Gait and balance in essential tremor: Variable effects of bilateral thalamic stimulation

Essential tremor (ET) is a multi‐faceted condition best known for postural and action tremor but also may include disordered gait and postural instability. Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus provides substantial tremor reduction yet some patients with bilateral VIM DBS have gait and balance impairment. This study examines gait and balance performance in 13 participants with ET who have bilateral VIM DBS compared with a matched control group. Participants with ET were tested with their stimulators off (DBS OFF) and on (DBS ON). For both standard and tandem walking, participants with ET walked significantly more slowly than controls, with significantly lower cadence, spending a lower percentage of the gait cycle in single limb support and a higher percentage in double support compared with controls. Participants with ET also had significantly lower tandem and one leg stance times, Berg balance scores, balance confidence, and required significantly greater time to perform the Timed Up‐and‐Go relative to controls. There were no significant differences in any gait or balance measures in the DBS OFF versus DBS ON conditions, but the effects of DBS on gait and balance were highly variable among individuals. Future studies are needed to determine why some individuals experience gait and balance difficulties after bilateral thalamic DBS and others do not. A better understanding of the mechanisms underlying gait and balance impairments in those with bilateral DBS is critical to reduce falls and fractures in this group. © 2008 Movement Disorder Society     

Norepinephrine and cardiovascular responses to maximal exercise in Parkinson's disease on and off medication

The aim of this experiment is to understand how Parkinson's disease (PD) medication affects the autonomic responses of individuals during an acute exercise stress test. Fourteen people with PD and fifteen healthy individuals age‐matched between 50 and 80 years performed a modified Bruce protocol. Subjects with PD performed the test once off medication (PD‐off) and then 1 week later on medication (PD‐on). Heart rate (HR), blood pressure (BP), VO₂, and norepinephrine (NE) levels were taken at rest and at peak exercise. At peak exercise HR, BP, and NE values for the PD‐on and PD‐off group were all significantly lower than healthy controls, regardless of whether subjects were on their medication. Autonomic abnormalities during exercise in this population appear to be disease manifested and not impactedby medications used to treat PD. We can assume, both on and off medication, this population will show markedly lower BP, HR, and NE responses. © 2009 Movement Disorder Society     

PTCH1 duplication in a family with microcephaly and mild developmental delay

With the exception of the X chromosome, genomic deletions appear to be more prevalent than duplications. Because of a lack of accurate diagnostic methods, submicroscopic duplications have been under-ascertained for a long period. The development of array CGH has enabled the detection of chromosomal microduplications with nearly the same sensitivity as deletions, leading to the discovery of previously unrecognized syndromes. Using a clinical targeted oligonucleotide array (CMA-V6.3 OLIGO), we identified an approximately 360-kb duplication in 9q22.32 in a 21-month-old boy with developmental delay, failure to thrive, and microcephaly. The same duplication was identified in the patient's mother who is also microcephalic and mildly delayed. We have sequenced the chromosomal breakpoints and determined the duplication as tandem in orientation and 363 599 bp in size. The duplicated segment harbors the entire PTCH1 gene. Deletions or loss-of-function mutations of PTCH1 result in basal cell nevus syndrome (Gorlin syndrome), whereas gain-of-function mutations were proposed to lead to holoprosencephaly 7. We propose that patients with microcephaly or holoprosencephaly of unknown origin should also be screened for PTCH1 duplication.     

Interstitial deletion of 6q25.2�Cq25.3: a novel microdeletion syndrome associated with microcephaly, developmental delay, dysmorphic features and hearing loss

Interstitial deletions of 6q are rare. We report a detailed clinical and molecular characterization of four patients with interstitial deletion involving 6q25. All of our patients presented with microcephaly, developmental delay, dysmorphic features and hearing loss, whereas two of them had agenesis of the corpus callosum. We determined the size, extent and genomic content of the deletions using high-density array-comparative genomic hybridization (a-CGH), and found that a common segment spanning 3.52 Mb within the 6q25.2–q25.3 region was deleted in all four cases. We hypothesize that a subset of genes in the commonly deleted region are dosage sensitive and that haploinsufficieny of these genes impairs normal development of the brain and hearing.     

Coexpression network based on natural variation in human gene expression reveals gene interactions and functions

Genes interact in networks to orchestrate cellular processes. Analysis of these networks provides insights into gene interactions and functions. Here, we took advantage of normal variation in human gene expression to infer gene networks, which we constructed using correlations in expression levels of more than 8.5 million gene pairs in immortalized B cells from three independent samples. The resulting networks allowed us to identify biological processes and gene functions. Among the biological pathways, we found processes such as translation and glycolysis that co-occur in the same subnetworks. We predicted the functions of poorly characterized genes, including CHCHD2 and TMEM111, and provided experimental evidence that TMEM111 is part of the endoplasmic reticulum-associated secretory pathway. We also found that IFIH1, a susceptibility gene of type 1 diabetes, interacts with YES1, which plays a role in glucose transport. Furthermore, genes that predispose to the same diseases are clustered nonrandomly in the coexpression network, suggesting that networks can provide candidate genes that influence disease susceptibility. Therefore, our analysis of gene coexpression networks offers information on the role of human genes in normal and disease processes.The functions of many human genes are unknown. It is not unusual that when one searches the literature on a gene, one fails to find any papers that provide information on its biological roles. Identifying gene function is difficult, especially if no hints, such as homologies to known genes, are available to direct the search. However, since genes work by interacting with other genes, we may learn about their functions through their neighboring genes (Stuart et al. 2003; Ayroles et al. 2009). Identifying gene function is increasingly important; in the last several years, genome-wide association studies (GWAS) have identified DNA variants that are associated with common complex diseases. But for many of these studies, the functional links between the susceptibility genes and the diseases are unknown.In this study, we used correlations in expression levels of more than 8.5 million human gene pairs in immortalized B cells from three data sets to infer gene coexpression networks. The resulting gene networks were based on correlations between genes that were found reproducibly in the three data sets. This provided us with gene networks in which we had high confidence in the gene correlations. We then used the networks to identify key biological processes and interactions among those processes in our cells. Then, we identified the functions of 36 human genes with no known functions and four genes that have been implicated in GWAS as susceptibility genes for common human diseases, including IFIH1, which was recently found to be associated with type 1 diabetes.     

Comfortably numb? Exploring satisfaction with chronic back pain visits

Background contextChronic back pain is a condition characterized by high rates of disability, health-care service use, and costs.PurposeThe purpose of this study was to identify factors associated with patients' satisfaction with their last health-care provider visit for chronic low back pain (LBP).Study design/settingA cross-sectional, state-level, telephone survey was administered to patients with chronic LBP.Patient sampleThe sample consisted of 624 individuals with chronic LBP who reported seeing a health-care provider in the previous year.Outcome measuresDependent variables included satisfaction with last visit for LBP and intent to seek care from additional providers. Independent variables included the Roland-Morris Disability Questionnaire, 3-month pain ratings using a 0 to 10 Likert scale, the Medical Outcomes Survey Short Form 12, and self-reported health service utilization (provider type, number of visits to health-care providers, medication use during the previous month, and treatments and diagnostic tests during the previous year).MethodsBivariate and multivariate analyses were used to explore how demographic, insurance-related, and health-related characteristics were associated with patient satisfaction.ResultsParticipants who were not satisfied with one or more aspects of their last clinic visit were younger (51.0 vs. 54.21 years), reported higher 3-month pain ratings (7.23 vs. 6.53), and were more commonly Hispanic (53.2% vs. 46.8% for other ethnicities) and uninsured (43.1% vs. 29.3% for other insurance groups). Those who intended to seek care from additional providers were younger (50.05 vs. 55.49 years), had higher 3-month pain ratings (7.20 vs. 6.46), had lower Short Form 12 mental health component scores (44.75 vs. 49.55) and physical component scores (30.07 vs. 31.55), and were more commonly black (54.6% vs. 45.4% for other racial groups) and uninsured (56.9% vs. 43.1% for other insurance groups). Narcotic use was associated with satisfaction (odds ratio=2.12, p=.01), whereas lack of insurance was associated with respondents' intent to seek care from additional providers (odds ratio=2.97, p<.01).ConclusionsFactors other than disability were associated with satisfaction with chronic LBP visits. Understanding the role of medication in satisfaction and its implications for the health behaviors of this highly disabled population may be particularly important.     

Factors for conversion in laparoscopic cholecystectomy for acute cholecystitis: Is timing important?

Aim: Laparoscopic cholecystectomy is regarded as the gold standard treatment for gallstones. Conversion to open cholecystectomy is still common, and preoperative factors to predict conversion are useful in clinical practice. The aim of this study was to evaluate preoperative factors that could predict conversion in acute cholecystitis. Methods: This is a retrospective review of 83 patients with a diagnosis of acute cholecystitis who had laparoscopic cholecystectomy carried out as an emergency operation. Clinical, biochemical, and operative factors were analyzed for association with conversion. Results: A total of 83 patients were recruited to this study. The overall conversion rate was 33.7% (28/83). A longer duration of symptoms before presentation (P = 0.005) and surgery that was carried out over 48 h after admission (P = 0.022) were associated with a higher conversion rate. Emergency operations that began between 20.00 hours and 08.00 hours were also associated with a higher rate of conversion (P = 0.003). Other factors that were associated with conversion included male sex (P = 0.004), low albumin level upon admission (P = 0.024), prolonged prothrombin time (P = 0.040), and a raised serum total bilirubin level (P = 0.024). ASA scores were found to be similar in both groups (P = 0.509). Multivariate analysis by logistic regression showed that the independent risk factors for conversion in emergency laparoscopic cholecystectomy were surgery >48 h after admission (P = 0.028), emergency operation started between 20.00 hours and 08.00 hours (P = 0.026), and longer duration of symptoms before presentation (P = 0.034). Conclusions: Laparoscopic cholecystectomy should be carried out within 48 h of the patient being admitted for acute cholecystitis. The operation should be carried out during the daytime.     

Classification and management of the tandem ossification of the posterior longitudinal ligament and flaval ligament

Objective To provide appropriate guidelines for treatment of tandem ossification of the posterior longitudinal ligament （OPLL） and flaval ligament （OFL）. Data sources Published articles about OPLL and OFL were selected using Medline and Embase electronic databases. Study selection An English literature search from January 1980 to December 2006 was conducted. Because many reported cases were incorporated in OFL studies, the key words for search were OFL or OFL and OPLL. The first step revealed 93 studies of which 13 reports of tandem OPLL and OFL （tandem ossification） were selected. Results All studies were case series or case report and advocated that the primary therapy for tandem ossification should be operative. The clinical outcomes of surgery were evaluated in most reports, predominantly using the JOA scores. Gender is the only factor which has prognostic value. A higher proportion of women was found in the failure group A two- stage classification of tandem ossification was developed to relate diagnosis to outcome. Conclusions All patients with suspected ossification of the spinal ligaments should undergo routine MRI screening of the whole spine. The correlation of the classification with surgical treatments needs further studies to validate its usefulness. Chin Med J 2009; 122（2）：219-224     

Bone Disease in Thalassemia: A Frequent and Still Unresolved Problem

Adults with β thalassemia major frequently have low BMD, fractures, and bone pain. The purpose of this study was to determine the prevalence of low BMD, fractures, and bone pain in all thalassemia syndromes in childhood, adolescence, and adulthood, associations of BMD with fractures and bone pain, and etiology of bone disease in thalassemia. Patients of all thalassemia syndromes in the Thalassemia Clinical Research Network, ≥6 yr of age, with no preexisting medical condition affecting bone mass or requiring steroids, participated. We measured spine and femur BMD and whole body BMC by DXA and assessed vertebral abnormalities by morphometric X‐ray absorptiometry (MXA). Medical history by interview and review of medical records, physical examinations, and blood and urine collections were performed. Three hundred sixty‐one subjects, 49% male, with a mean age of 23.2 yr (range, 6.1–75 yr), were studied. Spine and femur BMD Z‐scores < ?2 occurred in 46% and 25% of participants, respectively. Greater age, lower weight, hypogonadism, and increased bone turnover were strong independent predictors of low bone mass regardless of thalassemia syndrome. Peak bone mass was suboptimal. Thirty‐six percent of patients had a history of fractures, and 34% reported bone pain. BMD was negatively associated with fractures but not with bone pain. Nine percent of participants had uniformly decreased height of several vertebrae by MXA, which was associated with the use of iron chelator deferoxamine before 6 yr of age. In patients with thalassemia, low BMD and fractures occur frequently and independently of the particular syndrome. Peak bone mass is suboptimal. Low BMD is associated with hypogonadism, increased bone turnover, and an increased risk for fractures.