The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Such studies have been greatly facilitated by the introduction of selective cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and transport, as well as mice deficient in cannabinoid receptors or the endocannabinoid-degrading enzyme fatty acid amidohydrolase. In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson9s and Huntington9s disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few. An impediment to the development of cannabinoid medications has been the socially unacceptable psychoactive properties of plant-derived or synthetic agonists, mediated by CB 1 receptors. However, this problem does not arise when the therapeutic aim is achieved by treatment with a CB 1 receptor antagonist, such as in obesity, and may also be absent when the action of endocannabinoids is enhanced indirectly through blocking their metabolism or transport. The use of selective CB 2 receptor agonists, which lack psychoactive properties, could represent another promising avenue for certain conditions. The abuse potential of plant-derived cannabinoids may also be limited through the use of preparations with controlled composition and the careful selection of dose and route of administration. The growing number of preclinical studies and clinical trials with compounds that modulate the endocannabinoid system will probably result in novel therapeutic approaches in a number of diseases for which current treatments do not fully address the patients9 need. Here, we provide a comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy.

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The Endocannabinoid System as an Emerging Target of Pharmacotherapy

Newness and distinctiveness is claimed in the features of ornamentation as shown inside the broken line circle in the accompanying representation.

Display screen or portion thereof with graphical user interface

A surgical instrument can comprise a channel configured to support a staple cartridge and, in addition, an anvil pivotable between open and closed positions relative to the channel. The surgical instrument can further comprise a cutting member configured to incise tissue positioned captured between the staple cartridge and the anvil and, in addition, means for stopping the cutting member prior to a distal end datum, wherein the distal end datum can be defined by the distal-most staple cavity in the staple cartridge. In such embodiments, the incision within the tissue may not extend beyond the portion of the tissue that has been stapled.

Surgical stapling instrument with an articulatable end effector

A surgical severing and stapling instrument, suitable for laparoscopic and endoscopic clinical procedures, clamps tissue within an end effector of an elongate channel pivotally opposed by an anvil. An E-beam firing bar moves distally through the clamped end effector to sever tissue and to drive staples on each side of the cut. The E-beam firing bar affirmatively spaces the anvil from the elongate channel to assure properly formed closed staples, especially when an amount of tissue is clamped that is inadequate to space the end effector. In particular, an upper pin of the firing bar longitudinally moves through an anvil slot and a channel slot is captured between a lower cap and a middle pin of the firing bar to assure a minimum spacing. Forming the E-beam from a thickened distal portion and a thinned proximal strip enhances manufacturability and facilitates use in such articulating surgical instruments.

Articulating surgical stapling instrument incorporating a two-piece e-beam firing mechanism

A surgical instrument including a handle assembly, a first endoscopic portion, a motor, and a first end effector is disclosed. The first endoscopic portion is selectively connectable to a distal portion of the handle assembly and defines a longitudinal axis. The first endoscopic portion includes a housing adjacent its proximal portion and includes an actuation member. The motor is disposed in mechanical cooperation with the housing of the first endoscopic portion and is operatively connected to the actuation member for moving the actuation member substantially along the longitudinal axis. The first end effector is selectively connectable to a distal portion of the first endoscopic portion and is configured to perform a first stapling function.

Powered surgical instrument

A robot system for use in surgical procedures has two movable arms each carried on a wheeled base with each arm having a six of degrees of freedom of movement and an end effector which can be rolled about its axis and an actuator which can slide along the axis for operating different tools adapted to be supported by the effector. Each end effector including optical force sensors for detecting forces applied to the tool by engagement with the part of the patient. A microscope is located at a position for viewing the part of the patient. The position of the tool tip can be digitized relative to fiducial markers visible in an MRI experiment. The workstation and control system has a pair of hand-controllers simultaneously manipulated by an operator to control movement of a respective one or both of the arms. The image from the microscope is displayed on a monitor in 2D and stereoscopically on a microscope viewer. A second MRI display shows an image of the part of the patient the real-time location of the tool. The robot is MRI compatible and can be configured to operate within a closed magnet bore. The arms are driven about vertical and horizontal axes by piezoelectric motors.

Microsurgical robot system

The incidence of intracranial meningioma in Manitoba, Canada, was reviewed from 1980 through 1987. During that time, 193 tumors were diagnosed, with a male:female ratio of 1:2. This occurrence corresponded to crude incidence rates of 2.3/100,000 for all meningiomas and 0.17/100,000 for malignant meningiomas. Among malignant meningiomas, the male:female ratio was 1:1. The age-specific annual incidence rate increased with age up to the eighth decade where it peaked at 8.4/100,000. The distribution of histopathological subtypes was: 74 meningotheliomatous (38%), 64 transitional (33%), 14 malignant (7%), 14 fibroblastic (7%), seven psammomatous (4%), four angioblastic (2%), and 16 unknown (8%). The diagnosis of malignant meningioma was based on the World Health Organization criteria, with only Grade III and IV tumors included in this subtype. Clinical features did not allow for differentiation of benign from malignant neoplasms. Individuals with malignant tumors were, however, more likely to suffer paresis (50%) and less likely to be without deficit (14%) than their benign counterparts. The radiographic appearance of "mushrooming" was observed only in patients with malignant meningioma. All malignant tumors showed evidence of peritumoral edema; however, none exhibited calcification. During the 8-year study interval, the tumor recurred in 10 (71%) of the 14 patients with malignant meningioma. Tumor recurrence was accompanied by dedifferentiation from a more benign histology in four patients (2% of the total material).

Incidence and clinicopathological features of meningioma

Object. The authors' goal was to place a mobile, 1.5-tesla magnetic resonance (MR) imaging system into a neurosurgical operating room without adversely affecting established neurosurgical management. The system would help to plan accurate surgical corridors, confirm the accomplishment of operative objectives, and detect acute complications such as hemorrhage or ischemia. Methods. The authors used an actively shielded 1.5-tesla magnet, together with 15 mtesla/m gradients, MR console computers, gradient amplifiers, a titanium, hydraulic-controlled operating table, and a radiofrequency coil that can be disassembled. The magnet is moved to and from the surgical field by using overhead crane technology. To date, the system has provided unfettered access in 46 neurosurgical patients. In all patients, high-definition T1- and/or T2-weighted images were rapidly and reproducibly acquired at various stages of the surgical procedures. Eleven patients underwent craniotomy that was optimized after preincision imaging. ...

A mobile high-field magnetic resonance system for neurosurgery.

Purpose The purpose of this article is to update the neurosurgical community on the expanding field of surgical robotics and to present the design of a novel neurosurgical prototype. It is intended to mimic standard technique and deploy conventional microsurgical tools. The intention is to ease its integration into the "nervous system" of both the traditional operating room and surgeon. Concept To permit benefit from updated intraoperative imaging, magnetic resonance imaging-compatible materials were incorporated into the design. Advanced haptics, optics, and auditory communication with the surgical site recreate the sight, sound, and feel of neurosurgery. Rationale Magnification and advanced imaging have pushed surgeons to the limit of their dexterity and stamina. Robots, in contrast, are indefatigable and have superior spatial resolution and geometric accuracy. The use of tremor filters and motion scalers permits procedures requiring superior dexterity. Discussion Breadboard testing of the prototype components has shown spatial resolution of 30 microm, greatly exceeding our expectations. Neurosurgeons will not only be able to perform current procedures with a higher margin of safety but also must speculate on techniques that have hitherto not even been contemplated. This includes coupling the robot to intelligent tools that interrogate tissue before its manipulation and the potential of molecular imaging to transform neurosurgical research into surgical exploration of the cell, not the organ.

Surgical robotics: a review and neurosurgical prototype development

Technological developments in imaging guidance, intraoperative imaging, and microscopy have pushed neurosurgeons to the limits of their dexterity and stamina. The introduction of robotically assisted surgery has provided surgeons with improved ergonomics and enhanced visualization, dexterity, and haptic capabilities. This article provides a historical perspective on neurosurgical robots, including image-guided stereotactic and microsurgery systems. The future of robot-assisted neurosurgery, including the use of surgical simulation tools and methods to evaluate surgeon performance, is discussed.

Deon F. Louw

Papers

Microsurgical robot system

Incidence and clinicopathological features of meningioma

A mobile high-field magnetic resonance system for neurosurgery.

Surgical robotics: a review and neurosurgical prototype development

Robotics in neurosurgery.