tbuckley/cabot-search huggingface dataset:
Work Disability Among Individuals With Diabetes
Authors: Michael Von Korff, Wayne Katon, Elizabeth H.B. Lin, Gregory Simon, Paul Ciechanowski, Evette Ludman, Malia Oliver, Carolyn Rutter, Bessie Young
Journal: Diabetes Care (2005)

OBJECTIVE—Diabetes is rapidly increasing in prevalence among working-age adults, but little is known about the clinical characteristics that predict work disability in this population. This study assessed clinical predictors of work disability among working-age individuals with diabetes. RESEARCH DESIGN AND METHODS—In a cohort of diabetic individuals (n = 1,642) enrolled in a large health maintenance organization, excluding homemakers and retirees, we assessed the relation of diabetes severity, chronic disease comorbidity, depressive illness, and behavioral risk factors with work disability. Three indicators of work disability were assessed: being unable to work or otherwise being unemployed; missing ≥5 days from work in the prior month; and having severe difficulty with work tasks. RESULTS—In the study population, 19% had significant work disability: 12% were unemployed, 7% of employed subjects had missed ≥5 days from work in the prior month, and 4% of employed subjects reported having had severe difficulty with work tasks. Depressive illness, chronic disease comorbidity, and diabetes symptoms were associated with all three types of work disability. Diabetes complications predicted unemployment and overall work disability status, whereas obesity and sedentary lifestyle did not predict work disability. Among subjects experiencing both major depression and three or more diabetes complications, &amp;gt;50% were unemployed; of those with significant work disability, half met the criteria for major or minor depression. CONCLUSIONS—Depressive illness was strongly associated with unemployment and problems with work performance. Disease severity indicators, including complications and chronic disease comorbidity, were associated with unemployment and overall work disability status. Effective management of work disability among diabetic patients may need to address both physical and psychological impairments.
Time to relapse has prognostic value in patients with aggressive lymphoma enrolled onto the Parma trial.
Authors: C Guglielmi, F Gomez, T Philip, A Hagenbeek, M Martelli, C Sebban, N Milpied, D Bron, J Y Cahn, R Somers, P Sonneveld, C Gisselbrecht, H Van Der Lelie, F Chauvin
Journal: Journal of Clinical Oncology (1998)

PURPOSE The purpose of this study was to investigate the prognostic value of time to relapse in 188 adult patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) included on the Parma trial at the time of their first relapse. PATIENTS AND METHODS The median follow-up of these patients is 102 months after registration onto the Parma study. Time to relapse was calculated from initial diagnosis, and a cutoff of 12 months was used to separate 77 patients defined as early relapse from 111 patients defined as late relapse. RESULTS Patients with early and late relapses had significantly different overall response rates to salvage therapy with two courses of dexamethasone, high-dose cytarabine, and cisplatin (DHAP; 40% v 69%; P=.00007) and different 8-year survival rates (13% v 29%; P=.00001). Features at relapse with a negative prognostic value in univariate analysis were higher than normal lactic dehydrogenase (LDH) levels, tumor size greater than 5 cm, Ann Arbor stages III to IV, and Karnofsky score less than 80%. Therefore, multivariate analyses were performed. Time to relapse (P=.001) and LDH levels at relapse (P=.003) had independent prognostic value, whereas tumor size did not reach statistical significance in the logistic model that predicted overall response after two courses of DHAP. The study of prognostic factors for overall survival (OS) and progression-free survival (PFS) confirmed the prognostic value of time to relapse (P &lt; .0001 for OS and P=.005 for PFS) independent of response or treatment after two courses of DHAP. CONCLUSION Time to relapse may be used to stratify patients at time of first relapse of intermediate to high-grade non-Hodgkin's lymphoma.
Diagnosing testicular function using 31P magnetic resonance spectroscopy: a current review
Authors: J van der Grond
Journal: Human Reproduction Update (1995)

Patients with low sperm counts combined with normal concentrations of gonadotrophins, and in whom physical examination and post-ejaculatory urine analysis are normal, present a diagnostic dilemma. This situation can be caused by testicular failure or by ductal obstruction, which have very different clinical prognoses. Ductal obstruction might be correctable by microsurgical vasovaso/vasoepididymostomy, whereas this approach is of no use in primary testicular failure. A possible diagnostic step for these patients is a testicular biopsy to differentiate between hyposper-matogenesis and a normal gonad. However, to date testicular biopsy is seldom performed because of its invasive character. An alternative accurate, non-invasive method to assess testicular function could be very helpful in the evaluation of idiopathic azoosper-mia or idiopathic oligozoospermia. During the past decade, magnetic resonance (MR) spectroscopy has been developed from a scientific tool into a non-invasive clinical diagnostic tool and has also been used to study testicular function. Recent studies have shown that 31 P-MR spectroscopy, based upon differences in the ratio of peaks of phosphomonoester to P-adenos-inetriphosphate, is a non-invasive technique able to differentiate between groups of patients with testicular failure and ductal obstruction, and it correlates reasonably well with the averaged mean Johnsen score of testicular biopsy. The role for a non-invasive technique in the diagnosis of male infertility, such as 31P-MR spectroscopy, can be manifold. It serves not only as an alternative for biopsy but can also be used to assess obstruction as the cause of infertility in patients with subnormal sperm counts, and to predict the chances of pregnancy in patients planned for vaso-vasostomy to correct a prior vasectomy. However, the main limitation to MR spectroscopy becoming a universal clinical diagnostic technique is the limited availability of 1.5 Tesla MR scanners.
Prevention of Cardiovascular Disease
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2007)

Perspectives on the News commentaries are now part of a new, free monthly CME activity. The Mount Sinai School of Medicine, New York, New York, is designating this activity for 2.0 AMA PRA Category 1 credits. If you wish to participate, review this article and visit www.diabetes.procampus.net to complete a posttest and receive a certificate. The Mount Sinai School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
Right Bundle Branch Block, Right Precordial ST-Segment Elevation, and Sudden Death in Young People
Authors: Domenico Corrado, Cristina Basso, Gianfranco Buja, Andrea Nava, Lino Rossi, Gaetano Thiene
Journal: Circulation (2001)

Background —Patients with the ECG pattern of right bundle branch block and right precordial ST-segment elevation may experience sudden death in the setting of either arrhythmogenic right ventricular cardiomyopathy (ARVC) or a functional electrical disorder such as Brugada syndrome. Methods and Results —Among a series of 273 young (≤35 years) victims of cardiovascular sudden death who were prospectively studied from 1979 to 1998 in the Veneto Region of Italy, 12-lead ECG was available in 96 cases. Thirteen (14%; 12 males and 1 female aged 24±8 years) had right precordial ST-segment elevation, either isolated (9 cases) or associated with right bundle branch block (4 cases). At autopsy, all patients had ARVC (92%) except one, who had no evidence of structural heart disease. Compared with the 19 young sudden death victims with ARVC and no ST-segment abnormalities from the same series, those with AVRC and right precordial ST-segment elevation included fewer competitive athletes (17% versus 58%; P =0.03), more often died suddenly at rest or during sleep (83% versus 26%; P =0.003), and showed serial ECG changes over time (83% versus 0; P =0.015), polymorphic ventricular tachycardia (33% versus 0; P =0.016), and predominant fatty replacement of the right ventricular anterior wall (58% versus 21%; P =0.05), Conclusions —Right precordial ST-segment elevation was found in 14% of young sudden death victims with available ECG. It mostly reflected underlying ARVC with predominant right ventricular anterior wall involvement and characterized a subgroup of patients who share with Brugada patients the propensity to die from non–exercise-related cardiac arrest and to exhibit dynamic ECG changes and polymorphic ventricular tachycardia.
Cutaneous Vascular Lesions and Disseminated Cat-Scratch Disease in Patients with the Acquired Immunodeficiency Syndrome (AIDS) and AIDS-Related Complex
Authors: Jane E. Koehler
Journal: Annals of Internal Medicine (1988)

Cutaneous lesions develop frequently in patients infected with human immunodeficiency virus (HIV). We describe the clinical features of four patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex who developed angiomatous nodules involving skin and bone, 2 of whom were scratched by a cat. Some of these lesions were clinically indistinguishable from Kaposi sarcoma. When examined with Warthin-Starry staining and electronmicroscopy, these nodules were noted to contain numerous clumps of a bacterium. Immunoperoxidase staining with an antiserum raised against the cat-scratch disease bacillus stained these organisms in all patients. Cat-scratch disease is usually a self-limited infection, but complicated or prolonged infections have been described in both normal and immunocompromised hosts. In our patients infected with HIV, manifestations of systemic cat-scratch disease included angiomatous nodules, severe systemic symptoms of fever, chills, night sweats and weight loss, elevated erythrocyte sedimentation rate, and decreased hematocrit. Cutaneous lesions involved the face, trunk, and extremities and numbered 2 to greater than 60; osseous lesions involved the fibula, radius, femur, and tibia, and were present in two of four patients. Treatment with x-ray therapy, intralesional vinblastine, penicillin, dicloxacillin, cephradine, and nafcillin had no effect on any lesions; however, treatment with erythromycin, doxycyline, or antimycobacterial antibiotics resulted in complete and rapid resolution of the cutaneous and osseous lesions, and the accompanying signs and symptoms of systemic infection. In patients with AIDS or AIDS-related complex, angiomatous nodules should be carefully evaluated for the presence of this organism, which can be treated and cured with antibiotic agents.
Sleep Apnea and the Risk of Incident Gout: A Population‐Based, Body Mass Index–Matched Cohort Study
Authors: Yuqing Zhang, Christine E. Peloquin, Maureen Dubreuil, Edward Roddy, Na Lu, Tuhina Neogi, Hyon K. Choi
Journal: Arthritis & Rheumatology (2015)

Objective Sleep apnea is associated with hyperuricemia owing to hypoxia‐induced nucleotide turnover. We undertook this study to assess the relationship between incident sleep apnea and the risk of incident gout. Methods Using data from The Health Improvement Network in the UK, we identified individuals with a first‐ever physician diagnosis of sleep apnea. For each patient with sleep apnea, up to 5 individuals without sleep apnea were matched by sex, age, birth year, and body mass index (within ±0.5 kg/m 2 ). We estimated the incidence rates of gout and examined the relationship between sleep apnea and the risk of incident gout using a Cox proportional hazards model, adjusting for potential confounders. In addition, we assessed the rate difference in gout due to sleep apnea using an additive hazard model. Results Among 9,865 patients with newly diagnosed sleep apnea and 43,598 matched individuals without sleep apnea, we identified 270 incident cases of gout over 1 year of followup, resulting in incidence rates of 8.4 per 1,000 person‐years and 4.8 per 1,000 person‐years, respectively. The crude and multivariable rate ratios of incident gout in patients with sleep apnea were 1.7 (95% confidence interval [95% CI] 1.3, 2.2) and 1.5 (95% CI 1.1, 2.1), respectively. The corresponding rate differences between patients with sleep apnea and the comparison cohort were 3.6 (95% CI 1.6, 5.6) and 2.8 (95% CI 0.7, 4.9) per 1,000 person‐years. The effect of sleep apnea persisted across subgroups. Conclusion This general population–based study indicates that sleep apnea is independently associated with an increased risk of incident gout. Future research should examine the potential benefits of correcting sleep apnea–induced hypoxia on the risk of hyperuricemia and gout flares.
The Subplate and Early Cortical Circuits
Authors: Patrick O. Kanold, Heiko J. Luhmann
Journal: Annual Review of Neuroscience (2010)

The developing mammalian cerebral cortex contains a distinct class of cells, subplate neurons (SPns), that play an important role during early development. SPns are the first neurons to be generated in the cerebral cortex, they reside in the cortical white matter, and they are the first to mature physiologically. SPns receive thalamic and neuromodulatory inputs and project into the developing cortical plate, mostly to layer 4. Thus SPns form one of the first functional cortical circuits and are required to relay early oscillatory activity into the developing cortical plate. Pathophysiological impairment or removal of SPns profoundly affects functional cortical development. SPn removal in visual cortex prevents the maturation of thalamocortical synapses, the maturation of inhibition in layer 4, the development of orientation selective responses and the formation of ocular dominance columns. SPn removal also alters ocular dominance plasticity during the critical period. Therefore, SPns are a key regulator of cortical development and plasticity. SPns are vulnerable to injury during prenatal stages and might provide a crucial link between brain injury in development and later cognitive malfunction.
Perspectives of γδ T Cells in Tumor Immunology
Authors: Dieter Kabelitz, Daniela Wesch, Wei He
Journal: Cancer Research (2007)

Abstract Subsets of human γδ T cells recognize tumor cell–expressed ligands that are not seen by the T-cell receptor of conventional αβ T cells. Vδ1 T cells recognize MHC class I chain–related molecules A and B and UL-16–binding proteins expressed at variable levels on epithelial tumor cells and some leukemias and lymphomas. In addition, therapeutically used aminobisphosphonates and synthetic phosphoantigens activate Vδ2 T cells, the dominant subset of γδ T cells in human peripheral blood that display strong cytotoxicity towards various epithelial tumors. Intentional activation of γδ T cells in vivo and/or adoptive cell therapy with in vitro expanded γδ T cells holds considerable promise as a novel immunotherapy in certain types of cancer. [Cancer Res 2007;67(1):5–8]
Chronic lymphocytic leukemia: molecular heterogeneity revealed by high-throughput genomics
Authors: Dan A Landau, Catherine J Wu
Journal: Genome Medicine (2013)

Chronic lymphocytic leukemia (CLL) has been consistently at the forefront of genetic research owing to its prevalence and the accessibility of sample material. Recently, genome-wide technologies have been intensively applied to CLL genetics, with remarkable progress. Single nucleotide polymorphism arrays have identified recurring chromosomal aberrations, thereby focusing functional studies on discrete genomic lesions and leading to the first implication of somatic microRNA disruption in cancer. Next-generation sequencing (NGS) has further transformed our understanding of CLL by identifying novel recurrently mutated putative drivers, including the unexpected discovery of somatic mutations affecting spliceosome function. NGS has further enabled in-depth examination of the transcriptional and epigenetic changes in CLL that accompany genetic lesions, and has shed light on how different driver events appear at different stages of disease progression and clonally evolve with relapsed disease. In addition to providing important insights into disease biology, these discoveries have significant translational potential. They enhance prognosis by highlighting specific lesions associated with poor clinical outcomes (for example, driver events such as mutations in the splicing factor subunit gene SF3B1) or with increased clonal heterogeneity (for example, the presence of subclonal driver mutations). Here, we review new genomic discoveries in CLL and discuss their possible implications in the era of precision medicine.
Waking genioglossal electromyogram in sleep apnea patients versus normal controls (a neuromuscular compensatory mechanism).
Authors: W S Mezzanotte, D J Tangel, D P White
Journal: Journal of Clinical Investigation (1992)

Pharyngeal collapse in obstructive sleep apnea patients is likely a product of a sleep-related decrement in pharyngeal dilator muscle activity superimposed upon abnormal airway anatomy. We postulate that during wakefulness, increased pharyngeal dilator muscle activity in apnea patients compensates for diminished airway size thus maintaining patency. We studied the waking genioglossus (GG) electromyogram (EMG) activity in 11 OSA patients and 14 age-matched controls to determine if GG activity is higher in the awake state in apnea patients than controls. To make this determination, we developed a reproducible methodology whereby true maximal GG EMG could be defined and thus basal activity quantitated as a percentage of this maximal value. Therefore, direct comparisons of basal activity between individuals was possible. We observed apnea patients to have significantly greater basal genioglossal activity compared to controls (40.6 +/- 5.6% vs. 12.7 +/- 1.7% of maximum). This difference persisted when size-matched subsets were compared. This augmented GG activity in apnea patients could be reduced with positive airway pressure. We speculate that this neuromuscular compensation present during wakefulness in apnea patients may be lost during sleep leading to airway collapse.
TREATMENT OF TEMPORAL LOBE EPILEPSY
Authors: George A. Ojemann, MD
Journal: Annual Review of Medicine (1997)

▪ Abstract Initial management of patients with temporal lobe epilepsy is with antiepileptic drugs, but these control seizures in only half the patients. Patients refractory to drugs should be evaluated for resective surgery. That evaluation requires identification of a focus of onset of seizures, as well as establishing that the focus is in an area of the brain that can be removed with a low risk of new neurologic deficits. Techniques used in that evaluation, including electroencephalography, imaging, recording from intracranial electrodes, use of the intracarotid amobarbitol perfusion test, and the role of specialized studies such as positron emission tomography, are reviewed, along with the correlation of the findings on that evaluation to the control of seizures after surgery. The different surgical techniques for temporal lobe resections are also reviewed, along with the risks of surgery, particularly to recent memory, and the changes in quality of life following surgery.
Neurobehavioral Effects of Anticonvulsants-Reply
Authors: Michael R. Trimble
Journal: JAMA (1991)

<h3>In Reply.</h3> —The studies quoted in my editorial, in which volunteers were given anticonvulsant drugs and placebo, all were originally analyzed using the same statistical method,<sup>1</sup>in which the influence of initial variation in performance between subjects was eliminated by subtracting scores of pretreatment sessions from those obtained in the experimental sessions. The data on valproate sodium, phenytoin, and carbamazepine were therefore comparable. The important point is that they revealed differences in the profiles of behavioral toxicity between the drugs. The interpretation that these represented biologic differences is further supported by the observations that for phenytoin, significant correlations were found between serum levels and impaired performance on five tests.<sup>2</sup>Such pharmacokinetic and pharmacodynamic associations were not found for valproate or carbamazepine. The attempts by Loring and Meador to reanalyze our volunteer studies are simply not valid. It is an obvious statistical point that data from two totally independent
Histopathological studies on the effects of peroxynitrite on the lungs and trachea of rabbits
Authors: A.A. Farshid, G. Sadeghi-Hashjin, H.R. Ferdowsi
Journal: European Respiratory Journal (2002)

Peroxynitrite (ONOO − ) is the reaction product between nitric oxide and the superoxide anion. It is a biological oxidant and cytotoxic anion, produced in vivo , which might cause inflammation and damage to the lungs. This study was designed to investigate whether direct contact with peroxynitrite could cause pathological changes in the airways. Twenty New Zealand rabbits were divided into four experimental groups. They were anesthetised by intravascular injection of thiopental sodium, and peroxynitrite (0.5 mL of a 10 mM solution) was inoculated intratracheally. At 2 h, 24 h, 48 h, and 72 h postinoculation trachea and lungs were isolated for histopathology. The histopathological observations in the lungs were congestion, serous exudation, infiltration of leukocytes and degeneration, which were found to be time-dependent. Changes were similar at 48 and 72 h. Degenerative changes were not progressive. The changes in the trachea were congestion, oedema, leukocyte infiltration, and degeneration of tracheal epithelium. This study shows that peroxynitrite formation in the respiratory tract induces lung inflammation and degenerative changes.
P2X receptor-mediated visceral hyperalgesia in a rat model of chronic visceral hypersensitivity
Authors: G-Y Xu, M Shenoy, J H Winston, S Mittal, P J Pasricha
Journal: Gut (2008)

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterised by abdominal pain and bloating in association with altered bowel movements. Its pathogenesis and the underlying molecular mechanisms of visceral hyperalgesia remain elusive. Recent studies of somatic and other visceral pain models suggest a role for purinergic signalling mediated by the P2X receptor (P2XR) family.To examine the role of P2XR signalling in the pathogenesis in a rat model of IBS-like visceral hyperalgesia.Visceral hypersensitivity was induced by colonic injection of 0.5% acetic acid (AA) in 10-day-old rats and experiments were conducted at 8 weeks of age. Dorsal root ganglion (DRG) neurons innervating the colon were labelled by injection of DiI (1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate) fluorescence into the colon wall.Visceral hypersensitivity was reversed by TNP-ATP (2'-(or-3')-O-(trinitrophenyl) ATP), a potent P2X1, P2X3 and P2X2/3 receptor antagonist. Rapid application of ATP (20 microM) induced a fast inactivating current in colon-specific DRG neurons from both control and AA-treated rats. There was a twofold increase in the peak ATP responses in neurons from AA-treated rats. These currents were sensitive to TNP-ATP (100 nM). Under current-clamped conditions, ATP evoked a larger membrane depolarisation in neurons from neonatal AA-treated rats than in controls. P2X3R protein expression was significantly enhanced in colon-specific DRGs 8 weeks after neonatal AA treatment.These data suggest that the large enhancement of P2XR expression and function may contribute to the maintenance of visceral hypersensitivity, thus identifying a specific neurobiological target for the treatment of chronic visceral hyperalgesia.