Integration of target and effector information in human posterior parietal cortex for the planning of action

Recently, using event-related functional MRI (fMRI), we located a bilateral region in the human posterior parietal cortex (retIPS) that topographically represents and updates targets for saccades and pointing movements in eye-centered coordinates. To generate movements, this spatial information must be integrated with the selected effector. We now tested whether the activation in retIPS is dependent on the hand selected. Using 4-T fMRI, we compared the activation produced by movements, using either eyes or the left or right hand, to targets presented either leftward or rightward of central fixation. The majority of the regions activated during saccades were also activated during pointing movements, including occipital, posterior parietal, and premotor cortex. The topographic retIPS region was activated more strongly for saccades than for pointing. The activation associated with pointing was significantly greater when pointing with the unseen hand to targets ipsilateral to the hand. For example, although there was activation in the left retIPS when pointing to targets on the right with the left hand, the activation was significantly greater when using the right hand. The mirror symmetric effect was observed in the right retIPS. Similar hand preferences were observed in a nearby anterior occipital region. This effector specificity is consistent with previous clinical and behavioral studies showing that each hand is more effective in directing movements to targets in ipsilateral visual space. We conclude that not only do these regions code target location, but they also appear to integrate target selection with effector selection.     

Three-dimensional head and upper arm orientations during kinematically redundant movements and at rest

The three rotational degrees of freedom of the head and the upper arm exceed the number needed in a two-dimensional (2-D) facing or pointing task, respectively. Previous studies reported a reduction of the number of degrees of freedom from three to two, with one degree of freedom being a unique function of the other two (Donders' law). This study investigated whether three-dimensional (3-D) orientations of the head and arm are the same at rest and during movement for corresponding pointing or facing directions. Two separate experiments were performed: one focused on head orientations, the other focused on upper arm orientations. We instructed subjects to direct the nose or to point the extended arm in the direction of targets, which appeared in a quasi-random order at 2-s intervals. The head and upper arm orientations at rest were described by a 2-D surface with a scatter less than 3 or 4 degrees, respectively. Both for the arm and the head, orientations started and ended near the 2-D surface, but for a number of the target pairs, the orientations deviated from those predicted by the 2-D surface during movement in a way that was consistent and reproducible for movements between each target pair. For upper arm movements, we often found that deviations of arm orientations from the 2-D surface increased with increasing movement velocity. Such a positive correlation between deviation and movement velocity was not found for head movements. These results clearly indicate violations of Donders' law during movement and argue against several models for movement control found in the literature.     

Renal cell carcinoma with inferior vena cava tumor thrombi

Renal cell carcinoma is a unique neoplasm because of its common propensity to propagate into the renal vein and inferior vena cava (IVC) as tumor thrombus. Historically, the surgical difficulties encountered in removal of these cancers limited the ability of a single institution to obtain experience with large numbers of instances. Between January 1956 and July 1987, 68 patients with renal cell carcinoma extending into the IVC or right atrium underwent radical nephrectomy with vena cava thrombus extraction at the Cleveland Clinic. Twenty-five patients had partial resection of the IVC with reconstruction. Fifteen patients had partial resection and reconstruction of the IVC; however, because of narrowing of the infrarenal IVC, persisting bland thrombus in the proximal IVC or iliac veins or concern regarding postoperative pulmonary emboli, the infrarenal IVC was either ligated or clipped. Seven patients underwent cavectomy with division of the IVC. A right atriotomy was performed upon 14 patients and cardiopulmonary bypass was used in 20 patients, with 17 also having deep hypothermic circulatory arrest. The tumor thrombus was removed intact in 64 per cent of the patients and in multiple small fragments ("piecemeal") in 36 per cent of the patients. The mortality rate was 7 per cent. Survival was examined relative to extent of vena caval thrombus. Patients with extension into the atrium had a significantly worse prognosis than those with other levels of vena caval involvement. Other factors, such as lymph node status, perinephric fat involvement, resection of IVC and intact or "piecemeal" extraction, did not influence the survival rate. Patients with pre-existing metastases preoperatively had an extremely poor survival rate. The techniques now available for surgical resection of all levels of tumor thrombus of the IVC make resection feasible in most patients. In our opinion, the addition of deep hypothermic circulatory arrest has been a significant advance.     

Effect of empiric antiarrhythmic therapy in resuscitated out-of-hospital cardiac arrest victims with coronary artery disease

The effect of empiric antiarrhythmic therapy with quinidine and procainamide on long-term mortality was examined in 209 patients with coronary artery disease resuscitated after out-of-hospital cardiac arrest. The antiarrhythmic agent used was determined by the patient's private physician without knowledge of the study ambulatory electrocardiogram. Of the 209 patients, procainamide was prescribed in 45 (22%), quinidine in 48 (23%) and no antiarrhythmic therapy in 116 (55%). Digoxin therapy was initiated in 101 patients. The 2-year total survival rate for the quinidine, procainamide and nontreated patients was 61, 57 and 71% (p less than 0.05), and for sudden death was 69, 69 and 89% (p less than 0.01), respectively. These observations suggest that empiric antiarrhythmic therapy in survivors of out-of-hospital cardiac arrest did not affect total mortality and was associated with an increased frequency of sudden death.     

Systemic hematologic effects of PEG-rHuMGDF-induced megakaryocyte hyperplasia in mice

PEG-rHuMGDF injected daily in normal mice causes a rapid dose-dependent increase in megakaryocytes and platelets. At the same time that platelet numbers are increased, the mean platelet volume (MPV) and platelet distribution width (PDW) can be either decreased, normal, or increased depending on the dose and time after administration. Thus, PEG-rHuMGDF at a low dose causes decreases in MPV and PDW, MGDF at an intermediate dose causes an initial increase followed by a decrease in MPV and PDW, and PEG-rHuMGDF at higher doses causes an increase in MPV and PDW followed by a gradual normalization of these platelet indices. In addition to the expected thrombocytosis after 7 to 10 days of daily injection of high doses of PEG-rHuMGDF, a transient decrease in peripheral red blood cell numbers and hemoglobin is noted accompanied in the bone marrow by megakaryocytic hyperplasia, myeloid hyperplasia, erythroid and lymphoid hypoplasia, and deposition of a fine network of reticulin fibers. Splenomegaly, an increase in splenic megakaryocytes, and extramedullary hematopoiesis accompany the hematologic changes in the peripheral blood and marrow to complete a spectrum of pathologic features similar to those reported in patients with myelofibrosis and megakaryocyte hyperplasia. However, all the PEG-rHuMGDF-initiated hematopathology including the increase in marrow reticulin is completely and rapidly reversible upon the cessation of administration of PEG-rHuMGDF. Thus, transient hyperplastic proliferation of megakaryocytes does not cause irreversible tissue injury. Furthermore, PEG-rHuMGDF completely ameliorates carboplatin-induced thrombocytopenia at a low-dose that does not cause the hematopathology associated with myelofibrosis.     

Writer's cramp: Increased dorsal premotor activity during intended writing

Simple writer's cramp (WC) is a task‐specific form of dystonia, characterized by abnormal movements and postures of the hand during writing. It is extremely task‐specific, since dystonic symptoms can occur when a patient uses a pencil for writing, but not when it is used for sharpening. Maladaptive plasticity, loss of inhibition, and abnormal sensory processing are important pathophysiological elements of WC. However, it remains unclear how those elements can account for its task‐specificity. We used fMRI to isolate cerebral alterations associated with the task‐specificity of simple WC. Subjects (13 simple WC patients, 20 matched controls) imagined grasping a pencil to either write with it or sharpen it. On each trial, we manipulated the pencil's position and the number of imagined movements, while monitoring variations in motor output with electromyography. We show that simple WC is characterized by abnormally increased activity in the dorsal premotor cortex (PMd) when imagined actions are specifically related to writing. This cerebral effect was independent from the known deficits in dystonia in generating focal motor output and in processing somatosensory feedback. This abnormal activity of the PMd suggests that the task‐specific element of simple WC is primarily due to alterations at the planning level, in the computations that transform a desired action outcome into the motor commands leading to that action. These findings open the way for testing the therapeutic value of interventions that take into account the computational substrate of task‐specificity in simple WC, e.g. modulations of PMd activity during the planning phase of writing. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

EAACI Food Allergy and Anaphylaxis Guidelines: managing patients with food allergy in the community

The European Academy of Allergy and Clinical Immunology (EAACI) Food Allergy and Anaphylaxis Guidelines, managing patients with food allergy (FA) in the community, intend to provide guidance to reduce the risk of accidental allergic reactions to foods in the community. This document is intended to meet the needs of early‐childhood and school settings as well as providers of non‐prepackaged food (e.g., restaurants, bakeries, takeaway, deli counters, and fast‐food outlets) and targets the audience of individuals with FA, their families, patient organizations, the general public, policymakers, and allergists. Food allergy is the most common trigger of anaphylaxis in the community. Providing children and caregivers with comprehensive information on food allergen avoidance and prompt recognition and management of allergic reactions are of the utmost importance. Provision of adrenaline auto‐injector devices and education on how and when to use these are essential components of a comprehensive management plan. Managing patients at risk of anaphylaxis raises many challenges, which are specific to the community. This includes the need to interact with third parties providing food (e.g., school teachers and restaurant staff) to avoid accidental exposure and to help individuals with FA to make safe and appropriate food choices. Education of individuals at risk and their families, their peers, school nurses and teachers as well as restaurant and other food retail staff can reduce the risk of severe/fatal reactions. Increased awareness among policymakers may improve decision‐making on legislation at local and national level.