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.     

Evaluation of cellular substrates for antinuclear antibody determinations.

The immunofluorescent technique was employed to evaluate the sensitivity of 10 human and animal cell monolayers and tissue sections as substrates for titering the antinuclear antibody content of serum samples. The highest mean ranks of sensitivity, the relative ability of each substrate to maintain its sensitivity rank when 21 selected positive sera were tested, were achieved by two fibroblast cell lines, baby hamster kidney (BHK 21/C13) and human lung (WI-38), respectively. The least sensitive substrates were commercial rat kidney and liver tissue sections.     

Treatment of malignant gliomas in adults with BCNU plus metronidazole

Summary Twenty-six adult patients with astrocytomas were treated with BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) 180–240 mg/m² 1.V. every 6–9 weeks, with metronidazole 1.5 g/m² p. o. 12 h and 1 h before BCNU and again 6 h and 24 h after BCNU. Of twenty-two evaluable patients, 9 (41%) responded with evidence of reduced tumor size on CT scan, 3 (14%) stabilized and 10 (45%) failed. Patients with no prior chemotherapy or radiotherapy, good performance. status, low grade tumors, and age 50 years had the highest response rates, although differences were not statistically significant. Median survival and duration of response have not been reached with a median follow-up time of ten months. Hematological toxicity was dose-limiting and was probably not augmented by the metronidazole. There was one death from infection that was possibly drug-related. Gastrointestinal toxicity was substantial, and was probably increased by the metronidazole.While the combination of BCNU and metronidazole were tolerable, the response rate seen was no higher than that noted for BCNU alone, and further studies using this dose-schedule are not recommended in astrocytomas.Presented at the 13th International Congress of Chemotherapy, Vienna Austria, August 1983.     

Penetration of teniposide (VM-26) into human intracerebral tumors

Thirty-four consenting patients received VM-26 50–100 mg/m² I.V. before surgical resection of intracerebral tumor, and drug was measured using a high pressure liquid chromatographic technique. Sufficient tumor for analysis was obtained from 29 patients. Brain metastases (13 patients) had higher concentrations of V M-26 than did gliomas (13 patients). Concentrations were comparable in brain metastases and meningiomas (3 patients). Prolonged (24 h) infusion of V M-26 did not appear to result in higher tumor drug concentrations in 5 patients than did rapid (1 h) infusion in 24 patients. Pretreatment with Amphotericin-B 10 mg/m² 12 h and 1 h before VM-26 did not appear to have any effect on VM-26 uptake into 4 intracerebral tumors, although data were limited, and VM-26 concentrations were very high in 1 metastasis. Pretreatment with oral glycerol 500 mg/kg 18 h, 12 h, 6 h, and immediately before I.V. VM-26 may have resulted in increased penetration of VM-26 into 9 tumors, although confirmation is required. Amphotericin-B, glycerol, and operative conditions did not appear to alter VM-26 plasma pharmacokinetics.VM-26 4-demethylepipodophyllotoxin 9-(4-6-O-thenylidene-B-D-glucopyranoside) - VP-16 4-demethylepipodophyllotoxin 9-(4-6-O-ethylidene-B-D-glucopyranoside) Presented in Part at the 74th Annual Meeting of the American Association for Cancer Research, San Diego, California, May 25–28, 183(1).     

Six-year follow-up afterHelicobacter pylori eradication in peptic ulcer disease

Background  

The longterm outlook afterHelicobacter pylori (H. pylori) eradication in peptic ulcer disease is unclear.     

Agreement between proxy- and self-report scores on PROMIS health-related quality of life domains in pediatric burn survivors: a National Institute on Disability,Independent Living,and Rehabilitation Research Burn Model System Study

Quality of Life Research - To examine agreement between pediatric burn survivor self- and caregiver proxy-report on multiple PROMIS domains and examine factors associated with differences between...     

Health state utilities associated with treatment process for oral and injectable GLP-1 receptor agonists for type 2 diabetes

Quality of Life Research - Previous research suggests that treatment process can have an influence on patient preference and health state utilities. This study examined preferences and estimated...     

The changing faces of somatization

The prevalence of several diseases popularized by the media is examined in a group of 50 consecutive patients allegedly suffering from environmental hypersensitivity disorder. Ninety percent of patients reported suffering from at least one other "fashionable" condition, including food allergies that cause psychological symptoms, postinfectious neuromyasthenia, candidiasis hypersensitivity, and severe premenstrual syndrome. Each of the conditions named above was endorsed by at least 50% of patients. Multiple endorsements were common, and the patients' attribution of the etiology of their symptoms varied with time. Physicians must become adept at identifying and managing somatizing patients, and the public must be educated about somatization and provided with reliable information about "fashionable" illnesses.     

Building a strategic technology management program

Strategic technology management decisions are one of the best opportunities for healthcare providers to positively meet clinical needs, patient expectations and competitiveness goals. Technology management must not be treated as an event (annual capital budgeting) but as a well-thought-out, long-range business plan. A strategic technology management team should be formed that includes all the key strategic business areas, plus ad hoc members from the clinical and biomedical engineering areas. Current and future needs should be assessed and the performance of the plan monitored. A plan will help achieve buy-in from clinicians and reduce unwarranted expenditures on technology.