management.     

Determinants of walking function after stroke: differences by deficit severity

OBJECTIVES: To investigate the relationship of cardiovascular fitness (Vo(2)peak), neurologic deficits in balance and leg strength, and body composition to ambulatory function after stroke and to determine whether these relationships differ between those with milder versus more severe gait deficits. DESIGN: Cross-sectional correlation study. SETTING: Outpatient clinic of an academic medical center. PARTICIPANTS: Seventy-four people (43 men, 31 women; mean age +/- standard deviation, 64+/-10y) with chronic hemiparetic stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Thirty-foot (9.1-m) walk velocity, 6-minute walk distance, Vo(2)peak, Berg Balance Scale score, bilateral quadriceps eccentric torque, total and regional lean mass, and percentage of fat mass. RESULTS: Short-distance walking correlated significantly with cardiovascular fitness, balance, paretic leg strength, nonparetic leg strength, percentage of body fat, and paretic lean mass but not with nonparetic lean mass. Long-distance walking correlated significantly with cardiovascular fitness, balance, paretic leg strength, nonparetic leg strength, and paretic lean mass but not with percentage of body fat or nonparetic lean mass. Stepwise regression showed that cardiovascular fitness, balance, and paretic leg strength were independently associated with long-distance walking (r(2)=.60, P<.001). Variance in long-distance walking was largely explained by balance for those who walked more slowly (<.48m/s) for short distances (r(2)=.42, P<.001) and by cardiovascular fitness for those who walked more quickly (>.48m/s) for short distances (r(2)=.26, P=.003). CONCLUSIONS: Short-distance walking after stroke is related to balance, cardiovascular fitness, and paretic leg strength. Long-distance walking ability differs by gait deficit severity, with balance more important in those who walk more slowly and cardiovascular fitness playing a greater role in those who walk more quickly. Improved understanding of the factors that predict ambulatory function may assist the design of individualized rehabilitation strategies across the spectrum of gait deficit severity in those with hemiparetic stroke.     

Quality of life and neuropsychiatric disorders in patients with Graves' Orbitopathy: Current concepts

Graves' disease (GD) is an autoimmune chronic thyroiditis frequently associated with development of Graves' orbitopathy (GO) characterized by proptosis, strabismus, impairment of visual function, ocular surface inflammation and dry eye. As consequence, patients with GO experience impairment of quality of life and social function and could develop a neurobehavioral syndrome, ranging from anxious to depressive or psychotic disorders. To date, the pathogenic mechanism underlying neuropsychiatric disorders in patients with GD has not been clearly understood. In fact, the development of neuropsychiatric disorders in patients with GO has been associated with both the detrimental effects of the altered circulating thyroid hormones on the nervous system, and with the psychological discomfort caused by poor quality of life, reduced social interactions and relapsing course of the disease. This paper summarizes current evidence on neuropsychiatric abnormalities in Graves' disease focusing on its impact on QoL and psychosocial function. We remark the importance of a multidisciplinary approach and we emphasize the potential benefit of neuropsychiatric approach on disease perception, patient compliance to medical and/or surgical treatment and clinical outcomes.     

A comprehensive approach to identification of pathogenic FANCA variants in Fanconi anemia patients and their families

Fanconi anemia (FA) is a rare recessive DNA repair deficiency resulting from mutations in one of at least 22 genes. Two‐thirds of FA families harbor mutations in FANCA. To genotype patients in the International Fanconi Anemia Registry (IFAR) we employed multiple methodologies, screening 216 families for FANCA mutations. We describe identification of 57 large deletions and 261 sequence variants, in 159 families. All but seven families harbored distinct combinations of two mutations demonstrating high heterogeneity. Pathogenicity of the 18 novel missense variants was analyzed functionally by determining the ability of the mutant cDNA to improve the survival of a FANCA‐null cell line when treated with MMC. Overexpressed pathogenic missense variants were found to reside in the cytoplasm, and nonpathogenic in the nucleus. RNA analysis demonstrated that two variants (c.522G > C and c.1565A > G), predicted to encode missense variants, which were determined to be nonpathogenic by a functional assay, caused skipping of exons 5 and 16, respectively, and are most likely pathogenic. We report 48 novel FANCA sequence variants. Defining both variants in a large patient cohort is a major step toward cataloging all FANCA variants, and permitting studies of genotype–phenotype correlations.