Daniel Nyhan, MD

• Professor
• Division Chief, Cardiothoracic Anesthesia
• Anesthesia and Critical Care Medicine
• Johns Hopkins University
• Baltimore, Maryland

Unilateral blindness as a complication of patient positioning for spinal surgery: a case report worst high cholesterol foods purchase tricor overnight. Prevention of positional brachial plexopathy during surgical correction of scoliosis new zealand cholesterol chart buy discount tricor 160mg line. A novel device to simplify intraoperative radiographic visualization of the cervical spine by 26 cholesterol lowering foods and spices tricor 160mg generic. Clinical usefulness of somatosensory evoked potentials for detection of brachial plexopathy secondary to malpositioning in scoliosis surgery cholesterol levels chart south africa cheap tricor 160 mg on line. Femoral artery ischemia during spinal scoliosis surgery detected by posterior tibial nerve somatosensory-evoked potential monitoring 2.8 cholesterol ratio good discount tricor 160 mg free shipping. Combined single stage anterior and posterior osteotomy for correction of iatrogenic lumbar kyphosis cholesterol test fasting gum purchase tricor 160mg without prescription. Asymmetric postoperative visual loss after spine surgery in the lateral decubitus position. Visual loss in a prone-positioned spine surgery patient with the head on a foam headrest and goggles covering the eyes: an old complication with a new mechanism. Spinal cord evoked potential monitoring for cervical and thoracic compressive myelopathy. The value of somatosensory and motor-evoked potentials in predicting and monitoring the effect of therapy in spondylotic cervical myelopathy: prospective randomized study. Somatosensory evoked potential, neurological examination and magnetic resonance imaging for assessment of cervical spinal cord decompression. Simultaneous somatosensory evoked potential and electromyographic recordings during lumbosacral decompression and instrumentation. Microsurgical transdural discectomy with laminoplasty: new treatment for paracentral and paracentroforaminal cervical disc herniation associated with spinal canal stenosis. Spinal cord potential recordings from the extradural space during scoliosis surgery. Intraoperative neurophysiological monitoring in spine surgery: indications, efficacy, and role of the preoperative checklist. Motor-evoked potential monitoring for intramedullary spinal cord tumor surgery: correlation of clinical and neurophysiological data in a series of 100 consecutive procedures. Asymptomatic brain abscess as a complication of halo orthosis: report of a case and review of the literature. Delayed onset of generalized tonicclonic seizures as a complication of halo orthosis: case report. Adaptation of skull clamp for use in image-guided surgery of children in the first 2 years of life. Halo scalp ring: a form of localized scalp injury associated with caput succedaneum. Preoperative and intraoperative echocardiography to detect right-to-left shunt in patients undergoing neurosurgical procedures in the sitting position. Air embolism from wounds from a pin-type head-holder as a complication of posterior fossa surgery in the sitting position: case report. Quadriplegia following venous air embolism during posterior fossa exploration: a case report. Monitoring lung compliance and end-tidal oxygen content for the detection of venous air embolism. Air embolism through a ventriculoatrial shunt during posterior fossa operation: case report. Algorithms for the diagnosis of deep-vein thrombosis in patients with low clinical pretest probability. Semirigid instrumentation in the management of lumbar spinal conditions combined with circumferential fusion: a multicenter study. Deep vein thrombosis after major spinal surgery: incidence in an East Asian population. The risk of venous thromboembolism is increased throughout the course of malignant glioma: an evidence-based review. Prophylaxis for venous thromboembolism in hip fracture surgery: total costs and cost effectiveness in the Netherlands. The case against staged operative resection of cerebral arteriovenous malformations. Management of symptomatic deep venous thrombosis and pulmonary embolism on the neurosurgical service. Prevalence of perioperative complications after anterior spinal fusion for patients with idiopathic scoliosis. Evaluation of a screening protocol to exclude the diagnosis of deep venous thrombosis among emergency department patients. Diagnosis of lower limb deep venous thrombosis: a prospective blinded study of magnetic resonance direct thrombus imaging. Practical utility of the D-dimer assay for excluding thromboembolism in severely injured trauma patients. Upper extremities deep venous thrombosis: comparison of light reflection rheography and colour duplex ultrasonography for diagnosis and followup. Deep venous thrombosis treated with an inferior vena cava filter in a pregnant woman after recent neurosurgery: a case report. Outpatient use of low molecular weight heparin (dalteparin) for the treatment of deep vein thrombosis of the upper extremity. Clinical comparison of elastic supports for venous diseases of the lower limb and thrombosis prevention. Cost-effectiveness of low-molecular-weight heparin in the treatment of proximal deep vein thrombosis. Low molecular weight versus unfractionated heparin: a clinical and economic appraisal. Cost-effectiveness of the low molecular weight heparin reviparin sodium in thromboprophylaxis. Safety of deep venous thrombosis prophylaxis with low-molecular-weight heparin in brain surgery. Prophylaxis for deep venous thrombosis in craniotomy patients: a decision analysis. Prophylaxis for deep venous thrombosis in neurosurgery: a review of the literature. The morbidity of heparin therapy after development of pulmonary embolus in patients undergoing thoracolumbar or lumbar spinal fusion. Early intervention in massive pulmonary embolism: a guide to diagnosis and triage for the critical first hour. Pulmonary embolism: computer-aided detection at multidetector row spiral computed tomography. Delayed postoperative epidural hematoma formation after heparinization in lumbar spinal surgery. Rates and determinants of ventriculostomy-related infections during a hospital transition to use of antibiotic-coated external ventricular drains. Prevention of ventriculostomy-related infections with prophylactic antibiotics and antibiotic-coated external ventricular drains: a systematic review. Preoperative steroid use and the risk of infectious complications after neurosurgery. Prophylactic plastic surgery closure of neurosurgical scalp incisions reduces the incidence of wound complications in previously-operated patients treated with bevacizumab (Avastin) and radiation. Incidence of seizures after surgery for supratentorial meningiomas: a modern analysis. Cerebral aneurysms and arteriovenous malformations: implications for rehabilitation. Postoperative anticonvulsant prophylaxis for patients treated for cerebral aneurysms. Temporal lobe epilepsy surgery: outcome, complications, and late mortality rate in 215 patients. Postoperative epilepsy in patients undergoing craniotomy for glioblastoma multiforme. Incidence of postoperative epilepsy in children following subfrontal craniotomy for tumor. Seizures in patients with supratentorial oligodendroglial tumours: clinicopathological features and management considerations. Infectious intracranial complications of sinusitis, other than meningitis, in children: 12-year review. Incidence of seizures in patients with myelomeningocele: a multifactorial analysis. Cystic supratentorial gliomas: natural history and evaluation of modes of surgical therapy. The incidence of seizure disorder in children with acquired and congenital hydrocephalus. Anti-epileptic drugs for preventing seizures following acute traumatic brain injury. Antiepileptogenesis and seizure prevention trials with antiepileptic drugs: meta-analysis of controlled trials. Phenytoin plasma levels after intraoperative administration, for the prevention of post-craniotomy seizures. Management of 1000 vestibular schwannomas: hearing function in 1000 tumor resections. Hearing preservation in patients with acoustic neuromas via the middle fossa approach. Phenytoin versus leviteracetam for seizure prophylaxis after brain injury-a meta analysis. Add-on phenytoin fails to prevent early seizures after surgery for supratentorial brain tumors: a randomized controlled study. Predictive value of electrocorticography for postoperative epilepsy in patients with supratentorial meningioma. Disturbed cerebrospinal fluid circulation after subarachnoid hemorrhage and acute aneurysm surgery. Intracranial pressure and surgical decompression for traumatic brain injury: biological rationale and protocol for a randomized clinical trial. Avoidance of vascular compression in decompressive surgery for brain edema caused by trauma and tumor ablation. Traumatic brain swelling and operative decompression: a prospective investigation. Brain retractor edema during induced hypotension: the effect of the rate of return of blood pressure. The Brain Trauma Foundation, the American Association of Neurological Surgeons, the Joint Section on Neurotrauma and Critical Care. Decompressive craniectomy in patients with uncontrollable intracranial hypertension. Normal perfusion pressure breakthrough complicating surgery for the vein of Galen malformation: report of three cases. Cerebral hyperemia after arteriovenous malformation resection is related to "breakthrough" complications but not to feeding artery pressure. Neurosurgical outcomes in a modern series of 400 craniotomies for treatment of parenchymal tumors. Awake craniotomy with brain mapping as the routine surgical approach to treating patients with supratentorial intraaxial tumors: a prospective trial of 200 cases. Visualization of the pyramidal tract in glioma surgery by integrating diffusion tensor imaging in functional neuronavigation. Improving the extent of malignant glioma resection by dual intraoperative visualization approach. Risk of intracranial hemorrhage in glioma patients receiving anticoagulant therapy. Repeated surgery for glioblastoma multiforme: only in combination with other salvage therapy. Morbidity, mortality, and quality of life following surgery for intracranial meningiomas. Management of 1000 vestibular schwannomas: surgical management and results with an emphasis on complications and how to avoid them. A critical comparison of neurosurgical and otolaryngological approaches to acoustic neuromas. Incidence and management of complications of transsphenoidal operation for pituitary adenomas. Orbital floor fracture: an unusual complication of trans-septal transsphenoidal hypophysectomy. Endoscopic endonasal transsphenoidal surgery using a skull reference array and laser surface scanning. Carotid cavernous fistula and false aneurysms of the cavernous carotid artery: complications of transsphenoidal surgery. Pneumocephalus: effects of patient position on the incidence and location of aerocele after posterior fossa and upper cervical cord surgery. Novel devices for intraoperative monitoring of glossopharyngeal and vagus nerves during skull base surgery. Meningiomas involving the cavernous sinus: value of imaging for predicting surgical complications. Computed imaging stereotaxy: experience and perspective related to 500 procedures applied to brain masses. Complications in 622 cases of frame-based stereotactic biopsy, a decreasing procedure.

The experimental evidence for increases in brain energy metabolism during excitation in vivo comes in three different forms: as global steady-state changes brought on by general reductions or increases in brain activity; as localized responses to specific stimulation cholesterol levels chart usa buy tricor 160 mg visa, mostly the cerebral cortex; and as changes in substrates and metabolites in the circulation and in brain tissue cholesterol levels stress discount 160 mg tricor with mastercard. Focal activation responses in a number of stimulation studies of human brain (summarized in Table 49-8) fall into two fundamentally different categories of stimulation steak cholesterol chart order 160 mg tricor otc. It is important to note that the functional stages assigned to the global changes reflect major perturbations in consciousness that are not consistent with normal cognition cholesterol test kit for sale quality 160 mg tricor. In fact cholesterol quantity in food tricor 160mg mastercard, normal cognition is not accompanied by significant changes in global cerebral energy metabolism cholesterol test drinking coffee before generic 160mg tricor visa,149,150 thus suggesting that any local changes are matched by opposite changes elsewhere or affect regions so small that significance is not achieved. Stages of rat brain oxidative metabolism versus the rate of glutamate cycling measured by Sibson et al. Functional stages were inferred from the type and level of general anesthesia used in each experiment. The relative increases in glycolysis, blood flow, and oxidative metabolism are estimated for two categories of response to stimulation: passive, primary somatosensory stimulation ("mainly glycolytic") response and demanding, secondary somatosensory or motor ("mainly oxidative") response, listed in Table 49-8. Changing the oxidative capacity requires sustained stimulation for an extended period. Thus, brief transient increases in energy metabolism above the habitual level of activity apparently are not accompanied by commensurately increased oxygen consumption. In the brain, this consideration leads to the conclusion that the two categories of response are related to the known differential oxidative and glycolytic responsiveness of the neuronal and glial compartments (see the earlier section, "Metabolite Cycling"). To make sense and to give an accurate view of the dynamic relationships, the changes must be compared with the influx and efflux measurements of glucose, lactate, and oxygen during the activation. The equation allows changes in metabolites to be estimated by measurements of the circulation, or vice versa. Two examples of the use of this equation, in rodents and humans, are representative of this approach. Dienel and Cruz reviewed metabolite and circulatory changes in the rat brain during activation by manual stroking of the rat. The comparison shows that metabolites accumulate (particularly glucose and lactate) during the 5-minute activation period and decline (particularly glycogen) in the subsequent 15-minute recovery period. The changes show that the brains of these rats take up more metabolites than they use during the activation period, whereas they use more than they take up during recovery. These changes suggest that the four metabolic compartments are subject to different degrees of activation or undergo differential regulation of their oxidative and glycolytic capacities. Nutrition during brain activation: does cell-to-cell lactate shuttling contribute significantly to sweet and sour food for thought The calculations confirm that metabolites accumulate during exercise and decline slowly toward normal over the next half hour. These findings reveal a failure of oxidative metabolism to increase in parallel with stimulation, beyond the brief initial exhaustion of the putative oxygen reserve in mitochondria, whether because of limited oxygen delivery to the slice or because of a constitutive inability of mitochondria to match the increased pyruvate generation. Together, the changes in energy metabolism and metabolites show that metabolites accumulate during stimulation and decline during recovery. Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis. Since there is an increase in blood flow that accompanies activation, meaning that more oxygen is delivered, it follows that paradoxically there is an increase in oxyhemoglobin in the activated area. Recent considerations suggest that rates of glucose consumption determine the rates of blood flow, in part in response to the generation of lactate that may serve as a signal. This section describes attempts to identify agents to which blood flow does respond when brain tissue undergoes activation. The reader is referred to recent reviews for the in-depth treatment of neurovascular coupling. Perfectly matched flow-metabolism coupling, in contrast, maintains the same capillary oxygen tension profile and extraction fraction and hence cannot raise the oxygen pressure gradient in the absence of capillary recruitment or a decrease in mitochondrial oxygen tension. Kinetic analysis of cytochrome oxidase activity shows that increases in blood flow above the increase in oxygen consumption are needed to deliver more oxygen during excitation. The maximum oxygen delivery capacity is the upper limit of oxygen consumption and is reached when mitochondrial oxygen tension drops to the minimum level compatible with sustained cytochrome oxidase activity. When the rise in blood flow is enough to satisfy the increased need, oxygen extraction declines, and the average capillary oxygen tension is raised to a level consistent with the pressure gradient that delivers the necessary oxygen to the mitochondria. The decline is a measure of the relative increase in oxygenation in cerebral veins when blood flow increases. No change in oxygen consumption after a change in blood flow, therefore, implies a compensatory change in cytochrome c oxidase affinity for oxygen or cytochrome c or a change in the maximum reaction rate. Some studies of oxygen supply and delivery suggest that the affinity of cytochrome c oxidase for oxygen may change inversely with the oxidative metabolism of a tissue and thus preserve the sensitivity of the cytochrome c oxidase reaction to changes in the maximum velocity. Calculation of mitochondrial oxygen tensions in human brain, in association with strenuous body work, suggests that the tensions in brain may occasionally decline to an extent that is correlated with the emergence of fatigue189,190 and can be so severe that continued exertion is impossible. The fatigue is deemed cerebral because direct stimulation of the muscles of the subjects shows that contraction of these muscles is still possible. This evidence is consistent with the development of fatigue when ambient oxygen tensions are lower than normal. Recruitment of capillaries in the brain is relative at most; that is, it occurs by an increase in the uniformity of transit times rather than by an absolute increase in the number of perfused capillaries. Older studies of circulation in skeletal muscle show that a correlation exists between the increase in blood flow and the increase in lactate,197,198 thus suggesting that the increase in blood flow may reflect a glycolytic response, served by the increase of lactate levels in brain tissue. Pericytes Pericytes are contractile cells that form a grip around capillaries and venules in the brain as well as in the body as a whole. Originally known as Rouget cells after their discoverer, Charles-Marie Benjamin Rouget, pericytes earned their common name from their position on the abluminal aspect of the endothelial cells of the microvasculature. In the brain, pericytes perform hemostatic and homeostatic functions when they communicate with other cells of the neurovascular unit by direct physical contact and paracrine signaling. Also, when pericytes are absent, a number of neurotoxic proteins are not sufficiently degraded, with effects in the form of degenerative changes. It is synthesized in endothelial cells and neurons in proportion to the cytosolic concentration of unbound calcium. Regulation of Blood Flow the observation that oxygen consumption sometimes fails to increase during activation despite adequately increased blood flow. It delivers substrates such as glucose and amino acids and removes substances such as water, hydrogen ions, lactate, and pyruvate. Therefore, it is possible that increased oxygen delivery is not the most important mechanism served by increased blood flow. The theory of lactate as a volume transmitter means that the presence of lactate in the tissue at certain concentrations imparts information to the regulatory mechanisms of the tissue. By consideration of the steady state and non-steady state that brain tissue metabolism may occupy, the release of lactate to the tissue may be described as tonic during steady state and as phasic during non-steady state, respectively, when temporary increases of the concentration of lactate occur, in keeping with the terminology used for the monoaminergic volume transmitters. Another function of lactate as a signaling molecule for plasticity recently was unveiled. Effects on plasticity gene expression are observed both in primary neurons in culture and in the sensory-motor cortex in vivo. These results provide novel insights for the understanding of the molecular mechanisms underlying the critical role of astrocyte-derived L-lactate in long-term memory and reveal a novel action of L-lactate as a signaling molecule for neuronal plasticity. The source of the lactate appears to be aerobic glycolysis elicited by glutamate uptake into astrocytes in the steady state and glycogenolysis triggered by noradrenaline acting on 2 receptors in astrocytes in the non-steady state. The role of noradrenaline in the breakdown of glycogen suggests that this monoamine plays a special role in the phasic release of lactate. These actions imply that noradrenaline and lactate collaborate in second-messenger effects associated with working memory and memory consolidation. Recent evidence also shows that Ca2+ signaling may occur in response to stimuli other than neuronal excitation or may occur spontaneously,217 thus suggesting that changes in flow could occur without relation to functional activation of the cerebral cortex or synaptic activity. Metea and associates specifically ruled out glial K+ siphoning as a factor in neurovascular coupling. However, the available evidence suggests that an abundance of additional sources of energy is provided at the onset of activation and that the type of activation determines whether this energy is used. At this rate of pyruvate generation, the pyruvate concentration rises until the rate of pyruvate removal matches the rate of generation. The increase benefits the near-equilibrium conversion of pyruvate to lactate, transport into mitochondria, and export to the circulation. In the absence of increased oxidative phosphorylation, the increased glucose phosphorylation and pyruvate generation cause both the pyruvate and lactate levels and lactate efflux to rise in the tissue. Saturability in the relevant concentration range means that the concentration must undergo a greater rise for the flux to increase. The lactate concentration continues to rise with the concentration of pyruvate until the transport of pyruvate into mitochondria and subsequent oxidation, the conversion to lactate, and the efflux of lactate together match the rates of generation. The speed with which the pyruvate concentration rises depends on the turnover numbers of the enzymes and transporters removing pyruvate and hence on the affinities of these mechanisms for pyruvate. Mathiesen and colleagues showed that stimulation of cerebellar neurons in some cases led to increased blood flow despite inhibition of postsynaptic spiking activity by prevention of postsynaptic depolarization. If transport of pyruvate into mitochondria is rate limiting in functional stages 3 and 4 activation,74 the consumption of oxygen must depend on the cytosolic pyruvate concentration and hence on the rate of glycolysis, thus implying that oxygen consumption and lactate accumulation change in parallel. The slow or absent rise in oxygen consumption during passive stimulation could then be the consequence of a substantial lactate sink. This behavior is to be expected when the bulk of the activation affects compartments or cells with low oxidative capacity. The more substantial rise in oxygen consumption during more demanding stimulation is then the consequence of activation of compartments or cells with higher oxidative capacity. These two categories of response conveniently fit the properties of neuropil on one hand and more proximal sites of neurons and astrocytes on the other. These observations together suggest that glycolytic and oxidative reactions differ within cellular compartments and among cells, although the compartmentation is not complete (see "Metabolite Cycling" earlier). Thus, although recent measurements of the relative contributions of oxidative phosphorylation to the energy turnover in neurons and astrocytes show that 15% of the total energy turnover in brain tissue takes place in astrocytes at normal steady state,16,17 the astrocytes may contribute significantly more to the increase of nonoxidative metabolism during activation. Because brain energy metabolism is predominantly oxidative,183 the compartmentation suggests that the enhanced oxidative metabolism associated with brain activation occurs predominantly in the proximal synaptic structures of the neuropil. Thus, the models tend to illustrate rather than test the observation that spatial heterogeneities of the activities of glycolytic and oxidative metabolism in two or more compartments necessarily result in exchange of metabolites among the compartments, in quantities that depend on the degree of activation of the individual compartments. The claim that increased blood flow must occur simply to satisfy the demands for oxygen and glucose during neuronal excitation is a onedimensional solution for a very complex and heterogeneous system. Energy budget estimates suggest that most of the cerebral energy demand reflects the steady-state level of graded membrane depolarization rather than action potential generation and propagation. The increased energy supply is required to maintain the graded depolarization of neuronal membranes associated with changing sodium and potassium conductance. Increased energy turnover is not required to sustain hyperpolarization caused by decreased conductance of sodium or increased conductance of potassium or chloride. Glucose, pyruvate, and lactate occupy uniform tissue compartments, but the enzymes responsible for glycolysis and oxidative phosphorylation are unevenly distributed within and among the main cell populations. The bulk of information about cerebral metabolic rates, volumes of cells, and distribution of glycolytic and oxidative activities in vitro and in vivo in rodents and humans implies that cell bodies and extensions in the form of terminals, synapses, and end-feet differ substantially, with at least four identifiable compartments representing glial cell bodies, glial extensions into the neuropil ("astropil"), neuronal cell bodies and proximal dendrites, and neuroextensions into the neuropil and with an oxidative gradient from the neuronal cell bodies, through neuronal and astrocytic extensions into the neuropil, to the cell bodies of astrocytes. Substantial pyruvate and lactate generation occurs when the less oxidative compartments are activated more than the proximal neuronal sites. Although the resulting pyruvate and lactate accumulation is influenced by lactate exchange across the blood-brain barrier, the pyruvate and lactate pools thus accumulated are available for joint use by neurons and astrocytes. Astrocytes and, to a lesser extent, distal parts of the neurons contribute more pyruvate and lactate to the joint pool than do the proximal parts of neurons, which in turn extract more pyruvate and lactate. Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain. A model for the coupling between cerebral blood flow and oxygen consumption during neuronal stimulation. Oxygen consumption of cerebral cortex fails to increase during continued vibrotactile stimulation. Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Frequency-dependent changes in cerebral metabolic rate of oxygen during activation of human visual cortex. A communication channel model for information transmission in the blowfly photoreceptor. Internal brain state regulates membrane potential synchrony in barrel cortex of behaving mice. A quantitative description of membrane current and its application to conductance and excitation in nerve. Further investigations on a Mg++-Na+-activated adenosinetriphosphatase, possibly related to the active, linked transport of Na+ and K+ across the nerve membrane. The effect of sodium ions on the electrical activity of the giant axon of the squid. Vasoactive intestinal polypeptide induces glycogenolysis in mouse cortical slices: a possible regulatory mechanism for the local control of energy metabolism. Metabotropic receptor-mediated Ca2+ signaling elevates mitochondrial Ca2+ and stimulates oxidative metabolism in hippocampal slice cultures. The oxygen consumption of mammalian nonmyelinated fibres at rest and during activity. Activity-dependent energy metabolism in rat posterior pituitary primarily reflects sodium pump activity. Cerebral blood flow and oxygen uptake, and cerebrospinal fluid biochemistry in severe coma.

Similar neuropathologic findings were described in an experimental model of anaerobic brain abscess quitting cholesterol medication buy generic tricor 160 mg line,106 but capsule formation could not be divided into early and late stages because of delayed encapsulation cholesterol medication nightmares generic tricor 160mg mastercard. In all these studies cholesterol of 220 discount tricor online american express, capsule formation was less prominent on the ventricular than on the cortical surface cholesterol levels range normal buy tricor 160mg line. Alternatively cholesterol value chart order tricor 160 mg with mastercard, fibroblasts responsible for the capsule collagen may need to migrate from the meninges cholesterol definition health order 160 mg tricor otc,99 thereby accounting for the delay in capsule formation and the greater density of the capsule on its superficial surface. This thinner aspect of the capsule on its "deeper" surface probably explain the tendency for brain abscesses to rupture into the ventricular system rather than into the subarachnoid space. However, the histopathologic sequence of brain abscess formation was found to be different in an experimental rat model after inoculation with E. The histopathologic findings in brain abscesses after direct implantation differ from those produced by intracarotid embolization because metastatic abscesses induce only transient midline displacements, inflammatory cell infiltration is reduced, and collagen formation is slower around proliferating capsular vessels; this difference may have patient care implications because a lower level of encapsulation contributes to mortality. The brain is generally protected from infection by an intact blood-brain barrier, but once infection is established, immune defenses are usually inadequate to control it. Local opsonization in the brain is deficient, allowing encapsulated bacteria such as B. The continued release of proinflammatory mediators by activated glia and infiltrating peripheral immune cells may potentiate the subsequent recruitment and retention of newly recruited inflammatory cells and glia,118 thereby perpetuating the antibacterial inflammatory response. The functional importance of major abscess-associated T-cell subsets in modulating ongoing innate immune responses during infection has been assessed; manipulating Th1 and Th17 cells was found to expedite S. With progression to the late cerebritis stage, the acute inflammatory cells become mixed with macrophages and fibroblasts, and reticulin formation surrounds the necrotic center. As the capsule begins to form, increased numbers of fibroblasts and macrophages infiltrate the periphery, and mature collagen is deposited to form a capsule. The necrotic center then continues to decrease while marked gliosis develops outside the capsule. Despite the presence of virulence factors in the organisms that resist host defense mechanisms, the host inflammatory response is important in containment of the abscess, as has been examined with the use of immunosuppressed animals. Coadministration of dexamethasone also impaired the lymphocytic and fibroblastic response in a rat model of experimental S. Another study in dogs, which were immunosuppressed with azathioprine and prednisone 7 days before the intracerebral inoculation of -hemolytic streptococci, demonstrated that the immunosuppressed animals manifested a decreased inflammatory response characterized by a reduction in neutrophils and macrophages in the lesion, a decrease and delay in collagen deposition, and persistence of viable organisms into the late capsule stage. Although the decreased inflammatory response and edema initially led to less mass effect, the eventual size and area of the abscess may have become larger as a result of the diminished host response. Clinical Findings the clinical manifestations of brain abscess may run the gamut from indolent to fulminant; most are related to the size and location of the space-occupying lesion within the brain and the virulence of the infecting organism. The classic triad, fever, headache, and focal neurological deficits, is seen in less than 50% of patients with brain abscess. The clinical manifestations of brain abscess may also be defined by the infecting pathogen. Patients with Aspergillus brain abscess commonly manifest signs of a stroke syndrome as a result of ischemia or intracerebral hemorrhage, or both, that is referable to the involved areas of the brain. Patients with rhinocerebral mucormycosis initially have symptoms referable to the eyes or sinuses and complaints of headache, facial pain, diplopia, lacrimation, and nasal stuffiness or epistaxis. Axial contrast-enhanced T1-weighted magnetic resonance image demonstrating two rim-enhancing masses of the left periventricular white matter that represent abscesses. Because the organism has a proclivity for blood vessel invasion, thrombosis is a striking feature of the disease. Far-advanced disease is suggested by focal deficits such as hemiparesis, seizures, and monocular blindness. In one review of 22 cases from an at-risk population, half the patients were injection drug users and the basal ganglia was the most commonly involved site. Clinical findings include seizures, altered consciousness, headache, meningeal irritation, focal neurological deficits, abnormal behavior, and aphasia. On diffusion-weighted images, restricted diffusion (bright signal) may be seen and may distinguish abscesses from necrotic neoplasms. Neuroimaging may be quite sensitive in defining the findings in patients with fungal brain abscess. The lack of contrast enhancement in patients with mucormycosis is a poor prognostic sign because it indicates failure of host defense mechanisms to control the offending agent. At the time of aspiration, specimens should be sent for Gram stain, routine aerobic and anaerobic cultures, modified acid-fast smears, acidfast smears and culture, and fungal smears and culture. In patients with Aspergillus brain abscess, appropriate stains may reveal the presence of septate hyphae with acute-angle, dichotomous branching, whereas in patients with mucormycosis, tissue specimens may reveal irregular hyphae with right-angle branching. Histologic preparations of brain abscess specimens caused by Scedosporium species are indistinguishable from those caused by Aspergillus species. The hyphae of dematiaceous fungi may be brownish on hematoxylin-eosin staining but are not distinguishable from those of other molds. A, Transverse axial T1-weighted magnetic resonance image shows a bilobed lesion in the right frontal lobe and a second lesion in the left frontal lobe. B, Postcontrast T1-weighted image demonstrates peripheral enhancement of two lesions and subtle enhancement of another lesion in right frontal lobe (arrow). For patients in whom abscesses cause brain shift leading to brain herniation, neurosurgical intervention may be indicated irrespective of abscess size. After aspiration of abscess material and submission of specimens for special stains, histopathologic examination, and culture, empirical antimicrobial therapy should be initiated. Because antimicrobial therapy before aspiration may reduce the yield of bacterial cultures, it is reasonable to postpone initiation of antimicrobial therapy until after neurosurgery has been performed. Delaying antimicrobial therapy should be considered only in clinically stable patients and, therefore, every effort should be made to perform surgery in an expedited manner. In patients with no clear predisposing factors, a reasonable regimen to administer is the combination of vancomycin, metronidazole, and a third- or fourth-generation cephalosporin. Once the infecting pathogen is isolated, antimicrobial therapy can be modified for optimal treatment (Table 39-6); recommended dosages of agents in patients with normal renal and hepatic function are shown in Table 39-7. BacterialBrainAbscess the principles of antimicrobial therapy for bacterial brain abscess are to use agents that are able to penetrate the abscess cavity and have in vitro activity against the isolated pathogen,1,2,5,12,59,151-153 although no randomized controlled trials have examined the efficacy of specific antimicrobial agents in the treatment of bacterial brain abscess. Few studies have examined the penetration of specific antimicrobial agents into brain abscess pus, and some antimicrobial agents that penetrate may be inactivated in a purulent environment. It is also important to note that depending on the pathogenesis, a mixed infection may be present even though only one organism has been isolated, thus necessitating the use of more than one antimicrobial agent for therapy. Vancomycin has also achieved excellent penetration into brain abscess fluid after prolonged therapy. Meropenem has been efficacious in isolated cases of brain abscess, including one patient with a brain abscess caused by Enterobacter cloacae,159 so this agent may be especially valuable in patients with infections caused by resistant pathogens. In one 11-year retrospective study that compared intravenous cefotaxime and metronidazole with either intravenous imipenem or meropenem, meropenem therapy was associated with a significantly lower mortality rate and a lower seizure rate than imipenem. Surgical therapy is often required for the optimal approach to patients with bacterial brain abscess. However, in one retrospective review of 47 studies from 1990 to 2008, patients who underwent aspiration had a mortality of 6. Added if infection caused by methicillin-resistant Staphylococcus aureus is suspected, pending results of in vitro susceptibility testing. Ceftazidime or cefepime should be used if infection with Pseudomonas aeruginosa is suspected. Use of a specific agent depends on in vitro susceptibility testing of the isolated organism. Intraoperative ultrasound guidance is also helpful for the aspiration of small abscesses and can delineate abscess pockets. Complete excision by craniotomy is now infrequently performed because of the success of aspiration and closed-drainage techniques, although it may be required for patients with multiloculated abscesses in whom aspiration techniques have failed, for abscesses containing gas, or for abscesses that fail to resolve. Excision is usually required for posttraumatic abscesses that contain foreign bodies or retained bone fragments to prevent recurrence, for abscesses that result from fistulous communications. However, bur-hole aspiration has also been suggested as a satisfactory method of drainage in patients with cerebellar abscesses. Some have advocated using the more convenient "free" craniotomy, in which the overlying muscle. In this technique, the muscle is left attached to the bone flap, thus theoretically preserving blood supply to the bone. The osteoplastic bone flap potentially would have a lower risk of osteomyelitis in general and especially in the setting of an infection. However, no randomized studies have been performed that definitively resolve this procedural question. The optimal duration of medical treatment of bacterial brain abscess is unclear but has traditionally been 6 to 8 weeks for high-dose intravenous antimicrobial therapy,1,2,22,175 which is often followed by oral antimicrobial therapy for 2 to 3 months if appropriate agents are available. However, the efficacy of and necessity for additional oral antimicrobial therapy have not been established. If the abscess enlarges after 2 weeks of antimicrobial therapy, or fails to resolve after 3 to 4 weeks, further surgical aspiration or excision should be performed. Courses of 3 to 4 weeks of antimicrobial therapy may be adequate for patients who have undergone surgical excision of the brain abscess, whereas longer courses (up to 12 weeks with parenteral agents) may be required in patients treated with antimicrobial therapy alone. The Infection in Neurosurgery Working Party of the British Society for Antimicrobial Therapy recommends that intravenous therapy be used for 1 to 2 weeks for bacterial brain abscess179; depending on the clinical response, change to an oral regimen can be considered. Although this approach has been used in several series,18,180,181 it cannot be considered standard therapy in most patients with bacterial brain abscess. Biweekly neuroimaging studies performed for up to 3 months after completion of therapy have been suggested to monitor for reexpansion of the abscess and failure of resolution. The presence of a periventricular lucency is an absolute indication for immediate ventricular drainage regardless of the level of consciousness. Ventricular drainage should also be considered in patients with cerebellar abscesses with demonstrated mass effect, effacement, and/ or displacement of the fourth ventricle in the setting of overt or incipient hydrocephalus. Although the optimal approach to brain abscess most often requires a combined medical and surgical approach, certain groups of patients may be treated with medical therapy NocardialBrainAbscess In patients with Nocardia brain abscess, a sulfonamide, with or without trimethoprim, is recommended. In immunocompromised patients or those in whom therapy fails, combination treatment with regimens containing a third-generation cephalosporin or imipenem (or meropenem), along with a sulfonamide or amikacin, should be considered. Duration of therapy in patients with nocardial brain abscess ranges from 3 to 12 months,66,199 but it should probably be continued to 12 months in those who are immunocompromised. Some data have suggested that the lipid formulations of amphotericin B result in higher recovery rates than amphotericin B deoxycholate in patients with mucormycosis and hematologic diseases or solid organ transplantation, leading to a recommendation for use of a lipid formulation, usually liposomal amphotericin B, as first-line therapy. These agents may also decrease contrast enhancement of the abscess capsule in the early stages of infection, thereby being a false indicator of radiologic improvement. This decrease has been attributed to the introduction (~1970s) of neuroimaging, which allows early diagnosis and monitoring of response to therapy. In patients with an otitic focus of infection, mortality rates were shown to decrease from 35% from 1953-1977 to 14% from 1978 and 1989 and 3% from 1990-2011. A more favorable outcome was noted in one study of 142 patients when the Glasgow Coma Scale score was higher than 12 and the patients had no evidence of sepsis. In one review of 80 surgically treated brain abscess in 59 patients, immunosuppression, hematogenous spread, and advanced age were predictors of poor outcome. On the basis of this high postabscess epilepsy rate, patients should be advised on the risk of seizures and consideration should be given to prophylactic anticonvulsant therapy, although no randomized trials have assessed such an approach. AdjunctiveTherapy Therapy with corticosteroids should be initiated in patients with brain abscess who have associated edema and mass effect, progressive neurological deterioration, or impending cerebral herniation. The most common predisposing conditions are otorhinologic infections, especially of the paranasal sinuses, which are affected in 40% to 80% of patients. Other predisposing conditions are skull trauma, neurosurgical procedures, and infection of a preexisting subdural hematoma. Rare predisposing factors include cranial traction devices, nasal surgery, ethmoidectomy, and nasal polypectomy. Meningitis is an important predisposing condition in infants with cranial subdural empyema, which occurs in 2% to 10% of those with bacterial meningitis. Propionibacterium acnes may be isolated from patients after trauma, neurosurgical procedures, or dural allografts. Cranial epidural abscess refers to a localized collection of pus between the dura mater and overlying skull; because the abscess can cross the cranial dura along emissary veins, an accompanying subdural empyema may also be present. Cranial epidural abscess may also occur after head trauma, fetal scalp monitoring, halo pin penetration, and recent intracranial, transnasal, or transmastoid surgical procedures. The usual complaints are fever and headache, but the patient may not appear acutely ill, thereby leading to a delay in diagnosis. Diagnosis the diagnosis of cranial subdural empyema should be suspected in any patient with meningeal signs and a focal neurological deficit. The diagnosis of both subdural and epidural empyemas in postcraniotomy patients is problematic and often delayed. Sequential imaging studies may be valuable for documenting subtle changes, but the most useful tool is a high degree of suspicion. Altered mental status can occur and progress rapidly to obtundation and coma if the infection is not treated. However, these clinical findings may not be seen in patients in whom subdural empyema develops after cranial surgery or trauma, in those who have previously received antimicrobial therapy, in patients with infected subdural hematomas, or in those with metastatic infection to the subdural space. The clinical manifestation of cranial epidural abscess may be insidious and is usually overshadowed by the primary focus of Management Cranial subdural empyema is a surgical emergency because antimicrobial therapy alone does not reliably sterilize the empyema. The goals of surgical therapy are to achieve adequate decompression of the brain and to evacuate the empyema completely. When comparing craniotomy drainage with drainage after placement of bur holes, some studies have demonstrated a lower mortality rate in patients who have undergone craniotomy. However, selection bias may have played a role in these results because patients who underwent drainage via bur-hole placement may have been more ill and had a greater surgical risk. If bur-hole drainage is performed, multiple bur holes may be required to allow extensive irrigation.

The increased signal intensity on the preoperative T2-weighted image has resolved cholesterol and sodium definition purchase tricor 160 mg. These changes (arrows) are visible on a T1-weighted image (A) cholesterol medication welchol purchase cheap tricor on-line, a high-resolution computed tomographic image (B) cholesterol in dry shrimp 160 mg tricor otc, and a T2-weighted spin echo axial image (C) through the L4-L5 facets cholesterol hypertension medication order tricor 160mg fast delivery. Note the bony osteophyte along the anterior margin of the inferior facet at L4 on the right and the degenerative facet narrowing bilaterally cholesterol oxidase order discount tricor online. The bony changes are not as obvious on the T1- and T2-weighted images cholesterol levels and stroke risk buy 160mg tricor visa, but narrowing and asymmetrical soft tissue are clearly identifiable on magnetic resonance imaging. Alterations in alignment can lead to ligamentous laxity, followed by subsequent deterioration with loss of elasticity, calcification, and ossification. Exaggerated lordosis or severe disk space loss in the lumbar spine leads to close approximation and contact of the spinous processes and to degeneration of intervening ligaments. The opposing vertebral end plates define the superior and inferior margins of the disk space. Peripherally, the disk space is defined by the outer edges of the vertebral ring apophyses. Herniations can be AlignmentAbnormalities Spondylolisthesis can be classified as degenerative, isthmic, iatrogenic, and traumatic. Alterations in alignment can result from degenerative changes centered at the intervertebral disk, vertebral bodies, and facet joints, which can alter normal spinal movement. On the axial T1-weighted image (A), an ill-defined soft tissue mass is projecting medially off the left facet (arrow). On the contrastenhanced T1-weighted image (B), this soft tissue mass (arrow) is clearly outlined by peripheral enhancement. The T2-weighted image (C) demonstrates that this mass (arrow) has high-signal intensity, suggestive of fluid. Sagittal T1-weighted (A) and T2-weighted (B) spin echo images of the lumbar spine demonstrate grade I spondylolisthesis of L4 on L5 (arrows), as well as severe central canal stenosis and thickening of the posterior ligaments. Axial T1-weighted (C) and T2-weighted (D) images through the L4-L5 level demonstrate the severe central canal stenosis, thickened posterior ligaments, and severe bilateral degenerative facet changes. Localized displacement in the axial plane can be focal (less than 25% of the disk circumference) or broad based (between 25% and 50% of the disk circumference). Extension of disk material circumferentially (50% to 100%) beyond the edges of the ring apophyses is referred to as bulging and is not considered a form of herniation. The condition in which disk material has lost continuity with the parent disk is sequestration. Sagittal (A) and axial (B) T2-weighted images of the lumbar spine demonstrate disk extrusion (arrows) on the sagittal image with a narrow base. The axial image demonstrates posterior displacement of the S1 nerve root on the left as a result of this disk extrusion. Sagittal T2-weighted image (A) of the lumbar spine shows that the disk extends beyond the vertebral body margins (arrow); the axial T2-weighted image (B) shows the base to be broader than the posterior extent (arrow). Sagittal (G) and axial (H) T2-weighted images of the cervical spine demonstrate disk protrusion at the C5-C6 level and disk extrusion with an inferior fragment at the C6-C7 level. The axial image through the body of C7 demonstrates the rounded soft tissue mass centrally in the anterior epidural space. For acquired stenosis, there is no clear correlation between symptoms and the degree of stenosis. The most common symptoms are sensory disturbances in the legs, low back pain, neurogenic claudication, and weakness; pain is relieved with forward flexion. Extension worsens the degree of central and foraminal stenosis by 11%, whereas flexion appears to improve it by an average of 11%. Segmental instability, which can cause static and dynamic stenosis, is considered a cause of low back pain. Sagittal T1-weighted (A) and T2-weighted (B) images of the lumbar spine reveal the disk extrusion (white arrows) and an inferior fragment (A, black arrow). Diffuse central canal narrowing, evidence of a broad-based disk protrusion, and severe canal stenosis at the L4-L5 level are evident. Contiguous axial T1-weighted images (C and D) of the L4-L5 level demonstrate severe central canal stenosis (arrows). The lack of prognostic value of imaging studies also applies to the conservative management of spinal stenosis; prognostic imaging findings have not been correlated reliably with surgical success or even with whether patients will benefit from surgery. In a comparison of assessments by radiologists and clinicians, there was excellent agreement with the level of the abnormality; however, agreement was only fair (= 0. Metastases demonstrated on a sagittal T1-weighted spin echo image of the lumbar spine. Patchy and focal replacement of the marrow space is visible at all visualized levels. The marrow of the L2 vertebral body has been completely replaced, with loss of height and a convex posterior extension of the vertebral body into the spinal canal. Reversal of this signal intensity ratio after the age of 40 is a cause for concern. Lesions on T2-weighted imaging are more variable and can range from hypointense to hyperintense. It has, in most cases, replaced myelography for the evaluation of spinal cord compression because it depicts areas between the myelographic block. It is 95% accurate in detecting metastatic compression of the cord and cauda equina. There may be adjacent paraspinal soft tissue swelling, which may be detectable in the lumbar region as enlargement of a paravertebral soft tissue shadow, in the thoracic region as a paraspinal mass, and in the cervical region as prevertebral soft tissue swelling. Intense uptake in two adjacent vertebral bodies with loss of the disk space is visible on bone scans in patients with vertebral osteomyelitis. In the spine, it can be problematic to differentiate increased radionuclide uptake as a result of vertebral Metastatic Disease In the extradural space, the most common spinal neoplasms are metastatic lesions. Conventional radiographs usually remain negative until 50% to 70% of the bone has been destroyed. Bone scans have high sensitivity with larger lesions, especially if there is cortical involvement. Sagittal T1-weighted spin echo image (A) shows diffuse decreased signal intensity of the visualized osseous structures. The signal intensity of the intervertebral disk is higher than that of the vertebral body. T2-weighted image (B) shows diffuse decreased signal intensity of the marrow space. Whole-body technetium 99 bone scan (C) demonstrates diffuse increased activity throughout the spinal column. Sagittal (A) and coronal (B) multiplanar reformatted images from a computed tomographic data set of the lumbar spine. Destructive changes of the adjacent vertebral body margins of L4 and L5 are evident, each with an irregular contour and an ill-defined soft tissue mass. Malignancies, however, often appear similar to osteomyelitis on nuclear medicine studies because both exhibit increased uptake. The addition of intrathecal contrast material improves the delineation of epidural masses. Sagittal T1-weighted image (A) demonstrates decreased signal intensity of the L4 and L5 vertebral bodies with loss of end plate definition and confluent abnormal soft tissue extending across the disk space. Contrast-enhanced T1-weighted image (B) shows increase in marrow signal intensity and peripheral enhancement of the irregular disk space margins. The T2-weighted image (C) demonstrates nonanatomic high-signal intensity within the disk space. The presence of abnormal soft tissue in a paraspinal epidural location raises the differential consideration of inflammatory phlegmon versus abscess. These soft tissue masses encroach on the central canal and foramina in varying degrees. Epidural metastases may look like phlegmon; a large extruded disk that has migrated may demonstrate peripheral enhancement and must be differentiated from an abscess. Other differential considerations include epidural lipomatosis, which has a more characteristic fat signal on T1-weighted images, and epidural hematomas, whose appearances are more variable on T1- and T2-weighted images and usually demonstrate loss of signal on gradient echo images as a result of the presence of blood by-products. More recently, it has been suggested that restricted diffusion is characteristic of an abscess. Appropriate indications for imaging the spine in trauma include pain, neurological deficit, altered consciousness, and the presence of a high-risk mechanism of injury. The Canadian C-Spine Rule Study confirmed that "low-risk" patients (ambulatory, no midline tenderness, no immediate onset of pain, able to sit, or victims of simple rear-end motor vehicle collisions) who could actively rotate their heads 45 degrees in both directions do not require imaging. After administration of contrast agent (B), the full extent of the posterior epidural mass can be appreciated, as can the degree of spinal cord compression. Peripheral enhancement surrounds a nonenhancing loculated core, which is characteristic of an epidural abscess (long black arrows). The T2-weighted image (C) shows more confluent high-signal intensity throughout the entire region. The epidural abscess is difficult to identify on axial T1-weighted image (D) through the posterior epidural mass, although the spinal cord is markedly compressed anteriorly. Its character and nature are better appreciated on axial T1-weighted contrast-enhanced (E) and T2-weighted (F) images. Plain radiographs are also critical in the evaluation of instability in the absence of bony injury. Stability of the cervical spine is best assessed with dynamic imaging that includes flexion and extension views. This examination should be performed only on alert, cooperative patients without either neurological injury or radiographic evidence of unstable spinal injuries. Frequently, cervical mobility is limited by pain and muscle spasm at the time of the initial injury. Flexion and extension views may be more helpful when performed 7 to 10 days after the injury. Heavily T2-weighted sequences can be used to evaluate for nerve root avulsions and pseudomeningocele development. Ligamentous and soft tissue injuries are best visualized on fat-saturated T2-weighted images. The normal anterior and posterior longitudinal ligaments appear as continuous hypointense lines along the ventral and dorsal aspects of the vertebral bodies. In the presence of soft tissue injury, areas of increased T2 signal or discontinuity of the ligament may be visible. The requirement for special ventilators and monitors can often make it difficult or even impossible to image critically ill patients who have sustained trauma. Most bullets are nonferrous; however, the composition of the embedded projectile is rarely known in the acute setting. In theory, a ferrous fragment may become mobile in the magnetic field, which could result in greater damage to surrounding structures, although this has never been reported. MagneticResonanceImaging the use of gadolinium frequently aids in the distinction between "normal" postoperative changes and pathologic processes. It may, however, produce a mass effect in some situations, and it may be contiguous with the disk space. Disks, in contrast, do not usually enhance centrally within the first 20 minutes after the injection of paramagnetic contrast medium. Axial T1-weighted (A), contrast-enhanced T1-weighted (B), and T2-weighted (C) images through the L4-L5 disk in a patient with epidural fibrosis. The immediate preoperative study demonstrated aberrant soft tissue (arrows) in the anterior and left lateral epidural space. This was enhanced in a relatively homogeneous manner after administration of contrast material. Eight weeks postoperatively, the thecal sac had reexpanded, and the aberrant soft tissue, which continued to demonstrate homogeneous enhancement, had retracted somewhat. Scar tissue depicted on axial T1-weighted images before (A) and after (B) contrast enhancement after a left-sided laminectomy. The precontrast T1-weighted axial image shows aberrant soft tissue (arrow) in the left anterior epidural space. Contrast material caused relative homogeneous enhancement of this aberrant soft tissue (arrow) without evidence of a mass effect. Enhancing epidural scar is a common finding in the immediate postoperative period; the enhancement decreases over time. In the acute period, an epidural hematoma may not have peripheral enhancement, and the signal intensity characteristics of the soft tissue mass may reflect blood by-products. Unfortunately, the signal intensity of blood by-products that are characteristic on brain imaging is not always characteristic of the spine. In particular, the high-signal intensity noted on T1-weighted images is not as frequently encountered. Epidural abscesses usually have peripheral enhancement and, in the absence of osseous changes, may be difficult to distinguish from recurrent disk herniation or hematoma. The imaging findings of arachnoiditis are a reflection of the adhesion and clumping of nerve roots after inflammation. Recurrent disk herniation demonstrated on images through the lumbar spine after a right-sided laminectomy at the L5-S1 level. T1-weighted axial and sagittal images before contrast enhancement (A) reveal aberrant soft tissue (arrows) in the right anterior and lateral epidural space.

Rather cholesterol lowering foods and recipes tricor 160mg without a prescription, the properties that argue for all these different cells being classified as a single type are related primarily to function cholesterol levels hdl vs ldl discount tricor 160 mg on line. This property is significant not only for their adult function but also during cell development cholesterol lowering foods in malayalam buy generic tricor 160mg. It is this property that empowers these cells to function in such a rich array of computational behaviors cholesterol data chart cheap tricor 160mg mastercard. The light-sensitive stacks of photopigment-containing membrane are at the top cholesterol in eggs vs beef cheap 160mg tricor with visa, and the short cholesterol news order tricor discount, stubby axon is at the bottom. The peripheral process is at the top; the ganglion itself, containing the cell body, is at the lower right; and the central process is deployed within the central nervous system at the lower right. A typical neuronal impulse would travel from the dendrite at the left through the cell body to the axon hillock (initial segment), where an action potential would be generated, and end at the synaptic terminal. In B, a simple Purkinje cell dendritic spine (s) exhibits the characteristic features of a thin neck, bulbous head, and smooth endoplasmic reticulum. The Fine Structure of the Nervous System: Neurons and Their Supporting Cells, 3rd ed. Morphologically, the axon can be distinguished from the dendrite because it typically has a constant caliber over its entire length. Biochemically, the protein composition of the axonal membrane differs from the somatodendritic membrane, as do the structural proteins that make up the cytoskeleton, in particular the microtubule-associated machinery must be transported to sites on the cell that are up to a meter away. The electrical signal reaching the cell body from the dendrite travels to the point on the cell where the axon emerges. Soon after the axon leaves the cell body, a specialized region known as the initial segment (or axon hillock) can be identified. This part of the cell is the biochemical boundary of the axon and is the point of initiation of the action potential. Up to this point, the information packets from the dendrites and cell body travel primarily by electrotonic spread, with different packets of electrical activity coming together and summing in a graded (analog) manner. If the combined electrogenic signal reaching the axon from the cell body is sufficiently strong, the axon will fire and pass the information along; otherwise, the signal stops and proceeds no farther in the circuit. If the decision is a "go," the axon transforms the information into a selfpropagating electrical wave known as an action potential that travels undiminished down the axon to its end. The axon potential is an electrical signal that results from the coordinated functioning of sodium and potassium channels (see Chapter 58 for details), usually in collaboration with glial cells (see later). The synaptic terminal is the site where the information packet leaves the neuron for the next cell in the circuit. The morphology of the terminal is topologically complementary to the postsynaptic site to which it will transfer its information. The regular caliber of the axon and its linear array of constituent microtubules end, the axon swells in diameter, and a new collection of vesicles and mitochondria are found. When the axon potential reaches the presynaptic terminal, a series of biochemical events is initiated that results in the secretion of a burst of neurotransmitter; this enables the information packet to pass across the acellular gap of the synapse and initiates an electrical response in the next cell. Although the preceding description applies directly to many neurons, it is inadequate to fully describe the large number of cells that function as neurons in the human body. Although each neuron transmits information from one part of its cell body to another, the nature of the information transferred is often quite different from one cell to the next. These cells are neurons, but rather than receiving information from a preceding neuron in a circuit, their input comes in the form of signals in the environment. These signals can be grouped into three basic modalities: mechanical, chemical, and physical. MechanicalReceptors the simplest receptor cells of this type receive information about touch and pain. These receptor endings have different precisions and sensitivities and are specialized to receive different types of stimuli. Sometimes the neurite of a mechanoreceptor is wrapped around the interfusal muscle fibers of one of the striated muscles. The cellular deformation associated with movement of the axonal membrane activates a series of stretch-sensitive ion channels. The ionic current through these channels initiates the electrical activity that signals a sensory stimulus to the organism. A subset of mechanical receptors has evolved to serve the auditory and vestibular systems. The principal function of these cells is the same as for light touch receptors: deformation of a hair opens a number of specialized ion channels and results in the generation of an electrical signal. The difference in the acousticovestibular system is that "hairs" are actually cilia on the basal surface of the cell and hence are part of the receptor cell itself. Indeed, the ion channels that are opened in response to movement of the hair are located at the tip of the cilium. In the auditory system, the vibration of sound waves is transduced into the vibration of fluid in the cochlea. Receptor cells at different positions in the cochlear spiral respond to different auditory frequencies and transmit both pitch and volume information to the auditory system. In the vestibular system, a morphologically similar configuration of receptors is found in the semicircular canals. Movement of the head in any of the three orthogonal planes leads to movement of the fluid in the canals. This movement displaces the cilia of the vestibular receptors and initiates an electrical signal that is transmitted through the eighth nerve to the brain, where the vestibular system interprets the information to determine the orientation and movement of the organism in space. In each of Sensory Neurons the fundamental function of the nervous system is to enable an organism to respond quickly to its environment. The diversity of neuronal form occurs not only in the overall shape of the cell but also in the fine structure. These four different morphologies serve specific receptor functions, yet each is associated with a single neuronal cell type: the dorsal root ganglion neuron. The temperature receptors of the skin are one example of this group of receptor cells; the light-sensitive cells of the eye are another. These latter cells are known as photoreceptors, and they respond to electromagnetic radiation in the visible spectrum. They are further subdivided into rods and cones, depending on their wavelength specificity. Cones are narrowly tuned to transmit information about color, whereas rods have a broad frequency range and are most useful in low-light situations. These sacks contain the photosensitive pigment rhodopsin, which allows light energy to be transduced into an electrical signal. When light strikes the rhodopsin molecule, a chemical cascade occurs that is nearly identical to that described for the olfactory receptors. Thus, most axons terminate with synapses on the dendritic spines or shafts of other neurons. The networks of neurons formed by these interconnections are what allow an organism to perform complex behavioral responses to environmental stimuli. The movement of fluid causes the stereocilia to displace, opening a dedicated class of ion channel that depolarizes the cell and signals through the synaptic body to the afferent nerve fiber. The response of the cell can be modified centrally through depolarizations relayed through a reciprocal efferent connection. The fascicle branches into finer and finer rootlets in the zone of the target muscle and terminates in a motor end plate, a specialized synapse formed with a single muscle fiber. The complete end plate structure includes the surrounding Schwann cell, which forms a functionally interactive sheath around the entire synapse. This highly specialized nonneuronal cell is discussed in greater detail later in this chapter. The resulting change in conductance leads to an electrical "packet" of information that moves along the neuron to the rest of the brain. ChemicalReceptors A second class of receptors responds directly to specific chemicals, generating an electrical response that can be propagated to other parts of the nervous system. Receptors in this group are found in the papilla of the tongue, where they respond to the presence of salt, sweet, bitter, and sour, and project to the gustatory centers of the brain by way of the seventh and ninth cranial nerves. A more sophisticated and chemically diverse set of sensors in this class is found in the lining of the nasal epithelium. Family members of this receptor class number in the thousands, each apparently encoded by a different gene. Each receptor recognizes a different chemical structure and responds to the binding of the chemical by stimulating the release of the bound G protein that activates adenylate cyclase. This, in turn, leads to an elevation in cyclic adenosine monophosphate, which then opens a cyclic nucleotide-gated channel, leading to the generation of an electrical signal that is transmitted along the neuron to the olfactory portions of the brain. Neuronal Organization When several neurons link to form a circuit, sophisticated computational feats can be accomplished and useful work can be performed. Because of this higher level of organization, neurons can be categorized on the basis of not only their own shape and size, but also the role they play in a circuit. Projection neurons send long axons to other neurons in distant regions of the nervous system. Thalamocortical neurons (thalamus to cerebral cortex) and dentatorubral neurons (cerebellar dentate nucleus to red nucleus) are two examples of this type of cell. Local circuit interneurons, by contrast, have short, ramified axons; they participate mainly in local computational processes. Neurons can also be classified based on the function they perform within a circuit. In the simple descriptions of the previous sections, the firing of a neuron was assumed to stimulate the next neuron to fire as well. In fact, neurotransmitters can also inhibit the electrical activity of other neurons. The function of an inhibitory neuron, therefore, is to suppress the action of the downstream target, making it less likely to fire. The role of an inhibitory neuron is crucial to the more sophisticated functions of a neural circuit. It allows for the temporal or spatial sharpening of a response as neighboring cells are prevented from firing or the runaway tendency of a circuit is dampened. Neuronal Structure Neurons, like most other cells, are pale, clear, and difficult to see in living tissue. As a consequence, many of the significant advances in the study of the nervous system were made possible by improved methods of visualizing the nerve cell and its processes. The basophilic dyes are the oldest and still most widely used method of staining nervous tissue. Examination of nervous tissue stained with such reagents results in a clear picture of the cell body and proximal dendrites; axons and distal dendrites are usually invisible, so white matter and neuropil are generally clear of stain. During the 1800s, silver salts were found to have a special avidity for nervous tissue. Owing to their binding to neuronspecific classes of intermediate filaments, a variety of protocols were developed that revealed the neuronal axon with great clarity. Among this class of stains, the Bodian and Bielschowsky stains developed in the first half of the 20th century are still commonly used. In this procedure, pieces of tissue are incubated for many weeks in heavy metal salts. During this time, a small number of cells take up the salts, filling their entire intracellular spaces. Note the strong staining of nuclear heterochromatin (especially in the cell-dense granule cell layer) and the rough endoplasmic reticulum (Nissl substance) of the Purkinje cell. Human cortical neurons are stained with antibodies specific for neurofilament proteins, a major cytoskeletal component of neurons, dendrites, and axons. The dark precipitate was formed by subsequent incubation with an enzyme-linked antibody against rabbit immunoglobulin, followed by reaction with chromogenic enzyme substrates. Digoxigeninsubstituted nucleotides in the oligonucleotide probe are revealed with antidigoxigenin antibody. For unknown reasons, only 1% to 2% of the cells react in this fashion (seemingly at random). Although the technique reveals the finest details of dendritic structures, axons are more resistant to filling and are commonly invisible in Golgi preparations. In the second half of the 20th century, new technologies dramatically expanded our ability to visualize and analyze the nerve cells of the brain. Beginning in the 1950s and 1960s, the transmission electron microscope led to a quantum leap in the ability to resolve the details of nerve cellular structure. In this method, small pieces of tissue (typically 2 to 3 mm wide) are embedded in plastic and cut with a glass or diamond blade in sections ranging in thickness from tens to hundreds of nanometers. Before embedding, the tissues are usually stained with uranyl acetate, lead citrate, and osmium tetroxide, lipophilic dyes that reveal membrane structure with a high degree of clarity. Phosphotungstic acid is a frequently used stain that has a particular affinity for synapses. The resolution afforded by the electron microscope allows the fine structure of the cell to be revealed, and the organelles of the cell body can be analyzed.

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