16 research outputs found
Effect of Alemtuzumab (CAMPATH 1-H) in patients with inclusion-body myositis
Sporadic inclusion-body myositis (sIBM) is the most common disabling, adult-onset, inflammatory myopathy histologically characterized by intense inflammation and vacuolar degeneration. In spite of T cell-mediated cytotoxicity and persistent, clonally expanded and antigen-driven endomysial T cells, the disease is resistant to immunotherapies. Alemtuzumab is a humanized monoclonal antibody that causes an immediate depletion or severe reduction of peripheral blood lymphocytes, lasting at least 6 months. We designed a proof-of-principle study to examine if one series of Alemtuzumab infusions in sIBM patients depletes not only peripheral blood lymphocytes but also endomysial T cells and alters the natural course of the disease. Thirteen sIBM patients with established 12-month natural history data received 0.3 mg/kg/day Alemtuzumab for 4 days. The study was powered to capture ≥10% increase strength 6 months after treatment. The primary end-point was disease stabilization compared to natural history, assessed by bi-monthly Quantitative Muscle Strength Testing and Medical Research Council strength measurements. Lymphocytes and T cell subsets were monitored concurrently in the blood and the repeated muscle biopsies. Alterations in the mRNA expression of inflammatory, stressor and degeneration-associated molecules were examined in the repeated biopsies. During a 12-month observation period, the patients’ total strength had declined by a mean of 14.9% based on Quantitative Muscle Strength Testing. Six months after therapy, the overall decline was only 1.9% (P < 0.002), corresponding to a 13% differential gain. Among those patients, four improved by a mean of 10% and six reported improved performance of daily activities. The benefit was more evident by the Medical Research Council scales, which demonstrated a decline in the total scores by 13.8% during the observation period but an improvement by 11.4% (P < 0.001) after 6 months, reaching the level of strength recorded 12 months earlier. Depletion of peripheral blood lymphocytes, including the naive and memory CD8+ cells, was noted 2 weeks after treatment and persisted up to 6 months. The effector CD45RA+CD62L cells, however, started to increase 2 months after therapy and peaked by the 4th month. Repeated muscle biopsies showed reduction of CD3 lymphocytes by a mean of 50% (P < 0.008), most prominent in the improved patients, and reduced mRNA expression of stressor molecules Fas, Mip-1a and αB-crystallin; the mRNA of desmin, a regeneration-associated molecule, increased. This proof-of-principle study provides insights into the pathogenesis of inclusion-body myositis and concludes that in sIBM one series of Alemtuzumab infusions can slow down disease progression up to 6 months, improve the strength of some patients, and reduce endomysial inflammation and stressor molecules. These encouraging results, the first in sIBM, warrant a future study with repeated infusions (Clinical Trials. Gov NCT00079768)
Rising statin use and effect on ischemic stroke outcome
BACKGROUND: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have neuroprotective effects in experimental stroke models and are commonly prescribed in clinical practice. The aim of this study was to determine if patients taking statins before hospital admission for stroke had an improved clinical outcome. METHODS: This was an observational study of 436 patients admitted to the National Institutes of Health Suburban Hospital Stroke Program between July 2000 and December 2002. Self-reported risk factors for stroke were obtained on admission. Stroke severity was determined by the admission National Institutes of Health Stroke Scale score. Good outcome was defined as a Rankin score < 2 at discharge. Statistical analyses used univariate and multivariate logistic regression models. RESULTS: There were 436 patients with a final diagnosis of ischemic stroke; statin data were available for 433 of them. A total of 95/433 (22%) of patients were taking a statin when they were admitted, rising from 16% in 2000 to 26% in 2002. Fifty-one percent of patients taking statins had a good outcome compared to 38% of patients not taking statins (p = 0.03). After adjustment for confounding factors, statin pretreatment was associated with a 2.9 odds (95% CI: 1.2–6.7) of a good outcome at the time of hospital discharge. CONCLUSIONS: The proportion of patients taking statins when they are admitted with stroke is rising rapidly. Statin pretreatment was significantly associated with an improved functional outcome at discharge. This finding could support the early initiation of statin therapy after stroke
A prospective evaluation of the role for intraoperative x-ray in lumbar discectomy. Predictors of incorrect level exposure
Selected neurotrophins, neuropeptides, and cytokines: developmental trajectory and concentrations in neonatal blood of children with autism or Down syndrome
Features on Initial Computed Tomography Scan of Infarcts with a Cardiac Source of Embolism in the Ninds Stroke Data Bank
Background and Purpose: The Lack of Valid Criteria for the Clinical Diagnosis of Cardiogenic Embolism is a Major Problem in Both Patient Care and Research. the Aim of This Study Was to Identify Features on the Initial Computed Tomogram of the Brain that Discriminate between Patient Groups with and Without a Cardiac Source of Embolism. to Gain Insight into the Neuroradiological Features Relevant to the Diagnosis of Cardiac Embolic Stroke, We Studied the Initial Computed Tomogram of the 1,267 Patients with Ischemic Stroke and Such a Scan in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Data Bank. Methods: We Analyzed the Initial Computed Tomographic Data from 1,267 Patients with Ischemic Stroke in the NINDS Stroke Data Bank. based Solely on the Presence of Cardiac Sources of Embolism, We Defined Groups with High (N=244), Medium (N=165), and Low (N=858) Risk for Cardiogenic Embolism and Compared the Features on the Initial Computed Tomogram among These Three Groups. Results: Patients in the High-Risk Group Were Significantly MCirc Likely (P\u3c0.001) to Have Infarcts Involving One Half Lobe or Larger or Infarcts Involving Both Superficial and Deep Structures Than Patients in the Medium- or Low-Risk Groups. in Contrast, Deep Small Infarcts Had a Negative Association (P=0.004) with the Presence of a Cardiac Source of Embolism. There Was No Significant Trend Across Risk Groups in the Percent with Hemorrhagic Infarction, Regardless of Whether Patients with Anticoagulant Use at the Time of the Stroke Were Excluded. Conclusion: Although Some Features of the Initial Computed Tomogram Had Highly Significa Nt Associations with the Presence of a Cardiac Source of Embolism, the Predictive Value of These Features for an Embolic Source Was Low. © 1992 American Heart Association, Inc
99mTc-Sestamibi Scintigraphy to Monitor the Long-Term Efficacy of Enzyme Replacement Therapy on Bone Marrow Infiltration in Patients with Gaucher Disease.
Infarcts with a Cardiac Source of Embolism in the NINDS Stroke Data Bank: Neurologic Examination
To Gain Insight into Neurologic Signs Relevant to the Diagnosis of Cardiogenic Embolism, We Analyzed Data from 1,290 Patients with Cerebral Infarcts in the NINDS Stroke Data Bank. based Solely on the Presence of Potential Cardiac Sources of Embolism, We Divided Patients into Groups of High (N = 250), Medium (N = 167), and Low (N = 873) Risk of a Cardiogenic Mechanism for their Stroke. Diminished Level of Consciousness Was Highly Associated with the Presence of a Cardiac Source of Embolism. of the Four Primarily Cortical Deficits Assessed, Three (Visual Field Abnormalities, Neglect, and Aphasia) Showed a Highly Significant Graded Relationship to the Cardiac Risk Groups. for the Fourth Cortical Deficit (Other Nonlanguage Cognitive Functions), This Relationship Did Not Attain Statistical Significance. Conversely, Hemiparesis Without Sensory or Cortical Deficits Had a Strong Inverse Association to the Presence of a Cardiac Source of Embolism. This Inverse Association Was Weaker for Sensorimotor Strokes and Nonexistent for Pure Sensory Strokes. Although Some Neurologic Findings Had Highly Significant Associations with the Presence of a Cardiac Source of Embolism, their Predictive Value for an Embolic Source Was Low. © 1992 American Academy of Neurology
99mTc-sestamibi scintigraphy to monitor the long-term efficacy of enzyme replacement therapy on bone marrow infiltration in patients with gaucher disease
Assessing the skeletal response to enzyme replacement therapy (ERT) in Gaucher disease (GD) is problematic. We investigated the reliability of 99mTc-sestamibi scintigraphy in monitoring changes in bone marrow involvement induced by ERT. Methods: In 52 GD patients, the efficacy of ERT on bone marrow disease was monitored using at least 2 sequential 99mTc-sestamibi scans; 17 patients were receiving ERT at enrollment, and 35 were ERT-naïve. We elaborated a dose-response model by statistical analysis based on linear mixed models. Results: Patients whose marrow disease improved had received a significantly higher ERT dose per month than patients who did not improve. Significantly more patients reached near-disappearance of marrow disease if their disease burden at enrollment had been lower and the duration of clinical signs shorter. The response of the marrow scintigraphic score wasmore pronounced in ERT-naïve patients. No relevant effect of ERT on marrow disease was observed until platelet count and splenomegaly had improved. Conclusion: Although based on localized evaluation, changes in the 99mTc-sestamibi score closely correlated with the main determinants of ERT, with a definite dose-response relationship. The threshold at which ERT induced any improvement in bone marrow disease was 35-36 U/kg/mo; in ERT-naïve patients, the scintigraphic score declined by 1 unit after ERT at 28 U/kg/mo. COPYRIGHT © 2013 by the Society of Nuclear Medicine and Molecular Imaging, Inc
Infarcts with a Cardiac Source of Embolism in the NINCDS Stroke Data Bank: Historical Features
To Gain Insight into the Historical Features Relevant to the Diagnosis of Cardiac Embolic Strokes, We Studied the 1,290 Patients with Cerebral Infarcts in the NINCDS Stroke Data Bank. based Solely on the Presence of Cardiac Sources of Embolism, We Divided the Patients into Groups of High (N = 250), Medium (N = 166), and Low (N = 874) Risk of a Cardiogenic Mechanism for their Stroke. There Was a Highly Significant Graded Relationship between Increasing Risk of a Cardiac Source and a History, or Presence Of, Systemic Embolism, Abrupt Onset, and Diminished Level of Consciousness at Onset. These Clinical Features May Be Useful for Assessing the Likelihood of a Cardiac Embolic Mechanism in Patients with Cerebral Infarcts. © 1990 American Academy of Neurology