Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies

BACKGROUND: Idiopathic autonomic neuropathy is a severe, subacute disorder with a presumed autoimmune basis. It is indistinguishable from the subacute autonomic neuropathy that may accompany lung cancer or other tumors. Autoantibodies specific for nicotinic acetylcholine receptors in the autonomic ganglia are potentially pathogenic and may serve as serologic markers of various forms of autoimmune autonomic neuropathy. METHODS: We tested serum from 157 patients with a variety of types of dysautonomia. Immunoprecipitation assays with iodine-125-labeled epibatidine and solubilized human neuroblastoma acetylcholine receptors were used to detect autoantibodies that bound to or blocked ganglionic receptors. RESULTS: Ganglionic-receptor-binding antibodies were found in 19 of 46 patients with idiopathic or paraneoplastic autonomic neuropathy (41 percent), in 6 of 67 patients with postural tachycardia syndrome, idiopathic gastrointestinal dysmotility, or diabetic autonomic neuropathy (9 percent), and in none of 44 patients with other autonomic disorders. High levels of the binding antibodies correlated with more severe autonomic dysfunction (including the presence of tonic pupils). Levels of these antibodies decreased in patients who had clinical improvement. All seven patients with ganglionic-receptor-blocking antibodies had ganglionic-receptor-binding antibodies and had idiopathic or paraneoplastic autonomic neuropathy. CONCLUSIONS: Seropositivity for antibodies that bind to or block ganglionic acetylcholine receptors identifies patients with various forms of autoimmune autonomic neuropathy and distinguishes these disorders from other types of dysautonomia. The positive correlation between high levels of ganglionic-receptor antibodies and the severity of autonomic dysfunction suggests that the antibodies have a pathogenic role in these types of neuropathy.     

住院精神分裂症患者十年前后用药情况对比分析

目的对十年前后精神分裂症患者用药情况的变化进行调查分析.方法对十年前后两个五年段的各500份符合精神分裂症诊断标准的病历进行回顾性调查,并对各项指标进行对比分析.结果两组折算用药剂量经t检验差异无显著性(P>0.05);两组合并用药、合并抗胆碱药及疗效经χ2检验差异有显著性(P<0.01);十年后非典型抗精神病药物氯氮平在临床上的应用比例明显增大并上升为首位.结论十年前后两组抗精神病药的应用发生了明显变化,疗效好、副作用轻的非典型抗精神病药的应用比例明显增加.     

Aggressive Intraosseous Myofibroma of the Maxilla: Report of a Rare Case and Literature Review

Myofibroma (MF) is a benign mesenchymal myofibroblast-derived tumor, which occurs most frequently in children, and rarely affects the maxilla. We reported a case of an aggressive intraosseous lesion found in the maxilla of a 9-year-old female child. Intraorally, the swelling extended from tooth 12 to 16, causing displacement of teeth 13, 14, and 15. Computed tomography revealed a large osteolytic lesion causing thinning and cortical erosion. Microscopically, the lesion showed a proliferation of spindle-shaped cells, with elongated nuclei and eosinophilic cytoplasm, arranged in interlaced fascicles. The immunohistochemical analysis revealed cytoplasmic positivity for α-SMA and HHF-35, and negativity for desmin, laminin, S-100, β-catenin, and CD34. Ki-67 was positive in 8% of tumor cells. The diagnosis was MF. Herein, we describe an additional case of central MF arising in the maxilla, including clinical, imaging, microscopical, and immunohistochemical features, as well as a review of the literature.     

The technique and efficacy of axillary catheter analgesia as an adjunct to distraction elbow arthroplasty: A prospective study

A prospective study was done on 99 consecutive patients who underwent distraction elbow arthroplasty and postoperative continuous passive motion from 1986 to 1992. Postoperative axillary catheter infusion in 73 patients was compared with patient-controlled analgesia-opioid treatment in 26 patients. Group comparisons for analgesia, complications, time to initiation, and tolerance of postoperative continuous passive motion were made. The postoperative axillary catheter infusion group was more comfortable and had better postoperative continuous passive motion compliance than did the patient-controlled analgesia-opioid group. The postoperative axillary catheter infusion group had a 2.7% (2 of 73) incidence of respiratory toxicity. There was an 11.5% (3 of 26) incidence of respiratory depression in the patient-controlled analgesia-opioid group. Final arc range of motion was similar between postoperative axillary catheter infusion and patient-controlled analgesia-opioid groups. The data support the hypothesis that postoperative axillary catheter infusion provides better patient comfort and earlier postoperative continuous passive motion initiation, but they do not show additional improvement in the final arc of motion after distraction elbow arthroplasty as compared with a patient-controlled analgesia-opioid treatment group.     

Shoulder magnetic resonance imaging findings in manual wheelchair users with spinal cord injury

Objective: To investigate the prevalence of rotator cuff and long head of the biceps pathologies in manual wheelchair (MWC) users with spinal cord injury (SCI).Design: Cross-sectional study.Setting: Outpatient clinic at a tertiary medical center.Participants: Forty-four adult MWC users with SCI (36 men and 8 women) with an average age (SD) of 42 (13) years. SCI levels ranged from C6 to L1; complete and incomplete SCI.Outcome Measures: Participants’ demographic and anthropometric information, presence of shoulder pain, Wheelchair User’s Pain Index (WUSPI) scores, and magnetic resonance imaging findings of shoulder pathologies including tendinopathy, tendon tears, and muscle atrophy.Results: Fifty-nine percent of the participants reported some shoulder pain. The prevalence of any tendinopathy across the rotator cuff and the long head of biceps tendon was 98%. The prevalence of tendinopathy in the supraspinatus was 86%, infraspinatus was 91%, subscapularis was 75%, and biceps was 57%. The majority of tendinopathies had mild or moderate severity. The prevalence of any tears was 68%. The prevalence of tendon tears in the supraspinatus was 48%, infraspinatus was 36%, subscapularis was 43%, and biceps was 12%. The majority of the tears were partial-thickness tears. Participants without tendon tears were significantly younger (P < 0.001) and had been wheelchair user for a significantly shorter time (P = 0.005) than those with tendon tears.Conclusion: Mild and moderate shoulder tendinopathy and partial-thickness tendon tears were highly prevalent in MWC users with SCI. Additionally, the findings of this study suggest that strategies for monitoring shoulder pathologies in this population should not be overly reliant on patient-reported pain, but perhaps more concerned with years of wheelchair use and age.     

Machine learning algorithms for activity recognition in ambulant children and adolescents with cerebral palsy

Background

Cerebral palsy (CP) is the most common physical disability among children (2.5 to 3.6 cases per 1000 live births). Inadequate physical activity (PA) is a major problem effecting the health and well-being of children with CP. Practical, yet accurate measures of PA are needed to evaluate the effectiveness of surgical and therapy-based interventions to increase PA. Accelerometer-based motion sensors have become the standard for objectively measuring PA in children and adolescents; however, current methods for estimating physical activity intensity in children with CP are associated with significant error and may dramatically underestimate HPA in children with more severe mobility limitations. Machine learning (ML) models that first classify the PA type and then predict PA intensity or energy expenditure using activity specific regression equations may be more accurate than standalone regression models. However, the feasibility and validity of ML methods has not been explored in youth with CP. Therefore, the purpose of this study was to develop and test ML models for the automatic identification of PA type in ambulant children with CP.

Methods

Twenty two children and adolescents (mean age: 12.8?±?2.9 y) with CP classified at GMFCS Levels I to III completed 7 activity trials while wearing an ActiGraph GT3X+ accelerometer on the hip and wrist. Trials were categorised as sedentary (SED), standing utilitarian movements (SUM), comfortable walking (CW), and brisk walking (BW). Random forest (RF), support vector machine (SVM), and binary decision tree (BDT) classifiers were trained with features extracted from the vector magnitude (VM) of the raw acceleration signal using 10?s non-overlapping windows. Performance was evaluated using leave-one-subject out cross validation.

Results

SVM (82.0–89.0%) and RF (82.6–88.8%) provided significantly better classification accuracy than BDT (76.1–86.2%). Hip (82.7–85.5%) and wrist (76.1–82.6%) classifiers exhibited comparable prediction accuracy, while the combined hip and wrist (86.2–89.0%) classifiers achieved the best overall performance. For all classifiers, recognition accuracy was excellent for SED (94.1–97.9%), good to excellent for SUM (74.0–96.6%) and brisk walking (71.5–86.0%), and modest for comfortable walking (47.6–70.4%). When comfortable and brisk walking were combined into a single walking class, recognition accuracy ranged from 90.3 to 96.5%.

Conclusions

ML methods provided acceptable classification accuracy for detection of a range of activities commonly performed by ambulatory children with CP. The resultant models can help clinicians more effectively monitor bouts of brisk walking in the community. The results indicate that 2-step models that first classify PA type and then predict energy expenditure using activity specific regression equations are worthy of exploration in this patient group.

     

Dual endothelin‐1 receptor antagonism attenuates platelet‐mediated derangements of blood coagulation in Eisenmenger syndrome

Essentials

• Eisenmenger syndrome is characterised by thrombotic and hemorrhagic risks of unclear aetiology.
• Calibrated automated thrombography was used to assess these coagulation derangements.
• Platelet activity supported abnormalities in procoagulant and anticoagulant pathway function.
• Endothelin‐1 antagonism appeared to ameliorate these derangements.

Summary

Aims

The mechanisms underlying the competing thrombotic and hemorrhagic risks in Eisenmenger syndrome are poorly understood. We aimed to characterize derangements of blood coagulation and to assess the effect of dual endothelin‐1 receptor antagonism in modulating hemostasis in this rare disorder.

Methods

In a 10‐month recruitment period at a tertiary cardiology referral center, during which time there were over 14 000 outpatient consultations, consecutive subjects with Eisenmenger syndrome being considered for macitentan therapy (n = 9) and healthy volunteers (n = 9) were recruited. Plasma thrombin generation in platelet‐rich and platelet‐poor plasma was assessed by calibrated automated thrombography prior to and following therapy.

Results

Median peak plasma thrombin generation was higher in platelet‐rich plasma obtained from Eisenmenger syndrome subjects relative to controls (median peak thrombin [25th–75th percentile]: 228.3 [206.5–258.6] nm vs. 169.9 [164.3–215.8] nm ), suggesting a critical mechanistic role for platelets in supporting abnormal hypercoagulability in Eisenmenger syndrome. Abnormal enhanced sensitivity to the anticoagulant activity of activated protein C was also observed in platelet‐rich plasma in Eisenmenger syndrome, suggesting that derangements of platelet activity may influence the activity of anticoagulant pathways in a manner that might promote bleeding in this disease state. Following 6 months of macitentan therapy, attenuations in the derangements in both procoagulant and anticoagulant pathways were observed.

Conclusions

Abnormal platelet activity contributes to derangements in procoagulant and anticoagulant pathways in Eisenmenger syndrome. Therapies targeting the underlying vascular pathology appear to ameliorate these derangements and may represent a novel strategy for the management of the competing prothrombotic and hemorrhagic tendencies in this disorder.