A case of thalamic syndrome: somatosensory influences on visual orientation

The ability to set a straight line to the perceived gravitational vertical (subjective visual vertical, SVV) was investigated in a 21 year old woman with long standing left hemihypaesthesia due to a posterior thalamic infarct. The putative structures involved were the somatosensory and vestibular thalamus (VPL, VPM) and associative (pulvinar) thalamus. The SVV was normal when seated upright. When lying on her right side, line settings deviated about 17 degrees to the right, which is the normal A-effect. When lying on the hypaesthetic side the mean SVV remained close to true vertical-that is, the A-effect was absent, and there was a large increase in variability of the SVV settings. The findings support the view that the body tilt-induced bias of the SVV (A-effect) is largely mediated by somatosensory afferents. The finding that the A-effect was absent only when lying on the hypaesthetic side suggests that, during body tilt, the somatosensory system participates in visuogravitational orientation.     

A humoral response to oligodendrocyte-specific protein in MS: a potential molecular mimic.

OBJECTIVE: To determine the antibody response to oligodendrocyte-specific protein (OSP) in patients with MS. BACKGROUND: OSP is a recently identified CNS-specific myelin protein that is abundant and therefore a candidate autoantigen in MS. METHODS: The presence of anti-OSP antibodies was determined using Western blot analysis, peptide blots, and ELISA in patients with MS and in other neurologic and normal control subjects. RESULTS: Using Western blot analysis, seven patients with relapsing-remitting MS (RRMS) were found to contain anti-OSP antibodies in their CSF that were not present in control subjects. Peptide mapping determined that the antibody response was directed to a seven aa peptide (OSP 114-120), which has 71% homology with several common pathogenic proteins. Using OSP 114-120 as antigen, ELISAs were performed on CSF from 85 MS and 51 control patients. Eighty percent of the samples from RRMS patients followed at the University of California at Los Angeles had an ELISA reading above 0.55 optical density units, whereas all 20 control CSF samples had values less than 0.55 U. Similar results were found in specimens from an outside research bank. ELISAs performed on CSF using homologous viral peptides as antigen showed a close correlation with anti-OSP 114-120 ELISA readings, and in some, the readings were higher than those using OSP peptides. CONCLUSIONS: There is a specific humoral response directed against a region of OSP in RRMS patients that cross-reacts with several common viral peptides. This suggests a possible role for molecular mimicry in the development of MS.     

Synthesis of fully asymmetric diketopyrrolopyrrole derivatives

Diaryl-diketopyrrolopyrroles (DPP) are a widely studied class of chromophore that possesses unique properties which have been of great interest for use in conjugated polymers and as small molecules in optoelectronic devices. While previously only partially asymmetric DPP derivatives have been reported, here a novel methodology towards fully asymmetric DPP derivatives is demonstrated via the synthesis and condensation of novel alkylated thienyl pyrrolinone esters with aromatic nitriles followed by N-alkylation. Two fully asymmetric DPP structural isomers T-DPP-P and P-DPP-T were synthesised demonstrating the full customizability of the DPP core. A further two fully asymmetric DPP derivatives incorporating an ethylene glycol chain and a furan moiety were also synthesised, demonstrating the scope of this powerful methodology and it''s potential to largely broaden the library of available DPP derivatives.

Diaryl-diketopyrrolopyrroles (DPP) are a widely studied class of chromophore that possesses unique properties which have been of great interest for use in conjugated polymers and as small molecules in optoelectronic devices.     

Characterization of edible marijuana product exposures reported to United States poison centers

Context: Edible marijuana products are sold as brownies, cookies, and candies, which may be indistinguishable from counterparts without marijuana and are palatable to children and adults. The consumption of an entire product containing multiple dose-units may result in overdose.

Objective: To characterize edible marijuana exposures reported to US poison centers with subgroup analysis by age.

Methods: We analyzed single substance, human exposure calls coded to marijuana brownies, candies, cookies, beverages, or other foods reported to the National Poison Data System from January 2013 to December 2015. Calls were analyzed by state, age, gender, exposure route, clinical effect, therapies, and level of healthcare facility utilization.

Results: Four-hundred and thirty calls were reported: Colorado (N?=?166, 1.05/100,000 population/year) and Washington (96, 0.46) yielded the highest number of exposures. Three hundred and eighty-one (91%) calls occurred in states with decriminalized medical/recreational marijuana. The number of calls increased every year of the study. The most common age groups were: ≤5 years (N?=?109, 0.15/100,000 population/year) and 13–19 (78, 0.09). The most frequent clinical effects were drowsiness/lethargy (N?=?118, percentage?=?43%), tachycardia (84, 31%), agitated/irritable (37, 14%), and confusion (37, 14%). Children ≤5 years have more drowsiness/lethargy, ataxia, and red eye/conjunctivitis. No deaths were reported. The most common therapies administered were intravenous fluids (85, 20%), dilute/irrigate/wash (48, 11 %), and benzodiazepines (47, 11%). Three patients (ages 4, 10, and 57 years) received intubation. 97 (23%), 217 (50%), and 12 (3%) calls were managed at home, treated/released, admitted to a critical care unit, respectively.

Discussion: Although most clinical effects are minor, ventilatory support may be necessary for children and adults. We speculate the increasing exposures may be related to a combination of delayed absorption kinetics of Δ9-tetrahydrocannablnol, lagging packaging regulations, increased accessibility in decriminalized states, and increased familiarity of poison center specialists with edible product codes.

Conclusions: Edible marijuana exposures are increasing and may lead to severe respiratory depression.     

Horizontal ocular vergence and the three-dimensional response to whole-body roll motion

We evaluated the human binocular response to roll motion in the dark and during visual fixation with horizontal convergence. Six normal human subjects were exposed to manually driven, whole-body rotation about an earth-vertical, naso-occipital axis, under two conditions: (I) oscillation at 0.4 Hz (peak velocity 69+/-3.8 degree/s) in the dark, and whilst fixating an axial light-emitting diode at 48 cm ('near') and at 206 cm ('far'); (II) constant velocity rotation (56.5+/-3.1 degree/s) for 40 s, clockwise and counter-clockwise, in the dark, and sudden stops. Eye and head movements were monitored using scleral search coils. In head-fixed, angular velocity coordinates roll motion always evoked conjugate ocular torsion, with small conjugate horizontal and disconjugate vertical components. The resultant binocular eye responses were rotations about convergent axes. During oscillation with target fixation the convergence of the rotation axes was larger than that predicted by target geometry, producing disconjugate oscillations of vertical gaze about the target ('skewing'). Fast-phase eye movements were primarily resetting rotations about the same convergent rotation axes as the slow phases, but the small vertical velocity components had oscillatory, asymmetrical profiles. In response to velocity steps the slow-phase eye velocity decayed exponentially with time constants of 4.5+/-1.5 s for the torsional component and 5.8+/-1.9 s for the 'vertical vergence' component (right eye-left eye recordings). We conclude that in normal human subjects dynamic vertical canal stimulation with horizontal gaze convergence evokes rotation of the eyes about convergent axes and a small skewing of the eyes.     

Cholestasis and hepatic metastases: a factor contributing to extreme elevations of carcinoembryonic antigen

Records of 19 autopsied patients with metastatic carcinoma were studied to elucidate the contribution to the elevation of antemortem plasma carcinoembryonic antigen (CEA) levels (range, 5.9--136,000 ng/ml) of 1) liver pathology and dysfunction, 2) tumor morphology and CEA content, and 3) tumor spread and location. Liver function tests and plasma CEA recorded within 8 weeks of death, autopsy records of tumor spread, liver weight (as an index of liver tumor mass), and histologic sections were reviewed. Tissue CEA was demonstrated in 15 patients by an immunoperoxidase method. Cholestasis was seen in histologic sections of tissue from 8 of 10 patients, and elevated bilirubin was seen in 7 of 10 patients with hepatic metastases and CEA levels greater than 1,000 ng/ml In contrast, histologically observed cholestasis and elevated bilirubin were seen in only 1 of 8 patients with CEA less than 500 ng/ml. A significant correlation was found between the plasma CEA level and histologically observed cholestasis (P less than 0.01). Serum bilirubin also correlated significantly (P less than 0.01), but alkaline phosphatase did not. Liver weight (tumor mass) showed a positive correlation with cholestasis (P less than 0.01) but not with circulating CEA. Markedly elevated plasma CEA levels (greater than 1,000 ng/ml) seen preterminally may partially reflect impaired excretion of CEA by the hepatobiliary system rather than, or in addition to, preterminal increase in CEA-producing tumor.