Asymmetry of the occipital condyles: a computer-assisted analysis.

OBJECTIVE: To ascertain the incidence of asymmetry of the occipital condyles. The a priori hypothesis of symmetry (which is pervasive both in the determination of "subluxation" and in the means chosen for correction) was tested. DESIGN: Data set design was used with a convenience sample. The condyles were chosen for convenience of visualization from plain film radiographs. The study was retrospectively designed, albeit with prospective implications for analytic investigation. SETTING: The research department of Cleveland Chiropractic College, Kansas City, MO. PATIENTS OR OTHER PARTICIPANTS: One hundred fifty-one submentovertex radiographs were examined using a computer-assisted digitizer. The radiographs were randomly obtained from the patient files of two doctors of chiropractic who routinely use this type of radiograph in their patient analysis. INTERVENTIONS: The study was a side-to-side comparison of the condyles, which were subject to neither intervention nor change. MAIN OUTCOME MEASURES: Surface area of left and right condyles for 151 examined pairs. RESULTS: Analysis with Pearson's correlation coefficient implied a lack of symmetry between condyles (r = .37; p < .0001). The scatterplot revealed values widely dispersed about the regression line, and the standard error of the estimate was 36.7. CONCLUSION: The data suggest that the underlying premise of symmetry in chiropractic analysis needs to be reexamined.     

Topological analyses in APP/PS1 mice reveal that astrocytes do not migrate to amyloid-β plaques

Although the clustering of GFAP immunopositive astrocytes around amyloid-β plaques in Alzheimer’s disease has led to the widespread assumption that plaques attract astrocytes, recent studies suggest that astrocytes stay put in injury. Here we reexamine astrocyte migration to plaques, using quantitative spatial analysis and computer modeling to investigate the topology of astrocytes in 3D images obtained by two-photon microscopy of living APP/PS1 mice and WT littermates. In WT mice, cortical astrocyte topology fits a model in which a liquid of hard spheres exclude each other in a confined space. Plaques do not disturb this arrangement except at very large plaque loads, but, locally, cause subtle outward shifts of the astrocytes located in three tiers around plaques. These data suggest that astrocytes respond to plaque-induced neuropil injury primarily by changing phenotype, and hence function, rather than location.The role of astrocytes in amyloid-β deposition during Alzheimer’s disease—whether they prevent, potentiate, or have no effect on plaque formation—remains unknown. The peer-reviewed literature indicates that it is widely believed that amyloid-β plaques attract astrocytes, with statements such as “astrocytes migrate to amyloid-β plaques,” “amyloid-β plaques recruit astrocytes,” and variations thereof frequently appearing. The idea that astrocytes are attracted to plaques is an extension of the notion that astrocytes migrate to zones of injury (1, 2) and is mostly based on the immunohistochemical observation that amyloid-β deposits are typically surrounded by concentric rings of “reactive astrocytes,” defined by increased GFAP immunoreactivity and hypertrophy. However, recent studies question the capacity of astrocytes to move (3, 4). These suggest instead that astrocytes may be restricted to their birthplace (3), which in the neocortex seems to be within neuronal columns derived from radial glia (5). Recent stereological assessments of astrocytes in Alzheimer’s disease suggest that their most prominent change is phenotypic (i.e., GFAP immunoreactivity and hypertrophy) rather than proliferative (6). Thus, doubts have risen over the recruitment of astrocytes by plaques.Using the APPSwe/PS1dE9 (APP/PS1) double-transgenic mouse model of Alzheimer’s disease, we revisited the idea that astrocytes migrate to plaques. Our approach improved on the traditional GFAP immunohistochemical analysis postmortem in three ways. First, the analyses were performed in 3D reconstructions of images captured in vivo through cranial windows by two-photon microscopy. These materials are superior to sectioned specimens from fixed brains because they preserve true spatial relationships in 3D to great depths (up to 200 μm from the cortical surface), providing accurate positional information for each astrocyte. Second, astrocytes were labeled with sulforhodamine 101 (SR101), a selective fluorescent marker of reactive and nonreactive astrocytes (7), thus avoiding the bias of identifying only a subset of astrocytes as with GFAP. Third, astrocyte and plaque interactions were examined with two mathematical objects: the pair-correlation function g(r) and the characteristic length (L_C) of Voronoi cells. These combine global and plaque-centered perspectives and allow for quantitative comparisons to be made. The g(r) function was used to assess astrocyte topology, and we examined the effect of plaques on several tiers of astrocytes using L_C, a very sensitive approach that reveals changes in object position from the redistribution of astrocyte-associated domains approximated by Voronoi tessellation.Finally, we used simulations to help interpret astrocyte-to-astrocyte and astrocyte-to-plaque interactions and to investigate the effect on astrocyte topology of plaque loads in the upper limit of what could be present in older human patients.Using a statistical physics approach, we found that astrocytes resemble a liquid of objects of different sizes contained in a constant volume. This arrangement is globally unaltered by plaques except at the heaviest plaque loads.     

Fluoxetine in orthostatic hypotension of Parkinson's disease: A clinical and experimental pilot study

Summary— Recent clinical studies have reported a beneficial effect of fluoxetine, a serotonin reuptake inhibitor, in patients with severe refractory orthostatic hypotension. The present study was undertaken to investigate the effect of fluoxetine in orthostatic hypotension occurring during Parkinson's disease on both blood pressure values and number of clinical symptoms during orthostatic procedure evaluated using a validated clinical rating scale. In a pilot study performed in fourteen patients with idiopathic Parkinson's disease plus orthostatic hypotension, fluoxetine hydrochloride (20 mg orally daily during one month) significantly reduced the fall in systolic blood pressure [-33 ± 21 (SD) mmHg before fluoxetine vs -22 ± 19 mmHg after fluoxetine, P = 0.03] elicited by standing without modifying heart rate. The drug also significantly reduced the number of postural symptoms occurring during the orthostatic procedure [2.9 ± 1.5 (SD) before fluoxetine vs 1.2 ± 1.3 after fluoxetine, P = 0.006]. A similar pattern of response was obtained in an experimental model of neurogenic orthostatic hypotension obtained in chronically sino-aortic denervated dogs submitted to an 80° head-up tilt test procedure under chloralose anaesthesia. Fluoxetine did not change plasma noradrenaline levels. This pilot study suggests a slight but clinically significant effect of fluoxetine on both hemodynamic parameters and clinical symptoms in parkinsonian patients suffering from orthostatic hypotension.     

Transthecal digital block.

Transthecal digital nerve block is performed by a palmar percutaneous injection of local anaesthetic into the flexor tendon sheath. Total analgesia of the digit is achieved rapidly. This technique was carried out on 46 patients in the accident and emergency department. Successful anaesthesia was obtained in 45 patients. There were no complications.