White‐matter lesions along the cholinergic tracts are related to cortical sources of EEG rhythms in amnesic mild cognitive impairment

Does impairment of cholinergic systems represent an important factor in the development of amnesic mild cognitive impairment (aMCI), as a preclinical stage of Alzheimer's disease (AD)? Here we tested the hypothesis that electroencephalographic (EEG) rhythms, known to be modulated by the cholinergic system, may be particularly affected in aMCI patients with lesions along the cholinergic white‐matter tracts. Eyes‐closed resting EEG data were recorded in 28 healthy elderly (Nold) and 57 aMCI patients. Lesions along the cholinergic white‐matter tracts were detected with fluid‐attenuated inversion recovery sequences on magnetic resonance imaging. The estimation of the cholinergic lesion was performed with a validated semi‐automatic algorithm pipeline after registration to a stereotactic template, image integration with stereotactic masks of the cholinergic tracts, and normalization to intracranial volume. The aMCI patients were divided into two groups of high (MCI Ch+; N = 29; MMSE = 26.2) and low cholinergic damage (MCI Ch?; N = 28; MMSE = 26.6). EEG rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha 1 (8–10.5 Hz), alpha 2 (10.5–13 Hz), beta 1 (13–20 Hz), and beta 2 (20–30 Hz). Cortical EEG generators were estimated by LORETA software. As main results, (i) power of occipital, parietal, temporal, and limbic alpha 1 sources was maximum in Nold, intermediate in MCI Ch?, and low in MCI Ch+ patients; (ii) the same trend was true in theta sources. These results are consistent with the hypothesis that damage to the cholinergic system is associated with alterations of EEG sources in aMCI subjects. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.     

Neuromuscular paralysis and recovery in mice injected with botulinum neurotoxins A and C

Botulinum neurotoxin type A (BoNT/A) is commonly used in human therapy. This treatment may induce immunoresistance and preliminary evaluation of other botulinum neurotoxin serotypes suggested botulinum neurotoxin type C (BoNT/C) to be a good alternative to BoNT/A. Here, we have further characterized the biological activities of BoNT/C using a variety of experimental approaches. Muscle paralysis and time of recovery of mouse hind limb injected with BoNT/A or BoNT/C were assayed with the Digit Abduction Scoring assay. The extent and duration of paralysis were similar with the two toxin serotypes. Extensor digitorum longus or tibialis anterior muscles were dissected at times of complete paralysis and of complete recovery. Muscle weight and force were significantly reduced in mice injected with BoNT/A and BoNT/C, and some atrophy persisted for a long time. In BoNT/C-treated junctions, nerve terminal sprouting was prominent, indicating that the capacity to extend the field of innervation is not hampered by BoNT/C. BoNT/C induced a marked decrease in the frequency of miniature endplate potentials and in the amplitude of endplate potentials. 3,4-diaminopyridine reversed the effect of BoNT/C by increasing the amplitude of synchronized endplate potentials. The present study shows an extensive similarity in the biological activities of BoNT/A and BoNT/C, further supporting the suggestion that BoNT/C is a valid alternative to BoNT/A.     

Paediatric intestinal cancer and polyposis due to bi-allelic PMS2 mutations: case series, review and follow-up guidelines

BackgroundBi-allelic germline mutations of one of the DNA mismatch repair genes, so far predominantly found in PMS2, cause constitutional MMR-deficiency syndrome. This rare disorder is characterised by paediatric intestinal cancer and other malignancies. We report the clinical, immunohistochemical and genetic characterisation of four families with bi-allelic germline PMS2 mutations. We present an overview of the published gastrointestinal manifestations of CMMR-D syndrome and propose recommendations for gastro-intestinal screening.Methods and ResultsThe first proband developed a cerebral angiosarcoma at age 2 and two colorectal adenomas at age 7. Genetic testing identified a complete PMS2 gene deletion and a frameshift c.736_741delinsTGTGTGTGAAG (p.Pro246CysfsX3) mutation. In the second family, both the proband and her brother had multiple intestinal adenomas, initially wrongly diagnosed as familial adenomatous polyposis. A splice site c.2174+1G>A, and a missense c.137G>T (p.Ser46Ile) mutation in PMS2 were identified. The third patient was diagnosed with multiple colorectal adenomas at age 11; he developed a high-grade dysplastic colorectal adenocarcinoma at age 21. Two intragenic PMS2 deletions were found. The fourth proband developed a cerebral anaplastic ganglioma at age 9 and a high-grade colerectal dysplastic adenoma at age 10 and carries a homozygous c.2174+1G>A mutation.Tumours of all patients showed microsatellite instability and/or loss of PMS2 expression.ConclusionsOur findings show the association between bi-allelic germline PMS2 mutations and severe childhood-onset gastrointestinal manifestations, and support the notion that patients with early-onset gastrointestinal adenomas and cancer should be investigated for CMMR-D syndrome. We recommend yearly follow-up with colonoscopy from age 6 and simultaneous video-capsule small bowel enteroscopy from age 8.     

In vitro evaluation of the permeation through reconstructed human epidermis of essentials oils from cosmetic formulations

The permeation of essential oils through SkinEthic^® reconstructed human epidermis, (RHE), was studied in vitro to establish a convenient tool to monitor the kinetics of release of active principles from cosmetic formulations. Twelve days old human epidermis held on polycarbonate disks was revitalized by addition of growth medium and incubated at 37 °C in 5% CO₂ atmosphere for five days prior to investigation. A system of six custom designed glass Franz-type diffusion cells were used for the permeation studies at 34 °C. The diffusion kinetic for 8 selected terpenes (camphor, carvone, 1,8-cineole, linalool, menthol, α-thujone, menthone, t-anethole), chosen as analytical markers of a mixture of plant essential oils contained in a cosmetic formulation, was probed by HS/SPME–GC–MS analysis and elaborated according to Fick's first law to obtain skin permeability coefficients (P_S = 1.51, 1.47, 1.36, 0.80, 0.62, 0.40 and 0.14 × 10⁻³ cm/h, respectively). The method proved to be sensitive, simple and reproducible, and RHE represents a convenient model for safety/quality assessment of cosmetic formulations.     

Validating the six-minute walk test as a measure of recovery after elective colon resection surgery

Moriello C, Mayo NE, Feldman L, Carli F. Validating the six-minute walk test as a measure of recovery after elective colon resection surgery.

Objective

To provide evidence for construct and longitudinal validity of the six-minute walk test (6MWT) as a measure of postsurgical recovery.

Design

Data from a randomized clinical trial.

Setting

A major teaching hospital in a Canadian urban city.

Participants

Patients (N=63) undergoing elective colon resection.

Interventions

Not applicable.

Main Outcome Measures

Functional walking capacity was measured using the 6MWT at before surgery and at 3 and 6 weeks after surgery.

Results

At 3 weeks, 26 (41%) patients recovered to baseline or greater on the 6MWT distance, and 37 (59%) were at baseline or better by 6 weeks postdischarge. At all time points, the 6MWT distance correlated with age, the American Society of Anesthesiologists (ASA) score of surgical risk, albumin, the physical function subscale of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and the physical component summary score of the SF-36. Baseline 6MWT distance correlated with postoperative 6MWT recovery, and baseline SF-36 and ASA were associated with postoperative recovery. Patients with intraoperative complications had a clinically relevant lower 6MWT than those without complications at all time points.

Conclusions

This study provides evidence for construct validity and sensitivity to change for the 6MWT as a measure of surgical recovery.     

Thoracic epidural analgesia and the cardiovascular system

Thoracic epidural exerts a remarkable influence on the cardiovascular system (Table 1). With regard to cardiac electrical activity in animal models, TEA was found to lengthen repolarization and to protract the refractory period more at the ventricular site than at the atrium. The atrio-ventricular conduction and refractoriness are also prolonged. Human studies documented a slight impairment in the sensitivity of the baroreflexes sparing the sympathetically mediated responses to various stress if TEA is limited to the first five thoracic vertebrae. Although an overall reduced risk of perioperative dysrhythmias, TEA is not shown to decrease the incidence of postoperative atrial fibrillation.There are contradictory results from animal studies on the effect of TEA on ventricular function. In healthy patients, TEA seems to alter left ventricular contractility and reduce cardiac output, whereas in cardiac surgical patients, the left ventricular global and regional wall motion were better preserved.In a canine model, TEA improves regional blood flow by favoring the endocardium. In patients, TEA has been associated with a reduction of the major determinants of cardiac oxygen consumption without jeopardizing coronary perfusion pressure and even increasing the diameter of stenotic coronary segments. Thus, TEA lessens the severity of experimental acute myocardial ischemic injury and quickens the recovery after brief ischemic insult. In patients, changes in clinical markers of ischemic damage, such as Troponin T and Atrial Natriuretic Peptide, are not consistent, except for Brain Natriuretic Peptide, which is diminished. The overall incidence of myocardial infarction is also reduced.TEA produces functional hypovolemia by inhibiting the vasoconstrictor sympathetic outflow, oreover it interferes with the integrity of renin–angiotensin system, but increments vasopressin plasma concentration. Although TEA causes hypotension, it has a beneficial outcome during hemorrhagic shock.     

Laparoscopic bilateral simultaneous adrenalectomy: results of 11 operations

BACKGROUND: This study was undertaken to evaluate the outcomes of the simultaneous bilateral laparoscopic adrenalectomy. MATERIALS AND METHODS: This was a retrospective study, including 11 patients with bilateral adrenal lesions, affected by Cushing's syndrome (n=2), Cushing's disease (n=6), pheochromocytoma (n=2), and 1 adrenocorticotrophin-hormone-dependent hypercortisolism of unknown origin. RESULTS: Elevan bilateral adrenalectomies were carried out by the laparoscopic approach with no conversions. The operations were performed in 7 cases by the lateral transperitoneal adrenalectomy (LTLA), in 3 by the posterior approach (PRA), and in 1 by the combined approach. The mean size of the masses was 5 cm. (range, 4-13). The average operating time was 245 minutes for LTLA and 218 minutes for PRA (P<0.05). The estimated mean blood loss was 87+/-36 mL (range, 20-150). No patients required transfusions. The mean hospital stay was 5+/-1.8 days (range, 4-7). The mean follow-up was 34 months (range, 2-96). CONCLUSIONS: Our study confirms that the bilateral adrenalectomy by the minimally invasive technique is safe and effective, affording acceptable blood loss and morbidity with a short hospital stay.     

Evaluation of cuffed tracheal tube size predicted using the Khine formula in children

BACKGROUND: The correct size of cuffed endotracheal tube (CET) limits the risk of postintubation tracheal damage. The aim of this study was to compare the size of the CET used in children with the size predicted by the Khine formula [age (years)/4 + 3]. METHODS: After ethical committee approval, 204 children aged 1 day-15 years were included prospectively in the study. The choice of the size of the CET was made at the discretion of the attending anesthesiologist. The main criterion of judgment was the comparison of the leak before and after inflating the cuff at a pressure of 20 cm.H(2)O. Demographic data, tracheal tube size used and that predicted by Khine's formulae and side-effects were recorded. RESULTS: Overall, 21% of the CET were in accordance with the size predicted by the Khine formula. In the remaining patients, 72% were oversized and 7% undersized. In 12 cases, the size of CET chosen initially was modified: for a larger size in eight children and for a smaller size in four others. Six children (2.9%) presented with minor postoperative complications. CONCLUSIONS: Our data suggest that Khine's formula for predicting the appropriate tracheal tube size underestimates optimal size by 0.5 mm. We therefore recommend the use of the following formula: internal diameter of the CET = [age/4 + 3.5] in children >1 year of age which may be applied without increased risk of complications. The rate of tracheal reintubation as well as the detected leaks supports these recommendations.