The presence and origin of autoantibodies against α4 and α7 nicotinic acetylcholine receptors in the human blood: possible relevance to Alzheimer's pathology

Alzheimer's disease (AD) is characterized by a loss of α4β2 and α7 nicotinic acetylcholine receptors (nAChRs) in the brain and severe memory impairments. Previously, we found that antibodies elicited against extracellular domain of α7 nAChR subunit decreased the number of α7 nAChRs in the brains of mice and impaired episodic memory. Here we show that antibodies capable to bind α7(1-208) are present in the blood of both healthy humans and AD patients. In healthy individuals, their capacity to compete with [(125)-I]-α-bungarotoxin for the binding to α7(1-208) increased with age. The level of such antibodies was significantly elevated in children with severe form of obstructive bronchitis and in mice injected with Lewis lung carcinoma cells expressing both α4β2 and α7 nAChRs. Elevated antibody levels were accompanied with decreased surface nAChRs on the blood lymphocytes of children and of mice immunized with α7(1-208). Among AD patients, the level of α7 nAChR-specific antibodies was significantly larger in people 62.5 ± 1.5 years old with moderate or severe AD stages (15.2 ± 1.3 MMSE scores) compared to those of 76 ± 1.5 years old with the mild (22.7 ± 0.1 MMSE scores) AD stage. We concluded that α7(1-208) nAChR-specific antibodies found in the human blood are formed as a result of common infections accompanied with the destruction of respiratory epithelium. Elevated blood plasma levels of α7(1-208) nAChR-specific antibodies are characteristic for the early-onset AD and, therefore, are suggested as one of the risk factors for the development of this form of the disease.     

Alternative and Complementary Treatments for Metabolic Syndrome

Metabolic syndrome is defined by a cluster of cardiovascular disease risk factors that are associated with insulin resistance. In recent years, a number of innovative nutritional strategies have been proposed as safe alternative treatments to reduce the morbidity as well as the cost of treating metabolic syndrome. Of these, dietary supplementation with chromium picolinate or cinnamon extract has been studied most extensively. These interventions may attenuate insulin resistance and reduce the cardiovascular risk factors that together comprise the metabolic syndrome. However, more clinical trials are needed to determine the dose and duration of such treatments to make specific recommendations for populations with metabolic syndrome.     

A new predictive model for continuous positive airway pressure in the treatment of obstructive sleep apnea

Background

Numerous mathematical formulas have been developed to determine continuous positive airway pressure (CPAP) without an in-laboratory titration study. Recent studies have shown that style of CPAP mask can affect the optimal pressure requirement. However, none of the current models take mask style into account. Therefore, the goal of this study was to develop new predictive models of CPAP that take into account the style of mask interface.

Methods

Data from 200 subjects with attended CPAP titrations during overnight polysomnograms using nasal masks and 132 subjects using oronasal masks were randomized and split into either a model development or validation group. Predictive models were then created in each model development group and the accuracy of the models was then tested in the model validation groups.

Results

The correlation between our new oronasal model and laboratory determined optimal CPAP was significant, r = 0.61, p < 0.001. Our nasal formula was also significantly related to laboratory determined optimal CPAP, r = 0.35, p < 0.001. The oronasal model created in our study significantly outperformed the original CPAP predictive model developed by Miljeteig and Hoffstein, z = 1.99, p < 0.05. The predictive performance of our new nasal model did not differ significantly from Miljeteig and Hoffstein’s original model, z = ?0.16, p < 0.90. The best predictors for the nasal mask group were AHI, lowest SaO2, and neck size, whereas the top predictors in the oronasal group were AHI and lowest SaO2.

Conclusion

Our data show that predictive models of CPAP that take into account mask style can significantly improve the formula’s accuracy. Most of the past models likely focused on model development with nasal masks (mask style used for model development was not typically reported in previous investigations) and are not well suited for patients using an oronasal interface. Our new oronasal CPAP prediction equation produced significantly improved performance compared to the well-known Miljeteig and Hoffstein formula in patients titrated on CPAP with an oronasal mask and was also significantly related to laboratory determined optimal CPAP.

     

Validation study for use of an algorithm for the diagnosis of deep vein thrombosis in out-patients

In a previous study we demonstrated that the use of an algorithm can decrease unnecessary emergency venous duplex evaluations (VDE) in out-patients and increase the percentage of positive yields. The present study was undertaken to validate the safety of following such an algorithm. During a six month period we suspended the application of the algorithm and performed VDE on all requests for out-patients. A total of 94 requests were received from the Emergency Department and all were honored. Of the 94 out-patients who underwent emergency VDE for deep vein thrombosis (DVT), eleven were positive for DVT (11.8%) and 83 were negative (88.2%). Had the algorithm been applied for patients screening, all the 11 positive studies would have gone to emergency VDE (100%). 10 patients had proximal DVT and 1 had isolated peroneal DVT. The application of an algorithm for inclusion/exclusion of out-patients for emergency VDE is a safe and effective means for limiting emergency access to the non-invasive vascular laboratory.Presented in part at the 42^nd Annual World Congress International College of Angiology, San Diego, California, June 2000.     

Application of the orbito-cranial approach in pediatric neurosurgery

OBJECTIVE: This study evaluates the benefits of and indications for the orbito-cranial approach (OCA) in pediatric patients. METHODS AND RESULTS: The authors report their recent experience of using the OCA in 9 pediatric patients, 6 boys and 3 girls. The patients' ages ranged from 3 to 17 years (mean 9.6+/-5.16 years). Follow-up periods varied between 6 and 21 months (mean 12.6+/-5.9 months). Five patients were operated on for craniopharyngiomas, 2 for chiasmatic-hypothalamic astrocytomas, 1 for a recurrent hypothalamic gangliocytoma, and 1 for a hypothalamic hamartoma. In 7 cases a neuronavigation system (BrainLab) was utilized. The lesions were removed totally in 5 patients, near-totally in 1, subtotally in 2, and partially in 1 patient. An average increase of 30% in the area of vertical exposure significantly decreased the need for brain retraction. There was no mortality in this series. The only complications connected with the surgical approach were transient subgaleal cerebro-spinal fluid collections in 7 of 9 children and a subgaleal-peritoneal shunt placement in another patient. CONCLUSIONS: Our experience with this series of patients suggests that the OCA is as safe and beneficial in pediatric patients as it is in adults. It facilitates tumor removal by providing shorter access to and better exposure of the suprasellar area, thereby minimizing brain retraction.     

Sarcoma botryoides: MRI findings in two patients

We report the magentic resonance (MR) findings of sarcoma botryoides in two young pediatric patients with this tumor. There has been very little literature regarding the MR appearance of this subtype of rhabdomyosarcoma. In both cases, the tumor was vaginal in origin, as would be expected in this age group. We found areas of bright T2 signal within these lesions, intermixed with areas of lower T2‐signal tissue, which showed considerable enhancement. These imaging findings are reflective of the histologic architecture of these lesions, which are composed of separate myxoid and subepithelial cellular zones. In both cases, the extent of the tumor and lack of local invasion or metastatic disease were confirmed surgically, and both patients have undergone multiple postoperative MR studies that have shown lack of residual, recurrent, or metastatic disease. J. Magn. Reson. Imaging 2009;29:708–712. © 2009 Wiley‐Liss, Inc.     

Pharmacokinetics of CIPRODEX otic in pediatric and adolescent patients

OBJECTIVE: Describe the pharmacokinetics of ciprofloxacin and dexamethasone after administration of CIPRODEX Otic Suspension (CIP/DEX) into the middle ears of children. DESIGN: Open-label, single-dose, pharmacokinetic studies, administering four drops of CIP/DEX instilled into each middle ear through the tympanostomy tubes immediately following tube placement. Blood was collected for 6h and analyzed for ciprofloxacin and dexamethasone concentrations using a validated liquid chromatography and tandem mass spectrometry (LC/MS/MS) method. SETTING: The study was conducted through a referral pediatric otolaryngology practice with actual surgical procedures performed in an ambulatory care center. PATIENTS: Twenty-five randomly selected patients, 1-14 years of age (mean age, 5 years), receiving tympanostomy tubes. RESULTS: Peak ciprofloxacin plasma levels were observed at about 1h, with a mean C(max) of 1.33+/-0.96 ng/mL (range <0.5-3.45 ng/mL) and an estimated half-life of 3.0+/-1.2h. Peak dexamethasone plasma levels were observed within 2h with a mean C(max) of 0.90+/-1.04 ng/mL (range <0.05-5.10 ng/mL) and an estimated half-life of 3.9+/-2.9h. CONCLUSION: These results demonstrated low systemic exposure of ciprofloxacin and dexamethasone following topical otic administration in pediatric patients.     

Effects of single- and multiday ozone exposures on respiratory function in active normal children

Ventilatory function was measured twice daily on 46 healthy children aged 8-14 years on at least 7 days for each child during a 4-week period at a northwestern New Jersey residential summer camp in 1988. The highest 1-hr O3 concentration was 150 ppb, while the highest 12-hr H+ concentration (as H2SO4) was 18.6 micrograms/m3. The highest temperature-humidity index was 81 degrees F. The regressions of FVC, FEV1, FEF25-75, and PEFR on O3 in the hour preceding the afternoon function measurements yielded slopes essentially the same as those measured on other children at the same camp in 1984. Regressions of the changes in function between the late morning and late afternoon function measurements on average O3 concentration between them produced significant, but somewhat smaller effects, while regressions of morning function on O3 during the previous day indicated small but still significant effects. There were no significant correlations with other measured environmental variables including H+. Based on the results of this study and similar previous studies, we conclude that O3 exposures in ambient air produce greater lung function deficits in active young people in natural settings then does pure O3 in controlled chamber exposure studies because of: (1) longer exposures; (2) potentiation by other factors in the ambient exposures; (3) the persistence of effects from prior day's exposures; and (4) the persistence of a transient response associated with the daily peak of exposure. It follows that projections of likely effects in the real world from controlled chamber exposure studies should either have a large margin of safety, or the judgment of the extent of effects likely to occur among populations should be based directly on the effects observed in field studies.