Carol A. Ott, PharmD, BCPP

• Clinical Professor of Pharmacy Practice, Purdue University College of Pharmacy
• Clinical Pharmacy Specialist�Psychiatry, Eskenazi Health, Indianapolis, Indiana

https://www.pharmacy.purdue.edu/directory/ottc

They must be distinguished from the many acquired infectious skin care yogyakarta 150 mg cleocin overnight delivery, toxic acne guidelines buy cleocin canada, and immunological disorders that primarily affect the white matter skin care malaysia buy discount cleocin 150 mg on-line. Myelin acts as an electrical insulator for axons acne 2nd trimester purchase 150mg cleocin fast delivery, thereby markedly accelerating the velocity of the electrical impulses that they conduct acne 6 months postpartum 150 mg cleocin. The physiological significance of myelin may be appreciated by the fact that the most dramatic anatomical change occurring in the brain in the early years of life acne quiz order discount cleocin, when children are rapidly acquiring neurological skills, is the myelination of the nerve fiber tracts. Many enzymes not involved in the synthesis or maintenance of myelin are expressed in the myelin sheaths, including several that may be involved in signal transduction, ion channels, or the transport of large molecules. This finding has led to the speculation that myelin has more complex physiological functions beyond its role as an insulator of axons. Although the manifestations of this group of diseases are diverse, they generally share features attributable to the impairment of the central, and in some cases peripheral, myelin function. These include ataxia, spasticity, visual impairment (owing to involvement of the visual pathways from retina to cortex), disorders of higher cortical function (agnosia and aphasia) resulting from the dysfunction of association fibers, and, when the peripheral nervous system is involved, loss of reflexes. These values are all susceptible to change with the maturation of the white matter of the brain and in disease states. Specific patterns of abnormality are often highly suggestive of the diagnosis and may guide the clinician to the most appropriate diagnostic test, obviating the need for what might otherwise be a protracted and expensive series of investigations. Attempts to replace the defective or absent gene product by bone marrow or stem cell transplantation or by direct enzyme replacement have met with variable degrees of success, although the fundamental problem of transporting replacement macromolecules into the brain and spinal cord and targeting them to the appropriate subcellular organelle has not been overcome. Small molecule approaches designed to inhibit substrate accumulation, enhance residual endogenous enzyme activity, or manipulate gene expression are under investigation, but none of them has yet been proven beneficial in human disease. Additionally, the availability of these tests allows detection of heterozygotes (carriers) and antenatal diagnosis, creating opportunities for the prevention of these genetic diseases, particularly in at-risk populations. White Matter Further Reading Biffi A, Aubourg P, and Cartier N (2011) Gene therapy for leukodystrophies. Introduction the term leukoencephalopathy embraces essentially any disorder involving the white matter of the central nervous system. Such disorders may result from mutations in genes encoding the components of myelin or associated molecules, or may be acquired manifestations of vascular, inflammatory, infectious, traumatic, toxic, nutritional, or neoplastic diseases. Leukoencephalopathies, in general, produce symptoms and signs related to disruption of fiber tracts within the nervous system, particularly spasticity, visual impairment related to interruption of the visual pathways and, later in the illness, cognitive deficits related to disconnection of various cortical and subcortical regions. Some disorders impact both the gray and white matter, such as subacute sclerosing panencephalitis. In active disease, diffusion-weighted imaging and contrast enhancement are often positive. The genetic disorders typically present as slowly progressive neurodegenerative disorders that may initially present with cognitive impairment as in the case of childhood cerebral adrenoleukodystrophy or with motor symptoms as of the case with metachromatic leukodystrophy. Generally speaking, muscle stretch reflexes will be increased, but subsequently they may be lost in those disorders in which the peripheral nerves are also involved. These include metachromatic leukodystrophy, adrenoleukodystrophy, and Krabbe disease (globoid cell adrenoleukodystrophy). A relapsing and remitting course may occur in smallmolecule genetic disorders, which cause transient cerebral edema with or without residual injury or in the unusual disorder known as vanishing white matter disease (also known as childhood ataxia with central hypomyelination), in which the defect lies in any of the five genes encoding the subunits of eukaryotic translation initiation factor 2B. The inability to downregulate protein translation under conditions of stress is thought to lead to accumulation of excess protein, which then triggers the unfolded protein response pathway and leads to toxic effects through protein aggregation. These patients have a slowly progressive ataxic syndrome with acute exacerbations related to intercurrent illness. A relapsing remitting pattern is also seen in the most common leukoencephalopathy, multiple sclerosis. This pattern occurs both in children and adults, but there is a subgroup, primarily of adult women, who have a primary progressive form of the disease whose course may mimic a genetic leukodystrophy. In general, acute disseminated encephalomyelitis occurs in children, whereas multiple sclerosis is more likely in adults. A number of infectious disorders may produce a leukoencephalopathy or a panencephalopathy. Progressive multifocal leukoencephalopathy occurs in patients who are immunosuppressed either by their primary disease or iatrogenically and may present with unilateral signs, although it typically becomes more generalized over time. Human immunodeficiency virus infection itself, which may predispose to progressive multifocal leukoencephalopathy and other opportunistic infections, may present as a progressive dementia with significant involvement of the white matter. Patients who have hypertension, exposure to calcineurin inhibitors, or both, may develop a leukoencephalopathy, with or without gray matter involvement, classically involving the posterior portions of the hemispheres, although it may be much more widespread. Of course, in children and in adults, cessation of the cerebral circulation may produce hypoxic ischemic encephalopathy, which produces a profound white matter injury and loss as well as affecting the cortex. Patients who survive such injuries are usually left with varying combinations of spastic quadriparesis, dystonia, choreoathetosis or ataxia, or mixtures of all of these. Traumatic injury may produce focal white matter disease, and toxic exposures to agents such as cocaine and opioids can also produce leukoencephalopathies. Prescribed medications, particularly those used in cancer chemotherapy, may also cause white matter injury. Methotrexate, busulfan, carboplatin, and etoposide are particularly prominent in this respect. Classic nutritional deficiencies may produce widespread disruption of the white matter including B12 deficiency, which may reflect dietary insufficiency, impaired absorption related to lack of intrinsic factor, or excess consumption related to inborn errors of methylenetetrahydrofolate reductase deficiency. Immune-mediated disorders, such as systemic lupus erythematosus and other connective tissue disorders may cause injury to the white matter either directly or by inducing a 878 Encyclopedia of the Neurological Sciences, Volume 2 doi:10. Neoplasms themselves, including lymphomas and gliomatosis cerebri, may cause leukoencephalopathy directly or in association with their treatment. The term leukoencephalopathy is very broad and embraces a very large swath of clinical neurology. The recognition that a patient has a leukoencephalopathy is important in directing subsequent investigation toward a precise diagnosis and appropriate therapy. Shprecher D and Mehta L (2010) the syndrome of delayed post-hypoxic leukoencephalopathy. Subsequently, during his internal medicine would be better for him because of an irritable scar on his right index finger from a childhood injury. The scar frequently cracked and oozed blood, and in that era the risk of infection for him as a surgeon was deemed too great. This was perhaps a good choice for another reason, as fellow Philadelphia neurologist Charles W. In the winter of 1882, while examining at the Infirmary for Nervous Diseases connected with the Orthopedic Hospital, y a case of section of the inferior dental nerve, I discovered a new reflex. Because of his association with Mitchell, Lewis became particularly interested in neurology. At the Infirmary for Nervous Diseases, Lewis served as an assistant to Mitchell and then Osler and then succeeded Osler as chief. He was elected a fellow of the College of Physicians of Philadelphia in 1877, and was elected to the American Neurological Association in 1889. He became president of the medical staff at the Philadelphia Hospital and also served as a trustee of the University of Pennsylvania from 1896 to 1922 and as a manager of the Wistar Institute of Anatomy and Biology from 1896 until his death. When station became severely impaired, muscle stretch reflexes were also lost in the arms. Lewy, Fritz Heinrich B Holdorff, Schlossparkklinik, Berlin, Germany r 2014 Elsevier Inc. His scientific life was marked by frequent changes of discipline and institutions due in part to the exigencies of World War I and the difficulties faced by Jewish scientists during the subsequent years in Germany. Alzheimer is in the back row, third from right, and Fritz Heinrich Lewy is in the back row on the far right. Zugleich systematische Untersuchungen zur Klinik, Physiologie, Pathologie und Pathogenese der Paralysis agitans. He wrote his thesis in 1909 on La section totale de la moelle dorsale (Complete Section of the Spinal Chord). During World War I, he studied spinal injuries and became interested in neuropsychiatry. He wrote authoritatively on the frontiers with psychiatry and psychology, as well as on mysticism. However, it was Lhermitte who recognized the phenomenon as an important manifestation of multiple sclerosis. The sign may be present in other afflictions of the cervical spinal cord, including transverse myelitis, spondylotic spinal cord compression, injury, subacute combined degeneration, radiation myelopathy, cisplatin myelopathy, and among nitrous oxide abusers. The associated spinal cord lesion is usually located at the cervical and rarely the thoracic level. As suggested by Lhermitte, demyelination of the posterior column is always present, as was later confirmed pathologically and by magnetic resonance imaging studies. The lesion probably produces enhanced excitability of the ascending sensory tracts, making them sensitive to mechanical influences such as local pressure or stretch. Occasionally, the patient reports symptoms going up into the head or down one arm into the fingers. It may be a sign known as the barber chair sign, in which the patient may exhibit a startle jerk during the sensation of electric shock, elicited during the neurological examination when the patient is asked to flex the neck. It was not until 7 years later that Lhermitte described a woman with multiple sclerosis who experienced the symptom during her first attack. The symptom is suggestive of demyelination in the dorsal columns of the cervical cord and is thought to arise from focally demyelinated axons, which are exquisitely sensitive to mechanical stimulation, in this case stretching of the cord. In the case of neck trauma, there is often a latent period of approximately 3 months following a whiplash injury. Rarely, it may be seen in patients withdrawing rapidly from certain antidepressants, for example, paroxetine, and in this situation it can be treated with a single dose of fluoxetine. However, if the symptom persist, treatment with carbamazepine, clonazepam, or amitriptyline may be helpful. Spinal Cord Tumors, Biology of Encyclopedia of the Neurological Sciences, Volume 2 doi:10. Even in the absence of periodic fluctuations in the environment, a wide variety of physiological and behavioral functions, including the rhythms of body temperature, neurohormone secretion, sleep propensity and structure, vigilance, cognitive performance, and mood, continue to oscillate with an approximately 24-h rhythmicity. Importantly, each day, biological rhythms must be adjusted to their geophysical environment via external photic or nonphotic time-cues, or zeitgebers. Otherwise, these rhythms would shift by a small amount each day, and over several consecutive weeks, this would lead to a substantial desynchrony between endogenous daily rhythms and the environment. A specialized class of nonimage-forming, blue-light-sensitive photopigments called melanopsin, found in the retina, is thought to mediate the effects of light on the central circadian pacemaker, although participation of cones is also involved. The circadian system seems to be most sensitive to light of B460 nm, such that shorter wavelength light The nature of these interactions is such that relatively minor changes in the timing of sleep can have deleterious effects on alertness levels, sleep quality, and mood the following day. Accordingly, appropriately timed bright light exposure can have many practical and useful applications for the well-being of individuals experiencing sleep or mood disturbances associated with altered circadian rhythms. This article will focus on the two main applications for phototherapy, namely, its use as a means of fostering adaptive phase shifts in circadian rhythm disorders and also as a nonpharmacological therapeutic option for mood disorders. Appropriately timed bright light exposure can be used to alleviate symptoms associated with each. This misalignment may cause disturbances in sleep, particularly when attempting to sleep during the daytime, and may contribute to an increased risk of several health conditions, including cardiovascular diseases, metabolic syndrome, gastrointestinal disturbances, reproductive problems, psychological distress, and cancer. To achieve a phase delay of circadian 886 Encyclopedia of the Neurological Sciences, Volume 2 doi:10. More recently, phase advances and partial circadian resetting have been proposed as alternative treatment strategies for shift workers. The immediate activating effects of bright light exposure during night shifts also have the advantage of acutely increasing alertness and vigilance, as demonstrated in laboratory- and field-based studies of shift workers. Findings from field studies on shift workers have been promising, though in some cases, the direct stimulating effect of bright light, rather than its resetting effect, might have improved mood and performance during shifts. At the start of therapy, light exposure should be scheduled to begin after the time of habitual awakening, and should be progressively advanced each day until the target time interval is reached. Evening bright light It has been proposed that human tolerance to changes in lighting conditions with seasons varies according to a spectrum that includes at its end a clinical entity. There still remain some issues to be resolved, however, because if the disorder was solely caused by a phase-delay, mood would be expected to deteriorate following evening bright light exposure due to a worsening of the phase-delay shift. An alternative hypothesis is that light may have a direct action on brain mechanisms underlying emotion and mood processing, in a mechanism independent of the circadian system. This result implies an interaction between the bright light exposure and the serotoninergic system in mood regulation. Another study demonstrated similar improvements in mood for both morning and evening bright light (2500 lx) exposure compared to dim light. Consistent with a phase-advance hypothesis, a study by Parry and colleagues found that bright light (2500 lx) in the evening was more effective than morning light in symptom alleviation. However, a subsequent study by the same group reported comparable beneficial effects with bright white light (2500 lx) in the morning, bright white light (2500 lx) in the evening, and dim red light (o10 lx) in the evening (a putative placebo). Further supporting this is the description of patients with phase-advanced melatonin and cortisol rhythms. Interestingly, lithium, the primary mood-stabilizing treatment for bipolar disorder, has actions on the circadian pacemaker. If lithium accomplishes its therapeutic effects via a corrective phase delay of the circadian system, this may indicate that evening bright light exposure is an effective treatment option. Caution should be exercised when treating bipolar patients with bright light, however, because light can precipitate hypomania and mania in susceptible patients. A case series of light therapy during the depressed phase in bipolar women by Sit and colleagues indicated that short exposure (15 min) to morning bright light (7000 lx) was associated with the induction of mixed states, Light Therapy 889 whereas midday light therapy (12. Some studies utilizing light therapy techniques in bipolar depression have done so in combination with other chronotherapeutic approaches In a report by Colombo and colleagues investigating bipolar patients in the depressed phase undergoing wake therapy, bright morning light (2500 lx) exposure with or without concomitant lithium treatment was found to improve mood. Interestingly, patients exposed to 150 lx red light were equally improved, possibly due to supersensitivity to the effects of light in this patient population. Conclusion Bright light exposure is an effective intervention for inducing adaptive phase shifts in populations with circadian rhythm disorders, as well as a nonpharmacological means of alleviating symptoms associated with various mood disorders.

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Camillo Golgi and Santiago Ramon y Cajal are two notable scientists who studied neural microstructure acne topical medications buy generic cleocin 150 mg on line, producing intriguing images of stained neurons in the nineteenth and early twentieth centuries acne after shaving cleocin 150mg overnight delivery. Since then skin care 4men wendy buy cleocin on line amex, technical advances in glass acne vacuum discount cleocin 150mg on-line, lens coating acne quiz neutrogena buy 150 mg cleocin with mastercard, and objective manufacturing have led to vastly improved optical quality skin care 1006 cheap 150mg cleocin overnight delivery. New techniques such as polarization and phase contrast, and fluorescent, confocal, and two-photon microscopy have resulted in spatial resolution close to the theoretical limit for visible light. Super-resolution and holographic imaging techniques take microscopy beyond the classic resolution limit. Light reflected or emitted by the sample enters the objective and is separated from excitation light by dichroic mirrors. Epi-illumination mode is the most frequently used with fluorescent dyes or markers. Fluorescent Markers Special classes of chemicals, called fluorophores, can absorb one color (wavelength) of light and emit another. The strength of an emitted signal depends on the intensity of incident light and the fluorophore quantum yield. Return from the excited state to the ground state is accompanied by a photon emission. The wavelength of each excitation photon is larger (and the energy is smaller) than in single-photon microscopy. Excitation photons have longer wavelengths than emitted photons and experience less absorption in typical biological tissue, allowing deeper imaging. The photon density and temporal coincidence required by two- and three-photon fluorescence are only achieved using powerful pulsed lasers. Typical Components of the Microscope Typical components of the microscope include light source, field diaphragm, condenser with aperture diaphragm, sample Biological microscopy uses one of two illumination modes: transillumination or epiillumination. Any sample with enough contrast can be imaged in this brightfield transillumination mode. Histological stains or polarizing optics can enhance contrast of thin transparent sample. Field diaphragm, sample, and eye piece aperture (in black) represent an object set of conjugate planes, whereas the light source, condensor aperture, objective back aperture, and eyepiece eyepoint (in gray) represent an illumination set of conjugate planes. Polarization filter 2, if adjusted at 901 relative to filter 1, may block all the light. A sample placed between two polarization filters will rotate the polarization plane and result in observed intensity gradient (in otherwise low-contrast sample). In addition to fluorophore properties, it depends on the parameters of the objective. After passing through the second (objective or analyzer) prism, beams are converted into the same polarization plane and combine into interference patterns reflecting differences in optical path due to structural tissue elements. However, both the objective and condenser have to be specially made stress and strain free to avoid image quality loss. Effective axial resolution is greater than in conventional microscopes, but longer exposures are often required due to decreased signal intensity. As in conventional microscopy, the theoretical resolution limit is determined by the wavelength. High effective resolution allows colocalization of different fluorescent markers at whole-cell or subcellular levels. Both are based on light polarization: aligning the light wave oscillation in a specific plane. Light is split into two beams with orthogonal polarization directions by the condenser prism. Twophoton interaction requires critical density of photons achievable only in a small tissue volume. They cause less damage than short-wavelength lasers and penetrate deeper into biological tissues (up to 1 mm) enabling in vivo applications in both anaesthetized and freely behaving animals. These resolutions allow visualization of ultrastructural details of synaptic connections between neurons or in the neuromuscular junction. Despite the different illumination source, electron microscopes contain the same principal components as regular optical microscopes. The next phase is a decrease in light absorption due to compensatory decrease of local deoxyhemoglobin concentration, followed by the third phase due to capillary vasodilation. Part of the delivered energy is absorbed by the tissue and converted into heat, leading to thermoelastic expansion and high-frequency ultrasonic waves. The magnitude of the ultrasonic waves is proportional to optical absorption, revealing both local anatomical features and tissue oxygenation. Confocal and twophoton technology can further increase the effective spatial resolution. It allows light to penetrate into the scattering medium (biological tissue), achieving submicrometer resolution. MicroBrightField Stereoinvestigator and Neurolucida implement stereological cell counting and semiautomatic neuromorphology tracing. Finally, several image and neuronal structure repositories (Allen Brain Atlas, Neuromorpho. Org) and quantitative analysis tools (L-Measure, NeuroExplorer) serve as a virtual workbench for neuroscience research. The detector quantum efficiency (signal strength per photon) depends on the light wavelength, and is typically highest between 500 and 800 nm. Although improved dynamic range allows detection of fine gradients in image color, it also increases the size of the image and storage space. Lower resolution reduces the effective contrast and spatial detail discrimination ability. Using detectors for continuous video recordings, for example, for functional imaging or continuous focusing, poses timing limitations. Frequently, the highest speed in camera specifications is only achieved using limited regions of interest. Microscope systems can be fitted with image acquisition software that calculates optimal pixel sizes for each magnification objective. Image processing tools allow subtraction of a background (baseline) image, optimize image intensity distribution, and produce 2D projections from 3D image stacks. Svoboda K and Yasuda R (2006) Principles of two-photon excitation microscopy and its applications to neuroscience. Zakharenko S and Popov S (2000) Plasma membrane recycling and flow in growing dendrites. Several factors are involved in defining the cerebrovascular phenotype and relating them to degree of impairment. Vascular lesions include the type and size of vessels, origin and nature of vascular occlusion, and diffuse or focal integrity of the vessel wall components as critical variables in perfusion. The degree of parenchymal changes relative to cognitive domains and dysfunction is dictated by the presence of hemorrhage, distribution of arterial territories, the anatomical location (cortical vs. Arteriolar changes including intimal thickening, fibroid necrosis, and lipohyalinosis may be quantified as the sclerotic and hyalinosis indices. The progression of cellular events and manner of cell death, for example, apoptosis and autophagy occurring within the parenchyma after infarction, are important in assessing the severity of the lesions. Other variables to be noted include size of the incomplete infarct or perifocal hypoperfused (penumbra) zone and the presence of edema, pyknotic neurons, bulbous axons, shrunken oligodendrocytes, hemosiderin, neutrophils, lipid-laden macrophages, and intensity of astrocytosis or microgliosis. For the majority of these variables, semiquantitative methods with inherent limitations are the norm. However, there is still lack of critical standardized methods to assess lesion burden. Cystic infarcts (possibly also lacunar) with typically ragged edges were admixed in both cortical and subcortical structures. Large vessel and cardiac embolic events involving atherosclerosis, plaque rupture, intraplaque hemorrhage, thrombotic occlusion, and embolism, dissection and dolichoectasia may lead to macroinfarcts. Stenosis arising from atherothromboembolism associated with major arterial territories may be admixed in cortical and subcortical regions and rarely extends in smaller vessels beyond the circle of Willis. This, in turn, causes wide fluctuations in blood flow response and cerebral perfusion affecting the deeper cerebral structures. Lacunar Infarcts and Lacunes Lacunar infarcts appear less strongly associated with cognitive impairment than microinfarcts (Table 1). However, a recent thorough systematic review did not find differences between symptomatic and asymptomatic patients although cognition status was not assessed. Although the initiating factors causing the microangiopathy may be different, end-stage pathology invariably involves replacement of vascular smooth muscle with collagenous or other nontensile fibrillar material in both sporadic and familial cases. Small vessels of the brain including perforating arterioles and intracerebral end-arteries are causal in lacunar infarcts (lacunes or cystic lesions generally o2 cm) and microinfarcts. Because the tissue change is only visible by microscopic examination it is hence a microinfarct, which could resolve into a cyst or a lacune when in subcortical structures. Cavitated or trabeculated lesions and glial scars are difficult to relate to loss of cognitive function as large areas of brain would have to be screened. Lacunes may also masquerade as lacunar hemorrhages and dilated perivascular spaces. The weakening integrity of the vessel walls lowers perfusion with resultant cortical microinfarctions. In turn, hypoperfusion may also interfere with the arterial pulsations and with the interstitial fluid pressure, leading to reduced perivascular clearance of amyloid-b. Among these, it is neocortical rather than subcortical microinfarcts and, to a lesser extent, periventricular demyelination that predict progression of cognitive deficits. Microinfarcts most probably denote an undiscovered surrogate of underlying microvascular disease (Table 1). Leukoencephalopathy are accompanied by vacuolization and widening of the perivascular spaces. Although mild-to-moderate ischemic injury activates the myelin repair system, prolonged ischemia is thought to damage oligodendrocyte precursor cells that do not retain the ability to compensate for the myelin loss resulting in unsuccessful remyelination. With increasing severity all layers of the vessel wall show amyloid-b depositions accompanied by a loss of smooth muscle cells. The occipital lobe has been reported to be most frequently and most severely affected, followed by parietal, frontal, and temporal lobes. Apoptotic loss of cerebral vascular smooth muscle cells leading to wall thickening and fibrosis in small and medium-sized penetrating arteries are causal in subcortical infarction and cribriform change. Pantoni L (2010) Cerebral small vessel disease: From pathogenesis and clinical characteristics to therapeutic challenges. Neurological disease can interfere with all or part of these elements of bladder function. This section is a brief and highly simplified review of the anatomy, neuroanatomy, and physiology of the micturition reflex. Anatomy the bladder is a hollow, muscular viscus in the pelvis composed of interwoven smooth muscle cells, interspersed with elastin and connective tissues, and lined with transitional epithelium. The portion of the bladder muscle that contracts to expel urine is also known as the detrusor. It lies immediately posterior to the symphysis pubis, anterior to the uterus and vagina in women, and anterior to the rectum in men. The bladder and urethra are supported caudally by the muscles of the pelvic floor. The muscle fibers of the bladder condense into a funnel-like structure at the base, forming the bladder neck, also known as the internal sphincter. This structure is not a true circular sphincter but a coalescence of muscle as the bladder drains into the urethra. The female urethra is approximately 4 cm long and lies posterior to the symphysis pubis, adjoining the anterior vaginal wall. Midway along the urethra is a true sphincter composed of striated muscle, called the external sphincter. It is part of the pelvic floor musculature and surrounds the middle third of the urethra. The male urethra begins at the bladder neck and traverses the length of the prostate gland. The remainder of the urethra extends the length of the penile shaft and ends at the urethral meatus at the tip of the glans penis. Neuroanatomy Micturition is dependent on complex interactions between the peripheral somatic and autonomic nerves, spinal cord, and brain. The bladder receives its motor innervation through the parasympathetic pelvic nerves. The precise intramedullary location of detrusor motor neurons and their histological characteristics in the sacral spinal cord have not been described. The external sphincter receives somatic innervation via a branch of the perineal nerve, the second branch of the pudendal nerve. The sensory innervation of the autonomically innervated structures is presumed to be through the corresponding visceral afferents. The urethra distal to the external sphincter receives sensory innervation from branches of the pudendal nerve. The areas of the central nervous system specifically defined in bladder innervation include the cerebral cortex, the pons, and the conus medullaris. The principal afferent and efferent spinal pathways from detrusor motor neurons in the conus medullaris have been identified in the posterior superficial portion of the lateral columns. The spinal pathways for innervation of the external urinary sphincter have not been identified in humans. However, they can be assumed to resemble the organization of skeletal muscle, with ascending pathways in the posterior columns and descending tracts in the corticospinal and reticulospinal pathways. Areas near the nucleus locus ceruleus in the pons have been identified as crucial for the appearance of reflex detrusor contractions in certain quadriped animals.

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In the thoracic spine skin care routine for oily skin buy cleocin 150 mg line, the approach is similar to that in the lumbar spine acne on scalp cheap cleocin 150 mg with visa, except that the technique is usually retropleural and transthoracic and requires no retraction of significant lateral spinal musculature acne 1st trimester discount cleocin american express. The benefit of the thoracic approach is that it can be performed through much smaller incisions than a thoracotomy skin care center discount cleocin, wheareas simultaneously allowing the surgeon to avoid the awkward skin care secrets order cleocin 150mg on-line, more technically challenging thoracoscopic approach acne and pregnancy buy cleocin 150 mg amex. However, some common postoperative symptoms and risks are unique to the direct lateral approach. First, because the psoas is penetrated and retracted, some patients may develop transient spasm and mild weakness of hip flexion after surgery. Second, numbness, pain, or both may occur in the distribution of the genitofemoral nerve, which is at risk during the approach to the lateral spine and not easily monitored by standard electrophysiological monitoring. Postoperatively, this problem can manifest as a thigh, groin, or scrotal pain and can last from days to months. Third, aberrant vasculature may rest lateral to the spine and can be injured inadvertently. The nerves of the abdominal wall musculature can also be injured, but this risk is minimized by using blunt dissection. Radiculopathy, Lumbosacral 844 Encyclopedia of the Neurological Sciences, Volume 2 doi:10. He returned to the Mellon Institute and simultaneously pursued graduate studies at the University of Pittsburgh, where he received his PhD in 1962. In addition to the Nobel Prize, Lauterbur received many other awards and honors, including the Albert Lasker Award for Clinical Medical Research (1984), the National Medal of Science (1987), the National Medal of Technology (1988, with Damadian), and the National Academy of Sciences Award for Chemistry in Service to Society (2001). The exact frequency at which the nuclei precess is related to both the chemical and physical environment of the atom in the molecule. Lauterbur reasoned that by superimposing a weaker magnetic field that systematically varied with position onto a spatially uniform static magnetic field, he could create a magnetic field gradient, which would make it possible to determine spatial information from the sample. Because the resonance frequency of nuclei in an external magnetic field is proportional to the strength of the field, different regions of a sample in such a gradient field would have different resonance frequencies. Therefore, a given resonance frequency could be used to indicate a given position. Although Lauterbur clearly understood the potential of this technology for medical imaging, he was not successful in obtaining patents for his work. The university chose not to pursue patents, reportedly believing that any financial returns would not repay the costs. He applied for a patent for his scanning method in 1972, which was granted in 1974. Nevertheless, when the Nobel Prize was awarded to Lauterbur and Mansfield, Damadian protested vigorously and took out full page adds decrying the awards. Mansfield showed how the detected signals could be rapidly analyzed and transformed into an image. General Description and History Lead (Pb) is a naturally occurring heavy metal usually found in combination with other elements forming lead compounds and with other metals forming alloys. Lead sulfide, or galena, was ground into paste and used as a cosmetic in ancient Egypt. The intoxication of the Roman upper classes by lead in wines, syrups, and drinking water has been implicated as having contributed to the decline of Rome. From the nineteenth century onward, lead poisoning became a common hazard through exposure of workers involved in industrial uses of lead, such as in glazing, domestic water pipes, paints, plumbing, printing, manufacture of batteries, and lead pencils. Goadby, wrote his authoritative text on lead poisoning, Lead Poisoning and Lead Absorption, in 1912, and this has since served as a model textbook of industrial preventive measures. In the twentieth and twenty-first centuries, gasoline fumes and lead-based paint have been the principal sources of environmental lead, along with lead arsenate used as a pesticide in orchards. Another common source of lead exposure was leaching of lead from pipes used in older homes that are now being replaced by copper piping. Removal of the sources of lead exposure has reduced lead levels in the general population. Consequently, lead poisoning is less frequent nowadays in developed countries due to preventive action both domestically and occupationally. Many other sources of poisoning have been noted, including illegally distilled alcohol made by using leaded pipes and rainwater passed through leaded containers or conduits. In infants, a significant route of lead exposure is pica, the chewing of nonfood substances containing lead, in most cases from peeling paint and other objects and old glazing putty from windows. Screening programs have been developed in urban communities and studies have increased awareness of the significance of long-term low-level exposure. Routes of Absorption, Deposition, and Elimination the multiple points of entry of lead in the human body include the respiratory tract by the inhalation of lead dust, the gastrointestinal tract by absorption of lead in water and food substances grown in soil with high lead dust content, and by dermal contact with tetraethyl lead-containing substances. Two-thirds of the lead body burden in a normal healthy male is ingested and the remainder is inhaled. Iron and calcium deficiency increase the rate of gastrointestinal absorption and are significant risk factors for lead poisoning, especially among children. As ingested but unabsorbed lead is excreted by the intestinal tract, fecal excretion is a sensitive index of lead entering the body by ingestion. Diet influences the rate of lead absorption, and a high-fat, low-mineral diet increases whereas a high-mineral diet decreases lead absorption. Later, lead is transferred to teeth and bones, especially in the growing epiphyseal areas in children. This mobilization may be caused by acidosis or hypocalcemia, and in postmenopausal osteoporosis due to estrogen deficiency. There is a noteworthy association of blood levels of lead and those in bone in postmenopausal women who were not taking estrogen replacement therapy. Hence, lead toxicity has been noticed in elderly retired workers from battery manufacturing plants. Lead poisoning has also been the frequent result of use of lead-based paint for exterior decoration. Environmental exposures may derive from house demolition and work with lead pipes, production of wine or olives using domestic lead-containing vessels, or accidental contamination from toxic waste in rivers, oils, and waste effluents 848 Encyclopedia of the Neurological Sciences, Volume 2 doi:10. Bone lead is mobilized and transferred to more readily available compartments of the maternal circulation during pregnancy. Organic lead compounds are metabolized in the liver by cytochrome P450s in oxidative dealkylation reactions. Inorganic lead is metabolized by formation of complexes with protein and nonprotein ligands. Lead can cross the placental barrier and can be passed through breast milk, and children are more sensitive than adults. Lead has an affinity for deposition in brain tissue and peripheral nerves with major neurotoxic effects. As lead is toxic to mitochondrial function and interferes with calcium homeostasis, damage may involve multiple organs. Additionally, lead affects a number of key metabolic pathways within the cell because the metal interacts with sulfhydryl groups. As a result, an important enzyme required for energy production, glyceraldehyde phosphate dehydrogenase, is inhibited by lead, and certain similarly activated enzymes in the tricarboxylic acid cycle are affected. In addition, the metabolism of blood porphyrin is considerably deranged in lead intoxication. Patients with lead poisoning and those with the primary porphyrin disorder of acute intermittent porphyria often exhibit similar clinical findings. These laboratory animals had reduced numbers of cerebral cells and deficient myelin production in the nerve cell projections. Furthermore, lead exposure may alter the activity of neurotransmitters in the nervous system, such as acetylcholine and the catecholamines dopamine and norepinephrine. Toxic Effects of Lead Poisoning Clinical Neurotoxic Effects the clinical effects of absorbed lead vary individually. The age of the patient, the amount of lead absorbed and the rate of absorption, the presence of associated infections, and individual tolerance determined by genetic factors may change the clinical picture. Adults are affected with syndromes involving both the brain (encephalopathy) and peripheral nerve (neuropathy), whereas children develop mainly encephalopathy. In adults, the prodromal symptoms of lead poisoning are usually distinct and consist of progressive weakness and loss of weight associated with a gray color of the face, mild persistent headache, and a fine tremor of the muscles of the eyes, tongue, and face. Anorexia, mild nausea and vomiting, constipation, and vague abdominal pain are common. As the poisoning worsens, vomiting becomes intense with bloody diarrhea and abdominal pain or colic. Early in the illness, increasing irritability and nervousness occur, and with continued exposure memory impairment and partial or complete disorientation develop. In severe cases of poisoning, motor problems consisting of weakness of one or more extremities (monoplegia, diplegia, or hemiplegia) occur. Weakness of the shoulder girdle muscles and signs of neuropathy or peripheral nerve damage consisting of unsteady gait, impaired deep sensation, and absent deep tendon reflexes develop. Wasting of all four extremities may accompany, and even overshadow, the encephalopathic manifestations. Individuals become listless, lose weight and strength, and exhibit a stooped posture. They tire easily and complain of vague soreness throughout their muscles and joints. Tremors and twitching in the face and extremities may occur, alongside a syndrome consistent with motor neuron disease (amyotrophic lateral sclerosis). Peripheral sensory and motor nerve involvement is characteristic of chronic mild lead poisoning in adults. Sensory phenomena are manifested by tingling sensations (paraesthesias) and spontaneous pain. The motor impairment is more prominent, revealing weakness of greatest intensity in muscles receiving the greatest use. In adults, mononeuropathy or nerve damage to a single nerve sometimes occurs in the extremity most exposed to lead. In painters, exposure to lead paint typically leads to a radial nerve palsy or wrist drop in the hand that holds the paintbrush. In children, encephalopathy predominates and the syndrome differs from that of adults. When large amounts of lead are ingested, acute signs of increased intracranial pressure develop, with projectile vomiting and swollen optic discs (papilledema). Chronic lead poisoning may also cause personality changes and regressive behavior, with the child becoming irritable, restless, and often noisy and disobedient. In contrast to adult poisoning, cranial nerve palsies and motor involvement are usually absent. Blurred vision occurs as a result of the optic disc swelling and increased intracranial pressure. Although peripheral neuropathy is more characteristic of adult than child poisoning, when isolated nerve damage occurs, it commonly affects the peroneal nerve and causes a foot drop. A long series of studies of neuropsychological performance in lead workers and several meta-analyses have been made. The main emphasis has been on effects on attention, concentration, memory, visuospatial and visuomotor skills, speed of learning, and problem-solving ability. No threshold for the effects of lead on intelligence quotient has been determined. Extensive occupational and nonoccupational exposures among lower socio-economic groups during childhood could also account for the increased tibial bone lead. Raised levels of bone lead may be associated with cognitive decline in adulthood and among the elderly. Lead-induced brain disorders may mimic or exaggerate degenerative and vascular brain disease symptoms. Subclinical oxidative lead toxicity has been suggested to be responsible for some of the diseases and degenerative phenomena in the elderly. In a reassessment of all available information, it was concluded that neurobehavioral effects may occur at blood lead levels of 1. Electrophysiological studies have also been performed in children, in spite of the objective methodological difficulties. Toxic Effects of Lead in Other Organ Systems Elevated blood and bone lead levels are associated with elevated blood pressure, renal impairment degenerative diseases such as cataracts, and increased mortality. A cross-sectional analysis reported a strong association between lead blood levels and systolic and diastolic blood pressure values. An association of lead blood levels and baseline blood pressure was reported in a 4-year follow-up study of Korean lead workers, suggesting an acute as well as a cumulative effect of lead body burden on blood pressure. Many of the studies point out that a low socio-economic level may be associated with a greater health hazard from lead exposure in childhood and insufficient preventive care in adults. A systematic review of observational studies from database searches examined the evidence of an association between lead blood levels and cardiovascular outcomes. The findings of ischemic heart disease were suggestive, but not sufficiently robust. High lead blood levels were associated with a higher occurrence of peripheral vascular disease. Hyperuricemia due to increased reabsorption of uric acid often results in gouty arthritis, a condition that does not occur in other forms of renal failure. Thus, high exposure to lead impairs renal function, and the association with increased uric acid may predispose to gout. Because lead is a metabolic poison it might be expected to affect mortality in the general population, and studies in recent decades have corroborated this. The technique of K-X-ray fluorescence enables the quantitative measurement of cumulative lead in bone after lengthy exposure of decades, whereas lead blood levels reflect recent exposure to lead. Increased tibia lead was demonstrated in magnetic resonance imaging studies to be associated with brain volume decrease and white matter lesions.

Diseases

• Neutropenia intermittent
• Typhoid
• Osteopoikilosis
• Giardiasis
• Transverse limb deficiency hemangioma
• Aughton syndrome
• Fibrosing mediastinitis